Splenomegaly
Splenomegaly is the pathological enlargement of the spleen beyond its normal size, often resulting from infections, hematologic disorders, portal hypertension, or infiltrative diseases.
Splenomegaly
Splenomegaly literally means "spleen" (Greek: splēn) + "enlargement" (Greek: megalia). It refers to pathological enlargement of the spleen beyond its normal size. The spleen is normally not palpable on clinical examination; a palpable spleen generally indicates at least a 1.5- to 2-fold increase in size [1][2].
Splenomegaly is not a diagnosis in itself — it is a clinical sign that demands investigation for an underlying cause. [1]
Quantitative definitions (by imaging):
- Normal splenic length on ultrasound: up to ~12 cm (craniocaudal axis); some references use 13 cm as the upper limit.
- Splenomegaly: splenic length > 12–13 cm.
- Massive splenomegaly: spleen palpable ≥ 8 cm below the left costal margin, or crossing the midline, or extending into the pelvis [1][2].
Key Concept — Splenomegaly vs Hypersplenism
Splenomegaly and hypersplenism are related but distinct concepts. [1]
- Splenomegaly = physical enlargement of the spleen.
- Hypersplenism = a functional consequence of splenomegaly, defined by four criteria [2]:
- Pancytopenia (or at least one lineage cytopenia)
- Splenomegaly on examination/imaging
- Evidence of active (compensatory) bone marrow — the marrow is trying hard but the spleen is destroying cells faster
- Reversal of the cytopenias after splenectomy
Hypersplenism is NOT present in bone marrow infiltrative disease — because in infiltrative disease, the marrow itself is the problem, not the spleen. [2]
Splenomegaly is a sign, not a disease, so its epidemiology mirrors that of its underlying causes. In the Hong Kong context:
| Cause category | HK-relevant examples | Relative frequency |
|---|---|---|
| Liver disease / Portal hypertension | HBV-related cirrhosis (commonest cause of cirrhosis in HK, ~64–75% of cases) [3] | Very common |
| Haematological malignancies | CML, myelofibrosis, lymphomas, CLL | Common |
| Haemolytic anaemias | Thalassaemia (α-thal trait 5%, β-thal trait 3% in HK), hereditary spherocytosis | Common |
| Infections | EBV (infectious mononucleosis), malaria (imported), HIV, TB | Moderate |
| Autoimmune | SLE, RA (Felty syndrome) | Less common |
| Storage diseases | Gaucher disease | Rare |
Key HK-specific points:
- HBV is by far the most common cause of cirrhosis in Hong Kong (~64–75%), followed by HCV (~5–10%) and alcohol (> 5%) [3]. Cirrhosis → portal hypertension → congestive splenomegaly is therefore a bread-and-butter cause.
- Thalassaemia is prevalent in Southeast Asia and southern China. HbH disease (α-thalassaemia intermedia) causes mild-to-moderate splenomegaly; β-thalassaemia major causes marked splenomegaly [4][5].
- Malaria is uncommon in HK (imported cases only) but must be considered in travellers with fever and splenomegaly [6].
3. Anatomy and Function of the Spleen
- Location: Left upper quadrant (LUQ) of the abdomen, deep to the 9th–11th ribs posterolaterally, lying against the diaphragm.
- Relations: stomach (anteromedially), left kidney (posteromedially), splenic flexure of colon (inferiorly), tail of pancreas (hilum), left hemidiaphragm (superolaterally).
- Peritoneal attachments: gastrosplenic ligament (contains short gastric and left gastroepiploic vessels), splenorenal/lienorenal ligament (contains splenic vessels and tail of pancreas).
- Vascular supply: splenic artery (largest branch of the coeliac trunk) → tortuous course along superior border of pancreas → enters spleen at hilum. Short gastric arteries arise from the splenic artery near the hilum [7].
- Venous drainage: splenic vein → joins SMV to form the portal vein. This is why portal hypertension causes splenic congestion — the back-pressure transmits directly to the spleen through the splenic vein.
- Weight: ~150–200 g in adults (up to ~250 g considered normal).
Understanding the microanatomy is essential because different diseases enlarge different compartments:
| Compartment | Structure | Function | Diseases causing expansion |
|---|---|---|---|
| White pulp | Periarteriolar lymphoid sheath (PALS) = T cells; lymphoid follicles with germinal centres = B cells | Immune surveillance, antigen presentation, antibody production | Infections (reactive hyperplasia), lymphomas, leukaemias |
| Red pulp | Sinusoids + cords of Billroth (macrophage-rich reticular meshwork) | Filtration of old/abnormal RBCs, iron recycling, reservoir of monocytes/platelets | Haemolytic anaemias, congestion (portal HT), extramedullary haematopoiesis, myeloproliferative neoplasms |
| Marginal zone | Interface between red and white pulp; contains specialised B cells and macrophages | Captures blood-borne antigens, filters encapsulated bacteria | Marginal zone lymphoma |
Think of the spleen as performing four F's: Filtration, iFection defence (immune), Fetal haematopoiesis / extramedullary haematopoiesis, and blood-cell Factory reserve.
-
Filtration (culling and pitting)
- Culling: Removal and destruction of old, damaged, or abnormal RBCs (e.g., spherocytes, sickle cells, RBCs with inclusions). Macrophages in the cords of Billroth phagocytose these cells as they fail to squeeze through the inter-endothelial slits into the sinusoids.
- Pitting: Removal of intra-erythrocytic inclusions (Howell-Jolly bodies, Heinz bodies, siderotic granules, parasites) without destroying the cell — like picking dirt off a shirt.
- This is why post-splenectomy, you see Howell-Jolly bodies on blood film — because no one is pitting them out anymore.
-
Immune function
- Major site of opsonin production — especially IgM and complement (C3b, properdin, tuftsin).
- Filtering of encapsulated bacteria (Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis) — these organisms are poorly opsonised without splenic function, hence overwhelming post-splenectomy infection (OPSI).
- Contains the largest collection of organised lymphoid tissue in the body.
-
Haematopoiesis
- The spleen is a major haematopoietic organ in fetal life (2nd trimester).
- In adults, it can resume extramedullary haematopoiesis (EMH) when the bone marrow fails or is replaced (e.g., myelofibrosis, thalassaemia major) — this is a major cause of massive splenomegaly.
-
Reservoir / sequestration function
- Normally pools ~30% of platelets and a reservoir of monocytes.
- In splenomegaly, up to 90% of platelets may be sequestered → thrombocytopenia.
- Also sequesters RBCs and WBCs → pancytopenia (= hypersplenism).
High Yield — Why Splenomegaly Causes Pancytopenia
Pathophysiology of hypersplenism: (1) Increased destruction of blood cells by the expanded reticuloendothelial system; (2) Increased sequestration — pooling of cells in the enlarged splenic sinusoids; (3) Expansion of plasma volume (mechanism uncertain) diluting circulating cells. All three contribute to peripheral blood cytopenias. The order of cytopenia severity is usually anaemia > thrombocytopenia > leukopenia. [2]
4. Etiology (Causes of Splenomegaly) — Focus on Hong Kong
The causes of splenomegaly can be organised by pathophysiological mechanism — this approach helps you reason through them rather than memorise a list.
4.1 Classification by Mechanism
The GC lecture slide classifies causes into: [1]
Mechanism: Back-pressure in the portal venous system → splenic vein cannot drain → passive congestion of the red pulp → splenomegaly.
Portal hypertension → splenomegaly is a bidirectional relationship [1][3]:
- Portal hypertension causes congestive splenomegaly.
- Splenomegaly (from any cause) can also worsen portal hypertension through increased splenic blood flow.
| Level of obstruction | Causes |
|---|---|
| Pre-hepatic | Portal vein thrombosis, splenic vein thrombosis, compression by mass/tumour |
| Hepatic | Cirrhosis (HBV >>> HCV > alcohol > MASLD in HK) [3], schistosomiasis, veno-occlusive disease (post-chemotherapy) |
| Post-hepatic | Hepatic vein thrombosis (Budd-Chiari syndrome), IVC obstruction, right heart failure, constrictive pericarditis |
Why does right heart failure cause splenomegaly? Because elevated right-sided pressures transmit backwards → IVC → hepatic veins → portal system → splenic vein → splenic congestion. The same back-pressure mechanism causes hepatomegaly (nutmeg liver) and ascites.
Mechanism: Reactive hyperplasia of the white pulp (lymphoid expansion + germinal centre activation) and/or macrophage proliferation in the red pulp.
| Category | Organisms / Diseases | Notes for HK |
|---|---|---|
| Viral | EBV (infectious mononucleosis), CMV, HIV, viral hepatitis | EBV is a classic cause in young adults; spleen is fragile → risk of rupture |
| Bacterial | Infective endocarditis, TB, typhoid, brucellosis | IE causes splenomegaly via chronic immune stimulation and septic emboli [8]; TB is still relevant in HK |
| Parasitic | Malaria, leishmaniasis (kala-azar), schistosomiasis | Malaria — imported cases in HK; leishmaniasis causes massive splenomegaly (tropical) |
| Fungal | Disseminated histoplasmosis | Rare in HK |
According to Prof Kwong, EBV (infectious mononucleosis) is probably the only infection in HK that commonly gives rise to splenomegaly, given that the other infections listed are uncommon locally. [2]
4.1.3 Haematological Disorders
This is a major category and a favourite for exams. Subdivide into:
Mechanism: Increased RBC destruction → spleen works overtime destroying abnormal RBCs → work hypertrophy of the red pulp.
| Disorder | Mechanism of splenomegaly |
|---|---|
| Thalassaemia (major/intermedia) | Ineffective erythropoiesis + extravascular haemolysis + extramedullary haematopoiesis [4][5] |
| Hereditary spherocytosis | Spherocytes are rigid and cannot pass through splenic sinusoidal slits → trapped and destroyed |
| Autoimmune haemolytic anaemia (AIHA) | Antibody-coated RBCs opsonised and phagocytosed by splenic macrophages (extravascular haemolysis) |
| Sickle cell disease (early) | Repeated sickling → splenic sequestration (early childhood); later → auto-splenectomy from repeated infarction |
Why Thalassaemia Causes Splenomegaly — From First Principles
In thalassaemia, there is unbalanced globin chain production → excess unpaired chains precipitate → damage RBC membrane → shortened RBC survival (haemolysis) + ineffective erythropoiesis in the marrow. The spleen works overtime filtering and destroying these abnormal RBCs → work hypertrophy. In severe cases, the bone marrow cannot keep up, so the spleen (and liver) resume extramedullary haematopoiesis → further enlargement. Patients with thalassaemia major who are on regular transfusion develop iron overload → haemosiderosis also contributes. [4][5]
The GC lecture on splenomegaly specifically covers myeloproliferative neoplasms as a learning objective. [1]
Mechanism: Clonal proliferation of myeloid lineage cells → extramedullary haematopoiesis in the spleen → massive enlargement (especially myelofibrosis and CML).
| MPN | Key features | Degree of splenomegaly |
|---|---|---|
| Chronic Myeloid Leukaemia (CML) | Philadelphia chromosome t(9;22) → BCR::ABL fusion → constitutively active tyrosine kinase → uncontrolled proliferation. Most apparent physical exam finding = massive splenomegaly. [9] | Massive |
| Primary Myelofibrosis (PMF) | Progressive marrow fibrosis → marrow failure → compensatory extramedullary haematopoiesis in spleen and liver. JAK2 V617F (~50%), CALR, or MPL mutations. | Massive (often the largest spleens) |
| Polycythaemia Vera (PV) | JAK2 V617F (~95%). Increased red cell mass. Splenomegaly from congestion + extramedullary haematopoiesis. | Moderate |
| Essential Thrombocythaemia (ET) | JAK2, CALR, or MPL mutations. Elevated platelets. | Mild or absent |
CML classically presents with massive splenomegaly + marked leukocytosis with bimodal distribution of myelocytes and neutrophils + basophilia. [9]
| Disorder | Mechanism |
|---|---|
| Chronic Lymphocytic Leukaemia (CLL) | Accumulation of mature-looking but functionally incompetent B lymphocytes in spleen, marrow, nodes |
| Non-Hodgkin Lymphoma (NHL) | Lymphomatous infiltration of splenic white pulp (especially marginal zone lymphoma, mantle cell lymphoma) |
| Hodgkin Lymphoma | Less commonly causes splenomegaly than NHL |
| Hairy Cell Leukaemia | Rare B-cell neoplasm; "hairy" cells infiltrate and expand the red pulp → splenomegaly often prominent |
| Splenic marginal zone lymphoma | Indolent B-cell lymphoma specifically arising in the splenic marginal zone |
| Condition | Mechanism |
|---|---|
| Multiple myeloma | Rarely causes splenomegaly (marrow-based disease) |
| Systemic mastocytosis | Mast cell infiltration |
Mechanism: Immune complex deposition, lymphoid hyperplasia, or macrophage activation.
| Disease | Details |
|---|---|
| SLE | Splenomegaly in 10–46%, especially during active disease flares [11] |
| Rheumatoid arthritis (Felty syndrome) | Triad of RA + splenomegaly + neutropenia |
| Sarcoidosis | Non-caseating granulomatous infiltration |
| Still's disease (Adult-onset) | Systemic inflammation with hepatosplenomegaly |
Mechanism: Abnormal material accumulates within splenic macrophages or reticuloendothelial cells → physical expansion.
| Disease | Stored material |
|---|---|
| Gaucher disease | Glucocerebroside (β-glucocerebrosidase deficiency) — can cause massive splenomegaly |
| Niemann-Pick disease | Sphingomyelin |
| Amyloidosis | Amyloid fibrils |
| Cause | Details |
|---|---|
| Splenic cysts | Congenital (epidermoid) or acquired (post-traumatic pseudocyst, hydatid) |
| Splenic abscess | E.g., from IE with septic emboli; immunocompromised patients |
| Splenic infarction | Can cause acute painful splenomegaly (from haematological disorders or emboli) [7] |
| Metastatic tumour | Rare (spleen is an unusual site for metastases) |
Causes of Massive Splenomegaly — Mnemonic: 'CML Makes My Spleen Gigantic'
Massive splenomegaly (palpable ≥ 8 cm below costal margin or crossing midline): [1][2]
| Cause | Category |
|---|---|
| CML | MPN |
| Myelofibrosis | MPN |
| Malaria (chronic, tropical) | Infection (hyperreactive malarial splenomegaly) |
| Kala-azar (visceral leishmaniasis) | Infection |
| Gaucher disease | Storage |
| Thalassaemia major | Haemolytic |
| Lymphoma (some) | Lymphoproliferative |
| Polycythaemia vera (late) | MPN |
The classic exam-favourite mnemonic is "CML Makes Kala-azar Patients' Tummies Gigantic" — CML, Myelofibrosis, (visceral) Leishmaniasis, (chronic) malaria, Polycythaemia vera, Thalassaemia major, Gaucher disease.
The GC lecture also classifies causes by prevalence [1]:
| Category | Examples |
|---|---|
| Common | Cirrhosis/portal HT, haematological malignancies (CML, lymphoma), haemolytic anaemias, infections |
| Uncommon | SLE, sarcoidosis, amyloidosis |
| Rare | Storage diseases (Gaucher, Niemann-Pick), splenic tumours |
There are essentially five pathophysiological mechanisms by which the spleen enlarges. Understanding these is the key to approaching splenomegaly systematically:
| Mechanism | What happens | Examples |
|---|---|---|
| 1. Work hypertrophy (increased function) | Spleen upregulates its normal function — filtering abnormal cells or fighting infection | Haemolytic anaemias (spherocytosis, thalassaemia), immune-mediated destruction (AIHA, ITP) |
| 2. Congestive | Impaired venous drainage → passive engorgement of the red pulp | Portal HT (cirrhosis, portal/splenic vein thrombosis), right HF, Budd-Chiari |
| 3. Infiltrative | Abnormal cells or material deposited within the spleen | Leukaemias, lymphomas, storage diseases (Gaucher), amyloidosis |
| 4. Immune / inflammatory hyperplasia | Reactive expansion of white pulp from immune stimulation | Infections (EBV, IE, TB), autoimmune diseases (SLE, RA) |
| 5. Extramedullary haematopoiesis | Spleen resumes haematopoietic function when marrow fails or is replaced | Myelofibrosis, thalassaemia major |
In reality, many diseases involve more than one mechanism simultaneously. For example, myelofibrosis causes both infiltration AND extramedullary haematopoiesis. Thalassaemia causes both work hypertrophy AND extramedullary haematopoiesis.
5.1 Why Congestive Splenomegaly Occurs in Cirrhosis — In Detail
This is a very commonly examined concept [3]:
- Cirrhosis → diffuse hepatic fibrosis and formation of regenerative nodules.
- This distorts the hepatic architecture → increases intrahepatic vascular resistance (both mechanical obstruction from fibrosis AND functional vasoconstriction from increased endothelin / decreased nitric oxide in hepatic sinusoids).
- Increased resistance → portal hypertension (portal pressure gradient ≥ 6 mmHg; varices at ≥ 10 mmHg).
- Portal hypertension is also worsened by increased portal blood flow due to splanchnic vasodilation (increased NO in gut vasculature — a hyperdynamic circulation).
- The splenic vein drains into the portal vein → splenic venous drainage is impeded → passive congestion of the spleen → red pulp expansion → splenomegaly.
- The enlarged, congested spleen now sequesters and destroys more blood cells → hypersplenism → pancytopenia.
6. Relevant Classification Systems
| Grade | Description |
|---|---|
| Mild | Palpable just below costal margin (1–4 cm) |
| Moderate | Palpable 4–8 cm below costal margin |
| Massive | Palpable ≥ 8 cm below costal margin, crosses midline, or extends into pelvis |
6.2 By Mechanism (as above — Section 5)
| Acuity | Examples |
|---|---|
| Acute | Splenic sequestration crisis (sickle cell), acute infection (EBV), splenic infarction |
| Chronic | Cirrhosis/portal HT, CML, myelofibrosis, thalassaemia, storage diseases |
7. Clinical Features
| Symptom | Pathophysiological basis |
|---|---|
| Abdominal fullness / discomfort (LUQ) | Physical mass effect of the enlarged spleen stretching the splenic capsule and compressing adjacent structures (stomach, colon) [1] |
| Early satiety | Enlarged spleen compresses the stomach → reduced gastric capacity → patient feels full after small meals [1] |
| Left upper quadrant pain | Capsular stretching (constant dull ache) or splenic infarction (acute, severe, may radiate to left shoulder = Kehr's sign — referred pain via phrenic nerve C3–C5 irritation of the diaphragm) [7] |
| Left shoulder pain (Kehr's sign) | Splenic infarction or subcapsular haematoma → irritation of the left hemidiaphragm → referred pain to the left shoulder via the phrenic nerve |
| Symptoms of anaemia | Hypersplenism → increased RBC destruction/sequestration → fatigue, pallor, exertional dyspnoea [1] |
| Easy bruising / bleeding | Hypersplenism → thrombocytopenia → mucosal bleeding, petechiae, easy bruising [1] |
| Recurrent infections | Hypersplenism → leukopenia (especially neutropenia) → increased susceptibility to bacterial infections |
| Symptoms of the underlying cause | E.g., weight loss + night sweats (lymphoma/leukaemia), fever (infection/IE), joint pain (SLE/RA), jaundice (haemolysis/liver disease), bone pain (myelofibrosis) |
7.2 Signs
| Sign | How to elicit | Pathophysiological basis |
|---|---|---|
| Palpable spleen | Patient supine or in right lateral decubitus position; palpate from right iliac fossa moving upwards towards the left costal margin during deep inspiration (the spleen descends with the diaphragm on inspiration) | Spleen must be ~1.5–2× normal size before it becomes palpable; it enlarges towards the right iliac fossa along its long axis |
| Splenic notch | A notch palpable on the medial border of an enlarged spleen — pathognomonic for spleen (distinguishes it from left kidney) | Anatomical feature of the normal spleen that becomes palpable when enlarged |
| Dullness to percussion (Castell's sign, Traube's space) | Percussion over the lowest intercostal space in the left anterior axillary line on full inspiration → dullness suggests splenomegaly; also, loss of the normal tympany over Traube's space (left lower anterior chest wall, normally resonant because of the gastric air bubble) | Enlarged spleen replaces the air-containing stomach/bowel → dull percussion note |
| Unable to "get above" the mass | Cannot insinuate fingers between the mass and the costal margin (unlike a renal mass) | Spleen arises from under the ribcage — its upper pole is tucked beneath the ribs |
| Moves with respiration | Spleen moves inferomedially with inspiration | Spleen is attached to the diaphragm via the phrenicosplenic ligament |
| Non-ballotable | Unlike the kidney, the spleen is an anterior structure and not bimanually ballotable | Spleen is intraperitoneal and anterior; kidney is retroperitoneal |
| Sign | Basis |
|---|---|
| Pallor | Anaemia from RBC destruction/sequestration |
| Petechiae / purpura / bruising | Thrombocytopenia |
| Signs of infection | Leukopenia |
These are crucial because they guide your differential diagnosis on examination:
| Finding on examination | Suggests... | Why? |
|---|---|---|
| Stigmata of chronic liver disease (spider naevi, palmar erythema, gynaecomastia, caput medusae, jaundice, ascites) | Cirrhosis / portal hypertension | Liver synthetic failure + portal HT → collateral circulation, hormonal imbalance [3] |
| Lymphadenopathy (generalised) | Lymphoma, CLL, ALL, infection (EBV, HIV, TB) | Malignant or reactive lymphoid proliferation in both nodes and spleen |
| Massive splenomegaly without lymphadenopathy | CML, myelofibrosis | MPN primarily involves the marrow and spleen, not lymph nodes |
| Fever + changing cardiac murmur | Infective endocarditis | Chronic bacteraemia → immune complex deposition + septic emboli → splenomegaly [8] |
| Jaundice | Haemolytic anaemia, liver disease | Unconjugated hyperbilirubinaemia (haemolysis) or conjugated (hepatic) |
| Bone tenderness | Leukaemia, myelofibrosis | Marrow expansion / infiltration by malignant cells [10] |
| Pharyngitis + cervical lymphadenopathy + rash | EBV (infectious mononucleosis) | Classic triad; splenic enlargement from lymphoid hyperplasia |
| Skin rashes (malar rash, discoid) | SLE | Autoimmune multi-system disease [11] |
| Rheumatoid hands + neutropenia | Felty syndrome (RA + splenomegaly + neutropenia) | Long-standing seropositive RA |
| Plethora (ruddy complexion) | Polycythaemia vera | Increased RBC mass → facial plethora, conjunctival injection |
| Tear-drop RBCs + leukoerythroblastic picture on film | Myelofibrosis | Damaged RBCs squeezed through fibrotic marrow → tear-drops; immature cells released into circulation |
Exam Pearl: Distinguishing Spleen from Kidney on Abdominal Examination
| Feature | Spleen | Left Kidney |
|---|---|---|
| Palpable notch | Yes (medial border) | No |
| Moves with respiration | Yes | Slightly |
| Ballotable | No | Yes (bimanually) |
| Can get above | No (extends from under costal margin) | Yes (renal angle) |
| Percussion | Dull | Resonant (overlying bowel) |
| Direction of enlargement | Towards RIF | Towards midline/down |
Laboratory features of splenomegaly [1]:
| Finding | Basis |
|---|---|
| Anaemia | Increased RBC destruction + sequestration + haemodilution |
| Thrombocytopenia | Platelet pooling (up to 90% sequestered) + destruction |
| Leukopenia | WBC sequestration and destruction |
| Reticulocytosis (if haemolysis) | Compensatory marrow response to RBC loss |
| Raised LDH, indirect bilirubin, low haptoglobin (if haemolysis) | Markers of haemolysis |
| Blood film abnormalities | Depends on cause — e.g., tear-drop cells (myelofibrosis), target cells (thalassaemia), spherocytes (HS), blasts (leukaemia) |
The clinical features of splenomegaly can be classified into: (1) Pressure symptoms from the enlarged spleen (abdominal fullness, early satiety); (2) Symptoms related to pancytopenia (due to greater blood pooling in the spleen); and (3) Features due to the underlying disease (e.g., stigmata of chronic liver disease, features of portal hypertension). [1]
8. Approach to a Patient with Splenomegaly — Before DDx/Ix/Mx
When you encounter splenomegaly, think systematically through the following:
- Characterise the splenomegaly: Duration? Acute vs chronic? Any LUQ pain?
- Symptoms of hypersplenism: Fatigue (anaemia), bleeding (thrombocytopenia), infections (leukopenia)
- Constitutional symptoms: Fever, weight loss, night sweats (B symptoms → haematological malignancy, TB, lymphoma)
- Liver disease screen: Alcohol use, viral hepatitis risk factors (sexual history, IVDU, tattoos, blood transfusion, HBV carrier status in HK), jaundice, abdominal distension (ascites)
- Haematological clues: Prior blood counts, family history of anaemia/thalassaemia (HK!), ethnic background
- Infections: Travel history (malaria, leishmaniasis), TB contacts, EBV exposure, HIV risk
- Autoimmune: Joint pain, rash, photosensitivity, oral ulcers (SLE), rheumatoid features
- Drug history: Drugs causing haemolysis, aplastic anaemia, or liver disease
- Family history: Thalassaemia, hereditary spherocytosis, G6PD deficiency, storage diseases
- General inspection: Pallor, jaundice, plethora, lymphadenopathy, cachexia
- Hands: Clubbing, palmar erythema, Dupuytren's contracture, rheumatoid changes, Osler's nodes
- Face/neck: Malar rash (SLE), cervical lymphadenopathy, pharyngitis (EBV)
- Chest: Spider naevi, gynaecomastia, heart murmurs (IE)
- Abdomen:
- Spleen: as described above — start from RIF
- Hepatomegaly (liver disease, haematological infiltration)
- Ascites (portal HT)
- Caput medusae (portal HT collaterals)
- Legs: Oedema, petechiae, leg ulcers (thalassaemia, sickle cell)
- Lymph node survey: Cervical, axillary, epitrochlear, inguinal, popliteal [10]
9. Special Topic: Myeloproliferative Neoplasms (MPN) — Detailed
The GC lecture on splenomegaly specifically lists MPN as a learning objective. [1]
"Myelo-" = marrow, "-proliferative" = excessive growth, "neoplasm" = new abnormal growth.
MPNs are a group of clonal haematopoietic stem cell disorders characterised by excessive production of one or more myeloid lineages (granulocytes, erythrocytes, platelets, or monocytes) with retained maturation capacity (unlike acute leukaemia, where maturation is arrested).
| Disease | Predominant lineage | Driver mutation | Hallmark |
|---|---|---|---|
| CML | Granulocytes (neutrophils + myelocytes) | BCR::ABL (Philadelphia chromosome) | Massive splenomegaly, leukocytosis, basophilia |
| Polycythaemia Vera (PV) | Erythrocytes | JAK2 V617F (~95%) | Elevated Hb/Hct, plethora, pruritus (esp after hot bath), thrombosis |
| Essential Thrombocythaemia (ET) | Megakaryocytes/platelets | JAK2 (~55%), CALR (~25%), MPL (~5%) | Elevated platelet count, thrombosis ± bleeding |
| Primary Myelofibrosis (PMF) | Fibroblasts (reactive) + megakaryocytes | JAK2 (~50%), CALR (~25%), MPL (~5%) | Massive splenomegaly, leukoerythroblastic blood film, tear-drop cells, dry tap on marrow aspirate |
CML is defined by the presence of the Philadelphia chromosome t(9;22)(q34.1;q11.2) — no Philadelphia chromosome, not CML [9].
- Pathogenesis: The translocation creates the BCR::ABL fusion gene → encodes a constitutively active tyrosine kinase → drives uncontrolled proliferation of myeloid precursors.
- Phases: Chronic phase (CP) → Accelerated phase (AP) → Blastic crisis (BC). Most present in CP. (WHO 2022 debates the clinical utility of the AP given modern TKI therapy) [9].
- Clinical features:
- Treatment: Tyrosine kinase inhibitors (TKIs) — imatinib, nilotinib, dasatinib, ponatinib, asciminib — targeted therapy against BCR::ABL [9].
- Pathogenesis: Clonal haematopoietic stem cell disorder → abnormal megakaryocytes release fibrogenic cytokines (TGF-β, PDGF, FGF) → reactive fibrosis of the bone marrow → marrow failure → compensatory extramedullary haematopoiesis in the spleen and liver → massive splenomegaly.
- Blood film: Leukoerythroblastic picture (immature myeloid and erythroid precursors in peripheral blood — because marrow architecture is disrupted, and immature cells are released prematurely) + tear-drop cells (dacrocytes) (RBCs squeezed through fibrotic marrow).
- Bone marrow: "Dry tap" on aspiration (fibrosis prevents aspiration of liquid marrow) → need trephine biopsy to demonstrate reticulin/collagen fibrosis.
- JAK2 V617F mutation in ~95% → constitutive activation of JAK-STAT signalling → erythropoietin-independent erythropoiesis.
- Splenomegaly is moderate; develops from congestion and extramedullary haematopoiesis.
- Key clinical features: plethora, aquagenic pruritus (mast cell degranulation from basophilia), thrombotic events, erythromelalgia.
This is an important negative teaching point [12]:
In aplastic anaemia, there is NO lymphadenopathy and NO hepatosplenomegaly.
Why no splenomegaly in aplastic anaemia?
- The spleen's job is to filter and destroy abnormal RBCs.
- In aplastic anaemia, the bone marrow is hypoplastic/aplastic — it is not producing RBCs (or any blood cells adequately).
- The spleen has nothing abnormal to filter → no work hypertrophy → no splenomegaly.
- There are also no malignant cells to infiltrate the spleen.
- Therefore, if you see splenomegaly in a pancytopenic patient, aplastic anaemia is unlikely — think instead of hypersplenism, myelofibrosis, leukaemia, or hairy cell leukaemia [12].
Clinical Pearl
Do not confuse pancytopenia from hypersplenism with pancytopenia from aplastic anaemia. In hypersplenism, the marrow is hyperactive (compensating for peripheral destruction) and the spleen is enlarged. In aplastic anaemia, the marrow is hypoplastic and the spleen is normal-sized. The bone marrow biopsy is the definitive differentiator.
11. Special Topic: Splenomegaly in Specific Conditions Common in HK
- Splenomegaly occurs in IE due to chronic immune stimulation, immune complex deposition, and septic emboli [8].
- IE is a cause of fever of unknown origin — sneaky, like TB [8].
- Splenomegaly found on examination in IE patients → check for other signs: Osler's nodes, Janeway lesions, splinter haemorrhages, Roth spots, petechiae, changing murmurs.
- Splenomegaly in 10–46% of SLE patients, especially during active disease flares [11].
- Mechanism: Immune complex deposition, lymphoid hyperplasia, +/- macrophage activation syndrome (HLH).
12. Splenic Infarction and Rupture (Surgical Perspective)
- Aetiology: Haematological disorders (congestion by abnormal cells, e.g., leukaemia), embolic disorders (e.g., AF, IE).
- Clinical features: LUQ pain radiating to left shoulder (Kehr's sign), fever, pleuritic chest pain.
- Complications: Splenic rupture, splenic abscess (if non-sterile embolus, e.g., from IE), auto-splenectomy (repeated infarction → progressive atrophy, as in sickle cell disease).
- Aetiology: Abdominal trauma (most common), pathological rupture from a stretched, enlarged spleen (haematological disorders, EBV infection — the spleen becomes fragile and susceptible to even minor trauma).
- Clinical features: May present late (delayed rupture). Kehr's sign. Hypovolaemic shock (spleen is extremely vascular). Triad of left lower lobe atelectasis, elevated left hemidiaphragm, left pleural effusion.
- This is why patients with EBV-related splenomegaly are advised to avoid contact sports for 4–6 weeks — risk of traumatic splenic rupture.
High Yield Summary
-
Splenomegaly = pathological enlargement of the spleen; it is a sign, not a diagnosis. Always investigate the underlying cause.
-
Hypersplenism = splenomegaly + pancytopenia + active bone marrow + reversal after splenectomy. Not present in BM infiltrative disease.
-
Five mechanisms of splenomegaly: Work hypertrophy (haemolytic anaemias), Congestive (portal HT), Infiltrative (leukaemias, lymphomas, storage diseases), Immune/inflammatory hyperplasia (infections, autoimmune), Extramedullary haematopoiesis (myelofibrosis, thalassaemia major).
-
Massive splenomegaly causes: CML, myelofibrosis, chronic malaria, kala-azar (visceral leishmaniasis), Gaucher disease, thalassaemia major, lymphoma, PV.
-
In HK, commonest cause of congestive splenomegaly = HBV-related cirrhosis → portal hypertension. Thalassaemia is also prevalent.
-
CML = Philadelphia chromosome t(9;22) = BCR::ABL = constitutively active tyrosine kinase → massive splenomegaly + leukocytosis with bimodal myelocytes/neutrophils + basophilia. Treat with TKIs.
-
Myelofibrosis = marrow fibrosis → extramedullary haematopoiesis → massive splenomegaly + leukoerythroblastic film + tear-drop cells + dry tap.
-
Aplastic anaemia has NO splenomegaly (no abnormal cells for the spleen to filter).
-
Clinical features of splenomegaly: (a) Pressure symptoms (fullness, early satiety), (b) Hypersplenism (pancytopenia), (c) Underlying disease features.
-
Distinguish spleen from kidney: Splenic notch, moves with respiration, cannot get above it, non-ballotable, dull to percussion.
Active Recall - Splenomegaly
[1] Lecture slides: GC 086. Splenomegaly.pdf (objectives, causes, clinical features, classification by prevalence, MPN) [2] Senior notes: Ryan Ho Fundamentals.pdf (hypersplenism definition, massive splenomegaly causes, p397) [3] Senior notes: Block A - Abdominal distension_ ascites and cirrhosis.pdf (cirrhosis etiology in HK, portal HT pathogenesis) [4] Lecture slides: GC 097. Many members of the family have anaemia (MED).pdf (thalassaemia clinical features) [5] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf (thalassaemia pathogenesis, p578) [6] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf (malaria, p79) [7] Senior notes: Maksim Surgery Notes.pdf (splenic infarct, splenic rupture, p152) [8] Senior notes: Block A - Fever and a murmur_ Valvular heart diseases; Infective endocarditis.pdf (IE clinical features, p30) [9] Senior notes: Block A - High white cell count_ acute and chronic leukaemia; bone marrow transplantation; immunogenetics.pdf (CML, AML, ALL features, p3, p22) [10] Senior notes: Adrian Lui Pediatrics Notes.pdf (ALL features, p420) [11] Senior notes: Ryan Ho Rheumatology.pdf (SLE splenomegaly, p72) [12] Senior notes: Block A - Family history of anaemia_ inherited causes of anaemia; haemolytic anaemia; aplastic anaemia.pdf (aplastic anaemia features, p7-8) [13] Senior notes: Jerry's immunodeficiencies.pdf (CVID features, p1) [14] Senior notes: Block A - A jaundiced and incoherent patient_ liver failure.pdf (liver failure complications, p12)
Differential Diagnosis of Splenomegaly
When you find splenomegaly on examination, your job is to narrow the list systematically. You are not expected to memorise every rare cause; instead, you should use three practical filters that the GC lecture explicitly highlights [1]:
"Size of the spleen and how common the diseases can help narrow down differential diagnosis. Geographical location determines the possible infective causes of splenomegaly." [1]
So the three filters are:
- Size of the spleen (massive vs moderate vs mild) — different diseases produce different degrees of enlargement.
- Prevalence / how common — common things are common; think cirrhosis/portal HT and haematological malignancies first in HK.
- Geography / travel / epidemiology — malaria and leishmaniasis are imported diagnoses in HK; HBV-cirrhosis is the bread-and-butter local cause.
Additionally, the associated clinical features (lymphadenopathy? hepatomegaly? fever? blood film findings? stigmata of chronic liver disease?) are what truly separate one cause from another on the ward.
Below is a comprehensive table organised by category, cross-referenced with expected splenic size and key distinguishing features. Causes mentioned on lecture slides are bolded and italicised.
| Category | Differential Diagnosis | Expected Splenic Size | Key Distinguishing Features | Ref |
|---|---|---|---|---|
| Congestive / Portal HT | Portal hypertension (cirrhosis — HBV >> HCV > alcohol > MASLD in HK) | Moderate | Stigmata of CLD (spider naevi, palmar erythema, gynaecomastia), ascites, caput medusae, varices | [3][15] |
| Right heart failure / constrictive pericarditis | Mild–moderate | Raised JVP, peripheral oedema, tender pulsatile hepatomegaly (if TR), S3 gallop | [15] | |
| Budd-Chiari syndrome (hepatic vein thrombosis) | Moderate | Sudden-onset ascites + tender hepatomegaly; confirm with hepatic vein Doppler USG | [3] | |
| Portal / splenic vein thrombosis | Moderate–massive | May occur in MPNs (JAK2+), pancreatitis, intra-abdominal malignancy | [16] | |
| Infection — Viral | Infectious mononucleosis (EBV) | Mild | Pharyngitis, posterior cervical LN, palatal petechiae, atypical lymphocytosis on film, +ve Monospot/heterophile Ab; ampicillin rash; splenomegaly in 50–60%; risk of splenic rupture | [17][18] |
| CMV, HIV, viral hepatitis | Mild | CMV: similar to EBV but usually heterophile-negative; HIV: generalised LAD, risk factors | [15] | |
| Infection — Bacterial | Infective endocarditis | Mild | Fever, changing murmur, Osler's nodes, Janeway lesions, splinter haemorrhages, Roth spots, +ve blood cultures | [8] |
| TB | Mild–moderate | Fever, weight loss, night sweats, caseating granulomata; still relevant in HK | [15] | |
| Typhoid / Brucellosis | Mild | Travel history, specific cultures | [15] | |
| Infection — Parasitic | Malaria | Mild–moderate (acute); massive (chronic tropical splenomegaly) | Travel to endemic area, cyclic fevers, thick/thin blood films for parasites, thrombocytopenia | [6][15] |
| Visceral leishmaniasis (kala-azar) | Massive | Fever, pancytopenia, hypergammaglobulinaemia; tropical travel; rare in HK | [15] | |
| Schistosomiasis | Moderate | Portal HT pattern (periportal "pipestem" fibrosis), travel to endemic area | [15] | |
| MPN | Chronic Myeloid Leukaemia (CML) | Massive | Philadelphia chromosome t(9;22), BCR::ABL; leukocytosis with bimodal myelocytes/neutrophils, basophilia; TKI-responsive | [9] |
| Primary Myelofibrosis (PMF) | Massive | Leukoerythroblastic picture, tear-drop cells, dry tap on BM aspirate; JAK2/CALR/MPL | [9][19] | |
| Polycythaemia Vera (PV) | Moderate | JAK2 V617F (~95%); plethora, aquagenic pruritus, thrombosis, raised Hb/Hct | [1][15] | |
| Essential Thrombocythaemia (ET) | Mild or absent | Isolated thrombocytosis; JAK2/CALR/MPL; thrombosis or paradoxical bleeding (acquired vWD) | [1][16] | |
| Lymphoproliferative | Chronic Lymphocytic Leukaemia (CLL) | Mild–moderate | Older patients, incidental lymphocytosis, smear/smudge cells on PBS, LAD, CD5+CD19+CD23+ on flow cytometry | [20] |
| Non-Hodgkin Lymphoma (NHL) | Moderate–massive | LAD ± B symptoms; biopsy for histology; marginal zone and mantle cell lymphoma particularly involve spleen | [15] | |
| Hodgkin Lymphoma | Mild–moderate | Contiguous LAD, Reed-Sternberg cells on biopsy | [15] | |
| Hairy Cell Leukaemia | Moderate | Pancytopenia + monocytopenia (unique!), "hairy" cells on PBS, BRAF V600E mutation, red pulp infiltration | ||
| Acute Leukaemia | ALL | Moderate | Hepatosplenomegaly + LAD in up to 50%; peak age 2–5 y; blasts on film; CNS/testicular involvement | [10] |
| AML | Mild | Splenomegaly less prominent than ALL; gum hypertrophy in acute monoblastic subtype; Auer rods on film | [9] | |
| Haemolytic Anaemia | Thalassaemia intermedia/major | Mild (intermedia) to massive (major) | Low MCV, target cells, family history, HK prevalence (α-thal 5%, β-thal 3%); chipmunk facies in major | [4][5] |
| Hereditary Spherocytosis (HS) | Mild–moderate | AD inheritance, spherocytes on film, MCHC ≥ 36 g/dL, −ve DAT, ↓EMA binding, +ve osmotic fragility, pigmented gallstones | [21] | |
| Autoimmune Haemolytic Anaemia (AIHA) | Mild | +ve DAT (Coombs test); warm AIHA (IgG, extravascular) vs cold AIHA (IgM, intravascular); spherocytes on film; may be secondary to lymphoma/CLL/SLE | [12][22] | |
| Sickle Cell Disease | Mild (early); auto-splenectomy later | HbS on electrophoresis; painful crises; rare in HK Chinese | ||
| Autoimmune / Inflammatory | SLE | Mild | Malar rash, photosensitivity, oral ulcers, arthritis, serositis, cytopenias; splenomegaly in 10–46%, especially in active disease | [11] |
| Felty syndrome (RA) | Mild–moderate | Triad: RA + splenomegaly + neutropenia; long-standing seropositive RA | [15] | |
| Sarcoidosis | Mild | Non-caseating granulomata, bilateral hilar LAD, raised ACE, skin/lung/eye involvement | [15] | |
| Adult-onset Still's disease | Mild–moderate | Quotidian (daily-spiking) fever, salmon-coloured evanescent rash, hepatosplenomegaly, very high ferritin | ||
| Infiltrative / Storage | Gaucher disease | Massive | β-glucocerebrosidase deficiency; Gaucher cells (wrinkled tissue-paper macrophages) on BM; bone crises; Ashkenazi Jewish predominance | [15] |
| Niemann-Pick disease | Moderate–massive | Sphingomyelinase deficiency; hepatosplenomegaly in infancy | [15] | |
| Amyloidosis | Mild–moderate | Congo-red birefringence; nephrotic syndrome, restrictive cardiomyopathy, macroglossia | [15] | |
| Langerhans Cell Histiocytosis (LCH) | Mild | Lytic bone lesions, skin rash, diabetes insipidus; CD1a+/CD207+ on biopsy; children | [23] | |
| Other | Immune Thrombocytopenic Purpura (ITP) | Mild or absent | Isolated thrombocytopenia, no LAD, no hepatosplenomegaly typically; +ve anti-platelet Ab; increased megakaryocytes on BM | [24] |
| CVID | Mild–moderate | Recurrent sinopulmonary infections, hypogammaglobulinaemia; polyclonal lymphoproliferation + splenomegaly + LAD in ~1/3 | [13] | |
| Splenic cyst / abscess / infarct | Variable | Cyst: incidental; Abscess: fever + IE source; Infarct: acute LUQ pain + Kehr's sign | [7] |
This is the most practical first-pass filter. The GC lecture and senior notes explicitly classify by size [1][15]:
High Yield — Size-Based DDx from GC Lecture
Massive splenomegaly → Think CML, myelofibrosis (MPN/infiltration), chronic malaria, kala-azar, Gaucher, thalassaemia major [1][15].
Moderate splenomegaly → Think portal hypertension (cirrhosis) (vascular congestion), lymphomas (infiltration) [1][15].
Minimal / mild splenomegaly → Think haemolytic anaemias (thalassaemia intermedia, HbH, AIHA, ITP) (increased red pulp function) [1][15].
This is the second-pass filter — what else does the patient have alongside splenomegaly?
| Clinical Scenario | Think... | Reasoning |
|---|---|---|
| Splenomegaly + stigmata of CLD + ascites | Cirrhosis / portal HT | Congestive mechanism; commonest in HK (HBV) [3] |
| Splenomegaly + massive leukocytosis + basophilia | CML | Myeloid proliferation with full maturation; Philadelphia chromosome [9] |
| Splenomegaly + tear-drop cells + dry tap | Myelofibrosis | Marrow fibrosis → extramedullary haematopoiesis [9][19] |
| Splenomegaly + lymphadenopathy + smudge cells | CLL | Mature but fragile lymphocytes lyse on smear preparation [20][19] |
| Splenomegaly + pharyngitis + posterior cervical LAD + atypical lymphocytes | EBV (infectious mononucleosis) | Reactive lymphoid hyperplasia; epitrochlear LAD is particularly suggestive [17][18] |
| Splenomegaly + fever + changing murmur | Infective endocarditis | Chronic immune stimulation + septic emboli [8] |
| Splenomegaly + plethora + pruritus after hot bath | Polycythaemia vera | JAK2 V617F; increased RBC mass [1] |
| Splenomegaly + malar rash + arthritis | SLE | Immune complex-mediated; splenomegaly esp in active flares [11] |
| Splenomegaly + jaundice + spherocytes + −ve DAT | Hereditary spherocytosis | Membrane defect → splenic trapping [21] |
| Splenomegaly + jaundice + spherocytes + +ve DAT | Warm AIHA | Antibody-coated RBCs destroyed by splenic macrophages [12][22] |
| Splenomegaly + low MCV + target cells + family Hx | Thalassaemia | Unbalanced globin chains → haemolysis + extramedullary haematopoiesis [4][5] |
| Splenomegaly + pancytopenia + travel to tropics | Malaria or visceral leishmaniasis | Parasitic infection → splenic hyperplasia [6] |
| Splenomegaly + neutropenia + RA hands | Felty syndrome | Long-standing seropositive RA; triad [15] |
| Pancytopenia + NO splenomegaly + NO LAD | Aplastic anaemia | Marrow failure — nothing abnormal for spleen to filter; do NOT diagnose hypersplenism [12] |
Critical Negative DDx
Aplastic anaemia causes pancytopenia but does NOT cause splenomegaly or lymphadenopathy. The bone marrow is hypoplastic — there are no abnormal cells to infiltrate the spleen, and the spleen has nothing abnormal to filter. If you find splenomegaly in a pancytopenic patient, aplastic anaemia drops off the list — think hypersplenism (portal HT, MPN, hairy cell leukaemia) instead. [12]
The GC lecture emphasises that geographical location determines the possible infective causes of splenomegaly. [1]
| In Hong Kong | Outside Hong Kong (tropical/endemic) |
|---|---|
| HBV-cirrhosis / portal HT (most common congestive cause) | Chronic malaria → hyperreactive malarial splenomegaly (massive) |
| Haematological malignancies (CML, lymphoma, CLL) | Visceral leishmaniasis / kala-azar (massive) |
| Thalassaemia (α-thal 5%, β-thal 3%) | Schistosomiasis (portal HT pattern) |
| EBV (probably the only infection in HK that commonly causes splenomegaly — per Prof Kwong) [2] | Brucellosis, typhoid |
| TB (still relevant in HK) | Tropical splenomegaly syndrome |
| SLE, RA | Histoplasmosis |
The peripheral blood smear (PBS) is one of the most powerful tools for narrowing the DDx of splenomegaly [19]:
| PBS / CBC Finding | Points towards... | Why |
|---|---|---|
| Leukocytosis with left shift + basophilia | CML | Bimodal myelocyte/neutrophil peak; basophilia is characteristic [9] |
| Leukoerythroblastic picture + tear-drop cells | Myelofibrosis or marrow infiltration (by metastatic cancer) | Disrupted marrow architecture releases immature cells; tear-drop cells from squeezing through fibrotic marrow [19] |
| Smear / smudge cells | CLL | Fragile neoplastic mature lymphocytes lyse during slide preparation [19][20] |
| Atypical lymphocytes | EBV (infectious mononucleosis) | Reactive CD8+ T cells responding to EBV-infected B cells; NOT neoplastic — do not mistake as blasts [19] |
| Blasts ≥ 20% | Acute leukaemia (AML or ALL) | Diagnostic threshold; Auer rods confirm myeloid lineage (AML) [19] |
| Spherocytes | HS or AIHA | Membrane loss (HS) or partial phagocytosis of antibody-coated RBCs (AIHA); distinguish by DAT [21][22] |
| Target cells + low MCV | Thalassaemia | Relative excess membrane compared to cell content [4] |
| Sickle cells | Sickle cell disease | HbS polymerisation under deoxygenation |
| Parasitised RBCs | Malaria | Ring forms / trophozoites visible inside erythrocytes on thick/thin film [6] |
| Pancytopenia with normal/hypocellular marrow | Aplastic anaemia (NO splenomegaly) | Marrow failure, not peripheral destruction [12] |
| Pancytopenia with hypercellular/active marrow | Hypersplenism | Peripheral destruction/sequestration with compensatory marrow hyperplasia [2] |
| Pitfall | Explanation |
|---|---|
| Left kidney vs spleen | A large left kidney can mimic splenomegaly. Distinguish by: splenic notch, inability to get above spleen, non-ballotable, dull to percussion [15][25] |
| Hepatomegaly mistaken for splenomegaly | Riedel's lobe (anatomical variant of the right liver lobe) can extend into RLQ and be confused; always check for the notch |
| ITP | ITP typically does NOT cause splenomegaly — the spleen destroys antibody-coated platelets but does not enlarge significantly. If there IS splenomegaly, reconsider the diagnosis (secondary ITP from SLE, CLL, etc.) [24] |
| Aplastic anaemia | Pancytopenia WITHOUT splenomegaly — marrow problem, not splenic problem [12] |
| Multiple myeloma | Rarely causes splenomegaly (it is a marrow-based disease with bone involvement, not splenic involvement) — do not include it as a common cause [15] |
Exam Favourite — What Does NOT Cause Splenomegaly?
When the question asks about causes of splenomegaly, remember that aplastic anaemia and ITP (in its typical primary form) are classically associated with no hepatosplenomegaly. Aplastic anaemia has nothing for the spleen to process; in ITP the platelet destruction occurs in a non-enlarged spleen. Finding splenomegaly in either setting should prompt you to look for an alternative or additional diagnosis. [12][24]
Patients with MPN (especially JAK2-positive) have increased risk of both arterial and venous thrombosis, particularly in unusual sites such as mesenteric, portal, hepatic (Budd-Chiari) and cerebral veins. [16]
- If a patient presents with splenic/portal/hepatic vein thrombosis → screen for JAK2 mutation even if CBC does not yet show overt MPN features — the thrombosis can precede the cytosis [16].
- This means that Budd-Chiari syndrome (hepatic vein thrombosis → sudden-onset ascites + tender hepatomegaly + splenomegaly from portal HT) should trigger JAK2 screening.
- Extreme thrombocytosis with paradoxical bleeding → consider acquired von Willebrand disease (AvWD) — excess platelets consume vWF → bleeding tendency despite high platelet count [16].
High Yield Summary — Differential Diagnosis of Splenomegaly
-
Use three filters to narrow the DDx: (a) Size — massive vs moderate vs mild; (b) Prevalence — common vs uncommon; (c) Geography — local (HK: HBV cirrhosis, thalassaemia, EBV) vs imported (malaria, kala-azar).
-
Massive splenomegaly = CML, myelofibrosis, chronic malaria, kala-azar, Gaucher, thalassaemia major.
-
Moderate splenomegaly = portal HT / cirrhosis, lymphoma, PV, CLL.
-
Mild splenomegaly = haemolytic anaemias (thal intermedia, HbH, AIHA), infections (EBV, IE), SLE.
-
PBS is your best friend: smudge cells → CLL; tear-drops + leukoerythroblastic → myelofibrosis; basophilia + left shift → CML; atypical lymphocytes → EBV; spherocytes → HS or AIHA (use DAT to differentiate).
-
Aplastic anaemia and ITP do NOT cause splenomegaly — if you see splenomegaly with pancytopenia, think hypersplenism (portal HT, MPN, hairy cell leukaemia), not aplastic anaemia.
-
JAK2 screening for unusual-site venous thrombosis (mesenteric, portal, hepatic vein) — MPN can present with thrombosis before overt cytosis.
Active Recall - Differential Diagnosis of Splenomegaly
References
[1] Lecture slides: GC 086. Splenomegaly.pdf (take-home message, size-based DDx, geography, MPN overview) [2] Senior notes: Ryan Ho Fundamentals.pdf (hypersplenism definition, EBV as common HK infective cause, p397) [3] Senior notes: Block A - Abdominal distension_ ascites and cirrhosis.pdf (cirrhosis etiology in HK, portal HT pathogenesis) [4] Lecture slides: GC 097. Many members of the family have anaemia (MED).pdf (thalassaemia clinical features) [5] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf (thalassaemia pathogenesis, p578) [6] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf (malaria, p79) [7] Senior notes: Maksim Surgery Notes.pdf (splenic infarct, splenic rupture, p152) [8] Senior notes: Block A - Fever and a murmur_ Valvular heart diseases; Infective endocarditis.pdf (IE clinical features, p30) [9] Senior notes: Block A - High white cell count_ acute and chronic leukaemia; bone marrow transplantation; immunogenetics.pdf (CML, AML, ALL features, p3, p22) [10] Senior notes: Adrian Lui Pediatrics Notes.pdf (ALL features, p420) [11] Senior notes: Ryan Ho Rheumatology.pdf (SLE splenomegaly, p72) [12] Senior notes: Block A - Family history of anaemia_ inherited causes of anaemia; haemolytic anaemia; aplastic anaemia.pdf (aplastic anaemia features, haemolytic anaemia features, p3, p7-8) [13] Senior notes: Jerry's immunodeficiencies.pdf (CVID features, p1) [15] Senior notes: MBBS Final MB (Surgery) (Felix PY Lai).pdf (DDx table of splenomegaly, p130) [16] Senior notes: Block A - Leg swelling and chest pain_ deep vein thrombosis; pulmonary embolism; Thrombophilia.pdf (MPN thrombosis, JAK2 screening, p18) [17] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (EBV/IM clinical features, p1812) [18] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf (EBV/IM clinical features, p33) [19] Senior notes: Ryan Ho Haemtology.pdf (PBS interpretation, leukoerythroblastic picture, smudge cells, p47) [20] Senior notes: Maksim Medicine Notes.pdf (CLL features, p177) [21] Senior notes: Adrian Lui Pediatrics Notes.pdf (hereditary spherocytosis, p375) [22] Senior notes: Maksim Medicine Notes.pdf (haemolytic anaemia overview, p156) [23] Senior notes: Adrian Lui Pediatrics Notes.pdf (LCH, p441) [24] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf (ITP case, p613) [25] Senior notes: Ryan Ho GI.pdf (spleen palpation technique, Gardner's line, p21)
Key Preamble — Splenomegaly Has No "Diagnostic Criteria" of Its Own
Let's be clear from first principles: splenomegaly is a clinical sign, not a disease. There are no "diagnostic criteria" for splenomegaly in the way there are for SLE or multiple myeloma. Instead, what we need is:
- Confirmation that the spleen is truly enlarged (clinical examination ± imaging).
- A systematic investigative algorithm to identify the underlying cause.
- Knowledge of the specific diagnostic criteria for the individual diseases that cause splenomegaly (e.g., WHO criteria for MPN, Duke criteria for IE, etc.).
The GC lecture approach is practical: history, physical, investigations [1][15].
1. Confirming Splenomegaly
Five examination findings suggestive of splenomegaly [1]:
| Finding | Technique | Why it works |
|---|---|---|
| 1. LUQ mass | Palpate from RIF towards left costal margin along Gardner's line (RIF → umbilicus → tip of 10th costal cartilage → left anterior axillary fold) [25][26] | Spleen enlarges along its long axis towards the RIF; starting distally avoids missing massive splenomegaly |
| 2. Moves down with inspiration | Ask patient to take a deep breath while palpating | Spleen is attached to the diaphragm → descends with inspiration |
| 3. Cannot get above it | Attempt to insinuate fingers between mass and costal margin | Upper pole of spleen is tucked under ribs; unlike kidney, you cannot reach above it |
| 4. Dull to percussion | Percuss along Gardner's line; also assess Traube's space and Castell's spot | Solid splenic tissue replaces air-containing stomach/bowel |
| 5. Splenic notch | Feel for a notch on the medial border | Anatomical feature of the spleen; notch only palpable when spleen is enlarged > 10 cm in longest diameter [25][26] |
Advanced percussion techniques [26]:
- Traube's space: Margins = 6th rib (superior), mid-axillary line (lateral), left costal margin (inferior). Normally resonant (gastric air bubble). Loss of resonance = splenomegaly.
- Castell's method: Percuss at Castell's spot (lowest left intercostal space along the anterior axillary line) during full inspiration and expiration. Note becomes dull during inspiration if splenomegaly [26].
If spleen not palpable but splenomegaly suspected [25]:
- Turn patient to right lateral decubitus position.
- Hook the spleen with left hand at lower rib cage, applying firm pressure medially and downward → limits lower rib cage expansion → directs more intrathoracic pressure inferiorly at the diaphragm, making the spleen more prominent.
- In ascites: use dipping/ballottement (jabbing motion with stiffened fingers); note that the spleen may "float" to a more lateral position → ballot more laterally [25].
| Modality | Role in confirming splenomegaly | Key findings |
|---|---|---|
| Ultrasound abdomen | First-line imaging for confirming and measuring splenic size | Splenic length > 12–13 cm (craniocaudal); also assesses liver size/texture, portal vein diameter, portal vein flow, ascites, collaterals — all useful for detecting portal hypertension [3][27] |
| CT abdomen | More sensitive; better for characterising splenic lesions (infarcts, abscesses, cysts, masses) | Accurately measures splenic volume; can detect focal lesions, lymphadenopathy, hepatomegaly |
| FibroScan (transient elastography) | Not for spleen per se, but assesses liver stiffness to stage fibrosis (F0–F4) — helps confirm cirrhosis as the underlying cause [27] | Liver stiffness measurement (LSM): normal 2–7 kPa; F4 (cirrhosis) typically > 12–14 kPa depending on aetiology |
High Yield — USG Findings Suggesting Portal Hypertension
Ultrasound may detect [3][27]:
- Splenomegaly
- Nodular, small liver (suggesting cirrhosis)
- Increased portal vein diameter ( > 13 mm)
- Decreased / reversed portal vein flow (hepatofugal flow)
- Varices (peri-splenic, para-oesophageal collaterals)
- Ascites
USG is not sensitive for early portal hypertension, but it is non-invasive, widely available, and cheap — so it is the workhorse investigation used in clinical practice rather than HVPG [3].
2. Diagnostic Algorithm — Identifying the Underlying Cause
The approach follows the logical structure taught in the GC lecture: History → Physical → Investigations [1].
Step 1: History and Physical Examination
The GC lecture emphasises starting with history and physical examination [1]:
- History: As detailed in the Clinical Features section — liver disease risk factors (HBV status!), constitutional symptoms (B symptoms), infection/travel, autoimmune features, family history (thalassaemia), drug history.
- Physical examination: As taught — cardiac examination for murmur (evidence of bacterial endocarditis, capable of causing mild splenomegaly) [1]; lymphadenopathy; hepatomegaly; stigmata of CLD; signs of haemolysis (jaundice); autoimmune features.
Step 2: Baseline Blood Tests
These are ordered for every patient with unexplained splenomegaly:
| Investigation | What you're looking for | Interpretation |
|---|---|---|
| CBC with differential count | Cytopenias (hypersplenism), leukocytosis (leukaemia, infection), erythrocytosis (PV), thrombocytosis (ET) | The single most informative first-line investigation — directs all subsequent workup [19][28] |
| Peripheral blood smear (PBS) | Morphological clues — see table below | "Extremely valuable as it provides clues to aetiology" [12][19] |
| Reticulocyte count | Elevated = haemolysis or haemorrhage with intact marrow response | Reticulocytosis + anaemia → haemolytic process |
| LFT (liver function tests) | Hepatocellular damage (ALT/AST), synthetic function (albumin, PT/INR), cholestasis (ALP, GGT, bilirubin) | Deranged LFTs → work up liver disease [27][29] |
| Markers of haemolysis | LDH, unconjugated bilirubin, haptoglobin | LDH is the immediate differentiator for haemolysis — if high, indicates high turnover [12] |
| Renal function (RFT) | Creatinine, urea | Elevated urea out of proportion to creatinine → GI bleeding (HgB digestion in GI tract raises urea) [30]; renal impairment in myeloma |
| Inflammatory markers (CRP/ESR) | Infection, autoimmune, malignancy | Elevated in infection, flare of autoimmune disease |
| LDH | Elevated in haemolysis, leukaemia, lymphoma, myelofibrosis | LDH above upper limit of normal is a minor criterion for PMF diagnosis [31] |
Step 3: Peripheral Blood Smear — The Most Powerful Clue
The PBS is arguably the single most important investigation after the CBC [19]. It directs the entire subsequent workup:
| PBS finding | Diagnosis suggested | Next step |
|---|---|---|
| Left shift + basophilia | CML | Cytogenetics / FISH / PCR for BCR::ABL / t(9;22) [9] |
| Leukoerythroblastic picture + tear-drop cells (dacrocytes) | Myelofibrosis (or marrow infiltration by metastatic cancer) | BM trephine biopsy (expect "dry tap" on aspirate); JAK2/CALR/MPL [9][19] |
| Smear / smudge cells | CLL | Flow cytometry (CD5+, CD19+, CD20+, CD23+) [20][19] |
| Atypical lymphocytes | EBV (infectious mononucleosis) | Monospot (heterophile Ab), EBV serology (VCA IgM) [19] |
| Blasts ≥ 20% | Acute leukaemia | BM aspirate + trephine; MCICM workup [19] |
| Auer rods in blasts | AML (confirms myeloid lineage) | MCICM [19] |
| Faggot cells (multiple Auer rods) | APML (haematological emergency) | Urgent: ATRA + arsenic; FISH for PML::RARA [19] |
| Spherocytes | HS or AIHA | DAT (direct antiglobulin / Coombs test) — +ve = immune; −ve = HS [12] |
| Target cells + hypochromic microcytosis | Thalassaemia | Hb electrophoresis / HPLC; DNA analysis [4] |
| RBC fragments (schistocytes) | MAHA (TTP/HUS, DIC) | Coagulation profile, ADAMTS13 |
| Parasitised RBCs | Malaria | Thick and thin blood films; rapid diagnostic test (RDT) |
| Dysplastic WBCs | MDS | BM biopsy; cytogenetics |
| Polychromasia | Reticulocytosis (haemolysis or haemorrhage) | Reticulocyte count, haemolysis screen |
High Yield — MCICM Workup for Haematological Malignancies
MCICM = Morphology, Cytochemistry, Immunophenotype, Cytogenetics, Molecular genetics [19][28].
This is the standard systematic workup for any suspected haematological malignancy:
- Morphology: PBS + BM aspirate (cytology) + BM trephine (histology)
- Cytochemistry: Myeloperoxidase/Sudan Black B → myeloid lineage; no good markers for lymphoid
- Immunophenotyping: Flow cytometry (surface markers — CD classification)
- Cytogenetics: Karyotype, FISH for specific translocations
- Molecular genetics: PCR for fusion genes, NGS for mutations (JAK2, CALR, MPL, BCR::ABL, etc.)
3. Specific Investigations by Suspected Cause
| Investigation | Purpose | Key findings |
|---|---|---|
| LFT | Assess hepatocellular damage and synthetic function | ↑ALT/AST (hepatocellular), ↓albumin + ↑INR (synthetic failure), ↑bilirubin [27][29] |
| Viral hepatitis serology | Identify cause of cirrhosis (HK: HBV most common) | HBsAg, anti-HBc, HBV DNA; Anti-HCV, HCV RNA [3] |
| USG abdomen | Confirm cirrhosis, portal HT signs, screen for HCC | Small nodular liver, splenomegaly, ↑portal vein diameter, reversed portal flow, ascites [3][27] |
| FibroScan | Non-invasive assessment of fibrosis stage | LSM > 12–14 kPa → cirrhosis (F4); CAP for steatosis [27] |
| Upper endoscopy (OGD) | Screen for oesophageal/gastric varices | Varices present → portal HT confirmed; grade I–III; determines need for prophylaxis |
| AFP (alpha-fetoprotein) | HCC surveillance | ↑AFP + focal liver lesion on USG → suspect HCC |
| HVPG (hepatic venous pressure gradient) | Gold standard for portal HT diagnosis | HVPG = WHVP − FHVP; ≥ 10 mmHg = clinically significant portal HT; varices at ≥ 10; bleeding at ≥ 12 [3] |
HVPG is the gold standard but is NOT commonly used in clinical practice — too invasive, does not change management for most patients. USG is the workhorse. HVPG is mainly for research or selected cases [3].
How HVPG is performed [3]: Catheter inserted via internal jugular or femoral vein → guided into hepatic vein → (1) measure free hepatic venous pressure (FHVP) with balloon deflated → (2) inflate balloon and wedge it → measure wedged hepatic venous pressure (WHVP), which is a surrogate for portal pressure → HVPG = WHVP − FHVP.
| Investigation | Purpose | Key findings |
|---|---|---|
| Reticulocyte count | Confirm compensatory erythropoiesis | ↑ (typically > 2%) in haemolysis |
| LDH | Marker of cell turnover | Elevated — this is the immediate differentiator [12] |
| Unconjugated bilirubin | Product of haem metabolism | Elevated (pre-hepatic jaundice, urine is NOT tea-coloured) [12] |
| Haptoglobin | Binds free Hb released from lysed RBCs | Decreased / absent — consumed in mopping up free Hb [12] |
| Direct antiglobulin test (DAT / Coombs) | Distinguish immune from non-immune haemolysis | +ve → immune haemolytic anaemia (warm AIHA, alloimmune); −ve → non-immune (HS, thalassaemia, PNH, enzyme defects) [12] |
| PBS | Morphological clues | Spherocytes (HS/AIHA), target cells (thal), fragments (MAHA), agglutination (cold AIHA) [12] |
| EMA binding (flow cytometry) | Test for HS | ↓EMA binding on RBC skeletal proteins → HS [21] |
| Osmotic fragility test | Alternative test for HS (if EMA unavailable) | ↑fragility cf normal RBCs in hypotonic solutions [21] |
| Hb electrophoresis / HPLC | Detect haemoglobinopathy / thalassaemia | HbH (β4) in α-thal intermedia; ↑HbA2 in β-thal trait; abnormal Hb bands [4] |
| G6PD assay | Enzyme deficiency screen | ↓G6PD activity (may be falsely normal during haemolytic crisis due to reticulocytosis — retest later) |
| Ham's test / flow cytometry for CD55/CD59 | PNH | ↓CD55/CD59 on flow cytometry (PIGA gene mutation) [12] |
Algorithm for Haemolysis Workup
Confirm haemolysis first (↑LDH, ↑unconjugated bilirubin, ↓haptoglobin, reticulocytosis) → then perform DAT to classify as immune vs non-immune → then use PBS morphology and specific tests to reach the final diagnosis. [12]
The pre-test probability must be established before ordering DAT — some healthy individuals have a positive DAT without haemolysis, leading to false positives if used indiscriminately [12].
3.3 Myeloproliferative Neoplasm Workup
| Investigation | What it shows | Key findings by MPN subtype |
|---|---|---|
| CBC + PBS | First clue | CML: leukocytosis + basophilia; PV: ↑Hb/Hct; ET: ↑platelets; PMF: cytopenias + leukoerythroblastic film [9] |
| Cytogenetics / FISH / PCR for BCR::ABL | Confirms CML | Philadelphia chromosome t(9;22) = BCR::ABL fusion → pathognomonic for CML [9] |
| JAK2 V617F mutation | Screens for PV, ET, PMF | JAK2+ in ~95% PV, ~55% ET, ~50% PMF [9][16] |
| CALR mutation | Screens for ET, PMF (if JAK2 −ve) | CALR+ in ~25% ET, ~25% PMF |
| MPL mutation | Screens for ET, PMF (if JAK2/CALR −ve) | MPL+ in ~5% ET, ~5% PMF |
| Serum EPO level | Distinguish PV from secondary erythrocytosis | Low/undetectable EPO → PV (autonomous erythropoiesis); ↑EPO → secondary cause |
| BM aspirate + trephine biopsy | Essential for PMF; supportive for PV/ET | PMF: reticulin/collagen fibrosis (grade 2–3 for overt), megakaryocytic atypia, dry tap on aspirate [9][31]; PV: panmyelosis; ET: ↑megakaryocytes |
WHO 2022 Diagnostic Criteria — Key Concepts for Individual MPNs:
- Defined by BCR::ABL1 fusion gene — without it, it is not CML. Period.
- No formal "criteria checklist" needed — the molecular finding IS the diagnosis.
- Major criteria: (1) ↑Hb/Hct (Hb > 16.5 g/dL men, > 16 g/dL women; or Hct > 49%/48%); (2) BM biopsy showing panmyelosis with pleomorphic megakaryocytes; (3) JAK2 V617F or JAK2 exon 12 mutation.
- Minor criterion: Subnormal serum EPO.
- Diagnosis requires all 3 major, or first 2 major + minor.
For overt PMF, requires ALL 3 major criteria + at least 1 minor criterion:
| Major criteria | Minor criteria |
|---|---|
| 1. Megakaryocytic proliferation and atypia with reticulin/collagen fibrosis grade 2 or 3 | Anaemia not attributable to comorbid condition |
| 2. Not meeting WHO criteria for PV, ET, CML, MDS or other myeloid neoplasm | Leukocytosis ≥ 11 × 10⁹/L |
| 3. JAK2, CALR, or MPL mutation (or another clonal marker), or no reactive cause | Palpable splenomegaly |
| LDH above upper limit of normal | |
| Leukoerythroblastosis (overt PMF only) |
Note: Palpable splenomegaly and leukoerythroblastosis are minor diagnostic criteria for PMF — this is why clinical examination and PBS are so important [31].
| Investigation | Purpose | Key findings |
|---|---|---|
| Flow cytometry (peripheral blood) | Immunophenotyping | CLL: CD5+, CD19+, CD20+, CD23+, sIg+ [20] |
| Lymph node biopsy (excisional) | Gold standard for lymphoma diagnosis | Histological subtyping (e.g., DLBCL, follicular, marginal zone, mantle cell); Reed-Sternberg cells for HL |
| BM biopsy | Staging; assess marrow involvement | Lymphomatous infiltration pattern |
| CT TAP / PET-CT | Staging (Ann Arbor) | Nodal and extranodal disease extent |
| Cytogenetics + FISH | Prognostic and diagnostic | e.g., del(13q), del(11q), del(17p) in CLL [20] |
| Suspected infection | Investigation | Key finding |
|---|---|---|
| EBV | Monospot (heterophile Ab), EBV VCA IgM, EBV DNA PCR | +ve Monospot; +ve VCA IgM = acute infection [17] |
| IE | Blood cultures ×3 (from different sites, > 6h apart); echocardiography (TTE → TOE if needed) | +ve cultures + vegetations on echo → modified Duke criteria [8] |
| Malaria | Thick film (detect parasites) + thin film (speciate) + rapid diagnostic test (RDT) | Ring forms / trophozoites within RBCs [6] |
| TB | AFB smear + culture, TB PCR, CXR, tissue biopsy for granulomata | Caseating granulomata; +ve culture is gold standard |
| HIV | HIV Ag/Ab combo test (4th gen), confirmatory Western blot or HIV RNA PCR | +ve HIV Ag/Ab → +ve confirmatory test |
| Investigation | Purpose |
|---|---|
| ANA, anti-dsDNA, complement levels | SLE screen |
| RF, ACPA | RA / Felty syndrome |
| ACE level, CXR | Sarcoidosis |
| Serum protein electrophoresis (SPEP) + immunofixation | Paraprotein detection (myeloma, Waldenström's, amyloidosis) |
| Acid β-glucocerebrosidase assay | Gaucher disease |
| Immunoglobulin levels | Hypogammaglobulinaemia → CVID |
BM examination is indicated in unexplained cytopenias or leukocytosis where the cause is not clear from the peripheral blood [28].
| Component | What it assesses | When it's essential |
|---|---|---|
| Aspirate | Cytology (morphology), flow cytometry, cytogenetics, FISH, IgH/TCR PCR, NGS, iron staining (Perl's Prussian Blue), microbiological cultures [28] | Suspected leukaemia, MDS, staging of lymphoma, unexplained cytopenias |
| Trephine biopsy | Cellularity, degree of fibrosis, pattern of abnormal infiltration, immunohistochemistry [28] | Essential in myelofibrosis (dry tap on aspirate → need trephine to show fibrosis); metastatic infiltration |
Trephine takes longer to process (requires decalcification ~1 week) but provides architectural information that the aspirate cannot [28].
Site: Typically posterior iliac crest; alternatives include anterior iliac crest and sternum (aspiration only). Ensure you stay lateral — if you go medial you risk entering the retroperitoneum and hitting spleen, kidney, or iliac vessels [28].
4. Special Diagnostic Situations
Both cause microcytic anaemia, but in the context of splenomegaly, thalassaemia is far more likely [28]:
| Feature | Iron deficiency | Thalassaemia trait |
|---|---|---|
| RDW | High (variable cell sizes — acquired deficiency affects RBCs unevenly) | Normal/low (genetic defect → all RBCs equally affected) |
| RBC count | Low ( < 5 × 10¹²/L) | High (> 5 × 10¹²/L) |
| Mentzer index (MCV/RBC count) | > 13 → iron deficiency | < 13 → thalassaemia |
| Iron profile | ↓Fe, ↑TIBC, ↓ferritin | Normal iron studies |
| Hb electrophoresis | Normal | ↑HbA2 (β-thal trait), HbH (α-thal intermedia) |
| Feature | Hypersplenism | Marrow failure (e.g., aplastic anaemia) |
|---|---|---|
| Spleen | Enlarged | Normal [12] |
| Bone marrow | Hyperactive (compensatory) | Hypocellular |
| Blood film | May show features of the underlying cause (e.g., target cells in cirrhosis) | Normal morphology but reduced numbers; no abnormal cells |
| After splenectomy | Counts normalise | No improvement |
| Tier | Investigations | Purpose |
|---|---|---|
| Tier 1 (All patients) | CBC + DC, PBS, reticulocyte count, LFT, RFT, LDH, unconjugated bilirubin, haptoglobin, CRP/ESR, USG abdomen | Baseline screening → categorise the splenomegaly mechanism |
| Tier 2 (Directed by Tier 1) | Viral hepatitis serology, DAT, Hb electrophoresis, JAK2/BCR::ABL, flow cytometry, blood cultures, EBV serology, malaria films, autoimmune screen, SPEP | Targeted workup based on clinical suspicion |
| Tier 3 (If diagnosis still unclear) | BM aspirate + trephine (MCICM), CT TAP/PET-CT, LN biopsy, liver biopsy/FibroScan, specific enzyme assays (Gaucher), HVPG | Definitive diagnosis for complex cases |
High Yield Summary — Diagnostic Approach to Splenomegaly
-
Confirm splenomegaly: Five clinical signs (LUQ mass, moves with inspiration, cannot get above, dull, splenic notch) + USG abdomen (splenic length > 12–13 cm).
-
First-line bloods for ALL patients: CBC + DC, PBS, reticulocyte count, LFT, RFT, LDH, bilirubin, haptoglobin, CRP/ESR.
-
PBS is the most powerful single investigation — directs the entire workup: left shift + basophilia → CML; tear-drops + leukoerythroblastic → myelofibrosis; smudge cells → CLL; atypical lymphocytes → EBV; blasts → acute leukaemia; spherocytes → HS/AIHA.
-
USG abdomen detects portal HT signs (splenomegaly, small nodular liver, ↑portal vein diameter, reversed flow, varices, ascites) but is not sensitive for early portal HT. HVPG (≥ 10 mmHg) is the gold standard but rarely used clinically.
-
For haemolysis: Confirm with ↑LDH, ↑unconjugated bilirubin, ↓haptoglobin, reticulocytosis → then DAT to classify immune vs non-immune.
-
For MPN: BCR::ABL for CML; JAK2/CALR/MPL for PV, ET, PMF; BM biopsy for fibrosis grading (essential for PMF — dry tap + trephine showing reticulin/collagen fibrosis).
-
MCICM (Morphology, Cytochemistry, Immunophenotype, Cytogenetics, Molecular) is the systematic haematological malignancy workup.
-
BM trephine is essential in myelofibrosis (dry tap on aspirate) and provides architecture that aspirate cannot.
Active Recall - Diagnosis and Investigations of Splenomegaly
[1] Lecture slides: GC 086. Splenomegaly.pdf (approach: history, physical, investigations; five exam findings; size-based DDx) [3] Senior notes: Block A - Abdominal distension_ ascites and cirrhosis.pdf (HVPG, USG for portal HT, cirrhosis aetiology in HK) [4] Lecture slides: GC 097. Many members of the family have anaemia (MED).pdf (thalassaemia laboratory diagnosis) [6] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf (malaria diagnosis, p79) [8] Senior notes: Block A - Fever and a murmur_ Valvular heart diseases; Infective endocarditis.pdf (IE investigations, p30) [9] Senior notes: Block A - High white cell count_ acute and chronic leukaemia; bone marrow transplantation; immunogenetics.pdf (CML diagnosis, BCR::ABL, MPN features, p3, p22) [12] Senior notes: Block A - Family history of anaemia_ inherited causes of anaemia; haemolytic anaemia; aplastic anaemia.pdf (haemolysis workup, DAT, aplastic anaemia no splenomegaly, p3-4, p7-8) [15] Senior notes: MBBS Final MB (Surgery) (Felix PY Lai).pdf (DDx table, examination technique, p130) [16] Senior notes: Block A - Leg swelling and chest pain_ deep vein thrombosis; pulmonary embolism; Thrombophilia.pdf (JAK2 and MPN thrombosis, p18) [17] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (EBV/IM diagnosis, p1812) [19] Senior notes: Ryan Ho Haemtology.pdf (PBS interpretation, MCICM, leukoerythroblastic picture, p47) [20] Senior notes: Maksim Medicine Notes.pdf (CLL investigations and staging, p177) [21] Senior notes: Adrian Lui Pediatrics Notes.pdf (hereditary spherocytosis diagnosis, EMA, osmotic fragility, p375) [25] Senior notes: Ryan Ho GI.pdf (spleen palpation technique, Gardner's line, Traube, Castell, p21-22) [26] Senior notes: Ryan Ho Fundamentals.pdf (spleen palpation, advanced percussion methods, p73-74) [27] Senior notes: Maksim Medicine Notes.pdf (HBP investigations, FibroScan, USG, liver biopsy, p133) [28] Senior notes: Block A - Introduction to Haematological investigations (CBP, Clotting).pdf (BM examination, MCICM, Mentzer index, p1, p6, p15) [29] Senior notes: Learning_Points_All_Lectures.txt (LFT interpretation framework) [30] Senior notes: Block A - Coffee ground vomitus tarry stool upper GI bleeding.pdf (urea in GI bleeding, p9) [31] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (WHO criteria for PMF, p1453)
Management of Splenomegaly
This is the single most important concept to anchor everything that follows: splenomegaly is a sign, not a disease. Therefore, the management of splenomegaly is overwhelmingly the management of the underlying cause. You do not treat a big spleen any more than you treat a fever without knowing its source.
The management framework can be broken into three pillars [26][32]:
- Treatment of the primary cause (e.g., TKI for CML, antiviral for HBV-cirrhosis, JAK2 inhibitor for myelofibrosis)
- No treatment if the underlying cause is untreatable (observation/supportive care)
- Surgical treatment (splenectomy) if the splenomegaly itself is causing problems (e.g., increased transfusion requirement in thalassaemia, refractory cytopenias)
1. Treatment of the Primary Cause
This is the mainstay. Below are the management approaches organised by underlying aetiology, with emphasis on how treating the primary disease addresses the splenomegaly.
The spleen is enlarged because of congestive back-pressure. Treating the liver disease and managing portal hypertension is the strategy.
| Treatment | Mechanism / Indication | Details |
|---|---|---|
| Treat underlying liver disease | Remove the cause of cirrhosis → halt progression → potentially reduce portal pressure | HBV: antiviral therapy (entecavir, tenofovir) [3]; HCV: DAAs; Alcohol: abstinence; MASLD: weight loss ≥ 5–7% (non-fibrotic), ≥ 10% (fibrotic), GLP-1 RA emerging [33] |
| Variceal prophylaxis | Prevent life-threatening variceal haemorrhage | Non-selective beta-blockers (NSBB) (propranolol, carvedilol) → reduce portal inflow by blocking β₂-mediated splanchnic vasodilation; endoscopic variceal ligation (EVL) for high-risk varices |
| Ascites management | Reduce sodium/water retention | Low-salt diet ( < 2g Na/day), diuretics (spironolactone ± furosemide, 100:40 ratio), fluid restriction if dilutional hyponatraemia < 125 [3] |
| HCC surveillance | Early detection of hepatocellular carcinoma | USG + AFP every 6 months in at-risk patients [33] |
| Liver transplantation | Definitive treatment for decompensated cirrhosis | Resolves portal HT and splenomegaly; prioritised by MELD score |
In cirrhosis, splenomegaly and hypersplenism generally do not require splenectomy — treating the underlying portal hypertension and considering liver transplantation is the definitive approach. Splenectomy in cirrhotics carries high bleeding risk due to coagulopathy and is rarely performed.
1.2 Myeloproliferative Neoplasms
| Treatment | Details |
|---|---|
| First-line: Tyrosine kinase inhibitors (TKIs) | Imatinib, nilotinib, dasatinib, ponatinib, asciminib → specifically target the BCR::ABL constitutively active tyrosine kinase [9]. This is the textbook example of targeted therapy — you know the molecular target, you hit it directly. |
| Monitoring | Monitor molecular response using quantitative RT-PCR for BCR-ABL transcript → aim for major molecular response (MMR): BCR-ABL ≤ 0.1% (log 3 reduction). Complete molecular response does NOT mean zero — just below the detection limit of the test. [9] |
| HSCT | Reserved for patients unresponsive to TKI or CML in blastic phase (BC) → very good graft-versus-tumour effect, but no longer first-line given TKI efficacy [9] |
CML currently still cannot be "cured" per se — it is controlled long-term with TKIs, like diabetes with insulin. If you stop, disease may relapse. [9]
As CML responds to TKI, the spleen shrinks — often dramatically. Splenectomy is almost never needed for CML in the TKI era.
| Treatment | Details |
|---|---|
| JAK2 inhibitor (ruxolitinib) | First-line for symptomatic/intermediate-high risk PMF → reduces splenomegaly (often dramatically) and improves constitutional symptoms by blocking the JAK-STAT signalling pathway [32] |
| Allogeneic HSCT | Only potentially curative treatment for PMF; indicated in high-risk disease in younger/fit patients [9] |
| Splenectomy | Symptomatic relief in massive splenomegaly when drug therapy fails — but carries significant perioperative risk (30-day mortality ~6.3% in advanced MF) [32][34] |
| Supportive | Transfusions, EPO, danazol for anaemia; hydroxyurea for leukocytosis/thrombocytosis |
| Treatment | Details |
|---|---|
| Phlebotomy | Target Hct < 45% to reduce thrombotic risk |
| Low-dose aspirin | Reduces thrombotic events |
| Cytoreduction | Hydroxyurea (first-line); interferon-α (younger patients, pregnancy); ruxolitinib (second-line, especially if symptomatic splenomegaly) |
| Treatment | Details |
|---|---|
| Risk-stratified | Low-risk: observation + aspirin; High-risk: hydroxyurea or anagrelide for cytoreduction |
| Aspirin | Unless extreme thrombocytosis with acquired vWD (paradoxical bleeding — excess platelets consume vWF) [16] |
1.3 Lymphoproliferative Disorders
| Stage | Management |
|---|---|
| Early stage asymptomatic (Rai 0 / Binet A) | Close observation ("watch and wait") — treatment does NOT improve survival in early-stage CLL [20] |
| Indications for treatment | Advanced stage (Rai III/IV); Symptomatic (severe B symptoms, bulky LAD/splenomegaly); Active disease progression (lymphocytosis ↑ ≥ 50% over 2 months or doubling time ≤ 6 months); Disease-related complications (refractory AIHA/ITP, recurrent infections, Richter's transformation) [20] |
| Regimens | Young: FCR (fludarabine, cyclophosphamide, rituximab); Elderly: chlorambucil; Newer agents: ibrutinib (BTK inhibitor), venetoclax (BCL-2 inhibitor), rituximab/obinutuzumab (anti-CD20) [20] |
| Supportive | Blood products, leukapheresis for leukostasis |
- Treated per histological subtype and stage (Ann Arbor) — chemotherapy, immunotherapy (rituximab for CD20+ B-cell NHL), radiotherapy, HSCT for relapsed disease.
- Splenomegaly resolves with successful treatment of the lymphoma.
1.4 Haemolytic Anaemias
| Treatment | Details |
|---|---|
| Regular blood transfusion | Maintain Hb > 9–10 g/dL → suppresses ineffective erythropoiesis, prevents BM expansion, improves growth [35] |
| Iron chelation | Start when ferritin > 2000 ng/mL or ≥ 20 units transfused or age ≥ 3y → desferrioxamine (IV/SC), deferiprone (PO), deferasirox (PO); target ferritin 1000–2000 ng/mL [35] |
| Splenectomy | Indications: ↑ transfusion requirement or cytopenias due to hypersplenism; symptomatic splenomegaly → generally deferred till ≥ 4y (often much later) to reduce infection risk [35] |
| Allogeneic HSCT | Potentially curative — but NOT gold-standard yet (still transfusion ± chelation) due to transplant-related complications; requires HLA-matched sibling donor (uncommon in HK) [35] |
| Luspatercept | Newly approved (2019) for transfusion-dependent β-thalassaemia major; reduces transfusion burden |
| Treatment | Details |
|---|---|
| No specific treatment can target the underlying membrane defect [36] | |
| Folic acid supplementation | 1–2 mg/day (moderate/severe haemolysis); 5 mg/day if pregnant — because chronic haemolysis increases folate demand for compensatory erythropoiesis [36] |
| Transfusion | For severe anaemia |
| Splenectomy | At > 6–7 y for severe haemolysis to ↓ transfusion requirement → usually deferred to reduce sepsis risk [36] |
| Allogeneic HSCT | NOT used — unfavourable risk-benefit ratio [36] |
| Treatment | Details |
|---|---|
| Warm AIHA | First-line: corticosteroids (prednisolone 1 mg/kg/day); Second-line: rituximab, splenectomy; Third-line: azathioprine, mycophenolate, cyclophosphamide |
| Cold AIHA | Avoid cold exposure; rituximab (steroids less effective); splenectomy not helpful (destruction is complement-mediated, mainly intravascular/hepatic, not splenic) |
| Step | Treatment | Details |
|---|---|---|
| Observe | If platelet ≥ 30 × 10⁹/L and asymptomatic/minor mucocutaneous bleeding only | |
| 1st line | Glucocorticoids (dexamethasone pulse or prednisolone); IVIg (for rapid platelet rise, e.g., pre-procedure) | IVIg works by saturating Fc receptors on splenic macrophages → ↓ phagocytosis of antibody-coated platelets |
| 2nd line | Splenectomy (removes major site of platelet destruction and autoantibody production); Thrombopoietin receptor agonists (TPO-RAs): eltrombopag (PO), romiplostim (SC) — stimulate megakaryopoiesis | [34][37] |
| 3rd line | Rituximab, azathioprine, mycophenolate, fostamatinib (Syk inhibitor) |
| Infection | Treatment |
|---|---|
| EBV (IM) | Supportive (rest, analgesia, hydration); avoid contact sports for 4–6 weeks (risk of splenic rupture); NO amoxicillin/ampicillin (causes rash) [17] |
| IE | Prolonged IV antibiotics (4–6 weeks) per organism and sensitivity; surgery if valve destruction/heart failure [8] |
| Malaria | Artesunate (severe P. falciparum), chloroquine (P. vivax/ovale), primaquine (hypnozoites for P. vivax/ovale after G6PD testing) |
| TB | Standard anti-TB regimen (RHZE) |
2. Splenectomy — Indications, Contraindications, and Peri-operative Management
Two broad indications for splenectomy [1][34]:
| Category | Specific indications | Why |
|---|---|---|
| Diagnostic | Suspected splenic lymphoma (isolated splenic lesion with no other tissue available for biopsy) | Splenic biopsy is generally avoided — the spleen is highly vascular, so biopsy carries great risk of uncontrollable haemorrhage. Nowadays, if the lesion is very superficial/cortical, a percutaneous approach may be attempted [34] |
| Therapeutic | 1. Symptomatic relief in massive splenomegaly (e.g., myelofibrosis — less common) | Pressure symptoms (fullness, early satiety, pain) unresponsive to medical therapy |
| 2. Refractory ITP or AIHA | When medical therapy fails — spleen is the major site of platelet/RBC destruction [34][37] | |
| 3. Decrease transfusion requirement in thalassaemia major | Hypersplenism causes excessive RBC destruction → ↑ transfusion needs → ↑ iron overload [35] | |
| 4. Hereditary spherocytosis with severe haemolysis | Remove the site of spherocyte trapping/destruction [36] | |
| 5. Splenic rupture (traumatic) with haemodynamic instability | Life-saving emergency surgery [7] | |
| 6. Splenic abscess unresponsive to antibiotics | Drainage + removal of infected tissue | |
| 7. Hairy cell leukaemia (historical; less common now with cladribine/pentostatin) |
Important — Why Not Just Splenectomise Everyone?
Splenectomy is not done liberally because of the serious risk of post-splenectomy overwhelming sepsis (OPSI) — a life-threatening complication. The spleen is essential for filtering encapsulated bacteria and producing opsonising antibodies. Without it, patients have a 2–3× increased risk of infection, sepsis, and sepsis-related mortality that lasts for life. [32][34]
| Relative contraindication | Reasoning |
|---|---|
| Young age ( < 4–6 years) | Immature immune system → even higher risk of OPSI; splenectomy usually deferred to ≥ 4–7 years depending on the condition [35][36] |
| Severe coagulopathy / thrombocytopenia | Increased surgical bleeding risk; optimise platelet count pre-operatively |
| Portal hypertension with varices | Massively increased surgical bleeding risk from collateral vessels; alternative approaches preferred |
| Advanced age / poor performance status | High perioperative mortality (6.3% 30-day mortality reported in PMF splenectomy) [32] |
| Cold AIHA | Splenectomy is NOT helpful — destruction is primarily complement-mediated and intravascular/hepatic, not splenic |
| Approach | When |
|---|---|
| Laparoscopic splenectomy | Preferred when feasible (less pain, shorter hospital stay, fewer wound complications); suitable for mild-to-moderately enlarged spleens |
| Open splenectomy | Necessary for massive splenomegaly (e.g., CML, myelofibrosis) where laparoscopic approach is technically difficult or unsafe |
| Partial splenectomy | Occasionally used in children (thalassaemia, HS) to preserve some splenic immune function; not widely practised |
| Splenic artery embolisation | Alternative to splenectomy in high-risk surgical patients; reduces splenic size pre-operatively in massive splenomegaly to facilitate safer surgery; also used as a standalone palliative measure |
3. Post-Splenectomy — Overwhelming Post-Splenectomy Infection (OPSI) Prevention
The GC lecture take-home message explicitly states: "POST SPLENECTOMY INFECTIONS requires urgent treatment." [1]
This is one of the highest-yield exam topics related to splenomegaly.
Without the spleen, patients lose [32][38]:
- Mechanical filtration: Splenic sinusoids filter rigid particles > 1 μm including unopsonised bacteria.
- Macrophage function: Splenic macrophages phagocytose infected cells and bacteria.
- B-cell antibody production: The spleen accounts for ~50% of the body's immunoglobulin-producing B cells — critically important for producing antibodies against polysaccharide antigens on encapsulated bacteria [32].
The most dangerous organisms post-splenectomy are encapsulated bacteria [38]:
| Organism | Notes |
|---|---|
| Streptococcus pneumoniae | Most common cause of OPSI (~60–70%); polysaccharide capsule evades phagocytosis without splenic opsonisation |
| Neisseria meningitidis | Meningococcal sepsis |
| Haemophilus influenzae type b | Less common since Hib vaccination |
| Capnocytophaga canimorsus | Dog/cat bites — important in the asplenic patient [38] |
| Babesia, Plasmodium spp. | Intra-erythrocytic parasites normally filtered by the spleen |
The reasoning is elegant: encapsulated bacteria are protected by their polysaccharide capsule from complement-mediated killing in the bloodstream. Normally, the spleen's B cells produce IgM against these polysaccharide antigens, and splenic macrophages then phagocytose the opsonised bacteria. Without the spleen, these bacteria proliferate unchecked → fulminant sepsis within hours.
Vaccinations should ideally be given ≥ 2 weeks BEFORE elective splenectomy (to allow antibody response while the spleen is still present). If emergency splenectomy, vaccinate ≥ 2 weeks post-operatively.
| Vaccine | Schedule |
|---|---|
| Pneumococcal (PCV13 then PPSV23) | PCV13 first, then PPSV23 ≥ 8 weeks later; booster PPSV23 every 5 years |
| Meningococcal (MenACWY + MenB) | 2-dose series; booster every 5 years |
| Haemophilus influenzae type b (Hib) | Single dose if not previously vaccinated |
| Influenza | Annual — reduces risk of secondary bacterial infection |
| Measure | Details |
|---|---|
| Lifelong prophylactic antibiotics | Phenoxymethylpenicillin (Penicillin V) 250–500 mg BD — at minimum for 2 years post-splenectomy; many centres recommend lifelong, especially in children and immunocompromised patients |
| Emergency antibiotics | Patient should carry a supply of amoxicillin (or a fluoroquinolone if penicillin-allergic) to take at the first sign of fever or illness while seeking immediate medical attention |
| Patient education (MedicAlert bracelet/card) | Patient must understand they are at lifelong risk of OPSI; any febrile illness is a medical emergency requiring immediate antibiotics and hospital assessment |
| Animal bite prophylaxis | Must cover Capnocytophaga → amoxicillin-clavulanate is the antibiotic of choice for bite wounds in post-splenectomy patients [38] |
Two features that may appear alarming on CBC but are just consequences of splenectomy [34]:
| Finding | Explanation |
|---|---|
| Spurious leukocytosis | Without the spleen sequestering and destroying WBCs, circulating WBC count rises — this is expected and NOT infection |
| Thrombocytosis | Platelets are no longer pooled in the spleen (~30% normally sequestered) → platelet count rises, sometimes markedly |
| Howell-Jolly bodies on PBS | Nuclear remnants in RBCs that would normally be "pitted" out by the spleen → pathognomonic of functional asplenia |
| Target cells | Slightly thinner RBCs due to loss of splenic membrane remodelling |
Exam Pearl — Post-Splenectomy Blood Film
If an exam gives you a blood film with Howell-Jolly bodies, target cells, and spurious thrombocytosis/leukocytosis → think asplenic patient (post-splenectomy or functional asplenia from repeated splenic infarction, e.g., sickle cell disease).
4. Other Therapeutic Modalities
- Occasionally used for symptomatic splenomegaly in myelofibrosis in patients unfit for splenectomy or ruxolitinib.
- Low-dose radiation → temporarily shrinks spleen.
- Effect is transient — spleen regrows; not a definitive treatment.
- Risk of severe cytopenias post-radiation.
| Measure | Indication |
|---|---|
| RBC transfusion | Symptomatic anaemia from hypersplenism |
| Platelet transfusion | Active bleeding with severe thrombocytopenia |
| Folic acid supplementation | All chronic haemolytic anaemias — increased folate demand from compensatory erythropoiesis [36] |
| Iron chelation | Transfusion-dependent patients (thalassaemia major) — prevent iron overload [35] |
- For symptomatic splenic cysts (congenital epidermoid or post-traumatic pseudocysts).
- Can be performed open or laparoscopically [32].
- Drainage + excision of the cyst wall while preserving splenic parenchyma.
5. Management of Splenic Emergencies
| Scenario | Management |
|---|---|
| Haemodynamically unstable | Urgent laparotomy + splenectomy |
| Haemodynamically stable | CT TAP with contrast → grade by AAST splenic injury scale (Grade I–V); Grade I–III: conservative management (strict bed rest, repeat CT in 1 week, prophylactic vaccinations in case splenectomy later needed); Grade V: urgent laparotomy |
| EBV-related splenomegaly | Avoid contact sports for 4–6 weeks — fragile, enlarged spleen is vulnerable to rupture even with minor trauma [17] |
- Treat the underlying cause (leukaemia, emboli from AF/IE).
- Analgesia for pain.
- Splenectomy if: persisting symptoms, complications (splenic rupture, splenic abscess, auto-splenectomy from repeated infarction) [7].
| Clinical scenario | Primary treatment | Role of splenectomy |
|---|---|---|
| Cirrhosis / portal HT | Treat liver disease (antivirals, abstinence, weight loss), manage portal HT (NSBB, EVL) | Almost never; liver transplant is the definitive option |
| CML | TKIs (imatinib, nilotinib, dasatinib) | Rarely needed (TKIs shrink spleen) |
| Myelofibrosis | Ruxolitinib (JAK inhibitor); allo-HSCT if fit | For refractory symptomatic massive splenomegaly (high perioperative risk) |
| CLL | Watch and wait (early); chemo-immunotherapy or targeted agents (advanced) | Rarely |
| Thalassaemia major | Transfusion + iron chelation + potentially curative HSCT | Yes — ↓ transfusion requirement; defer to ≥ 4y |
| Hereditary spherocytosis | Folic acid, transfusion | Yes — for severe haemolysis; defer to > 6–7y |
| ITP (refractory) | Steroids → IVIg → TPO-RAs | Second-line for refractory ITP |
| AIHA (warm, refractory) | Steroids → rituximab | Second/third-line |
| EBV | Supportive | Only for rupture |
High Yield Summary — Management of Splenomegaly
-
Management of splenomegaly = management of the underlying cause. Treat the primary disease first.
-
Splenectomy indications: (a) Diagnostic — suspected splenic lymphoma; (b) Therapeutic — symptomatic massive splenomegaly refractory to medical therapy, refractory ITP/AIHA, ↓ transfusion requirement in thalassaemia major, hereditary spherocytosis with severe haemolysis, splenic rupture.
-
Splenectomy is not done liberally because of the risk of overwhelming post-splenectomy infection (OPSI) — 2–3× increased risk of sepsis from encapsulated bacteria (S. pneumoniae, N. meningitidis, H. influenzae, Capnocytophaga).
-
Pre-splenectomy vaccinations: PCV13 then PPSV23, MenACWY + MenB, Hib, annual influenza — ideally ≥ 2 weeks before surgery.
-
Post-splenectomy: Lifelong prophylactic penicillin V (at least 2 years, often lifelong); emergency antibiotics at hand; MedicAlert bracelet; annual influenza vaccination.
-
Post-splenectomy blood film: Howell-Jolly bodies, target cells, spurious leukocytosis and thrombocytosis — all expected, not pathological.
-
CML: TKIs are first-line; monitor molecular response (MMR = BCR-ABL ≤ 0.1%); HSCT reserved for TKI-unresponsive or blastic phase.
-
Myelofibrosis: Ruxolitinib (JAK inhibitor) for symptomatic splenomegaly; allo-HSCT only curative option; splenectomy is last resort (high mortality).
-
Thalassaemia major: Transfusion + chelation ± HSCT; splenectomy to ↓ transfusion needs (defer to ≥ 4y).
-
POST SPLENECTOMY INFECTIONS require urgent treatment — any febrile illness in an asplenic patient is a medical emergency.
Active Recall - Management of Splenomegaly
[1] Lecture slides: GC 086. Splenomegaly.pdf (take-home message on post-splenectomy infections, treatment discussion, MPN overview) [3] Senior notes: Block A - Abdominal distension_ ascites and cirrhosis.pdf (cirrhosis management, portal HT, HVPG) [7] Senior notes: Maksim Surgery Notes.pdf (splenic infarct, splenic rupture management, p152) [8] Senior notes: Block A - Fever and a murmur_ Valvular heart diseases; Infective endocarditis.pdf (IE management, p30) [9] Senior notes: Block A - High white cell count_ acute and chronic leukaemia; bone marrow transplantation; immunogenetics.pdf (CML treatment with TKIs, HSCT indications, molecular monitoring, acute leukaemia supportive care, p9, p22, p23, p28) [16] Senior notes: Block A - Leg swelling and chest pain_ deep vein thrombosis; pulmonary embolism; Thrombophilia.pdf (MPN thrombosis, acquired vWD, p18) [17] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (EBV management, splenic rupture risk, p1812) [20] Senior notes: Maksim Medicine Notes.pdf (CLL management, indications for treatment, regimens, p177) [32] Senior notes: Ryan Ho Haemtology.pdf (splenomegaly management, splenectomy indications, post-splenectomy issues, p90) [33] Senior notes: Block A - Gastroenterology Interactive Tutorial.pdf (MASLD management, HBV surveillance, p2) [34] Senior notes: Block A - Splenomegaly_ common causes of splenomegaly; myeloproliferative diseases.pdf (splenectomy indications, post-splenectomy CBC changes, p19) [35] Senior notes: Adrian Lui Pediatrics Notes.pdf (thalassaemia major management, iron chelation, splenectomy, HSCT, p367) [36] Senior notes: Ryan Ho Haemtology.pdf (hereditary spherocytosis management, p39) [37] Senior notes: Block A - Abnormal bleeding after tooth extraction_ bleeding tendency; thrombocytopenia.pdf (ITP treatment, TPO-RAs, p11) [38] Senior notes: Gen Clerk Anaes + Microbiology Summary.pdf (post-splenectomy organisms, bite wound prophylaxis, p14)
Complications of splenomegaly can be thought of in three layers — much like peeling an onion. You need to understand (A) complications arising from the spleen itself being enlarged, (B) complications of the underlying disease driving the splenomegaly, and (C) complications of the treatment (particularly splenectomy). All three are fair game in exams.
A. Complications Arising FROM the Enlarged Spleen
These are the direct mechanical and functional consequences of having a big spleen.
This is the hallmark complication of splenomegaly — examined frequently and must be understood from first principles.
Definition recap: Hypersplenism is the functional over-activity of an enlarged spleen causing peripheral blood cytopenias despite a compensating hyperactive bone marrow [2].
Pathophysiology (three mechanisms acting together):
- Increased destruction — The expanded reticuloendothelial system (macrophages in the cords of Billroth) traps and destroys more blood cells than normal.
- Increased sequestration / pooling — Blood cells are physically held in the enlarged sinusoidal network. Normally ~30% of platelets are pooled in the spleen; in massive splenomegaly, up to 90% may be sequestered.
- Plasma volume expansion — The mechanism is incompletely understood, but the expanded splenic vascular bed draws more plasma, producing a dilutional effect on circulating cell counts.
Clinical consequences:
| Cytopenia | Clinical manifestation | Why |
|---|---|---|
| Anaemia | Fatigue, pallor, exertional dyspnoea | RBCs destroyed and sequestered faster than marrow can compensate |
| Thrombocytopenia | Petechiae, purpura, mucosal bleeding, easy bruising | Up to 90% platelets sequestered; however, bleeding is usually mild because the platelets in the spleen can be mobilised during haemostatic stress |
| Leukopenia (esp. neutropenia) | Recurrent bacterial infections | WBCs sequestered; combined with neutropenia → susceptibility to bacterial infection |
Order of severity in hypersplenism is typically anaemia > thrombocytopenia > leukopenia [2]. The cytopenias are usually moderate and rarely life-threatening on their own, but they compound the effects of the underlying disease (e.g., a CML patient with both leukocytosis from disease and simultaneous thrombocytopenia from hypersplenism).
High Yield — Hypersplenism vs Aplastic Anaemia
Both cause pancytopenia, but:
- Hypersplenism: splenomegaly present, bone marrow is hyperactive (compensatory).
- Aplastic anaemia: NO splenomegaly, NO lymphadenopathy, bone marrow is hypocellular [12].
The bone marrow biopsy is the definitive differentiator. Never confuse the two.
A big spleen is a vulnerable spleen. The capsule is stretched thin, the parenchyma is engorged, and even minor trauma can cause catastrophic haemorrhage.
Why it happens: The spleen is one of the most vascular organs in the body. When enlarged, the capsule is under tension and the parenchyma is friable. A blow to the LUQ, a fall, or even vigorous palpation can tear the capsule.
Clinical features [7]:
- Kehr's sign: Left shoulder pain (referred pain via phrenic nerve C3–C5 from diaphragmatic irritation by blood tracking up to the left subdiaphragmatic space).
- Hypovolaemic shock: Tachycardia, hypotension, pallor — because the spleen is so vascular, bleeding can be massive and rapid.
- May present late (delayed rupture — blood initially contained by an intact capsule or omental adhesions, then ruptures days later).
- Triad: Left lower lobe atelectasis, elevated left hemidiaphragm, left pleural effusion [7].
High-risk scenarios for splenic rupture:
| Condition | Why the spleen is vulnerable |
|---|---|
| EBV (infectious mononucleosis) | Rapid lymphoid hyperplasia stretches the capsule; splenomegaly in 50–60% of IM patients; avoid contact sports for 4–6 weeks [17] |
| Thalassaemia major | Chronic extramedullary haematopoiesis + transfusional iron deposition |
| CML / Myelofibrosis | Massive splenomegaly → stretched capsule |
| Trauma (seat-belt injury, fall on left side) | Direct mechanical force [7] |
Why it happens: In conditions with marked splenomegaly, parts of the spleen may outgrow their blood supply, or abnormal cells may congest the splenic microcirculation, causing ischaemic necrosis. Alternatively, emboli (from AF, IE, or a mural thrombus) can lodge in the splenic artery branches.
Clinical features [7]:
- Acute LUQ pain radiating to the left shoulder (Kehr's sign, again — diaphragmatic irritation).
- Fever, nausea/vomiting, pleuritic chest pain.
- CT abdomen: wedge-shaped hypoattenuated area (classically peripheral, with the base at the capsule and the apex pointing toward the hilum).
Complications of infarction [7]:
- Splenic abscess — if the embolus is infected (e.g., from IE with septic emboli) → requires drainage ± splenectomy.
- Splenic rupture — necrotic tissue weakens the capsule.
- Auto-splenectomy — repeated infarctions cause progressive fibrosis and atrophy → eventual functional loss of the spleen (classically seen in sickle cell disease).
The spleen sits in a crowded neighbourhood. When it massively enlarges, it pushes things around:
| Structure compressed | Symptom | Mechanism |
|---|---|---|
| Stomach | Early satiety, nausea | Reduced gastric capacity from extrinsic compression [1] |
| Left kidney | Left flank discomfort, rarely hydronephrosis | Direct pressure on the renal hilum or upper ureter |
| Diaphragm | Left-sided pleuritic pain, dyspnoea | Upward displacement reduces left lung base expansion |
| Splenic flexure of colon | Altered bowel habit, constipation | Extrinsic compression of the colonic lumen |
Why: Sluggish flow through the enlarged, congested splenic vein → stasis → thrombosis. This is particularly common in MPN (especially JAK2-positive) where there is an intrinsic thrombotic tendency [16].
- Splenic vein thrombosis can worsen portal hypertension (left-sided/sinistral portal hypertension).
- May lead to isolated gastric varices (because the splenic vein feeds the short gastric veins → if splenic vein is blocked, blood diverts through gastric collaterals → isolated gastric varices without oesophageal varices).
B. Complications of the Underlying Disease (Selected High-Yield Examples)
The underlying disease that caused the splenomegaly often has its own complications. Below are the most exam-relevant, organised by disease category.
Portal hypertension contributes to the majority of complications of cirrhosis, but not all — HE, HCC, and liver failure are exceptions. [3]
| Complication | Mechanism | Key points |
|---|---|---|
| Variceal haemorrhage | Portal HT → portosystemic collaterals → oesophageal/gastric varices → rupture → massive UGIB | Life-threatening; varices develop at HVPG ≥ 10 mmHg, bleed at ≥ 12 mmHg [3]; primary prevention with NSBB (carvedilol) or EVL |
| Ascites | Portal HT + splanchnic vasodilation + ↓albumin → RAAS activation → Na/H₂O retention | Managed with salt restriction + diuretics (spironolactone ± furosemide, 100:40 ratio) [3] |
| Spontaneous bacterial peritonitis (SBP) | Bacterial translocation from gut to ascitic fluid (impaired gut barrier + immune dysfunction) | Diagnostic paracentesis: ascitic fluid PMN ≥ 250/mm³; Rx: IV ceftriaxone |
| Hepatic encephalopathy | Liver fails to clear ammonia → crosses BBB → astrocyte swelling | Lactulose + rifaximin |
| Hepatorenal syndrome | Splanchnic vasodilation → renal vasoconstriction → renal failure | Terlipressin + albumin |
| Hepatocellular carcinoma (HCC) | Chronic inflammation + regeneration → dysplasia → HCC | Surveillance: USG + AFP every 6 months [33]; HBV can cause HCC even without cirrhosis |
| Coagulopathy | ↓ Synthetic function → ↓ clotting factors; also ↓ platelets from hypersplenism | Balanced — both pro- and anti-coagulant factors decreased |
| Complication | Mechanism |
|---|---|
| Pigmented gallstones | Chronic haemolysis → ↑ unconjugated bilirubin → calcium bilirubinate stones precipitate in the gallbladder |
| Aplastic crisis | Parvovirus B19 infection → infects erythroid progenitors (via globoside/P antigen receptor) → transient halt of erythropoiesis → severe anaemia with low reticulocyte count (paradoxically, because the marrow stops making new RBCs) [12][39] |
| Folate deficiency | Chronic compensatory erythropoiesis consumes folate rapidly → megaloblastic crisis if not supplemented |
| Iron overload (transfusional haemosiderosis) | Each unit of blood contains ~200 mg iron; daily iron excretion is only ~1 mg → chronic transfusions in thalassaemia major → iron accumulates in liver (→ fibrosis, HCC), heart (→ heart failure), endocrine organs (→ DM, growth retardation, hypogonadism) [40] |
| Extramedullary haematopoiesis | Marrow expands into cortical bone (chipmunk facies, frontal bossing) and into liver/spleen → further hepatosplenomegaly |
| Osteoporosis / pathological fractures | Marrow expansion thins cortical bone |
Exam Pearl — Parvovirus B19 and Aplastic Crisis
Parvovirus B19 specifically infects erythroid precursors via the P antigen (globoside) receptor. In patients with a baseline high RBC turnover (any chronic haemolytic anaemia — HS, thalassaemia, sickle cell), even a temporary halt in erythropoiesis causes a dramatic drop in Hb because the shortened RBC lifespan means the patient depends on continuous rapid production. The hallmark is severe anaemia with a paradoxically LOW reticulocyte count — the opposite of what you'd expect in haemolysis. This is a self-limiting crisis (~10–14 days) as the virus is cleared, but the patient may need urgent transfusion during the nadir. [12][39]
| Complication | Mechanism |
|---|---|
| Thrombosis (arterial and venous) | Hyperviscosity from high cell counts + intrinsic platelet/endothelial activation (especially JAK2+); thrombosis can occur in unusual sites (mesenteric, portal, hepatic/Budd-Chiari, cerebral veins) [16] |
| Paradoxical bleeding (acquired vWD) | In extreme thrombocytosis (especially ET), excess platelets consume vWF → acquired von Willebrand disease → bleeding tendency despite high platelet count [16] |
| Blastic transformation | CML → accelerated phase → blast crisis (behaves like acute leukaemia, poor prognosis); PMF → transformation to acute myeloid leukaemia [9] |
| Gout / hyperuricaemia | High cell turnover → ↑ purine breakdown → ↑ uric acid |
| Tumour lysis syndrome | Especially upon initiating treatment → massive cell death → ↑ K⁺, ↑ PO₄³⁻, ↑ uric acid, ↓ Ca²⁺ → AKI, cardiac arrhythmia |
| Complication | Mechanism |
|---|---|
| Richter transformation | Transformation of CLL/SLL into aggressive large cell lymphoma (most commonly DLBCL) → sudden clinical deterioration with rapidly enlarging nodes, B symptoms, rising LDH [20] |
| Autoimmune cytopenias | AIHA, ITP — immune dysregulation in CLL → autoantibodies against own blood cells |
| Recurrent infections | Hypogammaglobulinaemia (non-functional B cells cannot produce adequate antibodies) |
| Complication | Mechanism |
|---|---|
| Splenic rupture | Rapid lymphoid hyperplasia → capsular stretching → rupture with minor trauma; manifest as abdominal pain and falling haematocrit [17] |
| Upper airway obstruction | Massive tonsillar enlargement in severe IM |
| "Ampicillin rash" | Almost ALWAYS occurs following administration of amoxicillin/ampicillin → generalised maculopapular rash; mechanism thought to involve transient immune dysregulation rather than true allergy [17] |
| Haemolytic anaemia | Cold agglutinins (IgM anti-i) can develop |
C. Complications of Splenectomy (Treatment-Related)
The GC lecture take-home message explicitly states: "POST SPLENECTOMY INFECTIONS requires urgent treatment." [1]
This is one of the most consistently tested topics related to splenomegaly.
| Timing | Complication | Mechanism |
|---|---|---|
| Immediate | Haemorrhage | Slipped ligature on splenic hilum vessels; haematemesis from gastric mucosal damage (short gastric vessels) [41] |
| Immediate | Injury to surrounding structures | Tail of pancreas (→ pancreatic fistula/abscess), stomach, left pleura (→ pleural effusion, left basal atelectasis), left kidney [41] |
| Early | Post-operative thrombocytosis | Platelets no longer pooled in the spleen → platelet count rises, sometimes markedly ( > 1000 × 10⁹/L); prophylactic aspirin if platelet > 1000 [41] |
| Early | Post-splenectomy septicaemia | Immediate vulnerability before adaptive immunity compensates; risk factors: young age, immunocompromised [41] |
This is the most feared long-term complication and the main reason splenectomy is not done liberally.
Definition: Fulminant sepsis in an asplenic patient, typically caused by encapsulated organisms, progressing from a trivial febrile illness to septic shock and death within hours.
Why it happens — the spleen's three immune roles are lost [32]:
- Mechanical filtration via splenic sinusoids (removes unopsonised bacteria).
- Macrophage phagocytosis of infected cells.
- IgM production against polysaccharide capsular antigens — the spleen accounts for ~50% of the body's Ig-producing B cells [32].
Without these, encapsulated bacteria evade the immune system because their polysaccharide capsule resists complement-mediated lysis, and without splenic opsonisation they cannot be phagocytosed.
| Organism | Notes |
|---|---|
| Streptococcus pneumoniae | Most common (~60–70% of OPSI) |
| Neisseria meningitidis | Meningococcal sepsis |
| Haemophilus influenzae type b | Less common since Hib vaccination |
| Capnocytophaga canimorsus | Dog/cat bites — must counsel asplenic patients about animal bite risk [38] |
| Babesia, Plasmodium spp. | Intraerythrocytic parasites normally cleared by splenic pitting |
Mnemonic (from surgery notes): "Some Nasty Killers Have Some Capsule Protection" — Strep pneumoniae, Neisseria meningitidis, Klebsiella, Haemophilus influenzae, Salmonella typhi, Cryptococcus, Pseudomonas [41].
Risk profile:
- 2–3× increased risk of infection, sepsis, and sepsis-related mortality — lifelong [32].
- Risk is highest in the first 2 years post-splenectomy but never returns to zero.
- Risk is greater in children (immature immune system) and immunocompromised patients.
- Sepsis can progress more rapidly without a spleen to contain bacteraemia.
Prevention — as covered in the management section:
- Pre-splenectomy vaccinations (PCV13 → PPSV23, MenACWY + MenB, Hib, annual influenza).
- Prophylactic penicillin V (at least 2 years, many centres recommend lifelong).
- Emergency antibiotics at hand; MedicAlert bracelet/card.
- Patient education: any febrile illness is a medical emergency requiring immediate antibiotics and hospital assessment [1].
These are expected findings, not complications per se, but may be confusing on blood tests if not anticipated:
| Finding | Explanation |
|---|---|
| Howell-Jolly bodies | Nuclear remnants in RBCs no longer pitted by the spleen → pathognomonic of asplenia |
| Target cells | Loss of splenic membrane remodelling → RBCs have relative excess membrane |
| Spurious leukocytosis | WBCs no longer sequestered/destroyed by the spleen → circulating count rises |
| Thrombocytosis | Platelets no longer pooled (~30% normally sequestered) → count rises, sometimes markedly |
| Pappenheimer bodies | Iron-containing siderotic granules no longer pitted |
| Nucleated RBCs | Normally removed by splenic filtration |
- Splenectomy increases the risk of venous thromboembolism.
- Particularly relevant in thalassaemia major post-splenectomy — splenectomised thalassaemia patients have increased thromboembolism risk due to platelet activation from abnormal RBC membrane phospholipid exposure + loss of splenic filtration of activated platelets + thrombocytosis [35].
- Also relevant in MPN post-splenectomy — already elevated baseline thrombotic risk is compounded.
| Source of complication | Specific complications |
|---|---|
| From the spleen itself | Hypersplenism (pancytopenia), splenic rupture, splenic infarction (→ abscess, auto-splenectomy), pressure effects (early satiety, dyspnoea), splenic vein thrombosis |
| From the underlying disease | Cirrhosis: variceal bleeding, ascites, SBP, HE, HRS, HCC. Haemolytic anaemias: gallstones, aplastic crisis (Parvo B19), iron overload, folate deficiency. MPN: thrombosis, blastic transformation, acquired vWD. CLL: Richter transformation, infections. EBV: splenic rupture, airway obstruction |
| From splenectomy | Immediate: haemorrhage, injury to pancreas/stomach. Early: thrombocytosis, early sepsis. Late: OPSI (encapsulated bacteria), thrombotic risk. Haematological: Howell-Jolly bodies, target cells, leukocytosis, thrombocytosis |
High Yield Summary — Complications of Splenomegaly
-
Hypersplenism is the cardinal complication — pancytopenia (anaemia > thrombocytopenia > leukopenia) from increased destruction, sequestration, and plasma volume expansion. Bone marrow is hyperactive (compensating).
-
Splenic rupture — life-threatening haemorrhage from a fragile, stretched capsule. High-risk in EBV (avoid contact sports for 4–6 weeks), thalassaemia major, CML, myelofibrosis, and trauma.
-
Splenic infarction — acute LUQ pain ± Kehr's sign; can lead to abscess (if infected embolus from IE) or auto-splenectomy (repeated infarction in sickle cell disease).
-
Parvovirus B19 aplastic crisis — specifically infects erythroid precursors → transient halt of erythropoiesis → severe anaemia with paradoxically LOW reticulocyte count in any chronic haemolytic anaemia.
-
Transfusional iron overload — each unit contains ~200 mg Fe; daily excretion only ~1 mg → deposits in liver (fibrosis, HCC), heart (heart failure), endocrine organs (DM, hypogonadism). Chelation is mandatory.
-
OPSI (overwhelming post-splenectomy infection) — fulminant sepsis from encapsulated bacteria (S. pneumoniae most common); lifelong risk; prevented by vaccinations, prophylactic antibiotics, and patient education. Any febrile illness post-splenectomy is a medical emergency.
-
Post-splenectomy blood film: Howell-Jolly bodies (pathognomonic), target cells, spurious leukocytosis and thrombocytosis — expected findings, not pathological.
-
MPN complications: Thrombosis in unusual sites (JAK2+), blastic transformation (CML → blast crisis, PMF → AML), acquired vWD in extreme thrombocytosis.
Active Recall - Complications of Splenomegaly
[1] Lecture slides: GC 086. Splenomegaly.pdf (take-home message on post-splenectomy infections, clinical features of splenomegaly) [2] Senior notes: Ryan Ho Fundamentals.pdf (hypersplenism definition, severity order, p397) [3] Senior notes: Block A - Abdominal distension_ ascites and cirrhosis.pdf (portal HT complications summary, variceal screening, ascites pathogenesis, p11, p23) [7] Senior notes: Maksim Surgery Notes.pdf (splenic infarct complications, splenic rupture features, p152) [9] Senior notes: Block A - High white cell count_ acute and chronic leukaemia; bone marrow transplantation; immunogenetics.pdf (CML phases, blastic transformation, HSCT complications, p22, p34) [12] Senior notes: Block A - Family history of anaemia_ inherited causes of anaemia; haemolytic anaemia; aplastic anaemia.pdf (haemolytic anaemia complications, parvovirus B19, hereditary spherocytosis complications, aplastic anaemia no splenomegaly, p12, p16) [16] Senior notes: Block A - Leg swelling and chest pain_ deep vein thrombosis; pulmonary embolism; Thrombophilia.pdf (MPN thrombosis in unusual sites, acquired vWD, JAK2, p18) [17] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (EBV splenic rupture, ampicillin rash, p1812) [20] Senior notes: Maksim Medicine Notes.pdf (CLL complications, Richter transformation, p177) [32] Senior notes: Ryan Ho Haemtology.pdf (post-splenectomy issues, splenic immune functions, 50% of Ig-producing B cells, p90) [33] Senior notes: Block A - Gastroenterology Interactive Tutorial.pdf (HCC surveillance indications, p2) [34] Senior notes: Block A - Splenomegaly_ common causes of splenomegaly; myeloproliferative diseases.pdf (splenectomy complications, post-splenectomy CBC changes, p19) [35] Senior notes: Adrian Lui Pediatrics Notes.pdf (thalassaemia major complications, iron overload, splenectomy risks, p367) [38] Senior notes: Gen Clerk Anaes + Microbiology Summary.pdf (post-splenectomy encapsulated organisms, Capnocytophaga, p14) [39] Senior notes: Block A - Many members of the family have anaemia.pdf (thalassaemia clinical syndromes, complications, p4) [40] Senior notes: Block A - Fever after a blood transfusion_ transfusion and related problems.pdf (transfusion haemosiderosis, iron per unit, organ deposition, p27) [41] Senior notes: Maksim Surgery Notes.pdf (splenectomy indications, surgical complications, OPSI pathogens mnemonic, p153)
High Yield Summary
-
Splenomegaly = pathological enlargement of the spleen; it is a sign, not a diagnosis. Always investigate the underlying cause.
-
Hypersplenism = splenomegaly + pancytopenia + active bone marrow + reversal after splenectomy. Not present in BM infiltrative disease.
-
Five mechanisms of splenomegaly: Work hypertrophy (haemolytic anaemias), Congestive (portal HT), Infiltrative (leukaemias, lymphomas, storage diseases), Immune/inflammatory hyperplasia (infections, autoimmune), Extramedullary haematopoiesis (myelofibrosis, thalassaemia major).
-
Massive splenomegaly causes: CML, myelofibrosis, chronic malaria, kala-azar (visceral leishmaniasis), Gaucher disease, thalassaemia major, lymphoma, PV.
-
In HK, commonest cause of congestive splenomegaly = HBV-related cirrhosis → portal hypertension. Thalassaemia is also prevalent.
-
CML = Philadelphia chromosome t(9;22) = BCR::ABL = constitutively active tyrosine kinase → massive splenomegaly + leukocytosis with bimodal myelocytes/neutrophils + basophilia. Treat with TKIs.
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Myelofibrosis = marrow fibrosis → extramedullary haematopoiesis → massive splenomegaly + leukoerythroblastic film + tear-drop cells + dry tap.
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Aplastic anaemia has NO splenomegaly (no abnormal cells for the spleen to filter).
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Clinical features of splenomegaly: (a) Pressure symptoms (fullness, early satiety), (b) Hypersplenism (pancytopenia), (c) Underlying disease features.
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Distinguish spleen from kidney: Splenic notch, moves with respiration, cannot get above it, non-ballotable, dull to percussion.
High Yield Summary — Differential Diagnosis of Splenomegaly
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Use three filters to narrow the DDx: (a) Size — massive vs moderate vs mild; (b) Prevalence — common vs uncommon; (c) Geography — local (HK: HBV cirrhosis, thalassaemia, EBV) vs imported (malaria, kala-azar).
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Massive splenomegaly = CML, myelofibrosis, chronic malaria, kala-azar, Gaucher, thalassaemia major.
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Moderate splenomegaly = portal HT / cirrhosis, lymphoma, PV, CLL.
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Mild splenomegaly = haemolytic anaemias (thal intermedia, HbH, AIHA), infections (EBV, IE), SLE.
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PBS is your best friend: smudge cells → CLL; tear-drops + leukoerythroblastic → myelofibrosis; basophilia + left shift → CML; atypical lymphocytes → EBV; spherocytes → HS or AIHA (use DAT to differentiate).
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Aplastic anaemia and ITP do NOT cause splenomegaly — if you see splenomegaly with pancytopenia, think hypersplenism (portal HT, MPN, hairy cell leukaemia), not aplastic anaemia.
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JAK2 screening for unusual-site venous thrombosis (mesenteric, portal, hepatic vein) — MPN can present with thrombosis before overt cytosis.
High Yield Summary — Diagnostic Approach to Splenomegaly
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Confirm splenomegaly: Five clinical signs (LUQ mass, moves with inspiration, cannot get above, dull, splenic notch) + USG abdomen (splenic length > 12–13 cm).
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First-line bloods for ALL patients: CBC + DC, PBS, reticulocyte count, LFT, RFT, LDH, bilirubin, haptoglobin, CRP/ESR.
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PBS is the most powerful single investigation — directs the entire workup: left shift + basophilia → CML; tear-drops + leukoerythroblastic → myelofibrosis; smudge cells → CLL; atypical lymphocytes → EBV; blasts → acute leukaemia; spherocytes → HS/AIHA.
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USG abdomen detects portal HT signs (splenomegaly, small nodular liver, ↑portal vein diameter, reversed flow, varices, ascites) but is not sensitive for early portal HT. HVPG (≥ 10 mmHg) is the gold standard but rarely used clinically.
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For haemolysis: Confirm with ↑LDH, ↑unconjugated bilirubin, ↓haptoglobin, reticulocytosis → then DAT to classify immune vs non-immune.
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For MPN: BCR::ABL for CML; JAK2/CALR/MPL for PV, ET, PMF; BM biopsy for fibrosis grading (essential for PMF — dry tap + trephine showing reticulin/collagen fibrosis).
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MCICM (Morphology, Cytochemistry, Immunophenotype, Cytogenetics, Molecular) is the systematic haematological malignancy workup.
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BM trephine is essential in myelofibrosis (dry tap on aspirate) and provides architecture that aspirate cannot.
High Yield Summary — Management of Splenomegaly
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Management of splenomegaly = management of the underlying cause. Treat the primary disease first.
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Splenectomy indications: (a) Diagnostic — suspected splenic lymphoma; (b) Therapeutic — symptomatic massive splenomegaly refractory to medical therapy, refractory ITP/AIHA, ↓ transfusion requirement in thalassaemia major, hereditary spherocytosis with severe haemolysis, splenic rupture.
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Splenectomy is not done liberally because of the risk of overwhelming post-splenectomy infection (OPSI) — 2–3× increased risk of sepsis from encapsulated bacteria (S. pneumoniae, N. meningitidis, H. influenzae, Capnocytophaga).
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Pre-splenectomy vaccinations: PCV13 then PPSV23, MenACWY + MenB, Hib, annual influenza — ideally ≥ 2 weeks before surgery.
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Post-splenectomy: Lifelong prophylactic penicillin V (at least 2 years, often lifelong); emergency antibiotics at hand; MedicAlert bracelet; annual influenza vaccination.
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Post-splenectomy blood film: Howell-Jolly bodies, target cells, spurious leukocytosis and thrombocytosis — all expected, not pathological.
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CML: TKIs are first-line; monitor molecular response (MMR = BCR-ABL ≤ 0.1%); HSCT reserved for TKI-unresponsive or blastic phase.
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Myelofibrosis: Ruxolitinib (JAK inhibitor) for symptomatic splenomegaly; allo-HSCT only curative option; splenectomy is last resort (high mortality).
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Thalassaemia major: Transfusion + chelation ± HSCT; splenectomy to ↓ transfusion needs (defer to ≥ 4y).
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POST SPLENECTOMY INFECTIONS require urgent treatment — any febrile illness in an asplenic patient is a medical emergency.
High Yield Summary — Complications of Splenomegaly
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Hypersplenism is the cardinal complication — pancytopenia (anaemia > thrombocytopenia > leukopenia) from increased destruction, sequestration, and plasma volume expansion. Bone marrow is hyperactive (compensating).
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Splenic rupture — life-threatening haemorrhage from a fragile, stretched capsule. High-risk in EBV (avoid contact sports for 4–6 weeks), thalassaemia major, CML, myelofibrosis, and trauma.
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Splenic infarction — acute LUQ pain ± Kehr's sign; can lead to abscess (if infected embolus from IE) or auto-splenectomy (repeated infarction in sickle cell disease).
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Parvovirus B19 aplastic crisis — specifically infects erythroid precursors → transient halt of erythropoiesis → severe anaemia with paradoxically LOW reticulocyte count in any chronic haemolytic anaemia.
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Transfusional iron overload — each unit contains ~200 mg Fe; daily excretion only ~1 mg → deposits in liver (fibrosis, HCC), heart (heart failure), endocrine organs (DM, hypogonadism). Chelation is mandatory.
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OPSI (overwhelming post-splenectomy infection) — fulminant sepsis from encapsulated bacteria (S. pneumoniae most common); lifelong risk; prevented by vaccinations, prophylactic antibiotics, and patient education. Any febrile illness post-splenectomy is a medical emergency.
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Post-splenectomy blood film: Howell-Jolly bodies (pathognomonic), target cells, spurious leukocytosis and thrombocytosis — expected findings, not pathological.
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MPN complications: Thrombosis in unusual sites (JAK2+), blastic transformation (CML → blast crisis, PMF → AML), acquired vWD in extreme thrombocytosis.
Lymphadenopathy
Lymphadenopathy is the abnormal enlargement of one or more lymph nodes, often indicating infection, inflammation, or malignancy.
Lymphoma
Lymphoma is a group of hematologic malignancies arising from the clonal proliferation of lymphocytes within lymphoid tissues, broadly classified into Hodgkin and non-Hodgkin types.