• 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:

Think of the spleen as performing four F's: Filtration, iFection defence (immune), Fetal haematopoiesis / extramedullary haematopoiesis, and blood-cell Factory reserve.

1. 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.

2. 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.

3. 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.

4. 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).

The GC lecture also classifies causes by prevalence ^[1]:

Laboratory features of splenomegaly ^[1]:

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]

When you encounter splenomegaly, think systematically through the following:

1. Characterise the splenomegaly: Duration? Acute vs chronic? Any LUQ pain?
2. Symptoms of hypersplenism: Fatigue (anaemia), bleeding (thrombocytopenia), infections (leukopenia)
3. Constitutional symptoms: Fever, weight loss, night sweats (B symptoms → haematological malignancy, TB, lymphoma)
4. Liver disease screen: Alcohol use, viral hepatitis risk factors (sexual history, IVDU, tattoos, blood transfusion, HBV carrier status in HK), jaundice, abdominal distension (ascites)
5. Haematological clues: Prior blood counts, family history of anaemia/thalassaemia (HK!), ethnic background
6. Infections: Travel history (malaria, leishmaniasis), TB contacts, EBV exposure, HIV risk
7. Autoimmune: Joint pain, rash, photosensitivity, oral ulcers (SLE), rheumatoid features
8. Drug history: Drugs causing haemolysis, aplastic anaemia, or liver disease
9. Family history: Thalassaemia, hereditary spherocytosis, G6PD deficiency, storage diseases

1. General inspection: Pallor, jaundice, plethora, lymphadenopathy, cachexia
2. Hands: Clubbing, palmar erythema, Dupuytren's contracture, rheumatoid changes, Osler's nodes
3. Face/neck: Malar rash (SLE), cervical lymphadenopathy, pharyngitis (EBV)
4. Chest: Spider naevi, gynaecomastia, heart murmurs (IE)
5. Abdomen:
   • Spleen: as described above — start from RIF
   • Hepatomegaly (liver disease, haematological infiltration)
   • Ascites (portal HT)
   • Caput medusae (portal HT collaterals)
6. Legs: Oedema, petechiae, leg ulcers (thalassaemia, sickle cell)
7. Lymph node survey: Cervical, axillary, epitrochlear, inguinal, popliteal ^[10]

"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).

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:
  • Massive splenomegaly (most apparent finding) ^[9]
  • Fatigue, weight loss, night sweats
  • Leukocytosis with bimodal distribution of myelocytes and neutrophils
  • Basophilia ^[9]
  • Moderately reduced erythropoiesis
  • Markedly increased megakaryopoiesis with frequent small hypolobated forms ^[9]
• 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.

• 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).

• Most frequent primary immunodeficiency ^[13].
• Polyclonal lymphoproliferation + splenomegaly, lymphadenopathy, nodular lymphoid hyperplasia of small bowel in ~1/3 of patients ^[13].
• Also associated with ITP and AIHA — both of which can independently cause splenomegaly.

• Splenomegaly is part of the constellation of portal hypertension in liver failure/cirrhosis ^[3][14].
• Other complications: ascites, SBP, variceal bleeding, hepatic encephalopathy, hepatorenal syndrome, coagulopathy, HCC ^[14].

• 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.

Five examination findings suggestive of splenomegaly ^[1]:

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].

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:

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:

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.

BM examination is indicated in unexplained cytopenias or leukocytosis where the cause is not clear from the peripheral blood ^[28].

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].

Both cause microcytic anaemia, but in the context of splenomegaly, thalassaemia is far more likely ^[28]:

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]:

1. Treatment of the primary cause (e.g., TKI for CML, antiviral for HBV-cirrhosis, JAK2 inhibitor for myelofibrosis)
2. No treatment if the underlying cause is untreatable (observation/supportive care)
3. Surgical treatment (splenectomy) if the splenomegaly itself is causing problems (e.g., increased transfusion requirement in thalassaemia, refractory cytopenias)

The spleen is enlarged because of congestive back-pressure. Treating the liver disease and managing portal hypertension is the strategy.

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.

Two broad indications for splenectomy ^[1][34]:

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]:

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.

Two features that may appear alarming on CBC but are just consequences of splenectomy ^[34]:

• 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.

• 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.

• 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].

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):

1. Increased destruction — The expanded reticuloendothelial system (macrophages in the cords of Billroth) traps and destroys more blood cells than normal.
2. 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.
3. 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:

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).

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:

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]:

1. Splenic abscess — if the embolus is infected (e.g., from IE with septic emboli) → requires drainage ± splenectomy.
2. Splenic rupture — necrotic tissue weakens the capsule.
3. 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:

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).

Portal hypertension contributes to the majority of complications of cirrhosis, but not all — HE, HCC, and liver failure are exceptions. ^[3]

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]:

1. Mechanical filtration via splenic sinusoids (removes unopsonised bacteria).
2. Macrophage phagocytosis of infected cells.
3. 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.

Causative organisms ^[38][41]:

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:

• 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.