Immune thrombocytopenia is an autoimmune disorder characterized by antibody-mediated platelet destruction and impaired platelet production, resulting in isolated thrombocytopenia and increased bleeding risk.

Immune Thrombocytopenia (ITP)

Most common cause of symptomatic thrombocytopenia in both children and adults ^[1]^[2]
Incidence: approximately 1–6 per 100,000/year in adults; ~4 per 100,000/year in children ^[1]^[2]
Prevalence: ~8 per 100,000 in children; ~12 per 100,000 in adults ^[2]
Age distribution:
- Children: peak incidence age 2–5 years ^[3]
- Adults: incidence increases with age, with a peak at > 60 years old ^[3]
Sex distribution ^[2]^[3]:
- Male predominance in infants and older adults (> 70 years)
- Female predominance in adolescents and young adults (18–45 years) — this is the classic "young woman" teaching point, though in older populations M:F ≈ 1:1
- Overall, studies show mixed results; the traditional teaching of "young women" is an oversimplification

Why does incidence increase with age? Older patients are more likely to have underlying conditions (CLL, autoimmune diseases, drug exposure) that trigger secondary ITP, and ageing of the immune system (immunosenescence) increases susceptibility to loss of self-tolerance.

ITP in Children vs Adults

This is clinically important because ITP in children is a distinct entity from adult ITP ^[3]:

Feature	Children	Adults
Onset	Often acute, post-viral	Often insidious
Spontaneous remission	High (70–80% within 6 months)	Low (~20%)
Risk of bleeding	Lower	Higher
Underlying disease	Rare	More common (secondary ITP)
Chronic ITP	~20%	~60–70%
Antecedent viral illness	Common (1–4 weeks prior)	Less common

3. Anatomy and Function: The Platelet and the Spleen

4. Aetiology and Classification

4.1 Classification by Aetiology

ITP is classified into three categories ^[1]^[2]^[3]:

Acquired immune-mediated thrombocytopenia associated with an underlying condition ^[1]^[2]^[3]
Causes (important list for exams):

Category	Examples
Autoimmune conditions	SLE, antiphospholipid syndrome, Evans syndrome (AIHA + ITP), IBD, RA
Immunodeficiency	CVID (most frequent primary immunodeficiency), HIV, selective IgA deficiency ^[4]
Infections	HCV, HIV, H. pylori, Dengue (can cause severe thrombocytopenia, even single digits), CMV, VZV ^[1]^[2]
Lymphoproliferative disease	CLL, lymphoma
Pregnancy-associated	Gestational thrombocytopenia (must differentiate from ITP)
Post-vaccination	MMR, others (rare)

H. pylori and ITP – Hong Kong Relevance

H. pylori infection is associated with ITP and is an important extra-GI manifestation of H. pylori ^[5]. In regions with high H. pylori prevalence (including Hong Kong and East Asia), testing and eradicating H. pylori can improve platelet counts in some ITP patients. This is a recommended step in the workup, especially in Asia.

Evans Syndrome

Evans syndrome = autoimmune haemolytic anaemia (AIHA) + ITP occurring simultaneously or sequentially. The presence of AIHA (positive DAT/Coombs test + anaemia + reticulocytosis) alongside thrombocytopenia should alert you to this diagnosis. It often signals an underlying immunodeficiency such as CVID or SLE ^[4].

ITP is further classified by the duration of disease ^[1]^[2]^[3]:

Phase	Duration	Notes
Newly diagnosed	Up to 3 months from diagnosis	Most paediatric cases resolve here
Persistent	3–12 months from diagnosis	Window for spontaneous remission
Chronic	> 12 months	More common in adults; less likely to remit

5. Pathophysiology

The pathophysiology of ITP is more complex than just "antibodies destroy platelets." There are multiple mechanisms at play:

6. Clinical Features

The majority of ITP patients are asymptomatic ^[3]. The clinical manifestations depend on the severity of thrombocytopenia:

Platelet Count	Expected Clinical Picture
> 50 × 10⁹/L	Usually asymptomatic; surgery/trauma may cause excessive bleeding
20–50 × 10⁹/L	Easy bruising; may have petechiae
10–20 × 10⁹/L	Mucocutaneous bleeding (epistaxis, gum bleeding, menorrhagia)
< 10 × 10⁹/L	Risk of spontaneous serious bleeding including intracranial haemorrhage (ICH)

ITP typically presents as a platelet-type (mucocutaneous) bleeding pattern rather than a coagulation-type (deep-seated) bleeding pattern ^[6].

Why mucocutaneous rather than deep-seated? Platelets are the "first responders" in haemostasis — they form the primary platelet plug at sites of vascular injury. When platelets are deficient, you lose this primary haemostatic barrier, leading to bleeding from small vessels in the skin and mucous membranes. Coagulation factor deficiency (e.g., haemophilia), by contrast, impairs the secondary fibrin clot that stabilises larger vessel injuries → deep-seated bleeding (joints, muscles). Both can cause intracranial haemorrhage ^[6].

6.2 Symptoms (with Pathophysiological Basis)

6.3 Signs (with Pathophysiological Basis)

This is crucial — finding any of these should make you question the diagnosis:

Sign	If Present, Consider
Lymphadenopathy	Lymphoma, CLL, leukaemia, infections
Hepatosplenomegaly	Chronic liver disease, lymphoproliferative disorders, hypersplenism
Fever	Infection, leukaemia, TTP
Joint swelling/rash	SLE, other autoimmune conditions
Congenital anomalies	Inherited thrombocytopenia (e.g., Fanconi anaemia, Wiskott-Aldrich syndrome)
Anaemia + reticulocytosis	Evans syndrome (AIHA + ITP), TTP/HUS
Abnormal WBC	Leukaemia, bone marrow failure

Why no splenomegaly in ITP? Unlike haemolytic anaemia where the spleen enlarges from increased RBC destruction, in ITP the spleen does not significantly enlarge because platelets are much smaller than RBCs and the volume of phagocytosed material is trivial. In fact, the spleen is normal in size in primary ITP. Palpable splenomegaly should prompt consideration of an alternative diagnosis (liver disease, lymphoma, etc.) ^[8].

This is a classic exam comparison ^[6]:

Feature	Platelet disorder (e.g. ITP)	Coagulation disorder (e.g. Haemophilia)
Bleeding sites	Skin, mucous membranes	Deep-seated (joints, muscles)
Petechiae	Yes	No
Ecchymoses	Small, superficial, multiple	Large, deep
Haemarthrosis	No	Yes
Onset after injury	Immediate	Delayed (hours)
Response to pressure	May help	Does not help
Sex	Both sexes	Males (X-linked)
PT/APTT	Normal PT, Normal APTT	Prolonged PT or APTT

From the GC 027 lecture: "Patient with platelet disorder — No change in PT, No change in APTT" ^[7]. This is because PT and APTT measure the coagulation cascade (factors), not platelet number or function. A platelet count and bleeding time (or PFA-100) are needed to assess platelet disorders.

7. Relevant Investigations (Overview — to be detailed in Diagnosis section)

This section provides a brief framework; the full diagnostic algorithm will follow in the next response.

Investigation	Expected Finding in ITP	Rationale
CBC	Isolated thrombocytopenia (low platelets, normal Hb, normal WBC)	Confirms the problem is platelet-specific
Peripheral blood smear	Large platelets (megathrombocytes), no schistocytes, no blasts, no dysplasia	Large platelets indicate young, newly released platelets (compensatory marrow response). Schistocytes → TTP/HUS
PT / APTT	Normal	Coagulation cascade is intact in ITP ^[6]^[7]
Reticulocyte count	Normal (unless concurrent AIHA → Evans syndrome)	To exclude haemolysis

Test	Purpose
HIV serology	Rule out HIV-associated ITP
HCV serology	Rule out HCV-associated ITP
H. pylori testing (urea breath test / stool antigen)	Especially in Asia — treatable cause
ANA, anti-dsDNA	Rule out SLE
Direct antiglobulin test (DAT/Coombs)	Rule out Evans syndrome (AIHA + ITP)
Immunoglobulins (IgG, IgA, IgM)	Rule out CVID
LDH, bilirubin, haptoglobin	Rule out concurrent haemolysis

High Yield Summary

Definition: ITP is an acquired autoimmune thrombocytopenia (platelet < 100 × 10⁹/L) due to immune-mediated platelet destruction and impaired production, in the absence of other causes.

Name Change: No longer "idiopathic thrombocytopenic purpura" — now "immune thrombocytopenia" (proven immune basis, not always purpuric).

Classification:

Primary vs Secondary (HIV, HCV, H. pylori, SLE, CLL, CVID, drugs)
Duration: Newly diagnosed (< 3 mo), Persistent (3–12 mo), Chronic (> 12 mo)
Drug-induced immune thrombocytopenia (DITP) is a separate category

Pathogenesis (3 mechanisms):

IgG autoantibodies (anti-GPIIb/IIIa, anti-GPIb/IX) → Fc-mediated phagocytosis in spleen
Autoantibodies bind megakaryocytes → impaired platelet production
CD8+ T cell–mediated platelet destruction + Treg dysfunction

Platelet lifespan: 7–10 days → 1–2 days

Clinical Features:

Mucocutaneous bleeding pattern (petechiae, purpura, epistaxis, gum bleeding, menorrhagia)
Dry purpura (skin) = low risk; Wet purpura (mucous membranes) = high risk
ICH is the most feared complication (< 1%)
No lymphadenopathy, no hepatosplenomegaly, no fever in primary ITP
PT and APTT are normal
Children: post-viral onset, high spontaneous remission (70–80%)
Adults: insidious onset, often chronic

Treatment overview: Steroids, IVIg (for ITP); platelet transfusion only for life-threatening bleeding; TPO-RAs (eltrombopag, romiplostim) for refractory ITP ^[7]^[1].

Active Recall - Immune Thrombocytopenia (ITP)

Differential Diagnosis of ITP

Here, the bone marrow is failing to make enough platelets. The key distinguishing feature from ITP is that in ITP, the marrow is healthy and actively producing platelets (megakaryocytes are normal or increased); in production failure, the marrow is abnormal ^[3]^[11].

Condition	Key Distinguishing Features from ITP	Why It Matters
Acute leukaemia (ALL, AML)	Pancytopenia (not isolated thrombocytopenia), circulating blasts on PBS, hepatosplenomegaly, lymphadenopathy, bone pain, fever ^[12]^[13]	The most important condition to exclude, especially in children. ITP has isolated thrombocytopenia — if Hb is low or WBC is abnormal, think leukaemia
Aplastic anaemia	Pancytopenia (anaemia + neutropenia + thrombocytopenia), no lymphadenopathy, no hepatosplenomegaly, hypocellular marrow ^[14]	Shares "no organomegaly" with ITP, but ITP has isolated thrombocytopenia — aplastic anaemia affects all three lineages
Myelodysplastic syndrome (MDS)	Older patients (> 60), dysplastic features on PBS (hypogranular neutrophils, pseudo-Pelger-Huët cells, oval macrocytes), may have pancytopenia or isolated cytopenia ^[3]^[11]	Important DDx in elderly patients with new-onset thrombocytopenia — this is why bone marrow biopsy is indicated in patients > 60 years old ^[1]^[10]
Bone marrow infiltration	Leukoerythroblastic picture on PBS (nucleated RBCs + left-shifted granulocytes + tear-drop RBCs), organomegaly, bone pain ^[15]	Metastatic cancer (breast, prostate, lung), lymphoma, myelofibrosis — all can crowd out normal haematopoiesis
Chemotherapy / Radiotherapy	History of recent cytotoxic treatment, pancytopenia ^[3]	Obvious from history — drug-induced marrow suppression is non-immune and distinct from DITP
Megaloblastic anaemia (B12/folate deficiency)	Macrocytic anaemia, hypersegmented neutrophils on PBS, pancytopenia if severe ^[3]	Severe B12 or folate deficiency can cause ineffective megakaryopoiesis → thrombocytopenia, but always with macrocytosis

The Critical Distinction: Isolated vs Non-Isolated Thrombocytopenia

ITP causes ISOLATED thrombocytopenia — the WBC and RBC lines are normal (unless the patient has coincidental iron deficiency from chronic bleeding, or Evans syndrome) ^[1]^[3]. If you see abnormalities in other cell lines (anaemia not explained by bleeding, leukopenia, leukocytosis, circulating blasts), you must consider bone marrow pathology and NOT diagnose ITP ^[7].

II. Increased Platelet Destruction

This is the category ITP belongs to. The challenge is differentiating ITP from other causes of peripheral platelet destruction.

Condition	Key Distinguishing Features from Primary ITP	Mechanism
Primary ITP	Diagnosis of exclusion: isolated thrombocytopenia, no other cause found	Anti-GPIIb/IIIa and anti-GPIb/IX autoantibodies → Fc-mediated splenic phagocytosis
Secondary ITP (SLE)	Malar rash, photosensitivity, arthritis, serositis, ANA+, anti-dsDNA+ ^[3]^[11]	Same antibody-mediated mechanism but driven by underlying autoimmune disease
Secondary ITP (HIV)	Risk factors for HIV, other HIV manifestations, HIV serology+ ^[1]^[2]	HIV directly infects megakaryocytes + immune dysregulation → autoantibody production
Secondary ITP (HCV)	Risk factors for HCV, abnormal LFTs, HCV serology+ ^[1]^[2]	Molecular mimicry, immune complex deposition, hypersplenism from cirrhosis
Secondary ITP (H. pylori)	Dyspepsia, positive urea breath test or stool antigen ^[1]^[2]	Molecular mimicry (CagA cross-reactivity), immune dysregulation; eradication can improve counts
Secondary ITP (CLL)	Older patient, lymphocytosis, smudge cells on PBS, lymphadenopathy ^[2]^[3]	Immune dysregulation from lymphoproliferative disease
Evans syndrome	AIHA + ITP: anaemia with reticulocytosis, positive DAT (Coombs test), ↑LDH, ↓haptoglobin, ↑unconjugated bilirubin ^[1]^[14]	Autoantibodies against both RBCs and platelets; think underlying CVID or SLE
Antiphospholipid syndrome (APS)	Recurrent thrombosis (arterial + venous), recurrent pregnancy loss, livedo reticularis, positive anticardiolipin/anti-β2GPI/lupus anticoagulant ^[16]	Antiphospholipid antibodies cause both thrombosis AND thrombocytopenia (immune-mediated platelet consumption) — a classic paradox
Drug-induced immune thrombocytopenia (DITP)	Temporal relationship with drug exposure; platelet count recovers on drug withdrawal; intermittent course paralleling drug use ^[3]^[10]	Drug binds platelet surface → neoantigen → drug-dependent antibodies → platelet destruction
Heparin-induced thrombocytopenia (HIT)	Occurs 5–10 days after heparin initiation; paradoxical thrombosis (not bleeding); moderate thrombocytopenia (nadir rarely < 20); positive anti-PF4/heparin antibodies ^[3]	Heparin-PF4 complex → IgG → FcγRIIA on platelets → platelet activation + aggregation → thrombosis + consumption

HIT – A Special Beast

HIT is NOT like other DITPs. Most drug-induced thrombocytopenias cause bleeding. HIT causes thrombosis — it is a prothrombotic thrombocytopenia. The mechanism is different: antibodies activate platelets (rather than just opsonising them for destruction). If you see a patient on heparin who develops new thrombocytopenia + a new clot → think HIT immediately. Do not give platelets (it fuels the fire).

These are critical DDx because they are medical emergencies and their management is completely different from ITP:

Condition	Key Distinguishing Features from ITP	Mechanism
Thrombotic Thrombocytopenic Purpura (TTP)	Pentad: MAHA (schistocytes on PBS) + thrombocytopenia + fever + renal impairment + neurological symptoms; ADAMTS13 activity < 10% ^[3]^[11]	Deficiency of ADAMTS13 → ultra-large vWF multimers → spontaneous platelet aggregation → microthrombi → RBC fragmentation + platelet consumption
Haemolytic Uraemic Syndrome (HUS)	Triad: MAHA + thrombocytopenia + acute kidney injury; often preceded by bloody diarrhoea (Shiga toxin–producing E. coli) in typical/diarrhoea-associated HUS ^[3]	Endothelial injury → microthrombi in renal vasculature
Disseminated Intravascular Coagulation (DIC)	Abnormal clotting profile: ↑PT, ↑APTT, ↑D-dimer, ↓fibrinogen; schistocytes on PBS; underlying trigger (sepsis, malignancy, obstetric emergency, APL) ^[3]^[11]^[17]	Systemic activation of coagulation → consumption of platelets AND clotting factors → both bleeding and thrombosis
Hypersplenism	Splenomegaly on examination (palpable spleen), often in context of chronic liver disease with portal hypertension ^[7]^[18]	Enlarged spleen pools/sequesters up to 90% of platelets (normally 30%) → peripheral thrombocytopenia despite normal marrow production

From GC 027 ^[7]: Isolated thrombocytopenia — Increased destruction → Chronic liver disease, Immune thrombocytopenia purpura, Drug induced. Note that the GC lecture groups chronic liver disease (hypersplenism) alongside ITP and DITP as the three key causes of isolated thrombocytopenia from increased destruction.

How to Differentiate TTP/DIC from ITP – Key Exam Point

The critical difference is the presence of MAHA (schistocytes on peripheral blood smear) and abnormal clotting profile in TTP/DIC, which are ABSENT in ITP ^[3]^[11].

From Felix Lai's case study ^[3]: "What are the useful investigations for exclusion of DIC?"

Peripheral blood film → fragmented red cells (schistocytes)
Clotting profile → ↑PT and APTT, ↑D-dimer, ↓Fibrinogen

In ITP: PBS shows NO schistocytes, clotting profile is NORMAL. This is how you tell them apart at the bedside.

Condition	Key Distinguishing Features	Mechanism
Hypersplenism (repeated for emphasis)	Splenomegaly + chronic liver disease stigmata + portal hypertension features (ascites, varices, caput medusae) ^[7]^[18]	Splenic pooling of platelets. Thrombocytopenia usually mild (70–100 × 10⁹/L), rarely < 40
Dilutional thrombocytopenia	Massive transfusion history (> 10 units pRBC in 24h)	Dilution of platelets by transfused RBCs and crystalloid; also consumption in trauma
Gestational thrombocytopenia	Mild thrombocytopenia (usually > 70 × 10⁹/L) in 3rd trimester, resolves postpartum, no prior history	Haemodilution + mildly increased platelet turnover in pregnancy; benign, no treatment needed

These are rare but important, especially in paediatrics and if the thrombocytopenia has been lifelong:

Condition	Key Distinguishing Features	Mechanism
Bernard-Soulier syndrome	Giant platelets on PBS, lifelong bleeding history, autosomal recessive ^[3]^[6]	Deficiency/dysfunction of GPIb/IX (vWF receptor) → defective platelet adhesion. "Bernard" = "Big" platelets (mnemonic)
Wiskott-Aldrich syndrome	Young male + small platelets + eczema + recurrent infections (X-linked recessive) ^[3]	WAS protein mutation → defective actin cytoskeleton in haematopoietic cells → small dysfunctional platelets + immunodeficiency
Inherited bone marrow failure syndromes	Congenital anomalies (e.g., Fanconi anaemia: short stature, café-au-lait spots, thumb/radial anomalies); pancytopenia, not isolated thrombocytopenia ^[3]^[14]	DNA repair defects → progressive marrow failure
Glanzmann's thrombasthenia	Normal platelet count but defective aggregation (this is a qualitative defect, not quantitative) ^[3]	Deficiency of GPIIb/IIIa → platelets cannot aggregate. Platelet count is normal — so this is NOT a DDx for thrombocytopenia per se, but for bleeding with normal platelet count
Grey platelet syndrome	Large, pale ("grey") agranular platelets on PBS ^[3]	Deficiency of α-granules → defective degranulation
MYH9-related disorders (May-Hegglin anomaly)	Giant platelets + Döhle body–like inclusions in neutrophils ^[10]	Myosin heavy chain mutation → defective megakaryocyte fragmentation

Congenital vs Acquired – How to Tell

Ask about duration and family history ^[6]:

Lifelong bleeding tendency, family history → congenital
Acute/recent onset, no family history → acquired (ITP, drugs, etc.)

ITP is NOT characterised by abnormal platelet morphology (lack of granules, uniform populations of large or small platelets). If such features are present on PBS, consider an inherited platelet disorder ^[3].

These don't cause thrombocytopenia but present with platelet-type bleeding despite a normal platelet count. They are DDx for "bleeding tendency" rather than "thrombocytopenia" per se, but worth mentioning because they can mimic the bleeding pattern of ITP ^[3]^[6]:

Condition	Mechanism
Aspirin / NSAIDs	Irreversible (aspirin) or reversible (NSAIDs) inhibition of COX-1 → ↓TXA2 → impaired platelet activation
Clopidogrel / Prasugrel / Ticagrelor	ADP receptor (P2Y12) antagonism → impaired ADP-dependent platelet aggregation
GPIIb/IIIa inhibitors (abciximab, eptifibatide, tirofiban)	Block the final common pathway of platelet aggregation
Uraemia	Uraemic toxins impair platelet function and platelet-vessel wall interaction → ↑bleeding time despite normal count ^[3]
von Willebrand disease	↓vWF → impaired platelet adhesion. Mucocutaneous bleeding pattern. Normal platelet count but ↑bleeding time, ↓vWF:Ag, ↓vWF:RCo, ± ↓Factor VIII ^[6]

Category	Conditions	Key Differentiating Feature from ITP
Artefact	Pseudothrombocytopenia	Platelet clumps on PBS; normalises in citrate tube
↓ Production	ALL, AML, AA, MDS, marrow infiltration, chemo/RT, megaloblastic anaemia	Pancytopenia / other lineage abnormalities / blasts / dysplasia
↑ Destruction – Immune	Secondary ITP (SLE, HIV, HCV, H. pylori, CLL), DITP, HIT, APS, Evans syndrome	Underlying disease features, drug history, DAT+, thrombosis in HIT/APS
↑ Destruction – Non-immune	TTP, HUS, DIC	MAHA (schistocytes), abnormal clotting profile (DIC), AKI (HUS)
Sequestration	Hypersplenism (CLD)	Splenomegaly, stigmata of chronic liver disease
Dilution	Massive transfusion, gestational	Clinical context
Congenital	Bernard-Soulier, WAS, Fanconi, MYH9 disorders	Lifelong history, family history, characteristic PBS morphology, congenital anomalies
Qualitative (normal count)	Aspirin/NSAIDs, uraemia, vWD	Platelet count is normal — bleeding from dysfunction, not deficiency

Common Exam Pitfalls

ALL in children mimicking ITP: A child with bruises and low platelets could be either. The key is to check the other cell lines and PBS for blasts. ITP = isolated thrombocytopenia with NO other abnormalities. ALL = usually pancytopenia with blasts, ± hepatosplenomegaly, ± bone pain ^[9]^[12].
TTP mimicking ITP: Both have thrombocytopenia. But TTP has schistocytes on PBS (MAHA) and ITP does not. Always examine the blood film. Missing TTP is fatal — TTP needs urgent plasma exchange, not steroids alone ^[3].
MDS in elderly: An elderly patient with new isolated thrombocytopenia could be either ITP or MDS. This is why bone marrow biopsy is recommended in patients > 60 years old with new thrombocytopenia ^[1]^[10].
SLE presenting as ITP: SLE can present with isolated thrombocytopenia before other manifestations appear. Always check ANA in new ITP ^[3].
Pseudothrombocytopenia: Don't forget the artefact. Always check PBS for clumps before diagnosing ITP ^[7]^[10].

High Yield Summary – Differential Diagnosis of ITP

ITP is a diagnosis of exclusion. The approach:

Rule out pseudothrombocytopenia (repeat CBC, check PBS for clumps, citrate tube)
Isolated or pancytopenia? → Pancytopenia = marrow pathology (AA, leukaemia, MDS)
Isolated thrombocytopenia with splenomegaly? → Hypersplenism (CLD)
Schistocytes on PBS? → TTP, HUS, DIC (NOT ITP)
Drug-related? → DITP, HIT
Secondary cause screen (HIV, HCV, H. pylori, SLE, CLL, CVID, DAT) → Secondary ITP
All negative → Primary ITP

Key DDx to remember (from Felix Lai case study ^[3]):

Bone marrow failure: Acute leukaemia, Aplastic anaemia, MDS, BM infiltration
Increased consumption: Hypersplenism, DIC, TTP

Red flags against primary ITP: Lymphadenopathy, hepatosplenomegaly, other cytopenia, schistocytes, blasts on PBS, bone pain, fever, congenital anomalies, abnormal clotting profile.

Active Recall - Differential Diagnosis of ITP

References

^[1] Senior notes: Adrian Lui Pediatrics Notes.pdf (p.386 — ITP diagnosis and management) ^[2] Senior notes: Ryan Ho Haemtology.pdf (p.117 — ITP classification and pathogenesis) ^[3] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf (p.606–613) and MBBS Final MB (Medicine) (Felix PY Lai).pdf (p.1366–1378) ^[6] Senior notes: Block A - Abnormal bleeding after tooth extraction_ bleeding tendency; thrombocytopenia.pdf (p.7–8) ^[7] Lecture slides: GC 027. Abnormal bleeding after tooth extraction.pdf (p.24 — Clinical situation: low platelet count) ^[9] AOS material: AOS - Paeds.pdf (p.1, Q10 — ALL vs ITP differentiation) ^[10] Senior notes: Maksim Medicine Notes.pdf (p.161–162 — platelet disorders DDx and ITP investigations) ^[11] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (p.1367–1370 — DDx of platelet disorders) ^[12] Senior notes: Block A - High white cell count_ acute and chronic leukaemia; bone marrow transplantation; immunogenetics.pdf (p.3 — clinical features of acute leukaemia) ^[13] Senior notes: Ryan Ho Fundamentals.pdf (p.390 — workup of high WCC / PBS interpretation) ^[14] Senior notes: Block A - Family history of anaemia_ inherited causes of anaemia; haemolytic anaemia; aplastic anaemia.pdf (p.6–8) ^[15] Senior notes: Ryan Ho Fundamentals.pdf (p.390 — leukoerythroblastic picture) ^[16] Senior notes: Block A - Leg swelling and chest pain_ deep vein thrombosis; pulmonary embolism; Thrombophilia.pdf (p.14 — antiphospholipid syndrome) ^[17] Senior notes: Block A - Introduction to Haematological investigations (CBP, Clotting).pdf (p.19 — DIC clotting profile) ^[18] Senior notes: Block A - Splenomegaly_ common causes of splenomegaly; myeloproliferative diseases.pdf (p.11)

Diagnostic Criteria, Diagnostic Algorithm, and Investigations for ITP

1. Diagnostic Criteria

The International Working Group (IWG) and American Society of Hematology (ASH) define ITP diagnosis as follows ^[1]^[3]:

Criterion	Requirement
Platelet count	< 100 × 10⁹/L (note: NOT < 150 — the threshold was lowered to avoid over-diagnosing people with mildly low-normal counts)
Isolated thrombocytopenia	WITHOUT anaemia (unless from bleeding → IDA) or leukopenia
No other apparent cause	History, physical examination, CBC, PBS, and baseline labs do not reveal another aetiology
Normal peripheral blood smear	No schistocytes, no blasts, no dysplasia, no abnormal platelet morphology suggestive of inherited disorder
Normal coagulation	PT and APTT should be normal ^[3]^[6]^[7]

Why < 100 and not < 150? About 2.5% of the healthy population has platelets between 100–150 × 10⁹/L as a normal variant (this is the lower tail of the Gaussian distribution). Using < 150 would label many healthy people as having ITP. The < 100 threshold has better specificity ^[1].

2. History and Physical Examination as Diagnostic Tools

Before ordering any blood test, the history and physical examination themselves are powerful diagnostic tools for ITP — not to confirm it, but to exclude mimics and identify secondary causes.

Domain	What to Ask	Why
Bleeding symptoms	Petechiae, purpura, ecchymosis, epistaxis, gum bleeding, menorrhagia, haematuria, GI bleeding	Characterise severity and pattern (mucocutaneous = platelet-type)
Duration	Acute vs chronic	Acute onset post-viral in children → classic ITP; chronic in adults → consider secondary causes
Preceding viral illness	URTI 1–4 weeks prior?	Molecular mimicry — classic trigger in childhood ITP
Drug history	Heparin, quinine, sulfonamides, vancomycin, GPIIb/IIIa inhibitors, recent vaccinations	Drug-induced immune thrombocytopenia must be excluded ^[3]
Medical history	HIV, HCV, SLE, CLL	These are the four classic secondary causes that must be screened for ^[1]^[2]^[3]
Liver disease / alcohol	Cirrhosis, portal hypertension	Hypersplenism and chronic liver disease as cause ^[7]
Family history	Family members with bleeding tendency or thrombocytopenia	Inherited platelet disorders (Bernard-Soulier, WAS, Fanconi)
Autoimmune symptoms	Rash, photosensitivity, arthralgia, sicca symptoms	SLE or other autoimmune disease → secondary ITP
Pregnancy	Trimester, prior platelet counts	Gestational thrombocytopenia vs ITP in pregnancy

Platelet count remains fairly constant in patients with ITP in the absence of therapy, in contrast to drug-induced thrombocytopenia due to intermittent drug exposure ^[3]. This temporal pattern is a helpful historical clue — if the platelet count fluctuates wildly in relation to drug cycles, think DITP.

The physical examination in ITP serves two purposes: (1) confirm bleeding signs, and (2) look for findings that should be ABSENT in primary ITP.

Findings expected in ITP:

Petechiae (dependent areas)
Purpura (dry and/or wet)
Ecchymoses

Findings that MUST BE ABSENT in primary ITP (red flags):

Finding	If Present, Consider
NO lymphadenopathy ^[3]	If present → leukaemia, lymphoma, CLL, infections
NO hepatosplenomegaly ^[3]	If present → CLD/hypersplenism, MPN, lymphoproliferative disease
NO skeletal abnormalities ^[3]	If present → inherited bone marrow failure (Fanconi anaemia)
Normal fundoscopy	Fundoscopic examination → assess for retinal haemorrhages → if present, indicates high risk of CNS bleeding ^[7]^[10]

Fundoscopy – Don't Forget This!

From GC 027 ^[7]: Assessment of bleeding risk → CNS bleeding: fundoscopic examination.

Fundoscopy: assess risk of ICH ^[10]. If retinal haemorrhages are found, the patient needs urgent treatment regardless of platelet count because retinal haemorrhage often indicates concurrent or imminent intracranial haemorrhage.

3. Investigations

The investigations for ITP are organised into three tiers:

Essential (every patient) — to confirm isolated thrombocytopenia and exclude common mimics
Secondary cause screening — to classify as primary vs secondary ITP
Selected/specialised — for atypical cases, older patients, or treatment-refractory disease

3.1 Essential Investigations (Tier 1 — Every Patient)

The single most important test.

Parameter	Expected in ITP	Interpretation
Platelet count	< 100 × 10⁹/L (can range from mild 100–150 to severe < 10) ^[3]	Confirms thrombocytopenia. Severity guides management
Haemoglobin	Normal (unless chronic blood loss → IDA)	If anaemia is present + reticulocytosis → think Evans syndrome or TTP. If the patient is anaemic → most likely bleeding and iron-deficiency anaemia ^[3]^[11]
WBC and differential	Normal	Abnormal WBC → consider leukaemia (blasts), infection (neutrophilia), CLL (lymphocytosis)
MCV	Normal	If macrocytic → consider MDS, B12/folate deficiency, liver disease

ABSENCE of other haematological findings is critical — ITP is NOT characterised by abnormal number or appearance of RBC or WBC or abnormal coagulation parameters ^[3]. The exception: Evans syndrome (10% of ITP patients) = AIHA + ITP ^[3].

EDTA Pseudothrombocytopenia – Step Zero

Most common cause of thrombocytopenia in any setting is pseudo → EDTA-dependent clumping of platelets ^[19]. The automated analyser counts platelet clumps as single large cells → falsely low count. Correct using citrate bottle ^[7]^[19]. Always check the PBS for clumps before diagnosing anything.

The second most important test — arguably equally important to the CBC.

Finding	Significance
Large platelets (megathrombocytes)	Reflective of increased platelet turnover ^[3] — the marrow is pushing out young, large platelets to compensate for peripheral destruction. Supports ITP
No platelet clumping	Required to confirm that thrombocytopenia is not artifactual due to platelet clumping ^[3]
No schistocytes	Rules out TTP, HUS, DIC (MAHA) ^[3]^[11]
No blasts	Rules out acute leukaemia ^[13]^[15]
No dysplastic cells	Rules out MDS ^[3]
No leukoerythroblastic picture	Rules out bone marrow infiltration ^[13]^[15]
Normal platelet morphology	ITP is NOT characterised by abnormal platelet morphology (lack of granules, uniform populations of large or small platelets) and should prompt consideration of an inherited platelet disorder if present ^[3]

Why are platelets large in ITP? When platelets are being destroyed rapidly, the bone marrow ramps up production. Newly released platelets (like reticulocytes in anaemia) are larger, more granular, and more haemostatically active. This also explains why ITP patients bleed less than expected for a given platelet count compared to patients with production failure (their platelets are "younger and fitter") ^[1].

Parameter	Expected in ITP	Why We Check
PT	Normal ^[6]^[7]	Patient with platelet disorder → No change in PT, No change in APTT ^[6]. An abnormal PT/APTT points away from ITP toward DIC, liver disease, coagulation factor deficiency
APTT	Normal ^[6]^[7]	If prolonged → consider lupus anticoagulant/APS, haemophilia, heparin use, acquired inhibitors
Fibrinogen	Normal	Low fibrinogen → DIC
D-dimer	Normal	Elevated → DIC, TTP

PT and APTT are indicated in patients with moderate or severe thrombocytopenia or with concerns about clinically important bleeding ^[3]. They are not to "diagnose" ITP but to evaluate for other potentially treatable causes of thrombocytopenia ^[3].

Exclusion of DIC – Key Exam Point

From Felix Lai case study ^[3]^[11]: "What are the useful investigations for exclusion of DIC?"

Peripheral blood film → fragmented red cells (schistocytes)
Clotting profile → ↑ PT and APTT, ↑ D-dimer, ↓ Fibrinogen level

If ALL of these are normal → DIC is excluded. In ITP: PBS shows NO schistocytes, clotting profile is entirely normal.

Finding	Significance
Normal	Expected in primary ITP (no haemolysis)
Elevated (reticulocytosis)	Suggests concurrent haemolysis → Evans syndrome (AIHA + ITP) or TTP. Triggers DAT testing

3.2 Secondary Cause Screening (Tier 2 — To Classify Primary vs Secondary)

These investigations are performed in all newly diagnosed ITP patients to identify treatable underlying conditions:

Test	Target	Rationale
HIV serology	HIV infection	ALL patients are tested for HIV because thrombocytopenia is a common presenting finding ^[3]
HCV serology	HCV infection	ALL patients are tested for HCV — HCV causes immune-mediated platelet destruction + hypersplenism from cirrhosis ^[3]
HBsAg	HBV infection	Part of pre-treatment workup (rituximab can reactivate HBV) ^[10]

Why HIV and HCV specifically? Both viruses commonly present with isolated thrombocytopenia as an early finding, sometimes before other symptoms manifest. Missing them means missing a treatable (and transmissible) infection ^[3].

Test	Rationale
Urea breath test or stool antigen test	H. pylori eradication can improve platelet counts in ITP patients who test positive. Especially important in Hong Kong / Asia where H. pylori prevalence is high ^[1]^[2]

H. pylori testing is recommended by both ASH and International Consensus guidelines for all ITP patients in regions of moderate-to-high prevalence. Eradication therapy alone can normalise platelets in 30–50% of H. pylori–positive ITP patients — a remarkable "free" treatment.

Test	Target	Rationale
ANA	SLE screen	SLE can present with isolated thrombocytopenia before other manifestations. A positive ANA prompts further workup (anti-dsDNA, complement levels) ^[3]
Anti-phospholipid antibodies	APS screen	APS causes both thrombocytopenia AND thrombosis ^[3]^[16]
RF	RA screen	RA can cause secondary ITP ^[3]

Finding	Significance
Negative	Expected in primary ITP (no immune haemolysis)
Positive	Suggests Evans syndrome (AIHA + ITP) → look for haemolysis markers (↑LDH, ↓haptoglobin, ↑unconjugated bilirubin, reticulocytosis) ^[3]^[14]

Evans syndrome occurs in ~10% of ITP patients ^[3]. The DAT detects IgG or complement (C3d) bound to the RBC surface. A positive DAT in the setting of anaemia + thrombocytopenia = Evans syndrome until proven otherwise.

Test	Rationale
Serum IgG, IgA, IgM	Screen for CVID (common variable immunodeficiency) — the most frequent primary immunodeficiency, which commonly presents with ITP ^[4]^[10]

Why check Ig levels? CVID presents with hypogammaglobulinaemia + autoimmune cytopenias (ITP and AIHA being the most common). If you diagnose "ITP" but don't check Ig levels, you may miss the underlying CVID — and the patient will continue getting recurrent infections.

Test	Rationale
Serum C3, C4	Low complement → suggests SLE or other complement-consuming autoimmune disease ^[3]

Test	Rationale
LRFT (Liver and Renal Function Tests)	Baseline before steroids; liver disease as cause of thrombocytopenia ^[10]
CMV pp65/PCR	CMV can cause thrombocytopenia; important before immunosuppression ^[10]
G6PD level	Important pre-treatment check in Hong Kong (high prevalence of G6PD deficiency) — some drugs used in ITP treatment can trigger haemolysis ^[10]

Maksim's Pre-Treatment Workup Checklist

Pre-Tx workup: LRFT, Ig pattern, HBsAg, CMV pp65/PCR, G6PD ^[10]. These are done not to diagnose ITP but to prepare for safe treatment (steroids, rituximab, etc.) and to catch important secondary causes.

Test	Result	Clinical Utility
Anti-platelet antibodies (MAIPA = Monoclonal Antibody Immobilisation of Platelet Antigens)	Positive in ~60% of ITP	Generally not useful for diagnosis. Low sensitivity but high specificity. Performed in QMH but does not change management ^[1]^[3]

Why is MAIPA not useful? A negative test does NOT rule out ITP (40% of true ITP patients are negative — low sensitivity). A positive test supports ITP but you've usually already made the diagnosis by exclusion. It also cannot differentiate primary from secondary ITP. The test is a "nice to know" but not a decision-maker.

3.4 Bone Marrow Examination (Tier 3 — Selected Cases Only)

This is one of the most tested exam points: bone marrow examination is NOT a routine component in the diagnostic evaluation of patients with typical features of ITP ^[1]^[3]^[10].

Indication	Rationale
Age > 60 years	To rule out MDS (myelodysplastic syndrome), which can mimic ITP with isolated thrombocytopenia ^[1]^[10]
Uncertain diagnosis	Atypical features that don't fit classic ITP
Poor response to first-line treatment (steroids)	Lack of response raises suspicion for alternative diagnosis
Before splenectomy	To confirm the diagnosis before an irreversible procedure
Other unexplained cytopenias	If there is anaemia (unexplained by bleeding) or leukopenia → marrow pathology
Dysplasia on PBS	Suggests MDS rather than ITP

Feature	Finding	Significance
Megakaryocytes	Normal or increased in number; left shift towards younger megakaryocytes ^[3]	Suggests a consumptive cause ^[11] — the marrow is trying to compensate for peripheral platelet destruction by increasing megakaryocyte production
Cellularity	Normal	Rules out aplastic anaemia (hypocellular) and leukaemia (hypercellular with blasts)
Erythropoiesis	Normal	No red cell lineage pathology
Myelopoiesis	Normal	No white cell lineage pathology
Fibrosis	Absent	Present in myelofibrosis
Blasts	< 5% (normal)	≥ 20% = acute leukaemia

Why are megakaryocytes increased? The bone marrow is responding appropriately to the peripheral platelet deficit. TPO levels (though not as high as in aplastic anaemia) still signal the marrow to ramp up megakaryocyte production. But the autoantibodies destroy the platelets as fast as they're made — like filling a bucket with a hole in the bottom.

Investigation	Indication	Purpose
CT brain	Headache, altered consciousness, focal neurology, severe thrombocytopenia (< 10 × 10⁹/L)	Rule out ICH ^[10]
Abdominal USS	Clinical suspicion of splenomegaly / liver disease	Confirm spleen size; assess for CLD/portal hypertension

Investigation	Tier	Expected in ITP	Primary Purpose
CBC	1	Isolated ↓ platelets; normal Hb, WBC	Confirm isolated thrombocytopenia
PBS	1	Large platelets, no clumps, no schistocytes, no blasts	Exclude pseudothrombocytopenia, TTP, leukaemia, MDS, inherited disorders
Clotting profile	1	Normal PT, APTT, fibrinogen, D-dimer	Exclude DIC, liver disease, coagulopathy
Reticulocyte count	1	Normal	Exclude concurrent haemolysis
HIV serology	2	Negative	Exclude HIV-associated ITP
HCV serology	2	Negative	Exclude HCV-associated ITP
H. pylori test	2	Variable	Treatable secondary cause
ANA, anti-dsDNA	2	Negative	Exclude SLE
aPL antibodies	2	Negative	Exclude APS
DAT	2	Negative	Exclude Evans syndrome
Ig levels	2	Normal	Exclude CVID
C3, C4	2	Normal	Exclude complement-consuming disease
HBsAg	2	Variable	Pre-treatment safety
LRFT	2	Normal	Baseline + exclude liver/renal disease
G6PD	2	Normal	Pre-treatment safety (HK population)
Anti-platelet Ab (MAIPA)	3	Positive in ~60%	Low sensitivity, high specificity; done at QMH but not clinically decisive
Bone marrow	3	↑ megakaryocytes, normal cellularity	Selected cases: age > 60, uncertain Dx, poor Tx response, pre-splenectomy
CT brain	3	Normal	If concern for ICH
Fundoscopy	1	Normal	Assess CNS bleeding risk ^[7]

High Yield Summary – Diagnosis of ITP

ITP is a diagnosis of EXCLUSION — no single confirmatory test.

Diagnostic criteria:

Isolated thrombocytopenia (platelet < 100 × 10⁹/L)
No anaemia, no leukopenia (unless Evans syndrome or bleeding-related IDA)
Normal PBS (large platelets, NO schistocytes, NO blasts, NO dysplasia, NO clumps)
Normal PT/APTT (platelet disorder does not affect coagulation cascade tests)
No other apparent cause after secondary cause screening

Essential workup:

CBC + PBS + clotting profile + reticulocyte count + fundoscopy
HIV, HCV, H. pylori, ANA, DAT, Ig levels (secondary cause screen)

Bone marrow: NOT routine. Do if: age > 60, uncertain Dx, poor response to steroids, pre-splenectomy, other cytopenias ^[1]^[3]^[10]

BM findings in ITP: Increased megakaryocytes (consumptive cause) + normal cellularity ^[3]^[11]

Anti-platelet antibodies (MAIPA): Low sensitivity (~60%), high specificity. Generally not useful but done at QMH ^[1]^[3]

GC 027 framework ^[7]: Repeat → Isolated or pancytopenia → Isolated = CLD/ITP/Drug → Fundoscopy for CNS risk → Treat

Active Recall - Diagnosis of ITP

References

^[1] Senior notes: Adrian Lui Pediatrics Notes.pdf (p.385–386 — ITP diagnosis, anti-platelet Ab, BM indications) ^[2] Senior notes: Ryan Ho Haemtology.pdf (p.117 — ITP classification, secondary causes) ^[3] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf (p.606–613) and MBBS Final MB (Medicine) (Felix PY Lai).pdf (p.1366–1375) ^[4] Senior notes: Jerry's immunodeficiencies.pdf (p.1 — CVID and ITP) ^[6] Senior notes: Block A - Abnormal bleeding after tooth extraction_ bleeding tendency; thrombocytopenia.pdf (p.7 — PT/APTT in platelet disorders) ^[7] Lecture slides: GC 027. Abnormal bleeding after tooth extraction.pdf (p.24 — Clinical situation: low platelet count) ^[10] Senior notes: Maksim Medicine Notes.pdf (p.161–162 — ITP investigations and pre-Tx workup) ^[11] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (p.1373–1375 — Case study: DIC exclusion, BM findings) ^[13] Senior notes: Ryan Ho Fundamentals.pdf (p.390 — PBS interpretation: blasts, leukoerythroblastic picture) ^[14] Senior notes: Block A - Family history of anaemia_ inherited causes of anaemia; haemolytic anaemia; aplastic anaemia.pdf (p.4–6 — AIHA diagnosis, DAT) ^[15] Senior notes: Ryan Ho Fundamentals.pdf (p.390–391 — marrow examination indications) ^[16] Senior notes: Block A - Leg swelling and chest pain_ deep vein thrombosis; pulmonary embolism; Thrombophilia.pdf (p.14 — APS) ^[19] Senior notes: Block A - Introduction to Haematological investigations (CBP, Clotting).pdf (p.3 — pseudothrombocytopenia, EDTA clumping)

Management of ITP: Algorithm and Treatment Modalities

These apply regardless of platelet count or whether pharmacological treatment is needed ^[3]^[10]^[20]:

Measure	Rationale
Consult haematologist ^[20]	ITP management is specialist-driven
Remove inciting drug if any ^[1]^[2]^[20]	DITP — the simplest "cure" if drug-related
Treat underlying infection (HCV, HIV, H. pylori) ^[1]^[2]^[20]	Secondary ITP may resolve with infection treatment alone
Avoid aspirin and other antiplatelet agents ^[1]^[2]^[3]^[10]^[20]	These impair the already-reduced platelet function → ↑ bleeding risk
Avoid IM injections, arterial puncture, deep vein puncture ^[3]^[10]	Risk of haematoma at injection/puncture sites
Activity restriction ^[3]^[10]	Encourage low-impact activities (e.g. swimming, golf); high-impact activities (e.g. football) are not advisable; protective gear should be used ^[3]
Tranexamic acid ^[10]	Antifibrinolytic — stabilises clots that do form; useful adjunct for mucosal bleeding (epistaxis, menorrhagia)
Withhold offending drugs ^[10]	Always review the drug chart

Why avoid aspirin/NSAIDs? These drugs inhibit COX-1 → ↓TXA2 → impaired platelet activation and aggregation. In a patient who already has too few platelets, further impairing the function of the few remaining ones is dangerous — it's like puncturing the tyres of the last car you have.

Treatment is indicated when ^[3]^[20]:

Indication	Details
Platelet count < 10 × 10⁹/L	Regardless of symptoms — risk of spontaneous ICH
Clinical evidence of bleeding with platelet 10–30 × 10⁹/L	Nose bleeding that cannot be stopped for > 15 mins; oral mucosal bleeding including gum bleeding or blood retention cyst (wet purpura); GI bleeding ^[3]
Severe bleeding regardless of platelet count	ICH; retinal haemorrhage ^[3]
Pre-procedure	Platelet count > 50 × 10⁹/L is considered safe for minor procedures ^[3]; > 80–100 for major surgery

6. First-Line Therapy: Corticosteroids

Steroids are the mainstay of initial treatment for ITP ^[1]^[2]^[3]^[7]^[10]^[20].

There are two main regimens; both are acceptable as first-line ^[1]^[2]^[10]^[20]:

Regimen	Dose	Key Points
Dexamethasone (pulse)	40 mg/day for 4 days (or 20–40 mg/day for 4 days) ^[1]^[2]^[10]^[20]	79% respond to pulse dexamethasone ^[2]; can be repeated for 1–4 cycles; no taper needed for short pulse
Prednisolone (conventional)	1 mg/kg/day for 2 weeks (adults) ^[1]^[2]^[10]^[20]; 2 mg/kg/day for 2 weeks (paediatrics) ^[3]	Then taper over 1–2 weeks; maximum give 8 weeks total ^[10]; if no response, taper over 1 week ^[10]

Dexamethasone vs Prednisolone: Pulse dexamethasone has the advantage of a shorter course with fewer cumulative steroid side effects. Response is faster but relapse upon withdrawal is common ^[2]. Prednisolone gives a slower rise in platelet count (median 4 days) but the effect is more sustained ^[2]^[3].

Side Effect	Mechanism
Cushingoid features (moon face, buffalo hump, truncal obesity)	Redistribution of fat due to altered lipid metabolism
Hypertension	Mineralocorticoid effect → Na+ and water retention
Diabetes mellitus	Gluconeogenesis ↑, insulin resistance ↑
Osteoporosis	↓ Osteoblast activity, ↑ osteoclast activity
Gastritis / peptic ulcer	↓ Prostaglandin-mediated gastric mucosal protection
Immunosuppression → increased infection risk	Suppression of cellular and humoral immunity
Cataract	Posterior subcapsular — mechanism poorly understood
Hypokalemia	Mineralocorticoid effect
Easy bruising	Dermal atrophy + capillary fragility
Fluid retention	Mineralocorticoid effect

From Felix Lai case study ^[3]: The patient had Cushingoid features with moon face, buffalo hump, and truncal obesity — classic steroid side effects. Monitor BP and urine sugar Q2 weeks during steroid treatment ^[3]. Recommend to take the drug after meal or with antacids ^[3].

When a patient is actively bleeding severely (ICH, massive GI bleed, retinal haemorrhage) or has platelet < 10 × 10⁹/L with wet purpura, you need to raise the platelet count fast. This is a haematological emergency ^[3]^[10]^[20].

Emergency treatment includes IVIg + High-dose methylprednisolone + Platelet transfusion ^[3]^[20].

Treatment	Mechanism	Onset	Duration
IVIg	Overwhelming the RES (see below)	24–48 hours ^[3]	Transient: 1–2 weeks
High-dose IV methylprednisolone	1 g IV over 1 hour daily for 3 days ^[20]	2–5 days	More sustained
Platelet transfusion	Temporary haemostatic plug	Immediate but rapidly destroyed	Hours at best

Why use all three simultaneously? Each addresses a different time window: platelet transfusion buys you minutes-to-hours (even though the transfused platelets are destroyed quickly by the autoantibodies, they still provide temporary haemostasis during active bleeding); IVIg raises count within 24–48 hours; steroids sustain the response over days to weeks. It's a "bridging" strategy.

8. IVIg (Intravenous Immunoglobulin) — Detailed

Parameter	Detail
Dose	0.4 g/kg/day for 5 days OR 1.0 g/kg/day for 2 days ^[20]; No difference between low-dose (500 mg/kg) or high-dose (2 g/kg) in efficacy ^[3]
Efficacy	80% effective ^[20]
Onset	24–48 hours
Duration	Lasts 2–3 weeks ^[20]
Administration	Infuse the drug gradually (5 mL/15min → 10 mL/15min → 20 mL/15min) and give it over 1–2 days rather than 4 days ^[3]
Premedication	Premedication with piriton (chlorphenamine) before infusion required ^[3] — to prevent infusion-related reactions (headache, chills, fever)

Indication	Rationale
Acute life-threatening bleeding ^[10]^[20]	Need rapid platelet rise (24–48h) — steroids are too slow
Pre-urgent procedure	Need to raise platelets quickly before surgery
Steroid-refractory acute bleeding	When steroids alone haven't worked fast enough
Paediatric ITP with significant bleeding	Rapid response needed; often used as 1st line in children ^[3]

IVIg in Paediatrics vs Adults — Note the Difference

In the paediatric ITP framework ^[3], IVIg is listed as 1st line therapy (because of rapid onset and the desire to avoid steroids in children when possible). In adults, corticosteroids are usually preferred as 1st line in stable patients ^[1]^[2]^[10]^[20], with IVIg reserved for acute/life-threatening scenarios. Know both approaches for the exam.

9. IV Anti-Rh(D) (Anti-D Immunoglobulin)

Alternative to conventional IVIg for patients whose RBC is Rh(D) +ve ^[3]^[10].

Limitation	Detail
Only works in Rh(D)-positive patients	Rh-negative patients lack the target for anti-D
Only works if spleen is present	Mechanism relies on splenic RES; useless post-splenectomy
Risk of alloimmune haemolytic anaemia	Associated with higher incidence of alloimmune haemolytic anaemia secondary to anti-Rh(D) ^[3]
Not indicated for routine clinical use	Due to haemolysis risk; reserved for specific situations ^[3]

11. Second-Line Therapies

These are used when corticosteroids fail, the patient relapses on steroid taper, or unacceptably high steroid doses are needed to maintain a safe platelet count ^[2]^[3]^[10]^[20].

TPO-RAs are the cornerstone of second-line therapy in modern ITP management ^[7]^[10]^[20].

Name breakdown: "Thrombopoi-etin" = "thrombo" (clot) + "poiein" (to make) + "-etin" (protein suffix) → the protein that makes clot-forming cells. "Receptor agonist" = stimulates the receptor.

Drug	Route	Dose	Mechanism
Eltrombopag	PO (oral)	25–75 mg/day	Binds to the transmembrane domain of the TPO receptor (c-Mpl) → activates JAK/STAT signalling → ↑ megakaryocyte proliferation and differentiation → ↑ platelet production
Avatrombopag	PO (oral)	20 mg/day	Same mechanism as eltrombopag; newer agent
Romiplostim	SC (subcutaneous)	1–10 μg/kg weekly	"Peptibody" — Fc-peptide fusion protein that binds the extracellular domain of the TPO receptor → mimics endogenous TPO → ↑ platelet production

Why do these work if the main problem in ITP is destruction, not production? Recall from the pathophysiology section that ITP also involves impaired platelet production (autoantibodies targeting megakaryocytes + inadequate TPO levels). TPO-RAs bypass this by directly stimulating megakaryocytes, essentially "overwhelming" the destruction by flooding the circulation with new platelets. It's like turning the tap on full to compensate for the drain being open.

Parameter	Detail
Response rate	> 60% ^[10]
Onset	1–2 weeks
Key advantage	Oral dosing (eltrombopag), avoids immunosuppression
Key side effects	Hepatotoxicity (eltrombopag — monitor LFTs), thrombosis risk, bone marrow reticulin fibrosis (reversible on discontinuation)
Important interaction	Eltrombopag chelates polyvalent cations (Ca²⁺, Mg²⁺, Fe²⁺, Al³⁺) — must be taken on an empty stomach, 4 hours apart from dairy, antacids, or iron supplements

Eltrombopag vs Romiplostim – Know the Difference

Eltrombopag: oral, binds transmembrane domain of TPO-R, hepatotoxicity risk, food interactions
Romiplostim: subcutaneous weekly injection, binds extracellular domain of TPO-R, injection-site reactions

Both are used as second-line therapy. The choice depends on patient preference (oral vs injection), comorbidities (liver disease → avoid eltrombopag), and availability.

Parameter	Detail
Mechanism	Monoclonal antibody against CD20 (a surface marker on B cells) → depletes B cells → ↓ autoantibody production
Dose	Typically 375 mg/m² weekly × 4 doses
Response rate	~60% initial response; ~30% sustained response at 5 years
Onset	Slow: 2–8 weeks
Key side effects	Infusion reactions, immunosuppression (↓ IgG over time), HBV reactivation (must check HBsAg before use), progressive multifocal leukoencephalopathy (PML — rare)
Contraindication	Active HBV infection; active severe infection

Why rituximab? If the problem is autoantibodies, why not eliminate the cells that make them? Rituximab depletes CD20+ B cells, including the autoreactive B cell clones producing anti-platelet antibodies. However, long-lived plasma cells (which are CD20-negative) continue to secrete antibodies, which is why the response may be incomplete or transient.

Parameter	Detail
Mechanism	Inhibits spleen tyrosine kinase (SYK) → SYK is a key signalling molecule downstream of the FcγR on macrophages → inhibits phagocytosis of antibody-coated platelets ^[10]
Dose	100–150 mg PO twice daily
Key advantage	Oral; targets the effector mechanism (phagocytosis) rather than the immune cause
Side effects	Hypertension, diarrhoea, hepatotoxicity

Why is fostamatinib conceptually elegant? It directly blocks the final step — the macrophage eating the platelet. Even if autoantibodies are still present and platelets are still opsonised, the macrophage can't act on the signal because SYK signalling is blocked. It's like cutting the phone line to the demolition crew.

These are generally used as steroid-sparing agents or in refractory cases ^[2]^[3]^[10]:

Drug	Mechanism	Notes
Azathioprine	Purine analogue → inhibits lymphocyte proliferation	Can be used for steroid-sparing in prolonged steroid use ^[2]; slow onset (months)
Mycophenolate mofetil (MMF)	Inhibits inosine monophosphate dehydrogenase → blocks purine synthesis in lymphocytes	Better tolerated than azathioprine in some patients
Cyclosporin A	Calcineurin inhibitor → blocks T cell activation	Monitor levels; nephrotoxic
Cyclophosphamide	Alkylating agent → non-specific lymphocyte destruction	Last resort; significant toxicity (gonadal failure, malignancy risk)
Danazol	Weak androgen; exact mechanism in ITP unclear	Sometimes used in chronic ITP; attenuating Fc receptor expression is hypothesised

12. Splenectomy — Surgical Treatment

Splenectomy is reserved for patients who have failed medical treatment ^[2]^[3]^[10]^[20]^[22].

Indication	Detail
Disease is refractory to steroid	Failed adequate trial of first-line therapy
Relapse after responding to steroid	Platelet count drops after successful initial treatment
High dose of steroids is required for maintenance of safe platelet count	Steroid dependence with unacceptable side effects

Requirement	Rationale
Bone marrow examination	Confirm the diagnosis before irreversible procedure ^[1]^[2]
Vaccination for encapsulated organisms	Pneumococcus, Haemophilus influenzae type b, Meningococcus — the spleen is critical for opsonisation of encapsulated bacteria; without it, patients are at risk of overwhelming post-splenectomy infection (OPSI) ^[3]^[22]
Patient education	Warn about lifelong increased infection risk; need to seek medical attention promptly for fevers

Issue	Detail
↑ Infection risk	Especially by encapsulated bacteria such as pneumococcus and haemophilus ^[3]; lifelong risk; prophylactic antibiotics are often recommended ^[3]
Thrombosis risk	Post-splenectomy thrombocytosis + loss of splenic filtration → ↑ risk of VTE; consider prophylactic anticoagulation in high-risk patients
CBC changes	Spurious leukocytosis after splenectomy; increase in platelet counts ^[22] — these are expected post-splenectomy findings, not pathology
PBS changes	Howell-Jolly bodies (nuclear remnants in RBCs normally removed by the spleen); target cells; acanthocytes

Post-Splenectomy Infections – Why Encapsulated Bacteria?

The spleen is the body's "quality control" filter for blood-borne pathogens. Encapsulated bacteria (pneumococcus, H. influenzae, meningococcus) are resistant to phagocytosis unless they are first opsonised by antibodies and complement. The spleen's marginal zone macrophages are uniquely efficient at clearing these opsonised bacteria. Without the spleen, even opsonised encapsulated bacteria circulate unchallenged → overwhelming sepsis → death within hours (OPSI). This is why vaccination is non-negotiable before splenectomy ^[3]^[22].

ITP in pregnancy requires special consideration because: (a) the mother may need treatment for bleeding, (b) IgG autoantibodies cross the placenta and can cause neonatal thrombocytopenia, and (c) the available drugs may be teratogenic ^[20].

From the Handbook of Internal Medicine ^[20]:

Scenario	Management
Platelet count > 30 × 10⁹/L and no bleeding	No treatment until 36 weeks gestation (or sooner if delivery is imminent)
Platelet count < 30 × 10⁹/L or clinically relevant bleeding	First-line: steroids (prednisolone — crosses placenta less than dexamethasone due to placental 11β-HSD inactivation) or IVIg
For delivery	Target platelet > 50 × 10⁹/L for vaginal delivery; > 80 × 10⁹/L for caesarean section; > 80 × 10⁹/L for epidural/spinal anaesthesia
Neonatal	Monitor neonatal platelet count (nadir at day 2–5); thrombocytopenia usually resolves within weeks as maternal IgG is cleared

Contraindicated in pregnancy: Eltrombopag and romiplostim (limited safety data), MMF (teratogenic), cyclophosphamide (teratogenic), danazol (virilisation of female fetus).

Line	Therapy	Mechanism	Onset	Key Points
General	Avoid ASA/NSAIDs, IM injections; treat secondary causes; activity restriction; tranexamic acid	—	—	For ALL patients
Observation	Watch and wait	—	—	Plt ≥ 30 and asymptomatic
1st line	Corticosteroids	↓ Ab production, ↓ FcR expression, ↓ capillary fragility	2–5 days	Dex 40mg × 4d or Pred 1mg/kg/d; max 8 weeks
Emergency	IVIg + IV methylpred + platelet transfusion	IVIg overwhelms RES; steroids sustain response; platelets buy time	IVIg: 24–48h	For life-threatening bleeding
2nd line	TPO-RAs (eltrombopag, romiplostim)	Stimulate megakaryocytes → ↑ platelet production	1–2 weeks	> 60% response rate
2nd line	Rituximab	Deplete CD20+ B cells → ↓ autoAb	2–8 weeks	Check HBsAg; ~30% sustained response
2nd line	Fostamatinib	SYK inhibitor → blocks macrophage phagocytosis	1–2 weeks	Oral; hypertension, diarrhoea
2nd line	Splenectomy	Remove destruction site + Ab factory	Days (post-op)	Defer 12–24 months; vaccinate; ~60–70% response
2nd/3rd line	Immunosuppressants (AZA, MMF, CsA)	Suppress lymphocyte proliferation	Weeks–months	Steroid-sparing agents
Rescue	Platelet transfusion	Temporary haemostasis	Minutes	ONLY for life-threatening bleeding

High Yield Summary – Management of ITP

Treatment threshold: Plt < 30 × 10⁹/L OR significant bleeding. Goal: safe platelet count, NOT normal platelet count.

General measures (ALL patients): Avoid aspirin/NSAIDs/IM injections; treat secondary causes (H. pylori, HIV, HCV); activity restriction; tranexamic acid.

1st line: Corticosteroids — Dexamethasone 40 mg/d × 4 days OR Prednisolone 1 mg/kg/d; max 8 weeks; 79% response to dex pulse.

Emergency (life-threatening bleeding): IVIg + High-dose IV methylprednisolone + Platelet transfusion ^[3]^[20].

IVIg: Rapid onset (24–48h), transient (1–2 weeks), 80% effective. Works by overwhelming the RES (saturating FcγR on macrophages). ^[3]^[20]

Platelet transfusion: INEFFECTIVE in ITP — only for life-threatening bleeding ^[1]^[3].

2nd line: TPO-RAs (eltrombopag PO, romiplostim SC) > 60% response; Rituximab; Fostamatinib; ± Immunosuppressants (AZA, MMF, CsA). ^[7]^[10]

Splenectomy: For steroid-refractory / relapsing / steroid-dependent ITP. Defer 12–24 months from Dx. Must vaccinate for encapsulated organisms (pneumococcus, H. influenzae, meningococcus) beforehand. Risk of OPSI and thrombosis. ^[3]^[10]^[22]

In pregnancy: No treatment if Plt > 30 and no bleeding until 36 weeks. Target Plt > 50 for delivery. ^[20]

Active Recall - Management of ITP

References

^[1] Senior notes: Adrian Lui Pediatrics Notes.pdf (p.385–386 — ITP management, platelet transfusion in ITP) ^[2] Senior notes: Ryan Ho Haemtology.pdf (p.116–118 — platelet transfusion indications, ITP management algorithm) ^[3] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf (p.611–613) and MBBS Final MB (Medicine) (Felix PY Lai).pdf (p.1371–1376) ^[7] Lecture slides: GC 027. Abnormal bleeding after tooth extraction.pdf (p.24 — treatment of platelet disorders: steroid, IVIg, TPO-RAs) ^[10] Senior notes: Maksim Medicine Notes.pdf (p.162 — ITP management, steroid regimens, second-line therapies) ^[20] Lecture slides: Handbook of Internal Medicine 2024.pdf (p.197 — ITP definition, investigations, management including pregnancy) ^[22] Senior notes: Block A - Splenomegaly_ common causes of splenomegaly; myeloproliferative diseases.pdf (p.19 — indications for splenectomy, post-splenectomy complications)

Complications of Immune Thrombocytopenia (ITP)

Complications in ITP arise from three distinct sources: (A) the disease itself (bleeding), (B) its natural history (chronicity and association with other autoimmune conditions), and (C) the treatments used to manage it (steroids, splenectomy, immunosuppression, TPO-RAs). Understanding each category requires mapping back to the underlying pathophysiology.

1. Complications of the Disease Itself

1.1 Haemorrhagic Complications

The primary danger of ITP is bleeding. The severity of bleeding correlates (imperfectly) with the degree of thrombocytopenia:

Platelet Count	Risk	Clinical Manifestation
> 50 × 10⁹/L	Very low	Excessive bleeding with surgery or major trauma only
20–50 × 10⁹/L	Low–moderate	Easy bruising, prolonged bleeding from cuts
10–20 × 10⁹/L	Moderate–high	Spontaneous mucocutaneous bleeding (epistaxis, gum bleeding, menorrhagia, petechiae)
< 10 × 10⁹/L	High	Risk of spontaneous serious haemorrhage including ICH

Remember: compared to similar platelet counts of other causes, ITP is associated with ↓ risk of bleeding ^[1]. Why? ITP platelets are young, large, more granular, and haemostatically more effective. A platelet count of 20 in ITP is functionally "better" than 20 in aplastic anaemia where the few platelets produced are also functionally impaired.

ITP does not exist in an immunological vacuum. The same loss of tolerance that produces anti-platelet antibodies can produce autoantibodies against other targets:

Associated Condition	Mechanism / Significance
SLE	ITP may be the presenting feature of SLE (years before other manifestations). Screen with ANA ^[1]^[2]^[3]
Antiphospholipid syndrome (APS)	Paradox: thrombocytopenia (bleeding risk) AND thrombosis risk coexist ^[1]^[16]
Autoimmune thyroid disease (Hashimoto's, Graves')	Shared autoimmune diathesis ^[23]
CVID	ITP is one of the most common autoimmune manifestations of CVID ^[4]

Whenever making a diagnosis of Hashimoto's thyroiditis, you should not stop there. It is often associated with other autoimmune diseases: thrombocytopenic purpura, SLE, type II diabetes, Sjögren's disease, pernicious anaemia ^[23]. The reverse is also true — ITP patients should be monitored for evolving autoimmune diseases.

3. Complications of Treatment

Steroid side effects are a major source of morbidity in ITP, especially with prolonged courses ^[3]:

Complication	Mechanism	Clinical Note
Cushingoid features (moon face, buffalo hump, truncal obesity)	Altered fat metabolism and redistribution	Cosmetically distressing; reversible on cessation
Hypertension	Mineralocorticoid effect → Na⁺ and H₂O retention	Monitor BP Q2 weeks ^[3]
Diabetes mellitus	↑ Gluconeogenesis, ↑ insulin resistance	Monitor urine sugar Q2 weeks ^[3]
Osteoporosis	↓ Osteoblast activity, ↑ osteoclast resorption, ↓ Ca²⁺ absorption	Risk of vertebral compression fractures; consider calcium + vitamin D + bisphosphonates for prolonged courses
Gastritis / peptic ulcer	↓ Prostaglandin-mediated mucosal protection	Take the drug after meal or with antacids ^[3]
Immunosuppression → infection	Suppression of cellular and humoral immunity	Increased risk of opportunistic infections (PJP, reactivation TB, fungal)
Cataract (posterior subcapsular)	Mechanism unclear; direct lens protein modification?	Screen with ophthalmology for prolonged use
Adrenal suppression	Exogenous steroids suppress the HPA axis	Must taper gradually, not stop abruptly; risk of adrenal crisis
Myopathy	Proximal muscle wasting	Weakness, difficulty rising from chair
Psychiatric effects	Mood lability, insomnia, psychosis	Especially with high-dose pulse therapy
Easy bruising	Dermal collagen atrophy + capillary fragility	Confounds clinical assessment of ITP bleeding

From Felix Lai case study ^[3]: Physical examination shows Cushingoid features with moon face, buffalo hump, and truncal obesity — illustrating real-world steroid complications in a refractory ITP patient. This is also why maximum steroid course should be 6–8 weeks ^[10] and why steroid-sparing agents are sought early.

3.2 Splenectomy Complications

Splenectomy is effective (~60–70% durable response) but carries lifelong risks ^[3]^[22]^[24]:

Why don't we just liberally do splenectomies? Risk of infection — life-threatening infection from encapsulated bacteria → overwhelming post-splenectomy infection (OPSI) ^[22].

Aspect	Detail
Mechanism	The spleen's marginal zone macrophages and splenic B cells are uniquely efficient at clearing opsonised encapsulated bacteria. Without the spleen, these bacteria circulate unchecked → fulminant sepsis → death within hours
Key pathogens	Streptococcus pneumoniae (most important), Neisseria meningitidis, Haemophilus influenzae type b, Klebsiella, Salmonella, Capnocytophaga canimorsus ^[22]^[24]
Risk factors for OPSI	Young age (immune system less mature), immunocompromised ^[24]
Prevention	Vaccination > 2 weeks pre-op if elective; ASAP if urgent ^[24]; PCV13 + PPSV23 (repeat Q5y), Hib vaccine, meningococcal ACWY vaccine, annual influenza vaccine ^[24]
Antibiotic prophylaxis	Prophylactic antibiotics are often recommended but their precise usefulness is undefined ^[3]; penicillin V in children; in adults, considered on a case-by-case basis
Patient education	Patient must be warned of increased risks of infection ^[3]; carry alert card; seek immediate medical attention for any febrile illness

Mnemonic for encapsulated organisms: "Some Nasty Killers Have Some Capsule Protection" — Streptococcus pneumoniae, Neisseria meningitidis, Klebsiella, Haemophilus influenzae, Salmonella, Cryptococcus, Pseudomonas ^[24].

Complication	Mechanism
Infusion reactions (headache, chills, fever, myalgia)	Immune complex formation, complement activation; why premedication with piriton (chlorphenamine) is given ^[3]
Aseptic meningitis	High-dose IgG crosses BBB → meningeal irritation; presents with severe headache, nuchal rigidity, CSF pleocytosis but negative cultures
Renal impairment	Osmotic nephrotoxicity from sucrose-containing IVIg preparations → renal tubular injury
Thrombotic events	↑ Blood viscosity from high protein load; ↑ procoagulant factors in IVIg preparations
Haemolysis	Passive transfer of anti-A or anti-B isoagglutinins in the IVIg preparation → haemolysis in non-group-O recipients
Anaphylaxis (rare)	Particularly in IgA-deficient patients who have anti-IgA antibodies — IVIg contains traces of IgA → anaphylactic reaction

Complication	Drug	Mechanism
Hepatotoxicity	Eltrombopag	Direct hepatocellular injury; requires regular LFT monitoring
Bone marrow reticulin fibrosis	Both	Chronic megakaryocyte stimulation → ↑ reticulin deposition; usually reversible on drug discontinuation; monitor with periodic PBS for leukoerythroblastic changes
Thrombosis / thromboembolic events	Both	Overshooting platelet count → ↑ thrombotic risk; dose titration needed
Rebound thrombocytopenia	Both	Discontinuation can cause platelet count to drop below pre-treatment baseline; taper slowly
Cataracts	Eltrombopag (preclinical, monitored)	Observed in toxicology studies; clinical significance uncertain

Complication	Mechanism
Infusion reactions	Cytokine release on B cell lysis → fever, rigors, hypotension
Hypogammaglobulinaemia	Progressive depletion of B cells → ↓ IgG production → ↑ infection risk over time
HBV reactivation	Loss of immune surveillance over latent HBV → fulminant hepatitis; must check HBsAg before use
Progressive multifocal leukoencephalopathy (PML)	JC virus reactivation due to immunosuppression; rare but fatal
Late-onset neutropenia	Mechanism unclear; occurs weeks to months after treatment

Drug	Key Toxicities
Azathioprine	Myelosuppression (check TPMT before starting — poor metabolisers at risk of severe pancytopenia), hepatotoxicity, ↑ infection risk
MMF	GI intolerance (diarrhoea, nausea), myelosuppression, teratogenic
Cyclosporin	Nephrotoxicity, hypertension, gingival hyperplasia, hypertrichosis
Cyclophosphamide	Gonadal failure/infertility, haemorrhagic cystitis (mitigate with mesna), secondary malignancy, myelosuppression

Category	Complication	Key Points
Disease	ICH	Most feared; < 1% in children; plt < 10 is high-risk
Disease	GI haemorrhage	Uncommon but can be significant
Disease	Menorrhagia / IDA	Common in women; chronic blood loss → iron deficiency
Disease	Fatigue	Underappreciated; multifactorial
Natural history	Chronicity	20% children, 60–70% adults
Natural history	Evans syndrome	AIHA + ITP in ~10%; screen for CVID/SLE
Natural history	Thrombosis	Paradoxical; young activated platelets, microparticles, APS overlap
Treatment: Steroids	Cushing, DM, HTN, osteoporosis, infection, cataracts	Max 6–8 weeks; taper required
Treatment: Splenectomy	OPSI, thrombocytosis, surgical injury	Vaccinate; lifelong infection risk
Treatment: IVIg	Infusion reactions, aseptic meningitis, haemolysis, thrombosis	Premedicate; risk in IgA deficiency
Treatment: TPO-RAs	Hepatotoxicity, reticulin fibrosis, thrombosis, rebound	Monitor LFTs; taper on cessation
Treatment: Rituximab	HBV reactivation, hypogammaglobulinaemia, PML	Screen HBsAg; monitor Ig levels

High Yield Summary – Complications of ITP

Disease complications:

ICH is the most feared complication — risk highest when plt < 10 × 10⁹/L. Screen with fundoscopy ^[7].
Iron-deficiency anaemia from chronic blood loss (menorrhagia, epistaxis, GI oozing) is the most likely cause of anaemia in ITP ^[3]^[11].
Evans syndrome (AIHA + ITP) in ~10% — screen with DAT, haemolysis markers; consider CVID/SLE ^[3]^[4].
Thrombosis is a paradoxical risk — young activated platelets + microparticles + APS overlap + treatment effects.

Treatment complications:

Steroids: Cushing syndrome, DM, HTN, osteoporosis, gastritis, infection, cataracts. Monitor BP + urine glucose Q2 weeks ^[3].
Splenectomy: OPSI from encapsulated bacteria (S. pneumoniae, N. meningitidis, H. influenzae). Must vaccinate pre-op. Post-splenectomy thrombocytosis (aspirin if plt > 1000). Howell-Jolly bodies on PBS = expected ^[22]^[24].
IVIg: infusion reactions (premedicate with piriton), aseptic meningitis, thrombosis, haemolysis in non-group-O.
TPO-RAs: eltrombopag → hepatotoxicity; both → reticulin fibrosis (reversible), thrombosis, rebound thrombocytopenia on cessation.
Rituximab: HBV reactivation (screen first), hypogammaglobulinaemia, PML (rare).

Active Recall - Complications of ITP

References

^[1] Senior notes: Adrian Lui Pediatrics Notes.pdf (p.385–386 — ITP clinical features, bleeding risk comparison, platelet transfusion) ^[2] Senior notes: Ryan Ho Haemtology.pdf (p.117–118 — ITP pathogenesis, classification, management) ^[3] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf (p.611–613) and MBBS Final MB (Medicine) (Felix PY Lai).pdf (p.1371–1376) ^[4] Senior notes: Jerry's immunodeficiencies.pdf (p.1 — CVID and ITP/AIHA association) ^[7] Lecture slides: GC 027. Abnormal bleeding after tooth extraction.pdf (p.24 — CNS bleeding risk assessment via fundoscopy) ^[10] Senior notes: Maksim Medicine Notes.pdf (p.162 — ITP management, CT brain for ICH) ^[11] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (p.1373–1375 — Case study Q5: anaemia in ITP = IDA from bleeding) ^[14] Senior notes: Block A - Family history of anaemia_ inherited causes of anaemia; haemolytic anaemia; aplastic anaemia.pdf (p.6 — AIHA diagnosis: DAT, haemolysis markers) ^[16] Senior notes: Block A - Leg swelling and chest pain_ deep vein thrombosis; pulmonary embolism; Thrombophilia.pdf (p.14 — APS thrombocytopenia + thrombosis) ^[22] Senior notes: Block A - Splenomegaly_ common causes of splenomegaly; myeloproliferative diseases.pdf (p.19 — splenectomy complications, OPSI, post-splenectomy CBC changes) ^[23] Senior notes: Block A - I am losing weight and sweating all the time_ causes of severe, weight loss; thyrotoxicosis; hypothyroidism.pdf (p.40 — Hashimoto's association with ITP) ^[24] Senior notes: Maksim Surgery Notes.pdf (p.153 — splenectomy indications, pre-op, specific complications, OPSI mnemonic and vaccination)

High Yield Summary

Definition: ITP is an acquired autoimmune thrombocytopenia (platelet < 100 × 10⁹/L) due to immune-mediated platelet destruction and impaired production, in the absence of other causes.

Name Change: No longer "idiopathic thrombocytopenic purpura" — now "immune thrombocytopenia" (proven immune basis, not always purpuric).

Classification:

Primary vs Secondary (HIV, HCV, H. pylori, SLE, CLL, CVID, drugs)
Duration: Newly diagnosed (< 3 mo), Persistent (3–12 mo), Chronic (> 12 mo)
Drug-induced immune thrombocytopenia (DITP) is a separate category

Pathogenesis (3 mechanisms):

IgG autoantibodies (anti-GPIIb/IIIa, anti-GPIb/IX) → Fc-mediated phagocytosis in spleen
Autoantibodies bind megakaryocytes → impaired platelet production
CD8+ T cell–mediated platelet destruction + Treg dysfunction

Platelet lifespan: 7–10 days → 1–2 days

Clinical Features:

Mucocutaneous bleeding pattern (petechiae, purpura, epistaxis, gum bleeding, menorrhagia)
Dry purpura (skin) = low risk; Wet purpura (mucous membranes) = high risk
ICH is the most feared complication (< 1%)
No lymphadenopathy, no hepatosplenomegaly, no fever in primary ITP
PT and APTT are normal
Children: post-viral onset, high spontaneous remission (70–80%)
Adults: insidious onset, often chronic

Treatment overview: Steroids, IVIg (for ITP); platelet transfusion only for life-threatening bleeding; TPO-RAs (eltrombopag, romiplostim) for refractory ITP ^[7]^[1].

High Yield Summary – Differential Diagnosis of ITP

ITP is a diagnosis of exclusion. The approach:

Rule out pseudothrombocytopenia (repeat CBC, check PBS for clumps, citrate tube)
Isolated or pancytopenia? → Pancytopenia = marrow pathology (AA, leukaemia, MDS)
Isolated thrombocytopenia with splenomegaly? → Hypersplenism (CLD)
Schistocytes on PBS? → TTP, HUS, DIC (NOT ITP)
Drug-related? → DITP, HIT
Secondary cause screen (HIV, HCV, H. pylori, SLE, CLL, CVID, DAT) → Secondary ITP
All negative → Primary ITP

Key DDx to remember (from Felix Lai case study ^[3]):

Bone marrow failure: Acute leukaemia, Aplastic anaemia, MDS, BM infiltration
Increased consumption: Hypersplenism, DIC, TTP

Red flags against primary ITP: Lymphadenopathy, hepatosplenomegaly, other cytopenia, schistocytes, blasts on PBS, bone pain, fever, congenital anomalies, abnormal clotting profile.

High Yield Summary – Diagnosis of ITP

ITP is a diagnosis of EXCLUSION — no single confirmatory test.

Diagnostic criteria:

Isolated thrombocytopenia (platelet < 100 × 10⁹/L)
No anaemia, no leukopenia (unless Evans syndrome or bleeding-related IDA)
Normal PBS (large platelets, NO schistocytes, NO blasts, NO dysplasia, NO clumps)
Normal PT/APTT (platelet disorder does not affect coagulation cascade tests)
No other apparent cause after secondary cause screening

Essential workup:

CBC + PBS + clotting profile + reticulocyte count + fundoscopy
HIV, HCV, H. pylori, ANA, DAT, Ig levels (secondary cause screen)