Platelets disorder
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platelet disorders thrombocytopenia petechiae blood smear
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Platelet Disorders — Medical Student Overview
Normal Platelet Physiology (Quick Recap)
Platelets (thrombocytes) are anucleate cell fragments derived from megakaryocytes. Normal count: 150,000–400,000/µL. They carry two key surface glycoprotein complexes:
- GP Ib/IX — receptor for von Willebrand factor (vWF); mediates adhesion
- GP IIb/IIIa — receptor for fibrinogen; mediates aggregation
Classification of Platelet Disorders
Platelet disorders fall into two broad categories:
| Category | Problem | Platelet Count |
|---|---|---|
| Quantitative | Too few (thrombocytopenia) or too many (thrombocytosis) | Abnormal |
| Qualitative | Normal count, but dysfunction | Usually normal |
1. THROMBOCYTOPENIA (Platelet count < 150,000/µL)
Clinical Bleeding Thresholds
- < 150,000 — thrombocytopenia by definition; minimal spontaneous bleeding
- 20,000–50,000 — increased risk of post-traumatic bleeding
- < 5,000–10,000 — risk of spontaneous bleeding (petechiae, ecchymoses, mucosal hemorrhage, CNS bleeds)
The bleeding pattern is superficial: petechiae, ecchymoses, mucous membrane hemorrhage (nosebleeds, gum bleeding, menorrhagia). This contrasts with coagulation factor deficiencies, which cause deep bleeds (hemarthrosis, hematomas). — Robbins & Kumar Basic Pathology
Causes of Thrombocytopenia
A. Decreased Platelet Production
- Generalized bone marrow failure: aplastic anemia, leukemia/marrow infiltration
- Selective: drugs (alcohol, thiazides, cytotoxic agents), infections (measles, HIV)
- Ineffective megakaryopoiesis: megaloblastic anemia, paroxysmal nocturnal hemoglobinuria (PNH)
B. Increased Platelet Destruction
| Mechanism | Example |
|---|---|
| Immune (autoimmune) | ITP, SLE |
| Immune (drug-induced) | Heparin (HIT), quinidine, sulfa |
| Immune (alloimmune) | Post-transfusion purpura, neonatal alloimmune |
| Non-immune (microangiopathic) | DIC, TTP, HUS |
| Infection-associated | HIV, EBV, CMV |
C. Sequestration
- Hypersplenism (the spleen normally sequesters ~30% of circulating platelets; in massive splenomegaly this rises to 80–90%)
D. Dilutional
- Massive transfusion (stored RBCs/FFP lack platelets)
Key Specific Disorders
Immune Thrombocytopenic Purpura (ITP)
- Autoantibodies (IgG) target platelet GP IIb/IIIa or GP Ib/IX → opsonized platelets destroyed by splenic macrophages
- Antibodies detectable in ~80% of cases
- Acute ITP: children, post-viral, self-limited
- Chronic ITP: women age 20–40; insidious onset (petechiae, easy bruising, epistaxis, gum bleeding)
- Bone marrow shows increased megakaryocytes (compensatory) — hallmark of destructive thrombocytopenia
- Treatment: immunosuppressants, IVIG, splenectomy (complete remission in >2/3 of patients)
Heparin-Induced Thrombocytopenia (HIT)
- Occurs in 3–5% of patients on unfractionated heparin after 1–2 weeks
- Mechanism: IgG antibodies bind platelet factor 4 (PF4)–heparin complex → immune complexes activate platelets via Fc receptors → platelet consumption AND thrombosis
- Paradoxically causes thrombosis (venous + arterial) despite low platelets — a high-yield exam point
- Treatment: stop heparin immediately; switch to direct thrombin inhibitors (argatroban, bivalirudin); low-molecular-weight heparin reduces (but does not eliminate) risk
Thrombotic Thrombocytopenic Purpura (TTP)
Classic pentad (mnemonic: FAT RN):
- Fever
- Anemia (microangiopathic hemolytic — MAHA)
- Thrombocytopenia
- Renal failure
- Neurologic symptoms (transient deficits)
- Pathogenesis: deficiency of ADAMTS13 (a metalloprotease that cleaves ultra-large vWF multimers). Without ADAMTS13, ultra-large vWF accumulates → platelet-rich microthrombi throughout the microcirculation
- Can be congenital (Upshaw-Schulman syndrome) or acquired (autoantibody against ADAMTS13)
- PT and aPTT are normal (unlike DIC) — key exam distinction
- Treatment: plasma exchange (replaces ADAMTS13 and removes antibodies)
Hemolytic Uremic Syndrome (HUS)
- Shares MAHA + thrombocytopenia with TTP
- Key difference: predominant acute renal failure; neurologic symptoms less prominent; more common in children
- Classic trigger: E. coli O157:H7 Shiga toxin → endothelial damage in renal microvasculature
- Complement dysregulation also plays a role
- PT/aPTT normal (unlike DIC)
TTP vs HUS vs DIC — Exam Table
| Feature | TTP | HUS | DIC |
|---|---|---|---|
| MAHA | ✓ | ✓ | ✓ |
| Thrombocytopenia | ✓ | ✓ | ✓ |
| Neurologic sx | Prominent | Rare | Variable |
| Renal failure | Mild | Severe | Variable |
| PT/aPTT | Normal | Normal | Prolonged |
| ADAMTS13 | ↓↓ | Normal | Normal |
| Fibrinogen | Normal | Normal | ↓ |
2. THROMBOCYTOSIS (Platelet count > 400,000/µL)
Reactive (Secondary) Thrombocytosis
- Most common cause
- Causes: iron deficiency, inflammation, infection, malignancy, splenectomy, tissue damage
- Platelets usually < 1,000,000/µL
- No increased thrombotic or bleeding risk — platelets are functionally normal
- Treat the underlying cause
Essential (Primary) Thrombocythemia (ET)
- Clonal myeloproliferative neoplasm (stem cell disorder)
- Platelet count often > 1,000,000/µL
- JAK2 V617F mutation present in ~50% of cases (confirms clonal origin; its absence does not rule out ET)
- Can cause both thrombosis AND bleeding
- Markedly elevated platelets (>1.5 million) can cause acquired von Willebrand disease (platelets bind and remove vWF from circulation) → paradoxical bleeding
- Treatment: hydroxyurea (cytoreduction), aspirin; anagrelide
3. QUALITATIVE PLATELET DISORDERS (Normal Count, Dysfunctional Platelets)
Inherited Disorders
| Disorder | Defect | Mechanism | Presentation |
|---|---|---|---|
| Bernard-Soulier Syndrome | ↓ GP Ib/IX | Cannot bind vWF → defective adhesion | Severe bleeding; giant platelets on smear |
| Glanzmann Thrombasthenia | ↓ GP IIb/IIIa | Cannot bind fibrinogen → defective aggregation | Severe bleeding; normal platelet count/size |
| Storage Pool Disease (δ-SPD) | ↓ dense granules (ADP/serotonin) | Defective release reaction | Mild-moderate bleeding |
| Hermansky-Pudlak Syndrome | ↓ δ-granules + albinism | Lysosomal trafficking defect | Bleeding + oculocutaneous albinism |
Both Bernard-Soulier and Glanzmann are autosomal recessive, present in childhood with severe bleeding. — Robbins & Kumar Pathologic Basis of Disease
Acquired Disorders
| Cause | Mechanism | Notes |
|---|---|---|
| Aspirin / NSAIDs | Irreversible inhibition of COX-1 → ↓ thromboxane A2 | Effect lasts platelet lifespan (~7–10 days) |
| Uremia | Multifactorial (↓ adhesion, secretion, aggregation) | Improved by dialysis, DDAVP, raising Hct to 27–32% |
| Cardiopulmonary bypass | Mechanical activation and exhaustion | Responds to platelet transfusion |
| Myeloproliferative/MDS | Intrinsic platelet defects, circulating paraproteins |
4. MORPHOLOGIC CLUES ON BLOOD SMEAR
| Finding | Diagnosis |
|---|---|
| Giant platelets | Bernard-Soulier, MYH9-related (May-Hegglin anomaly) |
| Small platelets | Wiskott-Aldrich syndrome |
| Agranular (gray) platelets | Gray platelet syndrome |
| Platelet aggregates | Pseudo-thrombocytopenia (EDTA artifact) — redraw in citrate |
| Schistocytes + low platelets | TTP, HUS, DIC (MAHA) |
| Platelet satellitism | EDTA-dependent artifact around neutrophils |
5. KEY DIAGNOSTIC LABS — Quick Reference
| Test | Purpose |
|---|---|
| CBC + peripheral smear | First step — always confirm automated counts with smear |
| PT/aPTT | Normal in ITP, TTP, HUS; prolonged in DIC |
| Fibrinogen + D-dimer | ↓ fibrinogen, ↑ D-dimer in DIC |
| ADAMTS13 activity | Confirms TTP when <10% |
| PF4-heparin antibody (ELISA + serotonin release assay) | HIT diagnosis |
| Platelet aggregation studies | Glanzmann (no aggregation with ADP/collagen), Bernard-Soulier (no ristocetin aggregation) |
| Bone marrow biopsy | ↑ megakaryocytes = destructive; ↓ = production failure |
| JAK2 V617F | Essential thrombocythemia / other MPNs |
Visual Reference
Thrombocytopenia Diagnostic Algorithm (Harrison's Principles):
Clinical petechiae in ITP (lower extremity distribution):
Oral wet purpura and petechiae in severe thrombocytopenia:
High-Yield Exam Mnemonics
- HIT = Heparin → IgG → PF4 → Thrombosis (counterintuitive: low platelets + clot)
- TTP = ADAMTS13 deficiency + MAHA + normal PT/PTT
- TTP vs HUS: TTP = brain; HUS = kidney (kids + E. coli)
- Glanzmann = aggregation defect (GP IIb/IIIa — "IIb/IIIa = aggrIIBregation")
- Bernard-Soulier = adhesion defect (GP Ib/IX — "Ib = adheIBsion")
- Aspirin effect: irreversible COX inhibition → lasts 7–10 days (entire platelet lifespan)
Sources: Robbins & Kumar Basic Pathology; Robbins, Cotran & Kumar Pathologic Basis of Disease; Harrison's Principles of Internal Medicine 22E (2025); Goldman-Cecil Medicine; Henry's Clinical Diagnosis and Management by Laboratory Methods
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