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PA20.1-2 | Platelet & Vascular Bleeding Disorders — Part 1
CLINICAL SCENARIO
A 6-year-old boy presents two weeks after a viral fever with pinpoint red spots over his legs and spontaneous gum bleeding, but NO joint swelling and NO deep muscle haematomas. His platelet count is 12,000/µL. His older brother had a knee haemarthrosis after minor trauma last year.
Same presentation, different diagnoses — the location and character of the bleeding already point you to the right system before you order a single test. Can you name the two systems at fault?
WHY THIS MATTERS
Platelet and vascular disorders are common exam scenarios and frequent clinical encounters — ITP alone affects ~5 per 100,000 people. Misclassifying a bleeding disorder leads to inappropriate treatment (e.g., giving FFP for thrombocytopenia, or missing a TTP pentad that demands urgent plasmapheresis). The pattern-recognition framework you build here applies every time you clerk a patient with unexplained bruising or bleeding.
RECALL
Before proceeding, recall from Year-1 Physiology:
• Primary haemostasis: platelet plug formation at the site of vascular injury — relies on intact vessel wall, VWF, and functional platelets.
• Secondary haemostasis: coagulation cascade generating fibrin to stabilise the platelet plug.
• Bleeding time (BT) / PFA-100: reflects platelet-vessel interaction. Prolonged in platelet and vascular disorders; normal in isolated coagulation factor deficiencies.
• PT and aPTT: test the extrinsic and intrinsic/common coagulation pathways respectively. Normal in pure platelet and vascular disorders.
The Two Bleeding Patterns: Primary vs Secondary Haemostasis
Primary vs Secondary Haemostasis: Clinical Bleeding Patterns
The clinical pattern of bleeding is the first and most important diagnostic discriminator.
Primary haemostasis bleeding (platelet + vascular defects) is mucocutaneous:
• Sites: skin (petechiae, purpura, ecchymoses), mucous membranes (epistaxis, gum bleeding, menorrhagia, gastrointestinal bleeding).
• Timing: immediate after injury — the platelet plug fails to form quickly.
• Petechiae (1–3 mm punctate haemorrhages) are essentially pathognomonic of thrombocytopenia or platelet dysfunction.
Secondary haemostasis bleeding (coagulation factor defects) is deep and delayed:
• Sites: muscles, joints (haemarthrosis), retroperitoneum, intracranial.
• Timing: delayed — a fragile platelet plug initially stops minor bleeding, but the lack of fibrin reinforcement leads to re-bleeding hours later.
• Haemarthrosis is virtually never seen in platelet/vascular disorders.
| Feature | Primary (Platelet/Vascular) | Secondary (Coagulation) |
|---|---|---|
| Sites | Skin, mucosae | Muscles, joints |
| Petechiae | Yes | No |
| Haemarthrosis | No | Yes (e.g., haemophilia) |
| Onset after injury | Immediate | Delayed |
| Bleeding time/PFA | Prolonged | Normal |
| PT/aPTT | Normal | Abnormal |
This table should become a mental template you apply to every bleeding history.
Primary vs Secondary Hemostasis Bleeding Patterns
SELF-CHECK
A 35-year-old woman has epistaxis and heavy periods. Laboratory results: platelet count 18,000/µL, bleeding time prolonged, PT normal, aPTT normal. Which pattern does this represent?
A. Primary haemostasis defect — platelet disorder
B. Secondary haemostasis defect — coagulation factor deficiency
C. Combined platelet and coagulation defect
D. Vascular structural abnormality with normal platelets
Reveal Answer
Answer: A. Primary haemostasis defect — platelet disorder
Normal PT and aPTT exclude coagulation factor deficiency. Prolonged bleeding time with mucocutaneous bleeding (epistaxis, menorrhagia) and severe thrombocytopenia points to a primary haemostasis (platelet) defect. This is the classic pattern of ITP.
Thrombocytopenia: Classification by Mechanism
Thrombocytopenia Classified by Mechanism
Thrombocytopenia (platelet count < 150,000/µL; clinically significant bleeding risk < 50,000/µL; spontaneous bleeding < 20,000/µL) is classified by mechanism — this directly guides management.
1. Decreased production (marrow failure to make platelets):
• Aplastic anaemia: pancytopenia; marrow hypocellular.
• Megaloblastic anaemia: B12/folate deficiency impairs nuclear maturation of megakaryocytes → ineffective thrombopoiesis.
• Marrow infiltration: leukaemia, metastases, myelofibrosis — replacement of megakaryocyte precursors.
• Drug/radiation toxicity: myelosuppression (chemotherapy, thiazides, alcohol).
• Lab clue: megakaryocytes absent or reduced on marrow biopsy.
2. Increased destruction / consumption (platelets made but removed rapidly):
• Immune: ITP (anti-platelet antibodies), drug-induced (heparin-induced, quinine), post-transfusion purpura.
• Microangiopathic: TTP, HUS, DIC — mechanical fragmentation in abnormal microvasculature.
• Hypersplenism: enlarged spleen sequesters up to 90% of the platelet pool (normally 30%); counts rarely < 50,000/µL.
• Lab clue: megakaryocytes normal or increased on marrow biopsy (reactive — the marrow is trying to compensate).
3. Dilutional (massive transfusion with packed red cells lacking platelets; cardiopulmonary bypass).
The marrow biopsy finding of normal/increased megakaryocytes is the key to distinguishing peripheral destruction from central production failure.
Immune Thrombocytopenic Purpura (ITP)
Immune Thrombocytopenic Purpura: Pathogenesis and Clinical Forms
Immune Thrombocytopenic Purpura (ITP) is the most common cause of isolated thrombocytopenia in otherwise healthy individuals. It is an autoimmune disorder and a diagnosis of exclusion — no underlying disease, drug, or infection explains it.
Pathogenesis:
• Autoantibodies (predominantly IgG) directed against glycoprotein IIb/IIIa (GPIIb/IIIa) and GPIb/IX on the platelet surface.
• Antibody-coated platelets are recognised and phagocytosed by Fc-receptor-bearing macrophages in the spleen (the spleen is thus both the site of antibody production and platelet destruction).
• T-cell–mediated cytotoxicity also contributes.
• Marrow response: megakaryocytes are normal or increased in number (reactive increase to compensate for peripheral loss) — this finding on marrow biopsy is diagnostically important.
Two clinical forms:
| Feature | Acute ITP | Chronic ITP |
|---|---|---|
| Age | Children (2–6 yr) | Adults (women > men) |
| Antecedent | Viral illness (1–2 wk prior) | Insidious, no clear trigger |
| Onset | Abrupt | Gradual |
| Spontaneous remission | 80–90% within 6 months | Uncommon; waxing/waning |
| Mechanism | Post-viral immune complex / molecular mimicry | Chronic autoimmunity |
Diagnosis of exclusion — must rule out: drug-induced thrombocytopenia, lupus (secondary ITP), HIV, HCV, hypersplenism, bone marrow disease.
Key labs:
• Isolated thrombocytopenia; rest of CBC normal.
• Peripheral smear: large platelets (young platelets released to compensate).
• Marrow: megakaryocytes increased (not needed routinely in young adults; consider in elderly to exclude MDS).
• PT, aPTT: normal.
Bone Marrow Histology: Normal vs ITP (Increased Megakaryocytes)
CLINICAL PEARL
ITP marrow biopsy rule: Increased megakaryocytes = peripheral destruction, not a marrow problem. Absent megakaryocytes = production failure (aplastic anaemia). This single finding on marrow biopsy separates two diametrically opposite treatment strategies: immunosuppression (ITP) versus stem-cell transplant or growth factor (aplasia).
SELF-CHECK
A 28-year-old woman has a platelet count of 9,000/µL, normal PT and aPTT, and large platelets on film. Bone marrow biopsy shows increased megakaryocytes. Anti-platelet IgG is detected. Which of the following best describes the mechanism?
A. Failure of megakaryocyte maturation due to B12 deficiency
B. IgG-mediated splenic phagocytosis of antibody-coated platelets
C. Microangiopathic mechanical fragmentation of platelets
D. Dilutional thrombocytopenia following massive transfusion
Reveal Answer
Answer: B. IgG-mediated splenic phagocytosis of antibody-coated platelets
The triad of isolated thrombocytopenia, large platelets (compensatory young platelets), and increased marrow megakaryocytes confirms peripheral destruction. Anti-platelet IgG targeting GPIIb/IIIa leads to Fc-receptor–mediated splenic macrophage phagocytosis — the hallmark mechanism of ITP.