Platelet Function Disorders, Glanzmann and Bernard-Soulier
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Direct answer
Platelet function disorders are inherited or acquired defects in platelet adhesion, aggregation or secretion that cause mucocutaneous bleeding despite a normal or near-normal platelet count. Glanzmann thrombasthenia is a GPIIb/IIIa defect with absent aggregation to most agonists, while Bernard-Soulier syndrome is a GPIb-IX-V defect with absent ristocetin-induced agglutination, giant platelets and often mild thrombocytopenia.
What you must remember
- Clinical picture: epistaxis, gum bleeding, menorrhagia and easy bruising, with a normal platelet count and normal PT and aPTT.
- Glanzmann thrombasthenia: autosomal recessive defect of GPIIb/IIIa (integrin αIIbβ3), the fibrinogen receptor, with absent aggregation to ADP, collagen, adrenaline and thrombin, and poor clot retraction.
- Glanzmann and ristocetin: ristocetin-induced agglutination is normal, because it does not depend on GPIIb/IIIa, which distinguishes Glanzmann from Bernard-Soulier.
- Bernard-Soulier syndrome: autosomal recessive deficiency of the GPIb-IX-V complex, with giant platelets and mild thrombocytopenia; responses to ADP, collagen and thrombin are preserved.
- Uraemic platelet dysfunction: uraemic toxins impair platelet function, and bleeding improves with dialysis, desmopressin or conjugated oestrogens.
- Storage pool disorders: dense granule deficiency reduces ADP and serotonin release, impairing secondary aggregation.
- Aspirin and NSAIDs: aspirin irreversibly acetylates cyclo-oxygenase for the life of the platelet, while NSAID inhibition is reversible; both prolong bleeding time and are the commonest acquired causes.
- Diagnosis: light transmission aggregometry screens function, while flow cytometry for CD41/CD61 or CD42b confirms the missing receptor.
Glanzmann versus Bernard-Soulier
The two inherited disorders are distinguished by the defective receptor, the platelet count and the response to ristocetin. The table sets out the key differences.
| Feature | Glanzmann thrombasthenia | Bernard-Soulier syndrome |
|---|---|---|
| Defective receptor | GPIIb/IIIa (αIIbβ3) | GPIb-IX-V complex |
| Inheritance | Autosomal recessive | Autosomal recessive |
| Platelet count | Normal | Normal or mildly reduced |
| Platelet size | Normal | Giant |
| Response to ADP and collagen | Absent | Normal |
| Ristocetin agglutination | Normal | Absent |
Flow cytometry identifies the missing receptor and is now the preferred confirmatory test, while aggregometry remains the functional screen. Both results must be read alongside the platelet count and the peripheral smear, since giant platelets point strongly to Bernard-Soulier syndrome.
Acquired causes, especially aspirin, NSAIDs and uraemia, must be excluded before a congenital diagnosis is made. They account for many cases seen in clinical practice and are often reversible.
Congenital defects usually declare themselves in childhood, with bleeding after minor trauma, dental extraction or menarche and a positive family history. Acquired defects appear in adults on antiplatelet drugs or with kidney failure. Treatment is tailored to the defect, with platelet transfusion for severe bleeding and recombinant factor VIIa in Glanzmann thrombasthenia when alloantibodies to GPIIb/IIIa are present.
Where the exam tries to catch you
Platelet function questions reward the candidate who links the receptor defect to the pattern of aggregation.
- Trap: assuming a normal platelet count excludes a significant bleeding disorder Correct: qualitative defects cause serious bleeding with normal counts, so aggregation or flow cytometry is needed.
- Trap: calling Bernard-Soulier a pure thrombocytopenia with normal function Correct: the GPIb-IX-V defect impairs adhesion, so ristocetin-induced agglutination is absent.
- Trap: attributing mucosal bleeding in a patient on aspirin to a congenital defect Correct: aspirin causes an acquired functional defect that resolves as new platelets form, and it is excluded before any congenital diagnosis.
- Trap: missing uraemia as a cause of bleeding in advanced kidney disease Correct: uraemic platelet dysfunction is reversible, improving with dialysis and desmopressin.
Frequently asked questions
What is the defect in Glanzmann thrombasthenia?
Glanzmann thrombasthenia is a defect in the GPIIb/IIIa integrin, also called αIIbβ3, which is the fibrinogen receptor needed for platelet aggregation. Platelets fail to aggregate to ADP, collagen, adrenaline and thrombin, although the platelet count is normal.
How does Bernard-Soulier syndrome differ from Glanzmann thrombasthenia?
Bernard-Soulier syndrome is a deficiency of the GPIb-IX-V complex with giant platelets and often mild thrombocytopenia. Glanzmann thrombasthenia has a normal count and normal platelet size, and ristocetin-induced agglutination is absent in Bernard-Soulier but normal in Glanzmann.
Which test confirms a platelet function disorder?
Light transmission aggregometry is the functional test that assesses platelet response to agonists such as ADP, collagen and ristocetin. Flow cytometry for CD41 and CD61, or for CD42b, identifies which receptor is missing and is commonly used for confirmation.
What causes uraemic platelet dysfunction?
Uraemic platelet dysfunction results from uraemic toxins impairing platelet adhesion and aggregation in chronic kidney disease. Bleeding improves with dialysis, and desmopressin or conjugated oestrogens are used when bleeding is significant.
Which common drugs cause an acquired platelet function defect?
Aspirin irreversibly inhibits platelet cyclo-oxygenase, while NSAIDs do so reversibly, and both prolong bleeding time. The aspirin effect lasts until new platelets are produced, typically 7 to 10 days after the last dose.