253 - Platelet Function and Formation Flashcards
How does Wiskott-Aldrich syndrome affect the platelet life cycle?
Interferes with platelet production
The Wiskott-Aldrich protein (WASp) is supposed to stabilize the platelet cytoskelton
Mutation -> impaired platelet production
Does antiplatelet therapy (aspirin) help more in arterial or venous thrombus?
Arterial
In venous thrombus, platelets play a role but various RBCs and other factors are also important
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When during primary hemostasis do platelets release thromboxane A2 and ADP?
What is their function?
When they are activated
They amplify platelet activation
- Platelet activation*
- -> Activates PL2*
- -> Produces arachadonic acid*
- ->>> COX pathway produces thromboxane A2*
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What is the primary symptom of a qualitative platelet defect?
Skin and mucocutaneous bleeding
If a platelet is not consumed during a clotting event, how does it know when it’s time to die?
Intrinsic mitochondrial pathway
- Caspases
- -> change in platelet membrane; phosphatidyl serine comes outside
- Marks the platelet for apoptosis
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C - Glanzmann Thrombasthenia
- Glanzmann:
- Aggregation with ristocetin
- No aggregation with ADP, epinephrine, collagen, arachadonic acid
- Bernard-Soulier:
- No aggregation with ristocetin
- Aggregation with everything else
What substance drives platelet development?
Thrombopoietin
What receptor on platelets binds to vWF?
GPIb
Which platelet disorder will have thrombocytopenia with large platelets?
Bernard-Soullier syndrome
- Defect in GPIb*
- No aggregation with ristocetin*
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Do white blood cells play a larger role in arterial or venous thrombosis?
Venous
After platelet activation (binding to collagen and vWF on the injured endothelium), list the remaining steps of primary hemostasis
- Platelet granule release (ADP)
- Thromboxane A2 synthesis (via COX pathway)
- Expresses GPIIb/IIIa to bind fibrinogen
- Expresses phosphatidyl serine so that clotting factors can assemble
After primary hemostasis, the area has a platelet plug and is set up for secondary hemostasis - the clotting cascade (thrombin generation to cleave fibrinogen -> fibrin)
What platelet receptor is defective in Glanzmann’s Thrombasthenia?
GBIIb/IIIa
Severe bleeding disorder in childhood
What is the average platelet lifespan?
8-10 days
Which of the following will have normal aggregation with ristocetin?
- Glanzmann thrombasthenia
- Bernard-Soullier
Glanzmann thrombasthenia
- But abnormal with other facotrs*
- Bernard-Soullier is opposite; normal with ADP, epinephrine, collagen, arachadonic acid, but no aggregation with ristocetin*
What platelet receptor is defective in Bernard-Soulier syndrome?
GB1b