251 - 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 cytoskeleton*
- Mutation -> impaired platelet production*
Does antiplatelet therapy (aspirin) help more in arterial or venous thrombus?
Arterial, because they are “platelet rich”
When during primary hemostasis do platelets release thromboxane A2 and ADP?
What is their function?
Platelets release thromboxane A2 when they are activated
They amplify platelet activation
- Platelet activation*
- -> Activates PL2*
- -> Produces arachadonic acid*
- ->>> COX pathway produces thromboxane A2*
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 apoptosis pathway
- Release of proapoptotic factors
- –> activation of caspases
- –> phosphotidylserines that were on the inner leaflet of membrane flip to the other leaflet
- –> marks the platelet for apoptosis
C - Glanzmann Thrombasthenia
-
Glanzmann Thrombasthenia: defect in GP2b/3a receptor –> platelets don’t bind fibrinogen and aggregate
- Aggregation with ristocetin
- No aggregation with ADP, epinephrine, collagen, arachadonic acid or with other agonists
-
Bernard-Soulier: defect in glycoprotein 1B (vWF receptor)
- No aggregation with ristocetin
- Aggregation with everything else
Ristocetin: antibiotic that activates vWF, which then binds to glycoprotein Ib on platelets
- If ristocetin is added to blood lacking vWF (or the vWF receptor), platelets will not aggregate
What substance drives platelet development?
Thrombopoietin (TPO)
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 (antibiotic that activates vWF)*
Do white blood cells play a larger role in arterial or venous thrombosis?
Venous
After platelets bind to collagen and vWF on the injured endothelium), list the remaining steps of primary hemostasis
- Platelet granule release ADP and Ca2+
- ADP helps platelets stick to the endothelium
- Ca2+ is necessary for coagulation cascade
- Thromboxane A2 synthesis (via COX pathway)
- ADP binds to P2Y12 receptor –> expression of GP2b/3a at platelet surface
- GPIIb/IIIa binds fibrinogen and links platelets together
- 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: receptor that binds fibrinogen to link to other platelets
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 aggregation with other factors
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 (vWF receptor)
What is the morphological difference between a platelet with granule deficiency and one that is normal but exhausted (used up)?
Exhausted platelets (used up) will have podocytes
Both will have absent granules
After endothelial injury, platelets bind to two endothelial substances and tether themselves to the site of injury
What are the two substances?
vWF and Collagen
First rolling, then tight adhesion
