253 - Platelet Function and Formation

Question 1

How does Wiskott-Aldrich syndrome affect the platelet life cycle?

Answer 1

Interferes with platelet production

The Wiskott-Aldrich protein (WASp) is supposed to stabilize the platelet cytoskelton

Mutation -> impaired platelet production

Question 2

Does antiplatelet therapy (aspirin) help more in arterial or venous thrombus?

Answer 2

Arterial

In venous thrombus, platelets play a role but various RBCs and other factors are also important

Question 3

When during primary hemostasis do platelets release thromboxane A2 and ADP?

What is their function?

Answer 3

When they are activated

They amplify platelet activation

• Platelet activation*
• -> Activates PL2*
• -> Produces arachadonic acid*
• ->>> COX pathway produces thromboxane A2*

Question 4

What is the primary symptom of a qualitative platelet defect?

Aka, what will the common clinical manifestation across all platelet disorders?

Answer 4

Skin and mucocutaneous bleeding

Question 5

If a platelet is not consumed during a clotting event, how does it know when it’s time to die?

Answer 5

Intrinsic mitochondrial pathway

• Caspases
• -> change in platelet membrane; phosphatidyl serine comes outside
• Marks the platelet for apoptosis

Question 6

Answer 6

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

Question 7

What substance drives platelet development?

Answer 7

Thrombopoietin

Question 8

What receptor on platelets binds to vWF?

Answer 8

GPIb

Question 9

Which platelet disorder will have thrombocytopenia with large platelets?

Answer 9

Bernard-Soullier syndrome

• Defect in GPIb*
• No aggregation with ristocetin*

Question 10

Do white blood cells play a larger role in arterial or venous thrombosis?

Answer 10

Venous

[remember that hemostasis from injurious processes causes the slowdown to allow leukocyte adhesion for platelets…

the same thing happens here in thromboses, where hemostasis plays a bigger role in venous]

Question 11

After platelet activation (binding to collagen and vWF on the injured endothelium), list the remaining steps of primary hemostasis

Answer 11

• 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)

Question 12

What platelet receptor is defective in Glanzmann’s Thrombasthenia?

Answer 12

GBIIb/IIIa

Severe bleeding disorder in childhood

Question 13

What is the average platelet lifespan?

Answer 13

8-10 days

Question 14

Which of the following will have normal aggregation with ristocetin?

1. Glanzmann thrombasthenia
2. Bernard-Soullier

Answer 14

Glanzmann thrombasthenia

• But abnormal with other facotrs*
• Bernard-Soullier is opposite; normal with ADP, epinephrine, collagen, arachadonic acid, but no aggregation with ristocetin*

Question 15

What platelet receptor is defective in Bernard-Soulier syndrome?

Answer 15

GB1b

Question 16

What is the morphological difference between a platelet with granule deficiency and one that is normal but exhausted (used up)?

Answer 16

Exhausted platelet will have podocytes

Both will have absent granules

Question 17

When during primary hemostatsis do platelets express GPIIb/IIIa receptors?

What do these receptors bind?

Answer 17

After activation and conformational change, platelets express GPIIb/IIIa

Binds fibrinogen

Leads to platelet aggregation

Also express anionic phospholipids (phosphatidyl serine) - basically a staging area where coagulation factors can assemble and activate fibrinogen -> fibrin

Question 18

After endothelial injury, platelets bind to two endothelial substances and tether themselves to the site of injury

What are the two substances?

Answer 18

vWF

Collagen

First rolling, then tight adhesion

Question 19

Which cells produce platelets?

Where?

Answer 19

Megakaryocytes

Bone marrow

Each megakaryocyte can produce 100’s-1000’s of platelets