251 - Platelet Function and Formation Flashcards

1
Q

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

A

Interferes with platelet production

  • The Wiskott-Aldrich protein (WASp) is supposed to stabilize the platelet cytoskeleton*
  • Mutation -> impaired platelet production*
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2
Q

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

A

Arterial, because they are “platelet rich”

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3
Q

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

What is their function?

A

Platelets release thromboxane A2 when they are activated

They amplify platelet activation

  • Platelet activation*
  • -> Activates PL2*
  • -> Produces arachadonic acid*
  • ->>> COX pathway produces thromboxane A2*
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4
Q

What is the primary symptom of a qualitative platelet defect?

A

Skin and mucocutaneous bleeding

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5
Q

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

A

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
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6
Q
A

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
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7
Q

What substance drives platelet development?

A

Thrombopoietin (TPO)

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8
Q

What receptor on platelets binds to vWF?

A

GPIb

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9
Q

Which platelet disorder will have thrombocytopenia with large platelets?

A

Bernard-Soullier syndrome

  • Defect in GPIb*
  • No aggregation with ristocetin (antibiotic that activates vWF)*
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10
Q

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

A

Venous

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11
Q

After platelets bind to collagen and vWF on the injured endothelium), list the remaining steps of primary hemostasis

A
  • 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)

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12
Q

What platelet receptor is defective in Glanzmann’s Thrombasthenia?

A

GBIIb/IIIa: receptor that binds fibrinogen to link to other platelets

Severe bleeding disorder in childhood

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13
Q

What is the average platelet lifespan?

A

8-10 days

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14
Q

Which of the following will have normal aggregation with ristocetin?

  1. Glanzmann thrombasthenia
  2. Bernard-Soullier
A

Glanzmann thrombasthenia

But abnormal aggregation with other factors

Bernard-Soullier is opposite; normal with ADP, epinephrine, collagen, arachadonic acid, but no aggregation with ristocetin

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15
Q

What platelet receptor is defective in Bernard-Soulier syndrome?

A

GB1b (vWF receptor)

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16
Q

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

A

Exhausted platelets (used up) will have podocytes

Both will have absent granules

17
Q

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

What do these receptors bind?

A

After activation and conformational change, platelets express GPIIb/IIIa (occurs after ADP binds to P2Y12 receptor)

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

18
Q

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

What are the two substances?

A

vWF and Collagen

First rolling, then tight adhesion

19
Q

Which cells produce platelets?

Where?

A

Megakaryocytes

Bone marrow

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