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38 Cards in this Set

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What division of hemostasis are platelets involved?
Primary hemostasis
From where do platelets come?
Megakaryocytes
- Break off ectoplasm
What is thrombopoietin and where is it produced?
Hormone that stimulates stem cell differentiation to megakaryocytes

Synthesized in liver
What is the normal range of platelets in serum?
150,000 - 400,000 / μL
What is the lifespan of a platelet?
7-10 days
Where are platelets found in the body?
Blood

1/3 of platelet mass pooled in spleen
How do enlarged spleen and splenectomies affect platelet counts?
Enlarged spleen:
- Decreased platelet count

Splenectomy:
- Increased platelet count
What are the characteristic features of a platelet?
Oblong disk

Anucleate

Mitochondria

Granules
What are the types of granules found in platelets and what are stored in each?
Dense granules:
- ADP
- ATP
- Serotonin
- Calcium

α-granules:
- Fibrinogen
- vWF
- PDGF

Lysosomes
- Hydrolytic enzymes
What are the major steps that platelets undergo in primary hemostasis?
Adhesion

Aggregation

Activation
What is the first hemostatic response to vessel rupture?
Platelet adhesion and aggregation
What role do platelets have in secondary hemostasis?
Coagulation factors bind to large surface area and become activated
What are the important platelet membrane receptors and what do they bind?
GPIb:
- vWF

GPIIb / IIIa:
- vWF
- Fibrinogen

GPIa:
- Collagen

PAR 1 / 4:
- Thrombin

PG2Y1 / PG2Y12:
- ADP
What components and actions are involved in platelet adhesion?
GPIb binding vWF

GPIIb / IIIa: binding vWF

These two events adhere vWF to the platelet and the complex to the subendothelium of the blood vessel
What components and actions are involved in platelet aggregation?
GPIIb / IIIa: binding fibrinogen

Synthesis of thromboxane A2 to expel platelet granules
What components and actions are involved in platelet activation?
PAR 1 / 4 binding thrombin

PG2Y1 / PG2Y12 binding ADP
What defect in primary hemostasis causes Bernard Soulier disease?
Defective GPIb platelet membrane protein
- Inhibits adhesion of vWF and adhesion to vessel subendothelium
What defect in primary hemostasis causes Glanzmann's thrombosthenia?
Defective GPIIb / IIIa platelet membrane protein:
- Inhibits adhesion of vWF and adhesion to vessel subendothelium
- Inhibits fibrinogen binding, hindering platelet aggregation
Describe the process of platelet granule release, including the molecular mechanisms and final results
1. Phospholipase A2 (in cytosol) frees arachadonic acid from phospholipid membrane

2. Arachadonic acid converted to thromboxane A2 via cyclooxygenase

3. Thromboxane A2 causes decreased levels of cAMP

4. Decreased cAMP causes platelet granule release
- Leads to platelet aggregation and vasoconstriction
What are the major steps in platelet activation?
Prostaglandin (thromboxane A2) synthesis-mediated release of platelet granules

Shape change
How do the shapes of platelets change during platelet activation and how does this affect hemostasis?
Pseudopod extension increases surface area causing:
- Increased platelet-platelet aggregation
- Clotting factor binding and activation
What steps of the coagulation cascade do platelets affect and how?
Exposed platelet phospholipid assists two calcium-dependent clotting cascade reactions:
1. Activation of F X via F IXa, F VIIIa, F VIIa, and Tissue factor
2. Activation of thrombin via prothrombin, F Va, and F Xa

Exposed platelet phospholipid anchors and juxtaposes clotting factors in proper orientation to foster activation
What are two natural inhibitors of platelet function?
Nitric oxide (NO)

Prostacyclin
Where is nitric oxide made and how does it affect platelets and hemostasis?
Made in endothelial cells and platelets

Inhibits platelet aggregation

Causes vasodilation
Where is prostacyclin made and how does it affect platelets and hemostasis?
Made in endothelial cells

Inhibits platelet aggregation by increasing cAMP

Vasodilation
How do aspirin, motrin, and ibuprofen affect platelet function?
Inhibitory

Inhibit cyclodeoxygenase causing:
- Decreased thromboxane A2
- Increased cAMP

Eventual inhibition of platelet granule release
How does dipyridanole affect platelet function?
Inhibitory

Decreases platelet response to activation via:
- Increasing cAMP
How does clopidogrel affect platelet function
Inhibitory

Inhibits platelet aggregation via:
- Blocking binding of ADP to PG2Y1 and PG2Y12 platelet receptors:
How do GPIIb / IIIa inhibitors affect platelet function?
Inhibitory

Decrease platelet adhesion and aggregation via:
- Blocking GPIIb / IIIa receptors from binding vWF and fibrinogen
How do PAR1 inhibitors affect platelet function?
Inhibitory

Decrease platelet activation via:
- Blocking PAR1 receptors from binding thrombin
What can too few platelets cause?
Mucosal bleeding
What can qualitatively abnormal platelets cause?
Bleeding
What can too many platelets cause?
Thrombosis (clotting)
How does platelet-associated bleeding present?
Mucosal bleeding

Epistaxis

Superficial bruising

Oozing from open wounds

(All immediate)
What laboratory tests are used to diagnose platelet deficiencies?
Peripheral blood count: Platelet count

Peripheral blood smear

Bone marrow test

Functional tests:
- Bleeding time
- Aggregation test
How would platelet production disorders and platelet destructive disorders appear on a bone marrow test?
Production disorders:
- Show decreased megakaryocytes

Destructive disorders:
- Increased megakaryocytes
What problem with platelets does a prolonged bleeding time suggest?
Either a qualitative or quantitative defect with platelets
How are aggregation tests done to examine platelet function?
Measure platelet response to agonists via optical density after combination