Exam: Hemostasis

Questions
1. Activated platelets release two types of cytoplasmic granules. Which two? Eventually these granules release their content, name few of the content of each granule.

2. Name the disease associated with deficiencies of GpIb.

3. Aspirin inhibits platelet aggregation and produces a mild bleeding defect, what is mechanism of aspirin?

4. Glanzmann thrombasthenia is a inherited disorder caused by deficiency of receptors that bind to fibrinogen, which one?

5. How does vitamin K deficiency effect the coagulation cascade?

6. Thrombin is the most important among the coagulation factors. Name at least two activities of thrombin.

7. One of fibrinogen breakdown product is important as a clinical marker of several thrombotic states. Which one?

8. The endothelium has platelet inhibitory effects. An obvious effect of intact endothelium is to serve as a barrier that shields platelets from subendothelial vWF and collagen. However normal
endothelium also releases a number of factors that inhibit platelet activation and aggregation. Name two.

9. Virchow triad, explain it.

10. Inflammation can lead to endothelial activation/dysfunction. What do we understand under endothelial activation/dysfunction?

11. How does factor V leiden predisposes to thrombosis?

Answers
1. Alpha-granules, dense granules
Alphagranules release proteins involved in coagulation: factor V, vWF and protein factors involved in wound healing: fibronectin, platelet factor 4, platelet derived growth factor (PDFG) and transforming growth factor-beta.
Dense granules contain adenosine diphosphate (ADP), serotonin and epinephrine.

2. Bernard Soulier syndrome

3. Aspirin inhibits cycooxygenase (COX) a platelet enzyme that is required for synthesis of thromboxane A2 (TxA2). TxA2 is a inducer of platelet aggregation.

4. GpIIb-IIIa

5. Each reaction step of coagulation cascade involves and enzyme, a substrate and a cofactor. The enzymatic actions that produce gamma-carboxylated glutamic acid use vitamin K as a cofactor.

6. Thrombin activities include:
- Thrombin converts soluble fibrinogen into fibrin.
- Amplifies coagulation process by activation factor XI, V and VIII.
- Thrombin is a potent inducer of platelet activation and aggregation through its ability to activate PARs (protease-activated receptor)

7. D-dimeer

8. Prostacyclin (PGI2), nitric oxide (NO) and adenosine diphosphate (degrades ADP)

9. Virchow's triad describes the three categories of factors that contribute to thrombosis.
      I. Endothelial injury
      II. Abnormal blood flow
      III. Hypercoagulability

10. Endothelial activation is a change of endothelium that promotes thrombosis.
- Pro-coagulant changes. Endothelial cells activated by cytokines downregulate the expression of thrombomodulin. Also inflamed endothelium downregulates anticoagulants such as protein C and tissue factor protein inhibitor.
- Antifibrinolytic effects. Activated endothelial cells secrete plasminogen activator inhibitors (PAIs), which limit fibrinolysis and downregulate the expression of t-PA.

11. The mutation renders factor V resistant to cleavage and inactivation by protein C.