Question 4(p.2)

College Answer

The main points expected in this answer were descriptions of platelet activation following exposure to collagen, platelet adhesion to the endothelium and ADP release and platelet aggregation secondary to activation of the GP11b/111a, COX-1 and other agents e.g. prostaglandin E2
Factors that interacted with platelet receptors e.g. platelet activating factor which increase aggregation and factors that inhibited platelet activation e.g. Prostaglandin I2 and nitric oxide gained marks.
Syllabus J2c
Reference: Power and Kam 1st edition p 247-249

Discussion

Role of platelets in primary haemostasis

• Platelets form the initial platelet plug in primary haemostasis, by:
• Adhesion to the denuded surface collagen via VWF, as well as directly
  • Collagen, laminin and other basement membrane components can bind platelets directly
  • These molecules also activate platelets
• Aggregation (platelet to platelet) mediated by fibrin and VWF
  • GPIIb/IIIa receptor protein mediates the linking of platelet to platelet by bridges of fibrinogen, fibrin and VWF
• Activation, which means
  • Degranulation (release of vasoactive and platelet-activating mediators, including ADP, serotonin, Factor V, and various vasoactive eicosanoids including thromboxane A2 which activates yet more platelets)
  • Shape change (flattening and extension of cellular projections)
  • Phosphatidylserine exposure on the platelet surface, which is essential for clotting factor binding
• Vasoconstriction is crucial to primary haemostasis, and this is mainly mediated by the products of platelet degranulation.

Role of platelets in secondary haemostasis

• Activated platelets act as the surface for most of the events which need to take place for secondary haemostasis.
• The exposure of negatively charged phospholipid on the platelet surface is crucial to this
• Amplification
  • Intrinsic pathway activation by the available thrombin and other platelet granule content leads to the increase in available clotting factors in the region of the platelet plug
  • The available thrombin activates factor XI and leads to the activation of FXI
  • Activate platelet surfaces act as sites of attachment for FVIIIa and FVa
• Propagation
  • Platelet-bound Factors FVIIIa  FVa and FX activate thrombin
  • This leads to the formation of a large amount of thrombin (the "thrombin burst")
  • The large amount of thrombin made available allows the generation of a large amount of fibrin from fibrinogen
• Contraction of platelets occurs in later stages of clot maturation

Jurk, Kerstin, and Beate E. Kehrel. "Platelets: physiology and biochemistry." Seminars in thrombosis and hemostasis. Vol. 31. No. 04. Copyright© 2005 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA., 2005.

Linden, Matthew D. "Platelet physiology." Haemostasis. Humana Press, Totowa, NJ, 2013. 13-30.

Gremmel, Thomas, Andrew L. Frelinger III, and Alan D. Michelson. "Platelet physiology." Seminars in thrombosis and hemostasis. Vol. 42. No. 03. Thieme Medical Publishers, 2016.

Kaushansky, Kenneth. "Thrombopoiesis." Seminars in hematology. Vol. 52. No. 1. WB Saunders, 2015.

Schulze, H., and R. A. Shivdasani. "Mechanisms of thrombopoiesis." Journal of thrombosis and haemostasis 3.8 (2005): 1717-1724.