Question 6

College Answer

The structure of the question outlined exactly what was expected. Platelets are formed in the bone marrow from budding of megakaryocytes. Granulocyte colony stimulating factor and  thrombopoeiten play a role in the process and they have a life span of about 10 days. It was expected candidates could describe or draw the structure detailing they have no nucleus, the presence of mitochondria and granules and provide some detail of the important external surface proteins (glycoproteins, ABO, human platelet antigens). Better answers also described the internal microtubule structure and related this to function (allows contraction and shape change).  The description of function required detail around the importance of platelet plug formation and the role of adhesion, aggregation and activation in this process.

Discussion

• Platelets are the essential cellular component of the haemostatic response.
• Formation of platelets
  • Stimulated by thrombopoietin in response to low platelet count or inflammation
  • (thrombopoietin is produced mainly by the liver)
  • Originate from the myeloid common erythrocyte/megakaryocyte precursor
  • Differentiation into megakaryocytes leads to endomitosis and polyploid proliferation
  • The megakaryocyte extends strings of protoplatelets into the bloodstream and disintegrates, undergoing apoptosis
  • The process of thrombopoiesis takes 8-10 days
  • Platelets in circulation have a lifespan of ~ 10 days, after which they undergo apoptosis
• Structure of platelets
  • Small (0.5-3μm) irregular anucleate cells
  • Contain:
    • mitochondria, ATP and glycogen
    • Dark granules and α-granules
    • Microtubules and surface-connected canaliculi
• Function of platelets
  • Adhesion to the denuded surface collagen via VWF, as well as directly
  • Aggregation (platelet to platelet) mediated by fibrin and VWF
  • Activation, which means
    • Degranulation (release of vasoactive and platelet-activating mediators)
    • Shape change (flattening and extension of cellular projections)
    • Phosphatidylserine exposure on the platelet surface, which is essential for clotting factor binding
  • 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.