Outline the formation, structure, and function of the platelet.
This question was divided in three sections to help candidates formulate an answer template. The first section required a brief outline of the formation of platelets from pluripotent stem cells via megakaryocytes. The second section required an outline of platelet structure highlighting the special features such as, an absence of a nucleus, the presence of an external glycocalyx layer, specific surface receptors, contractile proteins, dense tubular system and granules. The third section was about platelet function where the expected focus was on the role of platelets in haemostasis. This required outlining the mechanism of platelet plug formation by adhesion-activation-aggregation, interactions with the coagulation cascade and role of platelets in clot contraction as well as fibroblast invasion. Although many candidates were able to answer the first section reasonably well, there was a noticeable knowledge deficit in the latter two sections. A significant proportion of answers had missing information on platelet structure and lack of structure in outlining platelet function.
- 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
- mitochondria, ATP and glycogen
- Dark granules and α-granules
- Microtubules and surface-connected canaliculi
- External glycocalyx layer (thick, 20-30nm)
- 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
- 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
- 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.
Fritsma, George A. "Platelet structure and function." Clinical laboratory science 28.2 (2015): 125.