Question 15

Describe the sequence of haemostatic events following injury to a blood vessel wall until clot stabilisation.

[Click here to toggle visibility of the answers]

College Answer

A good answer was well structured and covered the areas of vasoconstriction, platelet adhesion, activation and aggregation, coagulation, clot retraction and anticlotting mechanisms. Many answers gave an overview of the haemostatic process but revealed insufficient knowledge of the processes involved. It was acceptable to give a classical view of clotting or to describe the cell-based model; or both. However, in several cases answers became confused by mixing up elements of the classical approach and cell-based model approach. Errors concerning details of the cell-based model were frequent. Many candidates did not include how the clot is limited to just the site of injury which happens in parallel with the formation of clot. Candidates should be aware that writing lengthy introductory statements attracted no marks and wastes time.

Discussion

Haemostatic events:

  • simultaneous activation of clotting factors and platelets to prevent blood loss.
  • Initiation:
    • tissue factor (TF)  is exposed
    • TF and Factor VIIa act to produce a small amount of thrombin (the extrinsic pathway)
    • Thrombin then activates platelets
  • Platelet plug formation occurs when platelets are exposed to TF and collagen:
    • Adhesion to the denuded surface collagen via VWF, as well as directly
    • Aggregation (platelet to platelet) mediated by fibrin and VWF
    • Activation (degranulation, shape change, phosphatidylserine exposure on the platelet surface)
  • 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 (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

References

McRae, Simon. "Physiological Haemostasis." Mechanisms of Vascular Disease (2018): p.177.

Gomez, Keith, and John H. McVey. "Normal haemostasis." Postgraduate haematology (2015): 676-698.

Zaidi, Abbas, and Laura Green. "Physiology of haemostasis." Anaesthesia & Intensive Care Medicine 20.3 (2019): 152-158.

Sira, James, and Lorna Eyre. "Physiology of haemostasis." Anaesthesia & Intensive Care Medicine 17.2 (2016): 79-82.

Rasche, H. "Haemostasis and thrombosis: an overview." European Heart Journal Supplements 3.suppl_Q (2001): Q3-Q7.

Palta, Sanjeev, Richa Saroa, and Anshu Palta. "Overview of the coagulation system." Indian journal of anaesthesia 58.5 (2014): 515.

Gil, Morayma Reyes. "Overview of the coagulation system." Transfusion Medicine and Hemostasis. Elsevier, 2019. 559-564.

Spronk, Henri MH, José WP Govers‐Riemslag, and Hugo Ten Cate. "The blood coagulation system as a molecular machine." Bioessays 25.12 (2003): 1220-1228.

Hoffman, Maureane, and Dougald M. Monroe III. "A cell-based model of hemostasis." Thrombosis and haemostasis 85.06 (2001): 958-965.