Hemostasis and Associated Disorders
Overview of Hemostasis
Hemostasis is a natural defence mechanism through which the blood system prevents bleeding from a blood vessel (Dave & LaPelusa, 2019). The process has several stages that are interlinked. These processes start once a trauma affects the lining of a blood vessel and culminates in the formation of a plug to close the damaged site of the blood vessel. The stages involved include vasoconstriction, formation of a platelet plug, the coagulation cascade, and clot formation (Dave & LaPelusa, 2019).
When a blood vessel ruptures, endothelins are released. The endothelins will trigger processes that result in vasoconstriction of the blood vessel to decrease blood flow to the affected area. Consequently, the injury of the epithelial wall, coagulation is activated. In this second stage, platelets will bind to the endothelial lining and the exposed collagen. The process is assisted by von Willebrand factor that stabilizes the growth of the platelet plug (Dave & LaPelusa, 2019). Platelets will release serotonin, prostaglandins, and phospholipids to help maintain the vasoconstriction, and adenosine diphosphate to reinforce the plug. If the bleeding does not stop, the process of clotting gets to the third stage, the coagulation cascade.
The blood clotting cascade
In the third stage, a blood clot is formed through a coagulation cascade. The stage involves the production of clotting factors in a cascade of chemical processes that result in the creation of a mesh, fibrin. The primary clotting factors are prothrombin, thrombin, and fibrinogen. Through various processes of activation of various factors, the coagulation cascade is a classical waterfall process with intrinsic, extrinsic, and common pathways (Perry (Ed.), 1999). The extrinsic path (tissue factor pathway) starts following damage to the surrounding tissue due to trauma. The extravascular cells come into contact with blood plasma leading to release of factor III. Following the release of factor VII and calcium, an activation complex forms leading to the activation of factor III. Finally, factor X is activated that activates the common pathway (Bhagavan & Ha, 2011).
The intrinsic pathway (contact activation pathway) involves factors in the bloodstream (Perry (Ed.), 1999). It occurs following activation by factor XII. In the body, factor XII is activated by negatively-charged molecules, including phosphates and inorganic polymers. Through an activation process, the intrinsic pathway culminates in the activation of factor X that lead to the common pathway. The common pathway results in fibrin formation to seal off the vessel. Factor X will activate prothrombin to thrombin, which then converts factor I to soluble fibrin protein strands (Bhagavan & Ha, 2011). Finally, factor XIII will stabilize the fibrin clot.
Anticoagulants
Warfarin: by inhibiting vitamin K epoxide reductase complex 1, warfarin leads to depletion of vitamin K reserve leading to a reduction in synthesis of factor II, VII, IX, and X (Greenstein & Greenstein, 2007). As a result, the clotting ability of the blood is reduced.
Heparin: inhibits antithrombin III leading to inhibition of activated clotting factors Xa and IIa. As a result, the clotting time is prolonged (Greenstein & Greenstein, 2007).
References
Bhagavan, N. V., & Ha, C. E. (2011). Essentials of medical biochemistry: with clinical cases. Academic Press.
Dave, H. D., & LaPelusa, A. (2019). Physiology, Hemostasis. In StatPearls [Internet]. StatPearls Publishing.
Greenstein, B., & Greenstein, A. (2007). Concise clinical pharmacology. Pharmaceutical Press.
Perry, D. J. (Ed.). (1999). Hemostasis and thrombosis protocols (Vol. 31). Springer Science & Business Media.