Clotting Cascade

Illustrate the clotting cascade and compare the mechanisms of action of the anticoagulants and their clinical indications.

The Clotting Cascade occurs when several circulating proteins interact in a cascading series of limited proteolytic actions and is the activated when intravascular conditions cause thrombi to develop. “At each step, a precursor protein is converted to an active protease that activates the next clotting factor, and finally, a solid clot is formed”(Woo & Wynne, 2011, p. 445). The process of clot formation and dissolution of the clot following repair of the injured tissue is termed hemostasis and is comprised of four major events:

1. Initial Phase: Vascular constriction in which the flow of blood to the area of injury is limited and Factor VII is activated.
2. Second Phase: Platelets become activated by thrombin and aggregate at the site of injury forming a temporary, loose platelet plug. Platelets clump by binding to collagen that becomes exposed following rupture of the endothelial lining of vessels. Upon activation, platelets release the nucleotide, additional platelets, and proteins (comprising Factor Xa and co-factors bound

1). The activate partial thromboplastin time (aPTT) is a “test used to measure and evaluate all the clotting factors of the intrinsic and common pathways of the clotting cascade and assesses factors I (fibrinogen), II (prothrombin), V, VIII, IX, X, XI, and XII”(Hammami, 2013, p. 1). When performed with prothrombin time (PT) test, it evaluates the extrinsic and common pathways of the coagulation cascade. The PT, along with the INR is used to assess the therapeutic of oral anticoagulants and can determine if the patient is at an increased risk of bleeding (if above range) or an increased risk of clotting (if below