1/05/14 20:50 Critical Role of Thrombin - The Coagulation Cascade: Review of Physiol Applications - Advances in Anticoagulation for Venous

Thromboembolism
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Urology - The Gold Journal
Weitz - The Coagulation Cascade: Review of Physiology and Clinical Applications - Figure 2
Critical Role of Thrombin
Coagulation is an orchestrated process that begins with vessel injury, as shown in Figure 2. For example, a serious vessel injury
might occur at the site where an atherosclerotic plaque ruptures or erodes, and this disruption of the vessel surface exposes
subendothelial collagen and Von Willebrand factor, which provide the nidus onto which platelets adhere and become activated.
Exposure of the subendothelium also results in the exposure of cells that constitutively express tissue factor. Tissue factor is the
spark for the coagulation cascade. It ignites a series of reactions that result in a burst of thrombin formation and it is this
thrombin that is the link between the injury, the spark, the coagulation process, platelet activation, and inammation.
As shown in the bottom center of the Figure, tissue factor triggers factor Xa generation. Factor Xa then converts prothrombin to
thrombin, and this thrombin amplies the whole process by feeding back to generate more thrombin, by serving as a potent
platelet agonist, and by converting brinogen to brin. It is then these brin strands that form the support structure for a clot.
Once the platelets are activated they begin to aggregate to form the plateletbrinthrombus that plugs the site of injury. Of
course if this happens in an artery such as a coronary artery or a cerebral artery this thrombus can ll the vessel lumen,
obstruct blood ow, and in the case of the heart lead to myocardial infarct, or in the case of the brain lead to a stroke.
[1]

[2]
If we look at this process in a little more detail, we go from vessel injury and tissue factor exposure to thrombin generation,
followed by thrombin conversion of brinogen to brin and the subsequent platelet activation, as shown in the next Figure. Weitz
JI. Am J Med 2013; published on-line at http://education.amjmed.com/00000.
References
[1] Coughlin SR. Thrombin signalling and protease-activated receptors. Nature. 2000;407:258-264.
[2] Monroe DM, Hoffman M, Roberts HR. Platelets and thrombin generation. Arterioscler Thromb Vasc Biol. 2002 ;22:1381-
1389.
1/05/14 20:50 Critical Role of Thrombin - The Coagulation Cascade: Review of Physiol Applications - Advances in Anticoagulation for Venous Thromboembolism
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