- Types of Anticoagulants
- The multilevel cascade of blood clotting system permits enormous amplification of its triggering signals. Moving down the extrinsic pathway, for example, proconvertin (VII), Stuart factor (X), prothrombin, and fibrinogen are present in plasma in concentrations of <1, 8="" 150="" and="" 4000="" mg="" ml-1="" respectively="" thus="" a="" small="" signal="" is="" very="" quickly="" amplified="" to="" bring="" about="" effective="" hemostatic="" control="" br="">
- On the other hand, clotting must be very strictly regulated because even one inappropriate clot can have fatal consequences. Indeed, blood clots are the leading cause of strokes and heart attack, the two major causes of human death.
Endogenous Inhibitors of Clotting
Thrombin plays a pivotal role in blood coagulation and Nature has designed several serine protease inhibitors (SERPINS) to regulate the its activity. These include antithrombin (major), heparin cofactor II, a2-macroglobulin, and a1-proteinase inhibitor.
Antithrombin is present in the plasma in significant concentrations (~2-3 mM). Antithrombin primarily neutralizes factor Xa and thrombin, in addition to inhibiting most active serine proteases of the clotting system. (To view a structure of antithrombin click here.)
Protein C is another plasma protein that limits clotting by being activated by thrombin to proteolytically inactivate proaccelerin (V) and antihemophilic factor (VIII).
Thrombomodulin, a cell membrane bound glycoprotein lining the vascular endothelium, specifically binds thrombin so as to convert it to a form with decreased ability to catalyze clot formation but with a >1,000-fold increased capacity to activate protein C.
Exogenous Inhibitors of Clotting
The control of clotting is a major medical concern. Several inhibitors have been developed with different mechanisms of anticoagulant action. These include the heparins, the coumarins, and the 1,3-indanediones.