First, prothrombin activator is formed as a result of rupture of a blood vessel or as a result of damage to special substances in the blood. Second, the prothrombin activator, in the presence of sufficient amounts of ionic calcium (Ca++), causes conversion of prothrombin to thrombin (Figure 1). Third, the thrombin causes polymerization of fibrinogen molecules into fibrin fibers within another 10 to 15 seconds. Thus, the rate limiting factor in causing blood coagulation is usually the formation of prothrombin activator and not the subsequent reactions beyond that point, because these terminal steps normally occur rapidly to form the clot.
Fig1. Schema for conversion of prothrombin to thrombin and polymerization of fibrinogen to form fibrin fibers.
Platelets also play an important role in the conversion of prothrombin to thrombin because much of the pro thrombin first attaches to prothrombin receptors on the platelets already bound to the damaged tissue.
Prothrombin and Thrombin. Prothrombin is a plasma protein, an α2globulin, having a molecular weight of 68,700. It is present in normal plasma in a concentration of about 15 mg/dl. It is an unstable protein that can split easily into smaller compounds, one of which is thrombin, which has a molecular weight of 33,700, almost exactly one half that of prothrombin.
Prothrombin is formed continually by the liver, and it is continually being used throughout the body for blood clotting. If the liver fails to produce prothrombin, in a day or so prothrombin concentration in the plasma falls too low to provide normal blood coagulation.
Vitamin K is required by the liver for normal activation of prothrombin, as well as a few other clotting factors.
Therefore, either lack of vitamin K or the presence of liver disease that prevents normal prothrombin formation can decrease the prothrombin to such a low level that a bleeding tendency results.
