Prolongation of prothrombin time in coagulation testing is associated with severe bleeding manifestation. Increased production of prothrombin heightens the risk of blood clotting. Factor Xa (in the presence of factor V) activates prothrombin into thrombin. They also have higher circulating clotting factors (vitamin K, prothrombin and platelets). Activation of prothrombin is crucial in physiological and pathological coagulation. VI was the factor that accelerated the conversion from prothrombin to thrombin. This cleaves prothrombin at two sites, converting it to thrombin. It may also increase the INR and prothrombin times in patients on warfarin. Manipulation of prothrombin is central to the mode of action of most anticoagulants. Most people with the prothrombin mutation (G20210A) never develop thrombosis. This prevents the formation of the active form of prothrombin and several other coagulant enzymes. For example, it is needed to carboxylate specific glutamic acid residues on prothrombin. Prolonged prothrombin and activated partial thromboplastin times are typical. In liver disease, prothrombin time is longer than usual. Coagulase reacts with prothrombin in the blood.