| 摘要 |
An anticoagulant composition containing an effective amount of factor Xa having the active serine site inactivated that functions rapidly and effectively in vivo to suppress coagulation. In a preferred embodiment, Factor Xa, a serine esterase that forms a complex with Factor Va, Ca++, and phospholipid to catalyze prothrombin activation, is first inactivated with an active site inhibitor, such as dansyl-glu- gly-arg-chloromethyl ketone, to form inactivated factor Xa. In another embodiment, Factor Xa is expressed from a gene sequence wherein the portion encoding the active serine region is modified. The inactivated protein retains the ability to bind to endogenous factor Va in vivo, and has a half-life of approximately ten hours. Administration of inactive factor Xa to the blood of a patient results in the formation of inactive factor Xa-Va complexes in vivo, thereby inhibiting coagulation. |
