Anticoagulant thrombins

Thrombin plays both procoagulant and anticoagulant roles in the blood coagulation cascade. This dual role is influenced allosterically by the binding of Na+ near the primary specificity pocket of the enzyme. Recent findings demonstrate that if is possible to engineer recombinant thrombins that have practically lost anticoagulant activity but retain their anticoagulant properties. These anticoagulant thrombins bear substitutions in or around the Na+ binding site, provide important clues on structure-function relations, and offer a promising alternative to current anticoagulant therapies. In addition, they demonstrate the importance of Na+ as a coagulation factor and broaden our understanding of the function and regulation of all vitamin K-dependent clotting enzymes. (Trends Cardiovasc Med 1998;8:340-350) (C) 1998, Elsevier Science Inc.