INHIBITORS TO CLOTTING FACTORS

Clot formation is the final result of interaction among multiple plasm a proteins; after activation, it results in the conversion of fibrinog en to fibrin and cross-linking of fibrin by activated factor XIII, whi ch stabilizes the formed clot. Deficiency or functional abnormality of the factors involved in these reactions causes bleeding disorders. Na tural inhibitors of clotting factors include antithrombin III, protein S, and protein C. When activated, these proteins inactivate specific clotting factors, providing a regulatory mechanism that serves to cont rol the coagulation response and limit the extension of the clot. Phys iologic or natural inhibitors should not be confused with acquired inh ibitors of coagulation factors, which are discussed in this review. In hibitors to coagulation factors, also known as circulating anticoagula nts, are antibodies that neutralize specific clotting proteins, thereb y interfering with their normal function. Antibodies may be directed a gainst isolated clotting factors, as is the case with factor VIII or I X inhibitors. On the other hand, the antiphospholipid antibodies are k nown to develop against multiple coagulation proteins. In contrast to patients with antibodies against isolated clotting factors, who common ly present with spontaneous bleeding, individuals with antiphospholipi d antibodies may be asymptomatic or present with venous or arterial th rombosis. In this article I refer to inhibitors developing in patients with hemophilia A or other congenital factor deficiency as alloantibo dies, and to spontaneous formation of antibodies in patients without p rior history of hemorrhagic diathesis as autoantibodies. The antiphosp holipid antibodies are discussed separately.