[Congenital deficiencies of natural anticoagulant systems responsible for recurrent thromboembolism]

The main characteristics of the blood coagulation system is its high potential of autoamplification. Cascade reactions consisting of successive activations of zymogens into their respective serine-proteinase active form culminate in the generation of thrombin, the central enzyme of the system. Blood coagulation is under control of two major natural regulatory mechanisms limiting the extension of the thrombus. The first one with antithrombin III as the central element, directly inhibits thrombin and other activated clotting factors in cooperation with heparans synthetized by the vascular wall. The second one, the protein C pathway, limits thrombin generation, through its ability to block the amplification potential of feedback reactions. The physiological significance of these regulatory mechanisms is clearly emphasized by the frequency of recurrent thrombotic episodes affecting subjects presenting an inherited deficiency of one of these components, estimated between 50 and 70%. Patients with protein S deficiency, the essential cofactor of activated protein C, exhibit a surprisingly high tendency to arterial thrombosis. The biological investigation of thromboembolic disease must be focused on antithrombin III, protein C and protein S deficiency using functional assays when available or feasible in order to detect both qualitative and quantitative defects.