MOLECULAR MARKERS OF HEMOSTASIS AND FIBRINOLYSIS AND INHIBITOR LEVELSIN UNSTABLE ANGINA-PECTORIS

Intracoronary thrombus formation is frequently observed in patients wi th coronary heart disease and an episode of unstable angina pectoris. This finding might implicate that either an activation of the coagulat ion cascade or a disturbance of the fibrinolytic system is involved in the pathogenesis of unstable angina pectoris. Several markers of an a ctivated hemostatic system were examined in different studies. As a co nstant finding, markers of elevated thrombin generation and activity ( thrombin-antithrombin III complex, fibrinopeptide A, prothrombin fragm ent F1+2) were elevated in at least a considerable part or in the majo rity of patients, depending on the respective study design and the obs ervation period. More specific analysis revealed that the contact phas e of the coagulation and the associated kallikrein-kinin system are in itially activated in these patients. Elevated d-dimer and fibrin monom er levels indicate the presence of a hypercoagulative state. Fibrinoge n itself is initially elevated and rises further due to an acute phase reaction pattern in this patient group. The fibrinolytic system in pa tients with unstable angina pectoris is markedly disturbed as indicate d by elevated plasminogen activator inhibitor and plasminogen activato r-antigen levels. Plasmin generation is not markedly increased as can be derived from the constant plasminogen and antiplasmin levels. Detai led analysis of additional plasma inhibitor systems (antithrombin III, C-1-esterase inhibitor, alpha-macroglobulin, protein C) did not provi de evidence for a pre-existing inhibitor deficiency as a cause of the acute coronary syndrome. Conclusion: In patients with coronary heart d isease and unstable angina pectoris, marked activation of the coagulat ion cascade resulting in a hypercoagulative state, in association with an activation of the contact phase-kallikrein-kinin system, is a comm on finding. These changes are paralleled by marked alterations of para meters of fibrinolysis. These pathological changes were observed not o nly in the acute phase but for a prolonged period after clinical stabi lization of the patients.