Molecular markers of hemostasis and fibrinolysis and inhibitor levels in unstable angina pectoris

Abstract

Summary Intracoronary thrombus formation is frequently observed in patients with coronary heart disease and an episode of unstable angina pectoris. This finding might implicate that either an activation of the coagulation cascade or a disturbance of the fibrinolytic system is involved in the pathogenesis of unstable angina pectoris. Several markers of an activated hemostatic system were examined in different studies. As a constant finding, markers of elevated thrombin generation and activity (thrombin-antithrombin III complex, fibrinopeptide A, prothrombin fragment F 1+2 ) were elevated in at least a considerable part or in the majority of patients, depending on the respective study design and the observation period. More specific analysis revealed that the contact phase of the coagulation and the associated kallikrein-kinin system are initially activated in these patients. Elevated d-dimer and fibrin monomer levels indicate the presence of a hypercoagulative state. Fibrinogen itself is initially elevated and rises further due to an acute phase reaction pattern in this patient group. The fibrinolytic system in patients with unstable angina pectoris is markedly disturbed as indicated by elevated plasminogen activator inhibitor and plasminogen activator-antigen levels. Plasmin generation is not markedly increased as can be derived from the constant plasminogen and antiplasmin levels. Detailed analysis of additional plasma inhibitor systems (antithrombin III, C 1 -esterase inhibitor, α-macroglobulin, protein C) did not provide evidence for a pre-existing inhibitor deficiency as a cause of the acute coronary syndrome. Conclusion : In patients with coronary heart disease and unstable angina pectoris, marked activation of the coagulation cascade resulting in a hypercoagulative state, in association with an activation of the contact phase-kallikrein-kinin system, is a common finding. These changes are paralleled by marked alterations of parameters of fibrinolysis. These pathological changes were observed not only in the acute phase but for a prolonged period after clinical stabilization of the patients.