ALTERATIONS OF COAGULATION AND FIBRINOLYTIC AND KALLIKREIN-KININ SYSTEMS IN THE ACUTE AND POSTACUTE PHASES IN PATIENTS WITH UNSTABLE ANGINA-PECTORIS

Background Unstable angina pectoris is frequently associated with intr acoronary thrombus formation. In a prospective study, we investigated in 35 patients with unstable angina pectoris markers of coagulation an d the kallikrein-kinin and fibrinolytic systems in the acute and posta cute phases. Methods and Results We determined serially in the patient s up to 10 days after admission factor XII and the beta-factor XIIa in hibition, kallikrein-like activity, prekallikrein, C-1-esterase inhibi tor, kallikrein inhibition, high molecular weight kininogen as indicat ors of the contact phase and bradykinin generation, thrombin-antithrom bin III (TAT) complex as marker of the activated coagulation cascade, fibrinogen, plasminogen, plasminogen activator inhibitor-1 (PAI-1), ti ssue-type plasminogen activator (TPA), and D-dimers as indicators of t he fibrinolytic system. Data were compared with those from control sub jects (n=25) and from patients with stable angina pectoris (n=25). In patients with unstable angina pectoris, initially the contact phase an d the kallikrein-kinin system were markedly elevated (factor XII, 96+/ -5% versus 117+/-5%; kallikrein-like activity, 35.7+/-2.9 versus 27.4/-1.3 U/L; high molecular weight kininogen, 52.7+/-5.2% versus 87.7+/- 3.9%; P<.01 versus control subjects). Contact-phase activation persist ed for the following 10 days, whereas the initially enhanced bradykini n generation normalized after 2 days. Furthermore, we had evidence of a hypercoagulative state (TAT, 10.9+/-3.1 versus 4.5+/-0.7 mu g/L, P<. 05; D-dimer, 474+/-81 versus 272+/-71 ng/mL) persisting longer than th e clinically symptomatic period in association with disturbed fibrinol ysis (TPA, 15.9+/-1.9 versus 5.1+/-0.4 ng/mL; P<.01; PAI-1, 9.9+/-2.6 versus 4.6+/-1.6 AU/mL; P=NS) in the presence of elevated fibrinogen l evels. Conclusions Our data indicate that in patients with unstable an gina pectoris, intracoronary thrombus formation is associated with a h ypercoagulative state, including activation of the contact phase and o f the kallikrein system and increased bradykinin generation. The persi stence of this hypercoagulative state, together with a disturbed fibri nolysis, might indicate an increased risk for further coronary events.