Alterations of coagulation and fibrinolytic and kallikrein-kinin systems in the acute and postacute phases in patients with unstable angina pectoris.

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Unstable angina pectoris is frequently associated with intracoronary thrombus formation. In a prospective study, we investigated in 35 patients with unstable angina pectoris markers of coagulation and the kallikrein-kinin and fibrinolytic systems in the acute and postacute phases. We determined serially in the patients up to 10 days after admission factor XII and the beta-factor XIIa inhibition, kallikrein-like activity, prekallikrein, C1-esterase inhibitor, kallikrein inhibition, high molecular weight kininogen as indicators of the contact phase and bradykinin generation, thrombin-antithrombin III (TAT) complex as marker of the activated coagulation cascade, fibrinogen, plasminogen, plasminogen activator inhibitor-1 (PAI-1), tissue-type plasminogen activator (TPA), and D-dimers as indicators of the fibrinolytic system. Data were compared with those from control subjects (n = 25) and from patients with stable angina pectoris (n = 25). In patients with unstable angina pectoris, initially the contact phase and 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 persisted for the following 10 days, whereas the initially enhanced bradykinin generation normalized after 2 days. Furthermore, we had evidence of a hypercoagulative state (TAT, 10.9 +/- 3.1 versus 4.5 +/- 0.7 micrograms/L, P < .05; D-dimer, 474 +/- 81 versus 272 +/- 71 ng/mL) persisting longer than the clinically symptomatic period in association with disturbed fibrinolysis (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 levels. Our data indicate that in patients with unstable angina pectoris, intracoronary thrombus formation is associated with a hypercoagulative state, including activation of the contact phase and of the kallikrein system and increased bradykinin generation. The persistence of this hypercoagulative state, together with a disturbed fibrinolysis, might indicate an increased risk for further coronary events.