Alterations of Coagulation and Fibrinolytic and Kallikrein-Kinin Systems in the Acute and Postacute Phases in Patients With Unstable Angina Pectoris

Abstract

Background 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. Methods and Results We determined serially in the patients up to 10 days after admission factor XII and the β–factor XIIa inhibition, kallikrein-like activity, prekallikrein, C ₁ -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 μg/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. Conclusions 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.