NO PROGNOSTIC IMPORTANCE OF RESISTANCE TO ACTIVATED PROTEIN-C IN UNSTABLE CORONARY-ARTERY DISEASE DESPITE SIGNS OF THROMBIN ACTIVATION

Resistance to activated protein C (APC resistance) is the single most important hemostatic defect associated with venous thromboembolic dise ase. However, little is known about this defect in arterial disease. T he aim of this study was thus to investigate the frequency and prognos tic importance of APC resistance and its influence on the coagulation system in one type of arterial thrombosis. In this study, 323 patients admitted to hospital because of unstable coronary artery disease, tha t is, unstable angina pectoris or non-Q-wave myocardial infarction, we re investigated and compared with a reference group of apparently heal thy individuals. The patients participated in a prospective, multicent er, randomized, and placebo controlled investigation evaluating the pr otective value of low molecular weight heparin (dalteparin) in unstabl e coronary artery disease. The APC ratio was assayed using a modified activated partial thromboplastin time reaction method to measure the r esponse to activated protein C. APC resistance was defined as an APC r atio less than or equal to 2.2. Signs of thrombin activation were meas ured by prothrombin fragment 1+2 levels. The 7.2% (23/318) occurrence of APC resistance found in patients did not differ from the 5.8% (4/69 ) level in the reference population (P = 0.16). A significant elevatio n of the prothrombin fragment 1+2 median level of 2.5 nM (interquartil e range, 1.9-3.2 nM) was found in the patients with APC resistance com pared with 1.7 nM (interquartile range, 1.2-2.4 nM) in the group with a normal APC ratio (P < 0.01). During the 150 day follow up period, th ere was no increased risk of cardiac events in patients with APC resis tance. Although accompanied by signs of increased thrombin formation, APC resistance does not seem to be an important risk factor for the de velopment of instability in coronary artery disease.