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 disease. However, little is. Known about this defect in arterial disease. The aim of this study was thus to investigate the frequency and prognostic 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, that is, unstable angina pectoris or non-Q-wave myocardial infarction, were investigated and compared with a reference group of apparently healthy individuals. The patients participated in a prospective, multicenter, randomized, and placebo-controlled investigation evaluating the protective value of low molecular weight heparin (dalteparin) in unstable coronary artery disease. The APC ratio was assayed using a modified activated partial thromboplastin time reaction method to measure the response to activated protein C. APC resistance was defined as an APC ratio </=2.2. Signs of thrombin activation were measured 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 elevation of the prothrombin fragment 1+2 median level of 2.5 nM (interquartile range, 1.9-3.2 nM) was found in the patients with APC resistance compared with 1.7 nM (interquartile range, 1.2-2.4nM) in the group with a normal APC ratio (P < 0.01). During the 150-day follow-up period, there was no increased risk of cardiac events in patients with APC resistance. Although accompanied by signs of increased thrombin formation, APC resistance doesnot seem to be an important risk factor for the development of instability in coronary artery disease.