Association of plasma levels of activated protein C with recanalization ofthe infarct-related coronary artery after thrombolytic therapy in acute myocardial infarction

Protein C is one of the most important antithrombotic components. After act ivation by the thrombin-thrombomodulin complex on endothelial cells, activa ted protein C (APC) inactivates factors Va and VIIIa, which leads to the in hibition of thrombin formation. We examined the association of plasma level s of APC with the responsiveness to coronary thrombolytic therapy of the in farct-related coronary artery in patients with acute myocardial infarction (AMI). Plasma levels of APC, thrombin-antithrombin III complex (TAT), and p lasminogen activator inhibitor (PAI) activity were measured in 32 consecuti ve AMI patients who underwent coronary angiography followed by thrombolytic therapy, and compared to the measurements in 23 control subjects. On admis sion, APC levels (ng/mL) were significantly elevated in patients with AMI, as compared with controls (2.5+/-0.4 vs. 1.2+/-0.2, 1.3+/-0.2, respectively , p<0.01). At discharge, plasma levels in AMI patients decline to values no t significantly different from those in controls. (1.2+/-0.2, 1.3+/-0.2, re spectively). TAT levels (ng/mL) were different among the groups in a fashio n similar to that of APC (14.1+/-3.1 on admission vs. 3.3+/-0.4 at discharg e, 1.8+/-0.1 in the control subjects, respectively, p<0.01). PAI activity l evels (IU/mL) were higher on admission than at discharge and higher than th e control subjects (19.7+/-1.8 vs. 10.5+/-1.0, 5.4+/-0.7, respectively, p<0 .01). Thirty-two patients with AMI were classified into two groups accordin g to the results of thrombolysis: the success group (24 patients) and the f ailure group (eight patients). APC levels were higher in the failure group than in the success group (5.1+/-0.7 vs. 1.6+/-0.2, p<0.01). TAT levels wer e also higher in the failure group than in the success group (30.8+/-9.6 vs . 8.6+/-1.7, p<0.01). PAI activity levels (IU/mL) were lower in the failure group than in the success group (13.5+/-3.1 vs. 21.7+/-2.1,p<0.05). There were correlations between APC and TAT levels both on admission (r=0.75, p<0 .0001) and at discharge (r=0.71,p<0.0001). Elevated APC was thought to corr elate with increased thrombin generation in patients with AMI. This study d emonstrated that there was a significant relation between plasma APC level and the responsiveness to thrombolytic therapy of the infarct artery. This study may also indicate that increased thrombin generation is a cause of th e resistance to thrombolytic therapy. (C) 1999 Elsevier Science Ltd. All ri ghts reserved.