PERSISTENT THROMBIN GENERATION DURING HEPARIN-THERAPY IN PATIENTS WITH ACUTE CORONARY SYNDROMES

Intravenous heparin, a fundamental therapy in the treatment of patient s with acute coronary syndromes, acts by inhibiting thrombin and activ ated factors X, IX, XI, and XII. It has also been demonstrated that he parin reduces plasma fibrinopeptide A, a marker of thrombin activity, but it is unknown whether it decreases prothrombin fragment 1+2, an in direct marker of thrombin generation. We measured the plasma levels of prothrombin fragment 1+2, fibrinopeptide A, and antithrombin III in 6 4 consecutive patients with unstable angina or myocardial infarction r eceiving intravenous heparin. Blood samples were obtained at baseline (before any treatment) and then at 90 minutes and 24 and 48 hours afte r the administration of an intravenous bolus of heparin (5000 IU) foll owed by a continuous infusion of 1000 IU per hour to maintain activate d partial thromboplastin time at more than double its baseline levels. In comparison with baseline, there was a significant decrease in fibr inopeptide A at 90 minutes and at 24 and 48 hours (baseline, 2.3 nmol/ L; 90 minutes, 1.15 nmol/L; 24 hours, 1.4 nmol/L; 48 hours, 1.2 nmol/L ; P<.0001) but no change in prothrombin fragment 1+2 levels (baseline, 1.27 nmol/L; 90 minutes, 1.3 nmol/L; 24 hours, 1.33 nmol/L; 48 hours, 1.29 nmol/L; P=NS). Antithrombin III activity decreased at 24 and 48 hours (baseline, 108%; 24 hours, 97%; 48 hours, 95%; P<.0001). Hence, in patients with acute coronary syndromes, intravenous heparin at a do se reaching an activated partial thromboplastin time that adequately s uppresses thrombin activity does not suppress increased thrombin gener ation.