Are activated clotting times helpful in the management of anticoagulation with subcutaneous low-molecular-weight heparin?

Background Enoxaparin has recently been shown to be superior to unfractiona ted heparin in patients with unstable angina/non-ST-elevation myocardial in farction. Theoretical advantages of low-molecular-weight heparin versus unf ractionated heparin include a higher ratio of anti-Xa to anti-IIa activity (3:1 for enoxaparin), a more predictable dose response that precludes the n eed for frequent monitoring, and the convenience of subcutaneous administra tion. Both activated partial thromboplastin time and activated clotting tim e (ACT) are used to monitor anticoagulation with heparin, and ACTs are now standard during percutaneous coronary intervention (PCI) with heparin. At d oses of up to 90 mg, subcutaneous enoxaparin leads to a modest dose-related increase in activated partial thromboplastin time, but the effect on ACT i s unknown. Methods Thrombolysis In Myocardial Infarction (TIMI) 11A was a multicenter, dose-ranging trial to evaluate the safety and tolerability of subcutaneous enoxaparin in patients with unstable angina/non-ST-elevation myocardial in farction. We obtained peak (mean 4.3 hours after enoxaparin) and trough (me an 11.5 hours after enoxaparin) anti-Xa levels and ACTs for 26 patients in the TIMI 11A trial. Results Despite doses of enoxaparin in the range of 89 +/- 19 mg every 12 h ours and significant increases in anti-Xa levels even at trough, there was no change in the ACT measured by HemoTec and only a small increase with Hem achron. The correlation of peak Hemachron ACT with peak anti-Xa levels was poor (R = 0.5, P = .08). Conclusions In contrast to heparin, ACTs are not useful for assessment of a nticoagulation with subcutaneous enoxaparin and should not be relied on in patients receiving enoxaparin who require acute PCI. Studies to determine t he optimal dose, safety, and efficacy of enoxaparin in patients undergoing PCI are underway.