The impact on coagulation of an intravenous loading dose in addition to a subcutaneousregimen of low-molecular-weight heparinin the initial treatment of acute coronary syndromes

Objectives We sought to quantify the impact of adding an intravenous loading dose to a subcutaneous regimen of enoxaparin in patients with an acute coronary syndrome (ACS). Background It is unclear whether an intravenous (IV) loading dose of enoxaparin should be added to a subcutaneous (SQ) regimen in patients with ACS. Methods Patients admitted with ACS were randomized to IV+SQ (n = 14) or SQ alone (n = 11) enoxaparin treatment. Coagulation markers were measured at nine time points during the first 24 h of treatment. Results The IV+SQ therapy immediately resulted in therapeutic anti-Xa levels, which remained significantly higher for 6 h compared with SQ alone, without reaching excessively high levels. A rapid decrease of plasma prothrombin fragments 1+2 (F1+2) levels was observed as soon as 5 min after the IV injection (33% lower; P = 0.007), and these levels remained lower up to 2 h after the start of treatment compared with SQ alone. The ex vivo thrombin generation time was maximally prolonged at 5 min post-injection in the IV+SQ group and remained significantly prolonged up to 6 h post-injection compared with SQ alone. The tissue factor pathway inhibitor plasma activity was immediately increased by 194% with IV+SQ, whereas the maximum increase with SQ alone was 47% at 3 h. Conclusions Therapeutic plasma levels of enoxaparin are achieved significantly earlier by an IV+SQ regimen compared with SQ alone, without leading to unacceptably high levels. As the risk of thrombotic complications is greatest early after admission, the observed differences in antithrombotic effects may translate into a clinical benefit. However, this remains to be established.