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CLINICAL STUDY

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

Nick R. Bijsterveld, MD^*,*, Arno H. Moons, MD^*, Joost C. M. Meijers, PhD, Marcel Levi, MD, Harry R. Büller, MD and Ron J. G. Peters, MD^*

^* Departments of Cardiology, Amsterdam, The Netherlands
Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Manuscript received December 16, 2002; revised manuscript received February 17, 2003, accepted April 24, 2003.

^* Reprint requests and correspondence: Dr. Nick R. Bijsterveld, Department of Cardiology, Room F3-241, Academic Medical Center, Meibergdreef 9, 1105 AZ, P.O. Box 22660, 1100 DD, Amsterdam, The Netherlands.
n.r.bijsterveld{at}amc.uva.nl

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.

Abbreviations and Acronyms   ACS   acute coronary syndrome   anti-Xa   anti-factor Xa   AUC   area under the curve   F1+2   prothrombin fragments 1+2   IV   intravenous   LMWH   low-molecular-weight heparin   SQ   subcutaneous   TFPI   tissue factor pathway inhibitor   TGT   thrombin generation time

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