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CLINICAL STUDY: INTERVENTIONAL CARDIOLOGY

The activated clotting time can be used to monitor the low molecular weight heparin dalteparin after intravenous administration

Jonathan D. Marmur, MD, FACC^*,*, Sunil X. Anand, BA, Ramanjit S. Bagga, MD, Jawed Fareed, PhD, Chi-Miau Pan, PhD, Samin K. Sharma, MD, FACC and Merwin F. Richard, MD

^* Department of Medicine, Division of Cardiology, SUNY Health Science Center at Brooklyn, Brooklyn, New York, USA
Zena and Michael A. Weiner Cardiovascular Institute, Mount Sinai School of Medicine, New York, New York, USA
Hemostasis and Thrombosis Research Laboratories, Loyola University Medical Center, Maywood, Illinois, USA
Research Division, International Technidyne Corporation, Edison, New Jersey, USA

Manuscript received April 3, 2002; revised manuscript received August 5, 2002, accepted August 19, 2002.

^* Reprint requests and correspondence: Dr. Jonathan D. Marmur, SUNY Health Science Center at Brooklyn, 450 Clarkson Avenue, Box 1257, Brooklyn, New York 11203, USA.
jonathan{at}marmur.com

OBJECTIVES: This study was designed to compare the dose response of dalteparin versus unfractionated heparin (UFH) on the activated clotting time (ACT), and to determine whether the ACT can be used to monitor intravenous (IV) dalteparin during percutaneous coronary intervention (PCI).

BACKGROUND: The use of low molecular weight heparin (LMWH) during PCI has been limited by the presumed inability to monitor its anticoagulant effect using bedside assays.

METHODS: This study was performed in three phases. In vitro, ACTs were measured on volunteer (n = 10) blood samples spiked with increasing concentrations of dalteparin or UFH. To extend these observations in vivo, ACTs were then measured in patients (n = 15) who were sequentially treated with IV dalteparin and then UFH. Finally, a larger monitoring study was undertaken involving patients (n = 110) who received dalteparin 60 or 80 international U (IU)/kg alone or followed by abciximab. We measured ACT (Hemochron), activated partial thromboplastin time (aPTT), plasma anti-Xa and anti-IIa levels, tissue factor pathway inhibitor (TFPI) concentration, and plasma dalteparin concentration.

RESULTS: Dalteparin induced a significant rise in the ACT with a smaller degree of variance as compared to UFH. Five min after administration of IV dalteparin 80 IU/kg the ACT increased from 125 s (122 s, 129 s) to 184 s (176 s, 191 s) (p < 0.001). The aPTT, anti-Xa and anti-IIa activities, and TFPI concentration also demonstrated significant increases following IV dalteparin.

CONCLUSIONS: The ACT and aPTT are sensitive to IV dalteparin at clinically relevant doses. These data suggest that the ACT may be useful in monitoring the anticoagulant effect of intravenously administered dalteparin during PCI.

Abbreviations and Acronyms   ACT   activated clotting time   aPTT   activated partial thromboplastin time   CVA   cerebrovascular accident   IU   international unit   IV   intravenous   LMWH   low molecular weight heparin   MI   myocardial infarction   PCI   percutaneous coronary intervention   TFPI   tissue factor pathway inhibitor   UFH   unfractionated heparin

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