Dalteparin dose-dependently increases ROTEM® thrombelastography parameters only at supratherapeutic anti-factor Xa levels: An in vitro study

Abstract

1. The low molecular weight heparin (LMWH) dalteparin is used, for example, to prevent primary venous thromboembolism in patients undergoing surgery or in medically ill patients. The anticoagulant activity of dalteparin can be monitored by measuring anti-factor Xa levels and activated partial thromboplastin time (aPTT); however, aPTT is an unreliable parameter in this case. The aim of the present in vitro study was to evaluate the thrombelastograph ROTEM(®) (Tem International, Munich, Germany) with respect to determining the anticoagulant activity of dalteparin at therapeutic and supratherapeutic plasma concentrations. 2. The ROTEM(®) parameters, namely coagulation time (CT), clot formation time (CFT) and maximum clot firmness (MCF), were measured using the reagents EXTEM and INTEM (Pentapharm, Munich, Germany) at increasing concentrations of dalteparin (0.01-10 μg/mL, which corresponded to anti-factor Xa levels of 1-1000 U/mL, respectively). 3. The mean CT measured using EXTEM was found to increase from 65.4 ± 27.9 s at baseline to 173.3 ± 112.2 s and 332.2 ± 200.7 s at drug concentrations of 1 and 10 μg/mL, respectively (P < 0.0001 for both). Moreover, the mean CFT value (EXTEM) increased from 97.7 ± 21.5 s at baseline to 187.6 ± 115.2 s (P = 0.0001) at a drug concentration of 10 μg/mL, which is greater than the therapeutic anti-factor Xa concentrations for LMWH. The results obtained when INTEM was used as the reagent were similar to those obtained using EXTEM. 4. In conclusion, the results indicate that the thrombelastograph ROTEM(®) can detect the anticoagulant effects of dalteparin only at supratherapeutic levels of anti-factor Xa.