Regular Article Markers of hemostatic system activation during treatment of deep vein thrombosis with subcutaneous unfractionated or low-molecular weight heparin Polona Peternel*, Martina Terbiz ˇan, Gregor Tratar, Mojca Boz ˇic ˇ, Dunja Horvat, Barbara Salobir, Mojca Stegnar Department of Angiology, University Medical Centre, Riharjeva 24, SI-1000 Ljubljana, Slovenia Received 20 July 2001; received in revised form 1 December 2001; accepted 14 January 2002 Accepting Editor: L. Muszbek Abstract Prothrombin fragments (F1 + 2), thrombin–antithrombin complexes (TAT) and D-dimers, markers of hemostatic system activation, were measured in 59 consecutive patients with deep vein thrombosis (DVT). Patients were randomly treated either with subcutaneous unfractionated heparin (UH) administered in two to three subcutaneous doses adjusted to activated partial thromboplastin time (APTT) or with low-molecular weight heparin (LMWH) (dalteparin) administered in a fixed dose of 200IU/kg body weight in one subcutaneous injection daily. Before treatment, F1 + 2, TAT and D-dimer were above the cut-off level in 27/59 (46%), 34/59 (58%) and all (100%) patients, respectively. Significant associations were observed between F1+2 and TAT (r = .66, P <.001), TAT and D-dimer (r = .36, P < .005) and F1 + 2 and D-dimer (r = .30, P < .050). On the third day of treatment, F1 + 2 and TAT significantly decreased to reference values in almost all patients (in 64/66 determinations of both F1 + 2 and TAT) and remained low on the seventh day of treatment. Compared to pretreatment values, a nonsignificant decrease of D-dimer was noted in both groups, but all values remained above the cut-off value. When markers of hemostatic system activation in the UH and LMWH groups were compared, no significant differences were observed. It was concluded that subcutaneous UH in an APTT-adjusted dose and subcutaneous LMWH in a once-daily weight-adjusted dose controlled these markers of hemostatic system activation in a similar manner. D 2002 Elsevier Science Ltd. All rights reserved. Keywords: Deep vein thrombosis; Activation markers; Unfractionated heparin; Low-molecular weight heparin 1. Introduction Unfractionated heparin (UH) administered either intra- venously or subcutaneously followed by warfarin has been the classical anticoagulant treatment of acute deep venous thrombosis (DVT) for the past 30 years [1]. In recent years, low-molecular weight heparin (LMWH) has become available for treatment of DVT. Several studies and meta- analysis have shown LMWH to be at least as effective and safe as UH [2–4]. Moreover, a once-daily regimen of subcutaneous LMWH (nadroparin) has been reported to be equally effective as a twice-daily regimen [5]. The anticoagulant response to UH varies widely intra- and inter-individually. Therefore, optimal anticoagulation with UH requires heparin monitoring either with activated partial thromboplastin time (APTT) or with antifactor Xa activity assay [6]. In contrast, no monitoring is advised in the majority of DVT patients treated with LMWH [7]. The effect of anticoagulant treatment on the activity of thrombotic process can also be followed by levels of markers of hemostatic system activation, namely prothrombin frag- ments 1 + 2 (F1 + 2), thrombin–antithrombin complexes (TAT) and D-dimer [8]. In the process of conversion of prothrombin to thrombin, F1 + 2 is released and therefore 0049-3848/02/$ – see front matter D 2002 Elsevier Science Ltd. All rights reserved. PII:S0049-3848(02)00023-3 Abbreviations: APTT, activated partial thromboplastin time; DVT, deep vein thrombosis; F1+2, prothrombin fragments 1+2; TAT, thrombin– antithrombin complex; LMWH, low-molecular weight heparin; UH, unfractionated heparin * Corresponding author. Tel.: +386-1-280-80-80; fax: +386-1-28-33- 155. E-mail address: polona.peternel@trnovo.kclj.si (P. Peternel). Thrombosis Research 105 (2002) 241 – 246