Optimal dosing of subcutaneous unfractionated heparin for the treatment ofdeep vein thrombosis

Twice-daily, inpatient, subcutaneous unfractionated heparin is at least as effective and safe as continuous intravenous unfractionated heparin for the treatment of acute deep vein thrombosis. Subcutaneous unfractionated hepar in therefore may be suitable for outpatient treatment of deep vein thrombos is. The purpose of this study was to develop a dosing nomogram for a dose e ach 12 hours (2 doses per day) 12-hourly subcutaneous unfractionated hepari n that is suitable for outpatient treatment of acute deep vein thrombosis. A cohort study was performed in patients with acute deep vein thrombosis in two phases. In both phases, the first subcutaneous loading dose of unfract ionated heparin was 317 U/kg, and the second dose was 231 U/kg. The activat ed partial thromboplastin time was measured daily, 6 hours after the mornin g injection, and subsequent doses of unfractionated heparin were adjusted a ccording to a nomogram, which was modified for phase II. Warfarin was start ed with unfractionated heparin. In phase I (14 outpatients), activated part ial thromboplastin time results were frequently subtherapeutic (9:14) the d ay after starting unfractionated heparin (day 1), and were frequently supra therapeutic (27:40) after the first 2 days of unfractionated heparin therap y. In phase II (21 patients), to explain the frequently subtherapeutic acti vated partial thromboplastin time results that were obtained on day 1, the activated partial thromboplastin time results were measured after the initi al loading dose. Mean activated partial thromboplastin time results of 86 a nd 61 seconds were obtained 6 and 12 hours after this dose, suggesting that 317 U/kg is a suitable subcutaneous loading dose. In contrast to phase I, in phase II, unfractionated heparin dose was not increased on day 1 in resp onse to a low activated partial thromboplastin time result. This reduced th e frequency of supratherapeutic activated partial thromboplastin time resul ts during the early days of therapy without increasing the frequency of sub therapeutic results. Warfarin therapy had a substantal effect on the activa ted partial thromboplastin time that appeared to account for a high frequen cy of supratherapeutic results during the later days of unfractionated hepa rin therapy; the activated partial thromboplastin time increased by 20 seco nds (95% CI, 14-27 seconds) with each increase in the International Normali zed Ratio of 1.0. We had limited success at developing a dosing nomogram fo r subcutaneous unfractionated heparin that reliably achieved activated part ial thromboplastin time results within the therapeutic range. However, as o ral anticoagulants directly increased activated partial thromboplastin time results, we suggest that adjusting unfractionated heparin dose to achieve prespecified activated partial thromboplastin time results may not be appro priate in patients who are receiving concomitant warfarin therapy. (C) 2000 Elsevier Science Ltd. All rights reserved.