Norris LA, Bonnar J, Smith MP, Steer PJ, Savidge G
Low molecular weight heparin (LMWH) is used increasingly for prophylaxis and treatment of venous thromboembolism during pregnancy. However, the prophylactic dose for patients at moderate risk varies between centers, and the recommended LMWH dose for the non pregnant patient is frequently used in pregnant women. The aim of this study was to investigate the effects of pregnancy on the pharmacokinetics of anti-Xa levels during moderate risk thromboprophylaxis with the LMWH, tinzaparin. In 24 pregnant women, one of three doses of tinzaparin (50, 75 or 100 IU/kg) were given according to the treating physician's assessment of their risk profile. Four-hour peak anti-Xa levels were measured throughout pregnancy and 24-hour profiles were measured at 28 and 36 weeks gestation. Doses were adjusted when peak anti-Xa levels fell below 0.1 IU/ml and, in some cases, when levels at 10 and 18 hours post injection were undetectable (<0.05 IU/ml). Our results showed that women receiving tinzaparin (50 IU/kg) frequently had peak (4 hour) anti-Xa levels below 0.1IU/ml and that 46% of these patients required dose adjustment. Similarly anti-Xa levels were also found to be low over the 24-hour period. A starting dose of 75 IU/kg, once daily, gave greater anti-Xa cover over the 24-hour period and may avoid the need for dose adjustment. The results suggest that the pharmacokinetics of tinzaparin are affected by pregnancy. Larger studies are required to determine whether an increased tinzaparin dose (75 IU/kg) would be more effective in the prevention of thrombosis during pregnancy than 50 IU/kg.
Coagulation Research Laboratory, Department of Obstetrics and Gynaecology, Trinity Centre for Health Sciences, St. James's Hospital, Dublin 8, Ireland. Inorris@tcd.ie