Weight-adjusted dosing of tinzaparin in pregnancy

Low molecular weight heparin (LMWH) is the preferred anticoagulant for the prevention and treatment of VTE in pregnancy. While dosing of LMWH based on weight alone is standard for most non-pregnant patients, there is no data on the utility of this approach in pregnancy.

To determine whether dosing of tinzaparin by current maternal weight, with adjustment for increasing weight, will achieve adequate levels of anticoagulation throughout pregnancy (target peak anti-Factor-Xa activity levels between 0.5-1.2IU/ml).

Consecutive pregnant women with acute VTE or requiring high-risk thromboprophylaxis (recurrent VTE, on long-term anticoagulation) at a single centre were approached for enrollment. Subjects were weighed and prescribed tinzaparin 175IU/kg SC once daily and a peak anti-Factor-Xa level was determined. Re-dosing and monitoring was repeated monthly, and subjects were withdrawn from weight-based dosing if consecutive anti-Factor-Xa levels were outside the target range. Subsequent dosing of tinzaparin was titrated to achieve a level in the target range in these women.

Thirteen subjects were recruited between January 2008 and May 2010, with one drop out lost to follow-up. Weight-based dosing failed to maintain therapeutic anticoagulation in 11 (92%) of women (95% CI 0.2% to 38.5%). The estimated dose requirement of tinzaparin per trimester increased from 14255IU in the first trimester to 16533IU in the second trimester to 17828IU in the third trimester (p<0.001). The estimated dose/kg required to maintain therapeutic anticoagulation increased across trimesters: 188.0IU/kg in the first trimester, 201.3IU/kg in the second trimester, and 208.6IU/kg in the third trimester (p=0.004). Treatment was well tolerated and no serious bleeding or recurrent thrombotic events occurred.

Weight-based dosing of tinzaparin failed to achieve therapeutic anticoagulation in the vast majority of women, although clinical outcomes were good. Doses of tinzaparin in excess of the manufacturer's recommended weight-based dose were required to maintain therapeutic levels of anticoagulation.