Value and Implications of the Anti-Xa Activity Monitoring for Prophylactic Dosing Adjustment of LMWH in Pregnancy: A Retrospective Study

Introduction: Low molecular weight heparins (LMWH) have stable pharmacokinetics. However, physiologic changes during pregnancy can alter pharmacokinetics of LMWH and make the biodisponibility of the drug less predictable. When starting prophylactic treatment with LMWH in pregnant woman, most physicians calculate the initial LMWH dose based on the body weight and adapt the dose according to the weight gain. An alternative method is to monitor the anti-Xa activity and adjust the LMWH dose accordingly. LMWH are for the moment the only anticoagulant available for prophylaxis of venous thrombo-embolism in pregnant women and prevention of severe pregnancy complications. Therefore, we conducted a study addressing the rationality of performing an anti-Xa activity monitoring regularly during pregnancy.

Methods: We retrospectively analyzed data from pregnant women undergoing prophylaxis with LMWH followed at the Hemostasis and Thrombosis Unit of the Saint-Luc University Hospital Unit. All the patients that had anti-Xa activity done at least three times during pregnancy were included in the study. The measurements of anti-Xa were done regularly every 6 weeks and the dose of LMWH was increased in case of anti-Xa activity lower than 0.3 U/ml. Initial LMWH dose was calculated based on the patient body weight and the first measurement of anti-Xa done 10 days afterwards.

Results: Out of 173 women evaluated in the study, 79% needed LMWH dose adjustment. 97 patients (56%) had one dose adjustment, 35 patients (20%) two and 5 patients (3%) three. The first augmentation of LMWH dose was needed before the patient gained body weight in 36,5% of cases. The average increase of the LMWH dose was 49%, 100% and 116% for the one, two and three dose adjustments, respectively. Under-dosing of LMWH, defined as anti-Xa activity <0,2 U/mL, was present in 12% of patients on the first monitoring versus 3,5% on the last monitoring visit. No severe side effects occurred during the treatment. Five patients (3%) had unfavorable outcome of the pregnancy.

Conclusions: This study demonstrates that regular monitoring of anti-Xa activity can help in maintaining the prophylactic levels of LMWH throughout the pregnancy. We also showed that the reduction of the anti-Xa activity is not always directly correlated with the weight gain in pregnant women. Therefore we recommend that LMWH dose adjustment should not be made based solely on the weight gain of the patient during pregnancy.