Benefits of Enoxaparin Prophylaxis in Pregnancy and Postpartum

Introduction

During pregnancy, changes in the coagulation and fibrinolytic systems increase the risk of thromboembolic disease. The presence of hereditary thrombophilia (most commonly Factor V Leiden mutation and prothrombin mutation) or acquired thrombophilia (antiphospholipid syndrome) in the medical history represents a higher risk, leading to further disruption of the balance between coagulative and anticoagulative mechanisms. 

Methodology and Study Progress

A total of 180 women participated in the multicenter prospective randomized LIVE-ENOX study at 12 centers in Israel. Inclusion criteria were thrombophilia, age ≥ 18 years, 5-10 weeks of pregnancy, and a history of spontaneous miscarriage (≥ 3 spontaneous miscarriages before the end of the first trimester, ≥ 2 losses in the second trimester, or fetal death in the third trimester). Women who had a spontaneous miscarriage within the last three months before inclusion in the study, women with a history of thromboembolic disease, epilepsy, thrombocytopenia, renal or hepatic insufficiency, or contraindications to low molecular weight heparins (LMWH) were excluded. 

Patients were randomized in a 1:1 ratio into two groups: the first group received 40 mg of enoxaparin once daily, and the second group received 80 mg of enoxaparin daily (2 x 40 mg). Instructed patients self-administered enoxaparin via subcutaneous injection using pre-filled syringes from the time of inclusion in the study throughout the pregnancy until postpartum. The primary endpoint of treatment efficacy was the birth of a live healthy baby. Additional indicators focused on safety included the presence of thrombocytopenia in the mother and adverse drug-related effects during the study. 

Results

More than 90% of the women (n = 166) completed the study. There was no significant difference in pregnancy outcomes between the dosage groups. 135 pregnancies resulted in the successful birth of a live healthy baby: 84.3% (n = 70) in the lower dosing group and 78.3% (n = 65) in the higher dosing group. No statistically significant differences were observed between types of thrombophilia. 

The main concerns associated with anticoagulant treatment are usually bleeding and heparin-induced thrombocytopenia (HIT). LMWHs are associated with a low risk of bleeding and a lower incidence of HIT, which was confirmed by the LIVE-ENOX study results. No cases of thrombosis, episodes of bleeding, or HIT were reported during enoxaparin administration in this study. Local allergic skin reactions at the injection site were observed in only a small number of women: 2.2% (n = 2) in the 40 mg cohort and 3.3% (n = 3) in the 80 mg cohort. 

Conclusion

The obtained data suggest that enoxaparin prophylaxis in pregnant women at risk, whether at a daily dose of 40 or 80 mg, is safe and leads to a favorable outcome, i.e., carrying to term a live and healthy baby. The study results, along with previous works by the authors, indicate that a lower dose of enoxaparin (40 mg/day) may be sufficient prophylaxis for thrombophilic women with standard risk, while a higher dose (80 mg/day) can be a safe option and provide benefits for women with particularly high thrombotic risk. Enoxaparin treatment was very well tolerated in both doses, with no clinically significant bleeding complications, thrombosis, or HIT. 

(lexi) 

Sources: 
1. Brenner B., Hoffman R., Carp H. et al. Efficacy and safety of two doses of enoxaparin in women with thrombophilia and recurrent pregnancy loss: the LIVE/ENOX study. J Thromb Haemost 2005; 3: 227–229, doi: 10.1111/j.1538-7836.2004.01090.x. 
2. Brenner B., Hoffman R., Blumenfeld Z. et al. Gestational outcome in thrombophilic women with recurrent pregnancy loss treated by enoxaparin. Thromb Haemost 2000; 83: 693–697, 10.1055/s-0037-1613894.