The clinical net benefit of venous thromboembolism prophylaxis in mild-risk thrombophilia and pregnancy: a systematic review and meta-analysis.

OBJECTIVE

As compared with pregnant patients with high-risk thrombophilias, less is known regarding the benefits of thromboprophylaxis in pregnant patients with mild-risk thrombophilias. The aim of this study is to assess the association of thromboprophylaxis in prevention of pregnancy-related venous thromboembolism (VTE) in women with known mild-risk inherited thrombophilia: heterozygous factor V Leiden (FVL) or prothrombin gene variant (PGV), Protein C and S deficiencies.

DATA SOURCES: For this study, the Medline, Embase, Lilacs, and the Cochrane Central Register of Controlled Trials (Central) were searched from inception to April 6, 2025.

STUDY ELIGIBILITY CRITERIA: Clinical trials and cohort studies were included. The study population included pregnant patients (antenatal) up until 6 weeks postpartum (puerperium) or pregnancy loss, and known mild risk of inherited thrombophilia: heterozygous FVL or PGV, Protein C or S deficiency. Included population received either pharmacologic thromboprophylaxis or not in the antenatal and puerperium period, or both. Types of thromboprophylaxis included were low molecular weight heparin, unfractionated heparin, low-dose aspirin, or combinations of these.

STUDY APPRAISAL AND SYNTHESIS

METHODS

Two trained reviewers independently extracted the information from each article. Statistical analysis was performed in OpenMeta[Analyst]. For categorical outcomes, information was reported in odds ratio (OR) with 95% confidence intervals. Information was pooled with a binary fixed-effect meta-analysis according to the expected heterogeneity. Heterogeneity was assessed using the I2 test.

RESULTS

Five studies, with a population of 1320 women, were amenable for meta-analysis of VTE and adverse events. Results showed an association with thromboprophylaxis and decreased risk of VTE (0.8% in the thromboprophylaxis group vs 4.4% in the no thromboprophylaxis group, OR 0.20, 95% CI 0.08-0.50, I2=0%). Meta-analysis for secondary outcomes, including major bleeding, all-cause and VTE-related mortality were unable to be performed due to low incidence in the included studies.

CONCLUSION

Overall, results show an association between thromboprophylaxis and decreased risk of VTE events when compared to no thromboprophylaxis in pregnant women with mild thrombophilia. VIDEO ABSTRACT.