doiSerbia

Efficacy and safety of nadroparin and unfractionated heparin for the treatment of venous thromboembolism during pregnancy and puerperium

Mitić Gorana (Clinical Centre of Vojvodina, Novi Sad)
Kovač Mirjana (Blood Transfusion Institute of Serbia, Belgrade)
Považan Ljubica (Clinical Centre of Vojvodina, Novi Sad)
Đorđević Valentina (Institute of Molecular Genetics and Genetic Engineering, Belgrade)
Ilić Vesna (Military Medical Academy, Belgrade)
Salatić Iva (Clinical Centre of Vojvodina, Novi Sad)
Lazić Radmila (Clinical Centre of Vojvodina, Novi Sad)
Antonijević Nebojša (Clinical Centre of Serbia, Institute of Cardiovascular Diseases, Belgrade)
Novakov-Mikić Aleksandra (Clinical Centre of Vojvodina, Novi Sad)

Introduction. The optimal treatment of pregnancy associated VTE (venous thromboembolism) has not been established yet. Objective. The assessment of the efficacy and safety of low molecular weight heparin (LMWH) nadroparin and unfractionated heparin (UFH) used for the treatment of pregnancy and puerperium related VTE. Primary study goals were to analyze the incidence of recurrent VTE (proximal extension or pulmonary thromboembolism), thrombocytopenia, major and minor hemorrhages and skin allergic reactions. The study also included the incidence of miscarriages, stillbirth and neonatal abnormalities. We also studied the relationship between the presence of thrombophilia and the occurrence of complications during VTE treatment. Methods. Seventy-two women with antepartal VTE treated with s.c. LMWH during entire pregnancy and 88 women with postpartal VTE initially treated with either s.c. LMWH or i.v.UFH were under follow-up during the entire treatment. Thrombophilia testing included antithrombin, protein C and protein S activity levels, Activated protein C (APC) resistance, LA, ACL, FV Leiden, FII G20210A and MTHFR C677T mutations. Results. Twice a day weight based therapeutic regimen was applied for LMWH and activated partial thromboplastin time (aPTT) adjusted UFH dosages. After 2-6 weeks of antepartal deep vein thrombosis (DVT) treatment the dose of nadroparin was reduced to intermediate level. The duration of LMWH therapy during pregnancy was 1-35 weeks, on average 16 weeks. One case (0.62%) of DVT propagation into the vena cava occurred in a woman with antithrombin deficiency treated with LMWH. Two women (1.25%) had minor bleeding and 5 (3.125%) had minimal bleeding, while 3 (1.9%) had skin allergic reactions. The rate of successful pregnancy outcome was 97.2%. There were no cases of stillbirth or neonatal congenital abnormalities. Thrombophilia was found in 86 women (53.7%). No statistically significant correlation between the presence of thrombophilia and treatment complications were found. Conclusion. Nadroparin is both safe and effective for the treatment of DVT during pregnancy and puerperium.

Keywords: pregnancy, venous thromboembolism, low molecular weight heparin, nadroparin