Monitoring of low-molecular-weight heparins in pregnant women with inherited thrombophilic disorders]

Women with thrombophilic disorders have higher risk for venous thromboembolism during pregnancy, as well as risk for vascular damages and complications, including preeclampsia and fetal loss. It is supposed that thrombosis prevention with low-molecular-weight heparins (LMWH) directed against recurrent fetal loss carries antiinflamatory and immunomodulation effects besides its well-known anticoagulation action. This study presents results from a retrospective analysis of 120 pregnant women on antithrombotic therapy with prophylactic doses of LMWH, during the period from 2010 to 2013. Women were recruited on the basis of genotyping done in advance in National Genetic Laboratory, Sofia and Laboratory "Genica". Allele frequencies of 12% of the mutation R506Q Factor V Leiden, 7% of G20210A in Prothrombin gene, 53% of 4G/4G in PAI and 28% of the mutation T677 in MTHFR were found (39% single defects, 50% double and 11% combained mutations). Majority of women studied (60%) had embryo loss (< 13th g.w.), 38 out of them were with one episode, 28 with two, and 4--with three pregnancy losses. Level of anti-Xa and monitoring of LMWH was done by chromogenic assay (Berichrom Heparin, Siemens) using coagulometer C 2000i. Anti-Xa inhibition was 0.35 +/- 0.11 IU anti-Xa/ml (0.18-0.60; n = 50) in response to Fraxiparine in dose of 0.3 ml/d, 0.45 +/- 0.09 IU anti-Xa/ml (0.26-0.60; n = 33) with 0.4 ml/d Fraxiparine, and 0.49 +/- 0.13 IU anti-Xa/ml (0.3-0.72; n = 37) with Clexane 40 mg/d. Five out of 120 women (4%) had values below 0.2 IU anti-Xa/ml and required increased doses of LMWH during the third trimester. Slight decrease of anti-Xa (14-20%) was observed during the third trimester. Five women suffered oedema, redness and pain oversensitivity at LMWH application, one woman demonstrated increased eosinophil count, and three other women had mild bleeding during the first weeks of anticoagulation therapy with higher levels of anti-Xa inhibition. Monitoring of LMWH is of help in the rare cases of bleeding during the first trimester of pregnancy, as well as in high risk pregnancies with insufficient anticoagulation response.