Abstract

Objective: Low-molecular-weight heparin (LMWH) and low-dose aspirin (LDA) given in combination were evaluated in females with five commonly inherited thrombophilia polymorphisms to address unexplained recurrent pregnancy loss (RPL). Materials and Methods: After excluding other causes of RPL, 106 of 183 females suffering RPL and diagnosed with inherited thrombophilia were studied along with 62 healthy, age-matched control subjects carrying one or more pregnancies successfully (no gestational complications or abortion). Test patients were given a combination of LMWH and LDA. All participants were screened for five thrombophilic mutations: factor V Leiden G1691A, prothrombin (FII) A20210G, PAI-1 4G/5G insertion/deletion, and two methylenetetrahydrofolate reductase (MTHFR) polymorphisms (C677T and A1298C). Results: With thromboprophylaxis, 73 of 84 (86.9%) pregnancies succeeded, representing a significant increase in the rate of live births (vs. 232 prior losses). Of the five test panel mutations, three or more (homozygous and/or heterozygous) were observed in 48 test patients (45.3%), whereas only three control subjects (4.8%) were similarly affected (p vs. controls), with PAI-1 4G/5G and MTHFR (C677T and A1298C) identified via binary logistic regression as independent correlates of habitual abortion. Conclusion: The risk of RPL increases with three or more homozygous or heterozygous genotypes in inherited thrombophilia, especially with PAI-1 4G/5G and MTHFR (C677T and A1298C). As in acquired thrombophilia, LMWH/LDA combination treatment may increase live birth rates in patients with inherited thrombophilia.

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