Inherited thrombophilia and thromboprophylaxis: a retrospective analysis of pregnancy outcomes in 106 patients

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 < 0.05). Frequencies of all five mutations were significantly higher in test patients (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.

The Role of Plasminogen Activator Inhibitor Type 1 (PAI-1) in Placenta-Mediated Pregnancy Complications: A Systematic Review

“…25,32,85 Sixty-eight (96%) studies were case-control studies, [22][23][24][25][26][27][28][29][30][31][33][34][35][36][37][38][87][88][89][90][91][92] while three were cohort studies. 32,39,86 In 26 studies (37%) the…”

“…Table 2 shows extracted data from the 11 studies investigating the association between PAI-1 levels in pregnant women and placenta-mediated pregnancy complications. Of the 71 included studies, 15 were rated good, 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 39 were rated fair, 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 and 17 were rated poor. 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92…”

“…Twenty-one studies investigated cases with preeclampsia, 22 24 34 35 36 45 47 49 54 61 67 69 70 71 72 73 74 75 86 87 92 45 studies investigated cases with pregnancy loss described as pregnancy loss, 27 29 31 39 50 51 52 59 60 64 66 68 81 90 91 miscarriage, 23 28 30 38 40 41 42 44 53 55 56 57 58 62 65 76 78 79 88 abortion, 37 43 48 63 77 83 89 fetal loss, 46 80 82 or intrauterine fetal death. 84 One study investigated cases delivering still birth, 33 one study investigated cases delivering newborns meeting the criteria for intrauterine growth restrictions, 26 and three studies investigated cases with various adverse pregnancy outcomes.…”

“…25 32 85 Sixty-eight (96%) studies were case–control studies, 22 23 24 25 26 27 28 29 30 31 33 34 35 36 37 38 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 87 88 89 90 91 92 while three were cohort studies. 32 39 86 In 26 studies (37%) the controls were matched to the cases. 22 23 25 28 …”

“…The association between PAI-1 genotype and pregnancy loss was investigated in 45 studies. 23 27 28 29 30 31 37 38 39 40 41 42 43 44 46 48 50 51 52 53 55 56 57 58 59 60 62 63 64 65 66 68 76 77 78 79 80 81 82 83 84 88 89 90 91 Pregnancy loss was described as miscarriage, abortion, fetal loss, or intrauterine fetal death. The definition differed across studies according to gestational week and number of pregnancy losses.…”