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Objectives: The aim of this study was to investigate the effect of low molecular weight heparin (LMWH) on incidence of adverse outcome in women with thrombophilias and previous severe pregnancy complications., Materials and Methods: The study included 116 women with history of severe preeclampsia, fetal growth restriction (FGR)  ≤5th percentile, severe placental abruption and stillbirth  >20 weeks carrying factor V Leiden or prothrombin mutations, or protein S or C deficiency. Eighty-seven women referred to us for follow-up were treated with LMWH starting from weeks 5-15 (study group, A). Twenty-nine non-treated women referred only for delivery in our institution constituted the control group (B)., Results: The incidence of severe pregnancy complications in previous pregnancies was similar in both groups. Following treatment with LMWH, the incidence of severe preeclampsia was 4.6% in group A compared to 21% in group B, p = 0.007. The incidence of FGR was 2.3% in group A compared to 21% in group B, p = 0.03. The incidence of stillbirth or placental abruption was 0% in group A compared to 7% in group B, p = 0.06. The total incidence of adverse outcome was 7% in group A compared to 55% in group B, p = 0.0001., Conclusion: LMWH treatment of women with previous severe pregnancy complications and thrombophilias significantly reduces the rate of recurrence.

Preeclampsia, intrauterine growth restriction and placental abruption greatly contribute to maternal and fetal morbidity and mortality. Thrombophilia is an inherited or acquired condition that predisposes individuals to venous and/or arterial thrombosis. Recently, three important inherited thrombophilias have been discovered. An inherited mutation in the gene coding for coagulation factor V (factor V Leiden), and a mutation in prothrombin that is associated with higher plasma levels of prothrombin. Both mutations result in an increased susceptibility to develop venous thrombosis. Hyperhomocysteinemia, which is associated with mutations in the gene for methylenetetrahydrofolate reductase, is a risk factor for venous and arterial thrombosis. The presence of antiphospholipid antibodies, an acquired thrombophilic condition, is associated with venous and arterial thrombosis. The term placental vasculopathy, is used to describe pathological placental changes that have been associated with preeclampsia, intrauterine growth restriction, placental abruption and fetal loss. The known thrombotic nature of the placental vasculopathy and the increased thrombotic risk with the presence of thrombophilias suggest, a cause-and-effect relationship between inherited and acquired thrombophilias and a number of severe obstetric complications. Testing patients with these complications for thrombophilias may have therapeutic implications for future pregnancies.

Hypercoagulability leading to placental thrombosis has been implicated in severe pregnancy complications. We compared the perinatal outcome in women with severe preeclampsia, intrauterine growth retardation (IUGR) and severe abruptio placentae and multiple acquired and inherited thrombophilias (study group, n=22) to matched women with similar complications and single thrombophilia (control group, n=22). Gestational age at delivery and birth weight were significantly lower in the study group compared to the control group (p<0.01) and among the study women with severe preeclampsia and IUGR. Severe pregnancy complications may occur earlier during pregnancy and more seriously affect perinatal outcome in women with multiple thrombophilias.

Pregnancy is hypercoagulable state. The field of thrombophilia; the tendency to thrombosis, has been developed rapidly and has been linked to many aspects of pregnancy. It is recently that severe pregnancy complications such as severe preeclampsia intrauterine growth retardation abruptio placentae and stillbirth has been shown to be associated with thrombophilia. Recurrent miscarriage and has also been associated with thrombophilia. Finally, thromboembolism in pregnancy as in the non-pregnant state is linked to thrombophilia. In this review all aspects of thrombophilia in pregnancy are discussed, and also all prophylactic and therapeutic implications.

Gestational vascular complications are a major cause of maternal and fetal morbidity.A growing body of evidence suggests a significant role for inherited thrombophilia in the development of gestational vascular complications. While the majority of women with thrombophilia will have an uneventful gestation, case-control studies demonstrated that thrombophilia is more prevalent in cohorts of women with pregnancy loss and early-onset pre-eclampsia. Placental abruption and severe intrauterine growth restriction (IUGR) may also be associated with thrombophilia. Placental pathological findings in women with thrombophilia are hallmarked by thrombosis and fibrin deposition potentially to a greater degree than in normal pregnancy. Preliminary non-randomized studies suggest a benefit for prophylaxis with unfractionated and low-molecular-weight heparin (LMWH), and prospective randomized trials are in progress to define whether LMWH is effective in preventing pregnancy loss and other gestational vascular complications in women with thrombophilia and previous fetal wastage.

Objective: To investigate the association between severe mid-trimester IUGR, whose causes are unknown in most cases, and maternal thrombophilias., Design: Case-control study., Setting: Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, The Sackler Faculty of Medicine, Tel Aviv University., Population: Twenty-six women with severe mid-trimester (22-26 weeks of gestation) IUGR (birthweight <3rd centile) and 52 matched multiparous women with normal pregnancies (controls)., Methods: After excluding pregnancies with vascular maternal disease, chromosomal and structural aberrations and cytomegalovirus infection, 26 women out of 35 with severe mid-trimester IUGR remained and composed the study group. Each was matched for age, ethnicity and smoking status with two healthy women who had normal pregnancies. All the women were tested for genetic and acquired thrombophilias at least eight weeks after delivery., Main Outcome Measures: Prevalence of maternal thrombophilias., Results: The frequency of thrombophilias was 69% in the study group compared with 14% in the control group [odds ratio (OR) 4.5; 95% confidence interval (CI) 2.3-9, P < 0.001]. The frequencies of factor V Leiden mutation, prothrombin gene mutation and protein S deficiency were significantly increased in the study group compared with the control group. The frequency of multiple thrombophilias was 33% in the study group versus none among the controls. Of the 26 pregnancies with severe mid-trimester IUGR, 13 ended in intrauterine fetal death before 25 weeks of gestation: 10 of these women had thrombophilia., Conclusion: Women with mid-trimester severe IUGR have an increased prevalence of inherited and acquired thrombophilias.

Objective: To compare placental pathology between women with and without thrombophilia who had severe preeclampsia, intrauterine growth retardation, severe abruptio placentae, or stillbirth., Methods: After delivery, 68 women with singleton pregnancies with one of the above complications were evaluated for an inherited thrombophilia: factor V Leiden, methylenetetrahydrofolate reductase and prothrombin gene mutation, and deficiencies of protein S, protein C, and antithrombin III. Thirty-two women were thrombophilic (group A), and 36 women were not (group B). There was no difference in maternal age, parity, and type of pregnancy complication. A single pathologist examined each placenta., Results: The gestational age at delivery, birth weight, and placental weight were significantly lower in group A. Three parameters showed significant differences between the groups: thrombophilic women had a higher number of villous infarcts (P <.01), more multiple infarcts (P <.05), and a higher incidence of placentas with fibrinoid necrosis of decidual vessels (P <.05)., Conclusion: Placentas of women with severe complications and thrombophilia have an increased rate of vascular lesions.

Obstetric complications, such as severe pre-eclampsia, fetal growth restriction, abruptio placentae, or stillbirth are associated with abnormally elevated second-trimester maternal serum alpha-fetoprotein (MSAFP) and beta subunit of human chorionic gonadotrophin (betahCG). This has been attributed to placental abnormalities. Women with thrombophilias have been shown to have abnormalities of the placenta resulting in adverse pregnancy outcome in these patients. The purpose of the present study was to evaluate whether women with pregnancy complications and inherited thrombophilias have abnormally elevated second-trimester MSAFP or betahCG. Sixty-two women with pregnancy complications were tested for inherited thrombophilias several months after delivery. The thrombophilia group included 29 women with pregnancy complications and an inherited thrombophilia and the control group included 33 other patients without thrombophilia. Patients in the thrombophilia group had a higher median MoM MSAFP compared to the controls (1.337 vs. 1.086, p=0.0516). The incidence of abnormally elevated MSAFP (>2.5 MoM) was also significantly higher in the thrombophilia group compared to controls (21% vs. 3%, p=0.04). Neither the median MoM betahCG nor the incidence of abnormally elevated betahCG were significantly different between the groups. We conclude that second trimester MSAFP, but not betahCG, is abnormally elevated in patients with thrombophilia and obstetric complications., (Copyright 2001 John Wiley & Sons, Ltd.)