Safety of low-molecular-weight heparin in pregnancy: A systematic review

Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
Thrombosis and Haemostasis (Impact Factor: 4.98). 06/1999; 81(5):668-72.
Source: PubMed


Unfractionated heparin (UFH) remains the anticoagulant of choice during pregnancy. Low-molecular-weight heparins (LMWH) are an attractive alternative to UFH due to their logistic advantages and their association with a lower incidence of osteoporosis and HIT. We reviewed all published clinical reports concerning the use of LMWH during pregnancy. In addition, participants of an international interest group contributed a cohort of pregnant women treated with LMWH. Pregnancies were divided into two groups; those with and those without maternal comorbid conditions. The number of adverse fetal outcomes and the occurrence of maternal complications were evaluated in the two groups. In the group of women with comorbid conditions (n = 290), 13.4% of the pregnancies were associated with an adverse fetal outcome. In contrast, in the group of women without comorbid conditions (n = 196), 3.1% were associated with an adverse outcome, which is comparable to that seen in the normal population. We conclude that LMWH appear to be a safe alternative to unfractionated heparin as an anticoagulant during pregnancy.

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    • "LMWH inhibits factor Xa more effectively than factor IIa to produce its antithrombotic effect [19]. LMWH does not cross the placenta and is safe for the fetus [20,21]. "
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    ABSTRACT: Recurrent miscarriage is a major women's health problem. Aspirin and heparin have been shown to have potentially beneficial effects on trophoblast implantation. However, few published data on this issue are available from developing countries. An open clinical trial was conducted at the Department of Obstetrics and Gynecology at Misurata Teaching Hospital in Libya from January 2009 to December 2010 to investigate the effects of treatment with low dose aspirin (LDA) versus treatment with low-molecular-weight-heparin (LMWH) in combination with LDA on patients with a history of recurrent miscarriages. A total of 150 women were enrolled in the study. Women were eligible for the study if they had a history of three or more consecutive miscarriages. Participants were randomly assigned to receive either LDA (75 mg daily) alone or a combination of LDA and LMWH (75 women per treatment group). The primary outcomes were the rate of miscarriages and live births for each group. Compared with the group who received LDA alone, the combination group had a significantly lower number of miscarriages (22/75 [29%] vs. 43/75 [47%], P < 0.001) and had a significantly higher number of live births (53/75 [71%] vs. 32/75 [42%], P < 0.001). Two preterm infants in the LDA group and three in the combination group were admitted to the neonatal intensive care unit. There were no significant differences in the mean (SD) birth weights of neonates born in either group (2955.4 +/- 560 vs. 3050 +/- 540 g for the LDA and combination groups, respectively, P = 0.444). There were no congenital abnormalities detected in either group. The combination of LDA and LMWH is better than LDA alone for the maintenance of pregnancy in patients with recurrent first trimester miscarriage.Trial registration: NCT01917799.
    BMC Research Notes 01/2014; 7(1):23. DOI:10.1186/1756-0500-7-23
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    • "Warfarin crosses the placenta and has the potential to cause teratogenicity and bleeding in the fetus [41-44]. Prophylactic LMWH does not cross the placenta [45] or increase the risk of serious adverse fetal outcomes [44-54], and does not appear to increase the risk of heparin-induced thrombocytopenia (<0.1%) or heparin-associated osteoporosis (<1%) [46,47,51,55-68]. However, prophylactic LMWH is expensive, inconvenient, uncomfortable to administer, may be associated with an increased risk of major obstetrical bleeding [46], and generally necessitates a planned delivery to permit epidural analgesia [46]. "
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    ABSTRACT: Background Pregnant women with prior venous thromboembolism (VTE) are at risk of recurrence. Low molecular weight heparin (LWMH) reduces the risk of pregnancy-related VTE. LMWH prophylaxis is, however, inconvenient, uncomfortable, costly, medicalizes pregnancy, and may be associated with increased risks of obstetrical bleeding. Further, there is uncertainty in the estimates of both the baseline risk of pregnancy-related recurrent VTE and the effects of antepartum LMWH prophylaxis. The values and treatment preferences of pregnant women, crucial when making recommendations for prophylaxis, are currently unknown. The objective of this study is to address this gap in knowledge. Methods We will perform a multi-center cross-sectional interview study in Canada, USA, Norway and Finland. The study population will consist of 100 women with a history of lower extremity deep vein thrombosis (DVT) or pulmonary embolism (PE), and who are either pregnant, planning pregnancy, or may in the future consider pregnancy (women between 18 and 45 years). We will exclude individuals who are on full dose anticoagulation or thromboprophylaxis, who have undergone surgical sterilization, or whose partners have undergone vasectomy. We will determine each participant's willingness to receive LMWH prophylaxis during pregnancy through direct choice exercises based on real life and hypothetical scenarios, preference-elicitation using a visual analog scale (“feeling thermometer”), and a probability trade-off exercise. The primary outcome will be the minimum reduction (threshold) in VTE risk at which women change from declining to accepting LMWH prophylaxis. We will explore possible determinants of this choice, including educational attainment, the characteristics of the women’s prior VTE, and prior experience with LMWH. We will determine the utilities that women place on the burden of LMWH prophylaxis, pregnancy-related DVT, pregnancy-related PE and pregnancy-related hemorrhage. We will generate a “personalized decision analysis” using participants’ utilities and their personalized risk of recurrent VTE as inputs to a decision analytic model. We will compare the personalized decision analysis to the participant’s stated choice. Discussion The preferences of pregnant women at risk of VTE with respect to the use of antithrombotic therapy remain unexplored. This research will provide explicit, quantitative expressions of women's valuations of health states related to recurrent VTE and its prevention with LMWH. This information will be crucial for both guideline developers and for clinicians.
    BMC Pregnancy and Childbirth 05/2012; 12(1):40. DOI:10.1186/1471-2393-12-40 · 2.19 Impact Factor
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    • "However , there are no high quality randomized clinical trials that compared different strategies of thromboprophylaxis in pregnant women with prior VTE. Several observational studies evaluated the risk of recurrent VTE with different treatment regimes, with some of these studies stratifying patients according to the perceived risk of recurrence [32] [61] [62]. "
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    ABSTRACT: Venous thromboembolism (VTE) is a leading cause of maternal mortality and morbidity during pregnancy in developed countries. The incidence of VTE per pregnancy-year increases about 4-fold during pregnancy and at least 14-fold during the puerperium. Risk factors include a personal history of VTE, presence of inherited or acquired thrombophilia, a family history of VTE and general medical conditions, such as immobilisation, overweight, varicose veins, some haematological diseases and inflammatory disorders. VTE is considered potentially preventable with the prophylactic administration of anticoagulants, but there are no high quality randomized clinical trials that compared different strategies of thromboprophylaxis in pregnant women. Balancing the absolute risk of VTE against the risks of exposure to anticoagulants, this review provides advice regarding which women may benefit from thromboprophylaxis during and after pregnancy.
    Thrombosis Research 02/2012; 129(6):673-80. DOI:10.1016/j.thromres.2012.01.017 · 2.45 Impact Factor
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