| Heparin rescues factor V Leiden-associated placental failure independent of anticoagulation in a murine high-risk pregnancy model. | |
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MedLine Citation:
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PMID: 23325830 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Low Molecular Weight Heparin (LMWH) is being tested as an experimental drug for improving pregnancy outcome in women with inherited thrombophilia and placenta-mediated pregnancy complications, such as recurrent pregnancy loss. The role of thrombotic processes in these disorders remains unproven and the issue of antithrombotic prophylaxis is intensely debated. Using a murine model of factor V Leiden-associated placental failure, we show that treatment of the mother with LMWH allows placental development to proceed and affords significant protection from fetal loss. Nonetheless, the therapeutic effect of LMWH is not replicated by anticoagulation; Fondaparinux and a direct Xa inhibitor, C921-78, achieve anticoagulation similar to LMWH but produce little or no improvement in pregnancy outcome. Genetic attenuation of maternal platelet aggregation is similarly ineffective. In contrast, even a partial loss of thrombin sensitivity of maternal platelets protects pregnancies. Neonates born from these pregnancies are growth retarded, suggesting that placental function is only partially restored. The placentae are smaller, but do not reveal any evidence of thrombosis. Our data demonstrates an anticoagulation-independent role of LMWH in protecting pregnancies and provides evidence against the involvement of thrombotic processes in thrombophilia-associated placental failure. Importantly, thrombin-mediated maternal platelet activation remains central in the mechanism of placental failure. |
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Authors:
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Jianzhong An; Magarya Waitara; Michelle Bordas; Vidhyalakshmi Arumugam; Raymond G Hoffmann; Brian G Petrich; Uma Sinha; Paula North; Rashmi Sood |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2013-1-16 |
Journal Detail:
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Title: Blood Volume: - ISSN: 1528-0020 ISO Abbreviation: Blood Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-1-17 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Division of Pediatric Pathology, Department of Pathology, Medical College of Wisconsin, Milwaukee, WI, United States; |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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