Document Detail


Maternal malaria induces a procoagulant and antifibrinolytic state that is embryotoxic but responsive to anticoagulant therapy.
MedLine Citation:
PMID:  22347435     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Low birth weight and fetal loss are commonly attributed to malaria in endemic areas, but the cellular and molecular mechanisms that underlie these poor birth outcomes are incompletely understood. Increasing evidence suggests that dysregulated hemostasis is important in malaria pathogenesis, but its role in placental malaria (PM), characterized by intervillous sequestration of Plasmodium falciparum, proinflammatory responses, and excessive fibrin deposition is not known. To address this question, markers of coagulation and fibrinolysis were assessed in placentae from malaria-exposed primigravid women. PM was associated with significantly elevated placental monocyte and proinflammatory marker levels, enhanced perivillous fibrin deposition, and increased markers of activated coagulation and suppressed fibrinolysis in placental plasma. Submicroscopic PM was not proinflammatory but tended to be procoagulant and antifibrinolytic. Birth weight trended downward in association with placental parasitemia and high fibrin score. To directly assess the importance of coagulation in malaria-induced compromise of pregnancy, Plasmodium chabaudi AS-infected pregnant C57BL/6 mice were treated with the anticoagulant, low molecular weight heparin. Treatment rescued pregnancy at midgestation, with substantially decreased rates of active abortion and reduced placental and embryonic hemorrhage and necrosis relative to untreated animals. Together, the results suggest that dysregulated hemostasis may represent a novel therapeutic target in malaria-compromised pregnancies.
Authors:
John W Avery; Geoffrey M Smith; Simon O Owino; Demba Sarr; Tamas Nagy; Stephen Mwalimu; James Matthias; Lauren F Kelly; Jayakumar S Poovassery; Joab D Middii; Carlos Abramowsky; Julie M Moore
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-02-07
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-02-20     Completed Date:  2012-07-31     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e31090     Citation Subset:  IM    
Affiliation:
Department of Infectious Diseases and Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, Georgia, United States of America.
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MeSH Terms
Descriptor/Qualifier:
Animals
Birth Weight
Blood Coagulation
Female
Fibrinolysis
Hemostasis
Heparin, Low-Molecular-Weight / therapeutic use
Humans
Malaria / blood,  complications*,  drug therapy
Mice
Placenta / blood supply,  parasitology
Pregnancy
Pregnancy Complications, Parasitic / blood*,  drug therapy
Thrombophilia / parasitology*
Treatment Outcome
Grant Support
ID/Acronym/Agency:
R01 AI050240/AI/NIAID NIH HHS; R01 HD046860/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Heparin, Low-Molecular-Weight
Comments/Corrections

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