Maternal malaria induces a procoagulant and antifibrinolytic state that is embryotoxic but responsive to anticoagulant therapy

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...

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Bibliographic Details
Published in:PloS one 2012-02, Vol.7 (2), p.e31090-e31090
Main Authors: Avery, John W, Smith, Geoffrey M, Owino, Simon O, Sarr, Demba, Nagy, Tamas, Mwalimu, Stephen, Matthias, James, Kelly, Lauren F, Poovassery, Jayakumar S, Middii, Joab D, Abramowsky, Carlos, Moore, Julie M
Format: Article
Language:English
Subjects:
Abortion
Animals
Anticoagulants
Antifibrinolytic agents
Biology
Birth Weight
Blood Coagulation
Childbirth & labor
Clinical outcomes
Coagulation
Deposition
Disease prevention
Embryos
Female
Fetuses
Fibrin
Fibrinolysis
Health aspects
Hemorrhage
Hemostasis
Hemostatics
Heparin
Heparin, Low-Molecular-Weight - therapeutic use
Humans
Infections
Infectious diseases
Inflammation
Low birth weight
Low molecular weights
Malaria
Malaria - blood
Malaria - complications
Malaria - drug therapy
Markers
Medical research
Medicine
Mice
Miscarriage
Molecular modelling
Molecular weight
Monocytes
Parasitemia
Pathogenesis
Pathology
Placenta
Placenta - blood supply
Placenta - parasitology
Plasmodium falciparum
Pregnancy
Pregnancy Complications, Parasitic - blood
Pregnancy Complications, Parasitic - drug therapy
Pregnant women
Thrombophilia - parasitology
Treatment Outcome
Vector-borne diseases
Womens health
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0031090