Maternal Malaria Induces a Procoagulant and Antifibrinolytic State That Is Embryotoxic but Responsive to Anticoagulant Therapy

• Type of Material: Article
• Authors: John W. Avery, University of Georgia; Geoffrey M. Smith, University of Georgia; Simon O. Owino, University of Georgia; Demba Sarr, University of Georgia; Tamas Nagy, University of Georgia; Stephen Mwalimu, University of Georgia; James Matthias, University of Georgia; Lauren F. Kelly, University of Georgia; Jayakumar S. Poovassery, University of Georgia; Joab D. Middii, University of Georgia; Carlos Abramowsky, Emory University; Julie M. Moore, University of Georgia
• Language: English
• Date: 2012-02-07
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2012 Avery et al.
• License: Creative Commons Attribution 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0031090
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 7
• Issue: 2
• Start Page: e31090
• End Page: e31090
• Grant/Funding Information: This work was supported by the National Institutes of Health grants R01 AI050240 and R01 HD046860 to JMM.
• Keywords: ADHESION MOLECULES; MOLECULAR-WEIGHT HEPARINS; Malaria; PLASMODIUM-FALCIPARUM MALARIA; Birth weight; Multidisciplinary Sciences; INTRAUTERINE GROWTH RESTRICTION; VENOOCCLUSIVE DISEASE; TISSUE FACTOR; Inflammation; Science & Technology; Embryos; Fibrinolysis; DISSEMINATED INTRAVASCULAR COAGULATION; Hemostatis; INFECTED ERYTHROCYTES; BLOOD-COAGULATION; PLACENTAL MALARIA; Fibrin; Pregnancy
• Research Categories: Health Sciences, Pathology; Biology, Microbiology; Health Sciences, Obstetrics and Gynecology

Abstract

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.