A role for coagulation in the pathogenesis of placental malaria
Avery, John Welch
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Malaria during pregnancy presents with increased rates of miscarriage, intrauterine growth restriction, premature delivery, and low birth-weight neonates. The cellular and molecular mechanisms that contribute to these poor birth outcomes are incompletely understood. A clinical feature of placental malaria (PM) that deserves greater attention is the presence of dysregulated hemostasis. The sequestration of malaria parasites within the placenta induces a proinflammatory state that we propose is accompanied by hyper-activation of the coagulation cascade. This dual homeostatic alteration likely underlies the excessive perivillous fibrin deposition known to occur in PM. Previous studies in our P. chabaudi AS/C57BL/6 model for malaria during pregnancy showed that mice infected in early pregnancy have complete fetal loss occurring by gestation day (GD) 12. This is the first report of aggressive anticoagulant therapy improving the pregnancy outcome in this model. Mice treated with low-molecular-weight heparin (LMWH) at a dose of 1000 IU/Kg every 12 hours displayed rescue of pregnancy at GD 12. Histopathology revealed that LMWH-treated mice have substantially decreased necrosis within the placental layers as well as within the embryo itself when compared to untreated animals. In treated mice, gross pathology indicated reduced conceptus hemorrhage with a concurrent diminution of embryonic in situ death and expulsion.