Fibrin deposition in the malaria-infected placenta

Abstract

Placental malaria is characterized by the accumulation of Plasmodium falciparum-infected red blood cells in the human placenta. This leads to maternal anemia and poor fetal outcome including low birth weight and possibly perinatal death. Primigravidae are more susceptible to the devastating consequences of malaria during pregnancy, suggesting the presence of gravidity-dependent immunological resistance among malaria-exposed women. Common features of placental malaria include monocyte infiltration to the maternal blood space and excessive fibrin deposition, an end-product of blood coagulation. The immune factors involved in the recruitment and activation of maternal immune cells to the placenta and their role in local hyper-coagulation are poorly understood. It is hypothesized that syncytiotrophoblasts, fetal cells facing the maternal blood circulation, secrete these cell mediators as well as pro-coagulants or anti-fibrinolytics, resulting in the influx of maternal immune cells and clotting/fibrin accumulation. To address this hypothesis, placental plasma samples were collected in malaria-endemic western Kenya and stratified according to placental malaria status and gravidity. The levels of plasminogen activator inhibitor-1 (PAI-1), which inhibits fibrin degradation, and Tissue Factor Pathway Inhibitor (TFPI), which suppresses clotting, were evaluated by ELISA. Additionally, protein was isolated from placental tissue of these women and semi-quantitative estimation of fibrin and PAI-1 protein by western blot was initiated. Ultimately, elucidation of the coagulation factors expressed during placental malaria, and how they are regulated, will contribute to understanding the immunopathogenic mechanisms occurring at the materno-fetal interface of the malaria-infected placenta.