Abstract
Malaria remains a highly prevalent disease in more than 90 countries and accounts for at least 1 million deaths every year. Plasmodium falciparum infection is often associated with a procoagulant tonus characterized by thrombocytopenia and activation of the coagulation cascade and fibrinolytic system; however, bleeding and hemorrhage are uncommon events, suggesting that a compensated state of blood coagulation activation occurs in malaria. This article (i) reviews the literature related to blood coagulation and malaria in a historic perspective, (ii) describes basic mechanisms of coagulation, anticoagulation, and fibrinolysis, (iii) explains the laboratory changes in acute and compensated disseminated intravascular coagulation (DIC), (iv) discusses the implications of tissue factor (TF) expression in the endothelium of P. falciparum infected patients, and (v) emphasizes the procoagulant role of parasitized red blood cells (RBCs) and activated platelets in the pathogenesis of malaria. This article also presents the Tissue Factor Model (TFM) for malaria pathogenesis, which places TF as the interface between sequestration, endothelial cell (EC) activation, blood coagulation disorder, and inflammation often associated with the disease. The relevance of the coagulation-inflammation cycle for the multiorgan dysfunction and coma is discussed in the context of malaria pathogenesis.
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ACKNOWLEDGMENTS
This work was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health(Bethesda, MD, USA).
The authors are grateful to Drs. José Marcos C. Ribeiro, Thomas E. Wellems, Robert W. Gwadz, and Kathryn C. Zoon (NIAID) for their continuous encouragement and support. We express our thanks to Drs. Richard O. Whitten, Jerrold M. Ward, and Terrie E. Taylor for their immunohistochemistry studies. The authors thank the reviewers for their time, comments, and suggestions and acknowledge NIAID intramural editor Brenda Rae Marshall for her assistance.
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