Endotheliopathy and Platelet Dysfunction as Hallmarks of Fatal Lassa Fever

• Published in: Emerging infectious diseases Vol. 26; no. 11; pp. 2625 - 2637
• Main Authors: Horton, Lucy E., Cross, Robert W., Hartnett, Jessica N., Engel, Emily J., Sakabe, Saori, Goba, Augustine, Momoh, Mambu, Sandi, John Demby, Geisbert, Thomas W., Garry, Robert F., Schieffelin, John S., Grant, Donald S., Sullivan, Brian M.
• Format: Journal Article
• Language: English
• Published: United States U.S. National Center for Infectious Diseases 01.11.2020; Centers for Disease Control and Prevention
• Subjects: Adolescent; Adult; Aged; Antigens; Ascites; Blood Coagulation; Blood platelets; Blood Platelets - pathology; Causes of; Child; Child, Preschool; coagulation; Development and progression; Diagnosis; Disease; Edema; Endotheliopathy and Platelet Dysfunction as Hallmarks of Fatal Lassa Fever; Endothelium; Endothelium - physiopathology; Enzymes; Fatalities; Female; Fever; Fibrinolysis; Health aspects; Health care; hemostasis; Humans; Infant; Laboratories; Lassa fever; Lassa Fever - diagnosis; Lassa Fever - epidemiology; Male; Middle Aged; Molecular weight; Permeability; Plasma; platelet; Platelet function disorders; protein C; Proteins; R&D; Research & development; Sepsis; Sierra Leone; Software; Thrombocytopenia; Tropical diseases; Young Adult; Sierra Leone; fibrinolysis; Lassa fever; viruses; vector-borne infections; hemorrhagic fever; platelet; zoonoses; hemostasis; protein C; coagulation
• ISSN: 1080-6040; 1080-6059; 1080-6059
• DOI: 10.3201/eid2611.191694

Lassa fever (LF) causes multisystem disease and has a fatality rate <70%. Severe cases exhibit abnormal coagulation, endothelial barrier disruption, and dysfunctional platelet aggregation but the underlying mechanisms remain poorly understood. In Sierra Leone during 2015-2018, we assessed LF patients' day-of-admission plasma samples for levels of proteins necessary for coagulation, fibrinolysis, and platelet function. P-selectin, soluble endothelial protein C receptor, soluble thrombomodulin, plasminogen activator inhibitor 1, ADAMTS-13, von Willebrand factor, tissue factor, soluble intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 were more elevated in LF patients than in controls. Endothelial protein C receptor, thrombomodulin, intercellular adhesion molecule 1, plasminogen activator inhibitor 1, D-dimer, and hepatocyte growth factor were higher in fatal than nonfatal LF cases. Platelet disaggregation occurred only in samples from fatal LF cases. The impaired homeostasis and platelet dysfunction implicate alterations in the protein C pathway, which might contribute to the loss of endothelial barrier function in fatal infections.