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Pathogenesis of Ebola Viral Haemorrhagic Fever: TTP-like Syndrome Associated with Hepatic Coagulopathy based on "Two Activation Theory of the Endothelium"

Jae Chang

Ebola viral haemorrhagic fever is rare but the lifethreatening haemorrhagic disorder associated with Ebola viral sepsis. The demise of the patient occurs due to severe inflammation, multi-organ dysfunction syndrome and haemorrhage associated with a poorly defined coagulopathy. Ebola virus causes endothelial injury that orchestrates inflammation and multi-organ dysfunction, especially in the liver. To address clinical and hematological features, a novel pathogenesis based on “two-activation theory of the endothelium” is proposed. Endothelial injury activates endothelial cells that promote various clinical syndromes such as consumptive thrombocytopenia, multiorgan dysfunction and thrombotic microangiopathy. Endotheliopathy initiates two independent molecular events at endothelial cells: 1) Release of inflammatory cytokines, and 2) Activation of the platelet and exocytosis of unusually large von Willebrand factor multimers. The former triggers activation of inflammatory pathway and the latter mediates activation of microthrombotic pathway. In Ebola viral sepsis, activation of inflammatory pathway causes inflammation, but activation of microthrombotic pathway manifests as disseminated intravascular microthrombosis (DIT). The pathogenesis of Ebola viral haemorrhagic fever is hepatic coagulopathy triggered by acute hepatic necrosis as a result of endotheliopathyassociated DIT, which could manifest as TTP-like syndrome.