Disseminated Intravascular Coagulation Pathogenesis in Severe Plasmodium falciparum Malaria: An Original Haemostatic Network Analysis in Nigerian Patients

This dissertation applies an original haemostatic network analysis framework to characterise the pathogenesis of disseminated intravascular coagulation (DIC) in severe Plasmodium falciparum malaria in Nigerian patients, addressing the incomplete mechanistic understanding of coagulation activation and fibrinolytic dysregulation in this high-mortality condition. DIC in severe malaria contributes significantly to mortality, yet a systems-level haemostatic network perspective integrating coagulation, fibrinolysis, platelet biology, and endothelial biomarkers has not been applied in the Nigerian context. A prospective case-series study with matched controls enrolled 120 severe malaria patients at the University of Maiduguri Teaching Hospital, 60 uncomplicated malaria controls, and 40 healthy controls. Comprehensive haemostatic profiling included thromboelastography, platelet flow cytometry, plasma D-dimer, fibrinogen, antithrombin III, plasminogen, alpha-2-antiplasmin, TPA-PAI-1 complex, soluble endothelial protein C receptor, and angiopoietin-1 and -2. All parameters were measured at admission and 48 hours after antimalarial initiation. Bayesian network modelling was applied to construct an original DIC Pathogenesis Network from the haemostatic data, identifying the most influential nodes driving the DIC phenotype. The network analysis identified the angiopoietin-2 to angiopoietin-1 ratio as the most upstream driver of the haemostatic network disruption, operating through EPCR pathway suppression and PAI-1 elevation, preceding platelet count falls and coagulation factor depletion. An original Malaria DIC Haemostatic Network Model is proposed with angiopoietin-2 as a novel therapeutic target. Keywords: disseminated intravascular coagulation, malaria, haemostatic network, Plasmodium falciparum, Nigeria.