Meta-Analyses and Meta-Regression Analyses Revealed That Crimean–Congo Hemorrhagic Fever Disease Associates with Coagulopathy Independently of Thrombocytopenia

Crimean–Congo Hemorrhagic Fever (CCHF) disease, caused by the CCHF virus (CCHFV), poses a significant fatality risk whose underlying pathological mechanisms, including the contribution of coagulation factors, imbalances and platelet abnormalities, remain poorly understood. Here we present a meta-analysis and meta-regression analysis using clinical data from coagulation assays and platelet parameters as predictive disease indices with the goal of uncovering pathognomonic factors and to pave a way for the development of effective therapeutic approaches. Methods: We systematically analyzed published studies reporting coagulation assays and platelet indices in patients with confirmed CCHF. Data from 1779 patients across the published studies were analyzed to assess associations between laboratory parameters and the fatality risk, while evaluating heterogeneity and prognostic significance. Results: Fatal outcomes were strongly associated with elevated liver enzymes (AST: 1116.71 ± 1454.08 IU/mL; ALT: 446.56 ± 457.41 IU/mL) and prolonged clotting times (PT: 19.53 ± 6.57 s; aPTT: 64.02 ± 23.13 s; INR: 1.53 ± 0.56). D-dimer levels did not significantly predict fatality. Thrombocytopenia and coagulopathy emerged as independent risk factors for adverse outcomes. Notably, protein C and protein S levels did not differ between survivors and non-survivors, suggesting that the coagulopathy is not purely consumptive or a result of impaired hepatic synthesis. In contrast, mildly reduced antithrombin levels (83.65 ± 19.90) were weighted toward increased mortality.