Impact of Viral Infections on the Hemostatic System

The coronavirus disease 2019 (COVID-19) pandemic has brought renewed attention to the significant but often overlooked impact of viral infections on the hemostatic system. This review explores the pathophysiological mechanisms underlying the interaction between viruses and hemostasis, directly through viral components or immune-mediated processes. Viruses are recognized as pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs) on innate immune cells such as neutrophils, monocytes, and platelets. This recognition triggers immune responses, including the production of type I interferons (IFN-α and IFN-β) and proinflammatory cytokines like interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), which recruit immune cells and induce pyroptotic cell death. Inflammatory cytokines contribute to endothelial dysfunction and coagulation activation, interacting with platelets, neutrophils, neutrophil extracellular traps (NETs), and the kallikrein-kinin system. Hyperactivation of the cytokine system, known as the cytokine storm, correlates with disease severity. Common features of viral infections include platelet activation and endotheliitis, leading to thrombocytopenia and microvascular thrombosis. Interestingly, similar pathogenic mechanisms in COVID-19 and viral hemorrhagic fevers (VHFs) result in contrasting clinical manifestations. While COVID-19 predominantly induces a thrombotic response characterized by endothelial damage, platelet hyperactivity, and complement activation, VHFs typically lead to hemorrhagic complications due to thrombocytopenia, consumptive coagulopathy, and vascular injury. These differences are influenced by the timing and location of coagulation activation, as well as the dynamics of immune responses. In COVID-19, coagulation initially occurs in the lungs, followed by systemic thrombotic phases, whereas VHFs rapidly progress to consumptive coagulopathy with hemorrhage, compounded by immune suppression.