Pathogenesis of leptospirosis-induced coagulopathy and hemorrhages

Physiological hemostasis is a balance between pro- and anticoagulant pathways, with multiple factors, regulators, and cellular components. Hemostasis is also closely associated with inflammation and immune response. In leptospirosis, a zoonotic disease caused by pathogenic spirochetal bacteria of the genus Leptospira, the hemostatic equilibrium is disturbed, resulting in coagulopathies that ultimately result in hemorrhages. Thrombocytopenia is a common complication in the affected patients and is often associated with poor clinical outcomes and high mortality. To date, the reports unraveling the origin of the molecular pathogenesis of leptospirosis hemostatic disturbances are scarce. In this review article, we summarize and analyze the complex pathophysiology of hemostatic impairment in the illness with a focus on the role of endotheliopathy, induction of pro-coagulant and pro-inflammatory states, and platelet dysfunction. We believe this can guide future studies aiming to unravel the molecular mechanisms underlying coagulopathy in leptospirosis to improve our understanding based on evidence, which will give insight into novel interventions to tackle the disease.