Neonatal Sepsis-Induced Coagulopathy: An Evolving Frontier at the Crossroads of Inflammation and Hemostasis

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host immune response to an infection. Sepsis is often associated with significant hemostatic disorders that may lead to extensive intravascular thrombosis, disseminated intravascular coagulation (DIC), multi-organ dysfunction syndrome (MODS), and increased mortality. Sepsis-induced coagulopathy (SIC) is currently recognized as an early distinct phase of hemostatic derangement caused by sepsis, and a prodrome of overt DIC. SIC is characterized by endovascular clotting activation, hypercoagulability, and consumption of clotting factors and platelets. DIC, traditionally considered the final stage of this process, is now recognized as a part of a continuum of pathophysiological dysregulation with a distinct clinical significance. Despite being extensively studied in the adult population, SIC remains poorly defined in neonates. The distinct characteristics of neonatal hemostasis, coupled with immunological immaturity, pose significant challenges to the direct application of adult diagnostic approaches of SIC in this population. This review focuses on the pathophysiological mechanisms of SIC and the unique characteristics of neonatal hemostasis, summarizes current knowledge regarding the underlying mechanisms of neonatal SIC, and explores the developmental interplay between inflammation and hemostasis. By integrating current evidence, the review aims to establish a conceptual framework that will guide future experimental and clinical studies directed toward improving the management and outcomes of neonates who develop coagulopathy during sepsis.