Revisiting the Concept of DIC: A Phenotype-guided Framework for Modern Hemostatic Medicine.

Disseminated intravascular coagulation (DIC) has long been described as a catastrophic systemic activation of coagulation with suppressed anticoagulant and fibrinolytic pathways, culminating in macro- and microvascular thrombosis, hypoperfusion, and multiple organ dysfunction. It may arise from acute inflammatory, traumatic, or infectious diseases, where consumption of fibrinogen, platelets, and coagulation factors, together with dysregulated fibrinolysis, lead to bleeding and poor outcomes. Contemporary evidence demonstrates that DIC is not a single or uniform pathological entity, but rather the advanced and convergent phase of distinct coagulopathies triggered by heterogeneous systemic insults such as sepsis, trauma, burns, malignancy, and obstetric complications. Similar to acute respiratory distress syndrome and dialysis-dependent renal failure, organ-failure syndromes with different etiologies, DIC should be recognized as advanced failure of the coagulation system, characterized by excessive thrombin generation, impaired fibrin formation, depletion of endogenous anticoagulants, and fibrinolytic imbalance. We propose reframing DIC as part of an etiologic and phenotype-guided framework within modern hemostatic precision medicine. The recognition of sepsis-induced coagulopathy (SIC), trauma-induced coagulopathy (TIC), and obstetric-associated coagulopathy (OAC), exemplifies this paradigm shift. Each condition exhibits unique inflammatory triggers, endothelial activation, and hemostatic trajectories evolving through identifiable phenotypes, from macrovascular hypercoagulability to microvascular fibrinolytic shutdown and, ultimately, to hypocoagulation, hyperfibrinolysis and hemorrhage. Early identification of these phenotypes through viscoelastic testing and biomarkers such as D-dimer, fibrinogen, protein C, antithrombin, and plasminogen activator inhibitor-1 allows targeted, goal-directed interventions. This strategy supports precision-guided anticoagulant therapy in thrombotic phenotypes and hemostatic resuscitation in hemorrhagic states, ultimately improving clinical outcomes in critically ill patients.