Thrombin Generation Measurement: A Novel Diagnostic and Prognostic Approach for Identifying Early-Stage Disseminated...

BackgroundDisseminated intravascular coagulation (DIC) is a complex hemostatic disorder characterized by simultaneous thrombosis and bleeding and is frequently observed in sepsis. Traditional coagulation assays such as prothrombin time (PT) and activated partial thromboplastin time (aPTT) primarily assess the initiation of clot formation but fail to capture the dynamic balance between procoagulant and anticoagulant forces. The thrombin generation (TG) assay provides a more comprehensive evaluation of coagulation, incorporating both propagation and decay phases, and may offer additional insight into sepsis-associated coagulopathy. This study investigated the diagnostic and prognostic utility of TG parameters across graded stages of DIC in septic intensive care unit (ICU) patients.MethodsIn this prospective observational study, 53 adult septic ICU patients contributed 151 plasma samples obtained longitudinally. Patients were classified as non-DIC, non-overt DIC, or overt DIC according to International Society on Thrombosis and Haemostasis criteria. Standard coagulation parameters and TG profiles were measured. Associations with DIC severity were examined using cumulative link mixed models with patient-level random effects. Sensitivity analyses explored transition-specific TG behavior. ICU mortality was evaluated using multivariable logistic regression and ROC analysis.ResultsIn univariate analyses, both conventional coagulation markers and TG parameters were associated with increasing DIC severity. In the final multivariable model, prolonged PT and aPTT, elevated D-dimer, and lower platelet count were the strongest independent predictors of DIC severity, whereas StartTail provided complementary kinetic information. Longitudinal analyses demonstrated progressive prolongation of StartTail and attenuation of reverse velocity index with advancing DIC stage and increasing SOFA scores, indicating worsening dysregulation of thrombin inactivation.ConclusionTG parameters, particularly late-phase kinetic features, reflect dynamic and stage-specific dysregulation of coagulation in sepsis-associated DIC. Although TG measures do not outperform conventional coagulation tests, they provide complementary mechanistic insight into thrombin regulation and consumptive coagulopathy. Larger multicenter studies are warranted to validate these findings.