Identification of patient population benefiting from anticoagulant therapy for sepsis-related coagulopathy based on the disseminated intravascular coagulation diagnostic criteria: a retrospective database study

Abstract

Abstract Background: The development of disseminated intravascular coagulation (DIC) in patients with sepsis has been repeatedly confirmed as a factor associated with poor prognosis. Anticoagulant therapy has been expected to improve sepsis patient outcomes, whereas no randomized controlled trials have demonstrated the survival benefit of anticoagulant therapies in non-specific overall sepsis. Patient selection based on the component of “high disease severity” in addition to “sepsis with DIC” has recently been shown to be important in identifying appropriate target for anticoagulant therapy. The aims of this study were to characterize “severe” sepsis DIC patients, and to identify the patient population benefiting from anticoagulant therapy.Methods: We conducted a retrospective sub-analysis of a prospective multicenter study and enrolled 1,178 adult patients with severe sepsis from 59 intensive care units. We examined the association of patient outcomes, including organ dysfunction and in-hospital mortality, with the DIC score and prothrombin time-international normalized ratio (PT-INR), one of the components of the DIC score, using multivariable regression models including the cross-product term between these indicators. Multivariate Cox proportional hazard regression analysis with non-linear restricted cubic spline including a three-way interaction term (anticoagulant therapy × the DIC score × PT-INR) was also performed. Anticoagulant therapy was defined as the administration of antithrombin, recombinant human thrombomodulin, or their combination.Results: The regression model showed that organ dysfunction and in-hospital mortality deteriorated with higher PT-INR values in the range of less than 1.5 and that this trend was more pronounced with higher DIC scores. Three-way interaction analysis demonstrated that anticoagulant therapy was associated with better survival outcome in patients with a high DIC score and high PT-INR. Furthermore, we identified a DIC score ≥ 5 and PT-INR ≥ 1.5 as the clinical threshold for identification of optimal targets for anticoagulant therapy.Conclusions: The combined use of the DIC score and PT-INR, one of the items of the score, helps to select the optimal patient population for anticoagulant therapy in sepsis-induced DIC. Diagnosing DIC with a sensitive DIC scoring system, followed by the identification of the optimal patient population for anticoagulant therapy may be useful for controlling sepsis-induced DIC. Trial registration: UMIN-CTR, UMIN000019588. Registered on November 16, 2015.