Age-Related Differences in the Survival Benefit of Anticoagulant Therapy in Sepsis in Accordance with the Japanese Association for Acute Medicine Disseminated Intravascular Coagulation Diagnostic Criteria: A Retrospective Sub-analysis of a Prospective Multicenter Study

Abstract

\n Background: Disseminated intravascular coagulation (DIC) is one of the major organ dysfunctions associated with sepsis. This study aimed to investigate the age-related differences in the survival benefit of anticoagulant therapy in sepsis in accordance with the DIC diagnostic criteria.Methods: We conducted a retrospective sub-analysis of a prospective multicenter study. Fifty-nine intensive care units in Japan, from January 2016 to March 2017 were included. Adult patients with severe sepsis based on the Sepsis-2 criteria were enrolled and divided into two groups as follows: anticoagulant group; patients who received anticoagulant therapy, and non-anticoagulant group; patients who did not receive anticoagulant therapy. Patients in anticoagulant therapy group were administered antithrombin, recombinant human thrombomodulin and their combination.Results: The multivariate Cox proportional hazard regression model including a three-way interaction term among anticoagulant therapy, DIC score and age showed that the increases in the risk were suppressed in patients receiving anticoagulant therapy in patients aged 60 to 70 years with high DIC scores. For patients aged 50 years, the risk in the non-anticoagulant group tended to increase concomitantly with increases in the DIC score in the low score range, while there was no increase in the risk in the high score range and favorable association of anti-coagulant therapy on hospital mortality was not found. In patients aged 80 years, the non-anticoagulant group indicated a certain risk regardless of the DIC score and the anti-coagulant therapy showed no beneficial effect on the decrease in risk of hospital mortality. Furthermore, anticoagulant therapy in the lower DIC score range increased the risk in patients aged 50 to 60 years.Conclusions: Anticoagulant therapy, the administration of antithrombin, recombinant human thrombomodulin, and their combination, were associated with decreased hospital mortality according to a higher DIC score in septic patients aged 60 to 70 years. Anticoagulant therapy, however, was not associated with a better outcome in relatively younger and older septic patients.Trial registration: UMIN-CTR, UMIN000019588. Registered on 16 November 2015.