Baseline characteristics of patients with and without hypercoaguable sepsis and the effect of afelimomab on mortality: a post hoc analysis from the MONARCS trial

Abstract

Tumor necrosis factor (TNF)α may modulate clot-promoting and inhibiting pathways, and have potentially important roles in disseminated intravascular coagulation (DIC). Purpose 1) To determine if differences in baseline characteristics exist between patients with and without hypercoaguable sepsis, and 2) to explore the effect of afelimomab (an anti-TNFα antibody) on mortality of hypercoaguable and non-hypercoaguable septic patients. Methods A post hoc analysis identified patients with a hypercoaguable state in the overall population enrolled in a large placebo-controlled sepsis trial investigating the safety and efficacy of afelimomab. A hypercoaguable state was defined by (1) platelet count below 140,000 per μl plus (2) D-dimer > 250 ng/ml. Patients were randomized to receive placebo or afelimomab. Results A total of 2634 patients were enrolled, and 1313 (49.8%) had baseline determinations of both platelets and D-dimer. The table describes the baseline characteristics of the two patient groups. Compared to those without laboratory evidence of consumption coagulopathy, patients with a hypercoagulable state had higher organ dysfunction scores, higher interleukin-6 levels and higher frequencies of positive blood cultures. Among the patients with evidence of consumption coagulopathy, 283 were treated with placebo and 311 with afelimomab. Mortality at 28 days was 43.8% vs 38.6% in placebo and afelimomab patients, respectively. In patients not meeting the definition of hypercoaguability, 376 and 343 received placebo and afelimomab; mortality was 35.9% and 26.5%, respectively. Table Absence of Hypercoaguable hypercoaguable state state (n = 594) (n = 719) Mean age (SD) 57.9 (17.0) 60.1 (17.0) Gender (M/F) 58.6% / 41.4% 61.6% / 38.4% Shock 399 (67.2%) 504 (70.1%) MOD score 9.1 6.3 Median interleukin-6 (pg/ml) 1360 908 Mean platelet count × 1000 (SD) 81.7 (35.6) 231.4 (141.7) Positive blood culture (%) 278 (46.8%) 226 (31.4%) G (+) bacteria only (%) 185 (31.1%) 207 (28.8%) G (–) bacteria only (%) 169 (28.5%) 177 (24.6%) Mixed G (+) and G (–) (%) 65 (10.9%) 102 (14.2%) Other or unknown (%) 175 (29.5%) 233 (32.4%) Conclusions Septic patients with evidence of consumption coagulopathy had more organ dysfunction and a higher rate of positive blood cultures. Afelimomab appears to be beneficial in reducing the mortality of septic patients with a hypercoaguable state.