1374: INTERLEUKIN-1Β INTERACTION WITH FIBRIN(OGEN) MAY ALTER EX VIVO CLOT CHARACTERISTICS IN SEPSIS

Introduction: Sepsis-induced coagulopathy (SIC) is characterized by abnormal clot characteristics, including increased clot formation, impaired clot lysis, and dense clot structure, leading to reduced fluid flow-through and sieving coefficient. Interleukin-1beta (IL-1β) is significantly elevated in sepsis. IL-1β can bind to fibrin(ogen) (Fg), and this interaction increases its inflammatory activities. We hypothesize that the interaction of IL-1β with Fg can lead to abnormal clot characteristics in SIC. Methods: We measured ex vivo fibrin polymerization (FP) via turbidity assay and fibrin clot structures via confocal microscopy using recombinant IL-1β, purified Fg, as well as platelet-poor plasma collected from children with sepsis and healthy controls (HC) in an observational cohort study. Moreover, we compared ex vivo clot characteristics with and without anti-IL-1β antibodies (Ab) in patients (pts) with SIC (defined as Disseminated Intravascular Coagulation score =/>4). Results: In 19 pts (sepsis n =10 and HC =9) with a similar mean age of 7.8 vs. 8.8 years (p =0.285), we observed increased maximum FP (mean absorbance at 405 nm of 0.15±0.08 vs. 0.09±0.026, p < 0.001), increased clot density (mean gray intensity of 985±767 vs. 250±211, p =0.032), reduced clot porous area (mean percent area of 50.8±0.42 vs. 54.6%±2.5, p < 0.001), decreased average pore size (mean area size of 9.75±5.8 vs. 18.1±11.9 um, p =0.012) and prolonged fluid transit time (74 min±48 vs. 30±16, p =0.02) in sepsis pts compared to HC. Addition of recombinant IL-1β in healthy plasma as well as in Fg resulted in ex vivo clot characteristics similar to those of septic pts. Pre-incubating the plasma of pts with SIC with anti-IL-1β-Ab resulted in a trend towards decreased FP (mean absorbance of 0.15±0.12 (baseline) vs. 0.086±0.05 (anti-IL-1β-Ab treated), p =0.12, n=4). Conclusions: Septic pts showed altered ex vivo clot characteristics compared to HC. Addition of IL-1β in healthy plasma and Fg resulted in ex vivo clot characteristics similar to those of pts with sepsis, suggesting its interaction with Fg. Furthermore, IL-1β neutralizing Ab may correct abnormal ex vivo clot characteristics in pts with SIC. Further studies on the role of IL-1β and Fg interaction in pts with SIC are needed.