Factor XIII in severe sepsis and septic shock

Abstract

Objective In sepsis, activation of coagulation and inhibition of fibrinolysis lead to microvascular thrombosis. Thus, clot stability might be a critical issue in the development of multiple organ dysfunction syndrome. Activated FXIII (FXIIIa) forms stable fibrin clots by covalently cross-linking fibrin monomers. Therefore, we investigated the impact of FXIII antigen and activity levels on disease severity and fatality in sepsis patients. Patients and methods FXIII subunit A (FXIIIA) and FXIII cross-linking activity (FXIIICA) were measured in 151 controls, in 32 patients with severe sepsis and 8 with septic shock. In addition, FXIII subunit B (FXIIIB) was measured in the sepsis patients. Moreover, clotting parameters were determined. Results Patients suffering from sepsis ( n = 40) had significantly ( p < 0.005) lower FXIIIA levels (median [range]: 36.5% [8.8–127.4%]) and FXIIICA levels (76.5% [9.4–266%]) as compared to healthy controls ( n = 151, 119% [31.3–283.2] and 122.4% [40.6–485.3], respectively). No difference in FXIIIA, FXIIIB and FXIIICA levels between survivors and non-survivors, nor between patients with severe sepsis and septic shock was found. The specific activity of FXIII (FXIIICA/FXIIIA, SA FXIII) was significantly ( p < 0.001) higher in sepsis patients (2.0 [0.8–5.3]) as compared to healthy controls (1.0 [0.4–5.1]). SA FXIII significantly ( p < 0.05) increased with fatality (non-survivors [ n = 13] vs. survivors [ n = 27]: 3.3 [1.2–5.0] vs. 1.9 [0.8–5.3]) and disease severity (septic shock vs. severe sepsis: 3.4 [1.8–4.3] vs. 1.9 [0.8–5.3]). Conclusion We show decreased FXIIICA and FXIIIA levels, but higher SA FXIII in sepsis as compared to controls. Increased SA FXIII correlates with disease severity and fatality in sepsis patients.