IgM-enriched immunoglobulin treatment significantly improves coagulation dysbalance in an experimental animal model of fulminant sepsis.

Abstract

INTRODUCTION: Inflammation and coagulation are closely interrelated process in the pathogenesis of sepsis. In this study, we investigated whether intravenous IgM-enriched immunoglobulin (IgM-IVIG) preparation could improve hemostatic abnormalities in a fulminant sepsis model. MATERIALS AND METHODS: Live Escherichia coli (E.coli) bacteria were administered to pigs with simultaneously (E. coli + Ig) or delayed (E. coli post Ig) of IgM-IVIG while control pigs received only physiological saline. Prothrombin time, activated partial thromboplastin time (APTT) and fibrinogen were measured by coagulometry. Hematologic parameters and soluble P-selectin were also measured. Furthermore, thrombin generation assay was carried out by fluorimetry and results were evaluated by the Thrombinoscope software. RESULTS: In septic pigs continous increase of fibrinogen levels and significant prolongation of APTT were observed. However, IgM-IVIG treatment significantly decreased fibrinogen levels and shortened the APTT after E. coli administration. In addition, in thrombin generation assay (TGA), that was performed without any exogenous coagulation trigger a significant increase of endogenous thrombin potential (ETP) and peak thrombin were observed in the E. coli-administered group which were abolished by IgM-IVIG treatment. Furthermore, in another TGA using phospholipid and tissue factor triggers, a significant decrease of ETP and thrombin peak were detected in septic-group, however IgM-IVIG treatment prevented the effect of E. coli. Increased level of soluble P-selectin was measured in E. coli-administered group, but it was attenuted by simultaneously administered IgM-IVIG treatment. CONCLUSIONS: We conclude that IgM-IVIG attenuates sepsis-induced hemostatic abnormalities, and the effect of simultaneously administered IgM-IVIG was more pronounced.