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

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.