The role of inflammation in intravenous immune globulin-mediated hemolysis

Intravenous immune globulin (IVIG) therapy has shown great success in a number of autoimmune and inflammatory conditions and its use continues to increase worldwide. There is growing awareness of significant side effects of high-dose IVIG: however, particularly severe hemolysis in patients that are non-group O. It has been proposed that IVIG-associated hemolysis may be heralded by an existing inflammatory condition. In the work presented herein, we have provided a review of the pathophysiology of inflammation, particularly as it applies in immune-mediated red blood cell hemolysis, and a summary of previous publications that suggest an association between IVIG-mediated hemolysis and a state of existing inflammation. In addition, preliminary results from a prospective study to address the mechanism of IVIG-associated hemolysis are provided. These preliminary data support the idea of an existing inflammatory condition preceding overt hemolysis after high-dose IVIG therapy that: 1) is restricted to non-group O patients, 2) is seen when using IVIG doses of more than 2 g/kg, 3) involves an activated mononuclear phagocyte system, 4) may be presaged by a significant increase in the anti-inflammatory cytokine interleukin-1 receptor agonist, and 5) is independent of secretor status.