Elucidation of the mechanism of IVIG-associated hemolysis

Intravenous immunoglobulin (IVIG) is a blood product used to treat a number of health conditions, such as myasthenia gravis, itmnune thrombocytopenia, Guillain-BmTe Syndrome, and solid organ transplant rejection. IVIG is produced from thousands of human plasma donors at high costs, and has problematic side effects, including a type of injury to red blood cells known as hemolysis. The occurs because IVIG is made from so many donors and results in the incorporation of many kinds of antibodies that may be as harmful as they are helpful, especially if they react with a given patient's blood type molecules. Although there are manufacturing requirements to minimize these "isohemagglutinins" (anti-A/anti-B antibodies, in the ABO blood group system), there are increasing reports of IVIG administration resulting in hemolysis. In extreme cases hemolysis can result in severe anemia, kidney failure, heart failure and death. People who are blood group A and to lesser extent group B or AB seem to hemolyze more frequently after receiving IVIG at high doses, but for unlmown reasons some people seem more likely to hemolyze than others, even with the same blood group or dose of IVIG. To date, there have been no systematic studies examining individual patient factors that best predict susceptibility to IVIG-associated hemolysis. This study aims to identify these risks by following a large number ofiVIG recipients and waiting to see which ones develop hemolysis and which ones don't. Additional tests will be performed to see if the reasons for hemolysis can be better understood. The major objectives of this work are therefore (1) To decipher the pathways that end in hemolysis with high-dose IVIG; and (2) To identify a patient factors that best predict who is most likely to hemolyze when administered IVIG.

BRANCH, Donald

Canadian Blood Services

Intramural Research Grant Program

Ontario

$393,712