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Even small doses of intravenous immune globulin (IVIG) can cause acute, severe anemia, researchers warned.

Two such cases in Guillain-Barré syndrome patients after a total dose of only 125 to 225 g of IVIG each were reported by Sofya Pintova, MD, of Mount Sinai School of Medicine in New York City, and colleagues.

"Physicians should be aware of these rare sequelae so they will be prepared to manage them," the group wrote in the September 6 issue of the New England Journal of Medicine.

IVIG is known as a cause of hemolytic anemia, but only in large doses, they noted.

The problem is that the concentrated antibodies supplied by IVIG -- used in immune deficiency disorders as well as neurologic conditions and Guillain-Barré syndrome -- can have unintended and unexpected consequences, including hemolysis and false positive results on serologic tests.

IVIG passively transfers anti-A or anti-B antibodies as well as anti-Rh antibodies and antibodies to viral infection, but the amount of antibodies in a given lot of IVIG is no longer reported on the package insert.

These antibodies can be found through elution of red cells, the researchers noted.

Both of their cases had positive results on Coombs' tests for antiglobulin leading to premature red cell destruction, though the only unexpected antibody detected was anti-A1.

"Hemolysis is self-limiting, and the transfusion of type O packed red cells should be used to treat the anemia," they recommended.

The 60-year-old man treated for 5 days with 45 g IVIG per day and the 68-year-0ld woman treated with 25 g per day for 5 days showed progressively declining hemoglobin counts during treatment that reached a nadir of 7.7 and 5.9 g/dL, respectively, on day 10.

After type O transfusions on day 10, hemoglobin levels improved and hemolysis subsided in both cases.

The researchers noted that it's impractical to evaluate a patient's serological state before giving IVIG to anticipate problems.

Other previously reported adverse reactions to the treatment include headache, renal insufficiency, hepatitis C, meningeal irritation, and thrombosis.

One recent study showing promise for low-dose IVIG in Alzheimer's disease reported a stroke in one of the 24 patients treated, assumed to be because its high viscosity increases ischemic risk.