Intravenous immune globulin: myocardial infarction and cerebrovascular and thrombotic adverse reactions

In Canada the use of intravenous immune globulin ( IVIG ) is reported to have increased by approximately 115% over the past 7-8 years, making Canada one of the highest per capita users of IVIG in the world.
In this context of increasing use, it is important that health professionals recognize some of the serious adverse reactions suspected of being associated with the use of these products.

IVIG consists mostly of concentrated IgG manufactured from large pools of human plasma. Health Canada has authorized the use of a number of commercial brands for such indications as replacement therapy for primary or secondary immunodeficiency syndromes and treatment of idiopathic thrombocytopenic purpura. In addition, IVIG is often used off-label either as a passive immunizing agent or as an immunomodulator for the treatment of a growing number of conditions.

From October 1997 to July 2007, Health Canada received 10 reports of stroke ( reported as stroke, mini stroke, cerebral infarction or cerebrovascular accident ), 6 reports of thrombosis ( reported as thrombosis, thrombophlebitis or deep venous thrombosis ), 4 reports of myocardial infarction, 2 reports of pulmonary embolus and 1 report of transient ischemic attack ( TIA ) suspected of being associated with IVIG. Of the 21 patients involved, 2 had more than one adverse reactions. The median age was 61 ( range 28-88, age not provided in 1 report ).

The suspected products were reported as Gammagard S/D ( stroke, myocardial infarction, pulmonary embolism, thrombosis ), Gamunex/IGIVnex ( thrombosis, stroke, TIA ) and Gamimune N ( stroke, myocardial infarction ); the brand of IVIG was not specified in 3 reports ( stroke, myocardial infarction, thrombosis).

Two patients received IVIG for common variable immune deficiency, and 17 were prescribed it off-label for polyneuropathy ( 4 reports ), myositis ( 3 ), myasthenia gravis ( 2 ), dermatologic conditions ( 3 ) and other conditions ( 5 ). The indication for IVIG was not documented in 2 reports.

The number of days between the infusion of IVIG and the adverse reactions varied depending on the type of reaction. Nine reported strokes occurred within a day after the IVIG administration, with most occurring during the infusion; the tenth stroke occurred 3 days after the last dose. Three myocardial infarctions occurred during the infusion, and the fourth occurred 9 days later. The adverse reactions occurred within 1 day of IVIG administration for TIA, within 11 days for pulmonary embolism and within 2 weeks for thrombosis.

Information on dose and infusion rate was often lacking or incomplete in the reports. Risk factors for the reported adverse reactions were documented in all the reports of myocardial infarction, pulmonary embolism and TIA, in 8 of the 10 reports of stroke and in 4 of the 6 reports of thrombosis. Strokes resulted in the most serious outcomes ( 1 death, 4 cases of persistent sequelae ).

Serum viscosity has been shown to increase following IVIG administration.Although several possible mechanisms have been proposed, some authors have postulated that the change in serum viscosity during IVIG administration together with mild dehydration and other risk factors ( e.g., age, atherosclerosis ) contribute to the development of a threshold facilitating the production of thrombotic adverse reactions. Five reports noted the concomitant use of diuretics, which may have contributed to a rise in serum viscosity.

Source: HealthCanada, 2008


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