What is the risk for transmission of infectious agents through IVIG to treat common variable immunodeficiency (CVID)?

Updated: Oct 16, 2018
  • Author: C Lucy Park, MD; Chief Editor: Harumi Jyonouchi, MD  more...
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Answer

The potential for transmission of pathogens cannot be completely ruled out. In 1993 and 1994, transmission of hepatitis C virus (HCV) was reported in recipients of one of two IVIG products that did not undergo viral inactivation steps during manufacturing. All IVIG products currently marketed in the United States now undergo viral inactivation and removal.

In order to reduce potential contamination of pathogens, all plasma for manufacture is tested at various levels and retested by viral marker and nucleic acid technology (NAT).

Viral inactivation is achieved by dry heat, pasteurization, or irradiation solvent-detergent treatment, low pH exposure, or caprolate treatment. Viral removal is necessary to reduce the risk of transmission of nonenveloped viruses and include precipitation, chromatography, and filtration including nanofiltration.

Because of the introduction of various viral inactivation and removal processes, relatively large viruses, such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), and HCV, are readily inactivated and can be effectively removed.

No case of HIV infection has resulted from treatment with IVIG because retroviruses are readily inactivated by the cold ethanol precipitation. The main concern is prions that transmit spongiform encephalopathy or referred to as variant Creutzfeldt-Jacob disease (vCJD).

Currently, no blood tests or inactivation methods are applicable to prions. Fortunately, prions have not been detected directly in human blood and the potential for efficient removal of prions by the current manufacturing processes have been documented.

Acute and chronic renal failure has been reported, most often in patients with preexisting renal disease who received sucrose-containing IVIG solutions. IVIG products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients at risk for acute renal failure include patients with any degree of preexisting renal insufficiency, diabetes mellitus, age older than 65 years, volume depletion, sepsis, paraproteinemia, or patients receiving known nephrotoxic drugs. Those products containing sucrose as a stabilizer accounted for a disproportionate share of the total number.

For patients at increased risk, monitoring BUN and creatinine levels before starting the treatment and prior to each infusion is necessary. If renal function deteriorates, the product should be discontinued.

Other rare reactions to IVIG include aseptic meningitis, lymphocytic pleural effusion, thromboembolism, coagulopathy, and immune hemolysis. Suspected causes of these adverse events are hyperosmolarity, presence of activated factor XI, and high sodium content. However, these are from anecdotal observation, and establishing precise guidelines for reducing the risk of adverse events is difficult.


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