What are the treatment steps for an immune globulin (IG) overdose?

Management of Immune Globulin Overdose

There is no specific antidote or reversal agent for immune globulin overdose; management is entirely supportive and focused on monitoring and treating potential complications, particularly hemolysis, renal dysfunction, and thrombotic events.

Immediate Assessment and Monitoring

Critical Parameters to Monitor

• Hemoglobin and hematocrit should be checked 48-72 hours post-infusion, as hemolysis typically manifests 5-10 days after IVIG administration in 32% of high-dose cases, with 19% experiencing clinically significant hemolysis 1
• Renal function including creatinine and blood urea nitrogen must be monitored closely, as IVIG can exacerbate or cause de novo renal impairment, particularly in patients with underlying chronic kidney disease 2, 3
• Direct antiglobulin test (DAT) and markers of hemolysis including lactate dehydrogenase, haptoglobin, indirect bilirubin, and reticulocyte count should be obtained if hemoglobin drops 4
• Serum ferritin as an indicator of macrophage activation associated with hemolysis 1
• Liver enzymes should be monitored prospectively as standard practice with IVIG therapy 2

High-Risk Patient Identification

• Non-O blood group patients (particularly A, AB) are at significantly increased risk for hemolysis, as anti-A and anti-B isoagglutinins in IVIG products cause red cell destruction 1, 5, 4
• First-time IVIG recipients and those not on immunosuppressive medications have higher hemolysis risk 1
• Patients with pre-existing renal impairment require especially vigilant monitoring, as IVIG can worsen kidney function 3
• Patients with cardiovascular disease or diabetes mellitus are at increased thrombosis risk and may require slower infusion rates or subcutaneous administration 2

Supportive Management by Complication

For Hemolysis

• Stop further IVIG administration immediately if hemolysis is detected 4
• Provide red blood cell transfusion support as needed for symptomatic anemia or hemoglobin <7 g/dL 4
• Ensure adequate hydration to maintain renal perfusion and prevent acute kidney injury from hemoglobinuria 4
• Monitor for progression with serial complete blood counts every 24-48 hours until hemoglobin stabilizes 1
• Note that hemolysis is typically macrophage-mediated without complement consumption, so complement levels (C3/C4) remain normal 1

For Renal Dysfunction

• Discontinue or reduce IVIG dose based on severity of renal impairment 3
• Optimize hydration status while avoiding volume overload 3
• Discontinue other nephrotoxic medications if possible 2
• Consider switching to subcutaneous immunoglobulin in patients with compromised kidney function, as this route may have lower renal risk 3
• Nephrology consultation should be obtained for acute kidney injury or worsening chronic kidney disease 3

For Thrombotic Complications

• Assess for signs of thrombosis including deep vein thrombosis, pulmonary embolism, stroke, or myocardial infarction, particularly in patients with paraproteins or cardiovascular risk factors 2
• Slow infusion rate or hold further doses if thrombosis is suspected 2
• Anticoagulation should be initiated per standard protocols if thrombosis is confirmed 2

For Hyperviscosity (if applicable with very high immunoglobulin levels)

• Plasmapheresis should be considered for symptomatic hyperviscosity, though this is more relevant to underlying conditions like Waldenström macroglobulinemia rather than IVIG overdose itself 2
• Note that plasmapheresis immediately after IVIG will remove the administered immunoglobulin, so timing must be carefully considered 2

Important Clinical Caveats

Product-Specific Considerations

• Liquid, non-lyophilized IVIG products (Gamunex, Gammagard Liquid, Privigen) have higher isohemagglutinin titers (1:2 to 1:64) and are associated with increased hemolysis risk compared to lyophilized products 4
• However, low-titer products may be hyperosmotic and carry risks of acute renal failure or thrombosis 4

Timing of Complications

• Hemolysis is typically delayed, appearing 5-10 days after infusion completion in 84% of cases, not immediately 1
• This delayed presentation means patients may have already been discharged, emphasizing the need for scheduled follow-up assessment within 5-10 days post-infusion 1

What NOT to Do

• Do not administer additional IVIG to "dilute" or counteract the overdose, as this will only worsen potential complications 1, 4
• Do not assume immediate safety if the patient appears well immediately post-infusion, given the delayed nature of most complications 1
• Avoid assuming O blood type patients are at equal risk for hemolysis; they have significantly lower risk compared to non-O patients 1, 5

Follow-Up Protocol

• Schedule reassessment at 5-10 days post-infusion for all patients who received high-dose IVIG, particularly non-O blood types 1
• Repeat laboratory monitoring including complete blood count, renal function, and hemolysis markers at this visit 1
• Document the event and consider alternative immunoglobulin products or routes (subcutaneous) for future therapy if complications occurred 3