Table 2:

Adverse effects associated with intravenous immunoglobulin use

Adverse eventFrequency, %Risk factorsMechanism of actionPreventive strategies and treatmentSeverity
Flu-like syndrome: flushing, headache, chills, low-grade fever, nausea, malaise, mild hypotension, muscle aches during infusion1–15
  • Fast infusion rate

  • IgA proportion

  • First infusion of IVIg

  • Fc receptor–mediated release of prostaglandins, platelet-activating factor and cytokines from leukocytes

  • Aggregation of IgG, leading to complement activation

  • Formation of immune complex

  • Slow infusion rate

  • Discontinuation of infusion

  • Product brand substitution

  • Premedication with one or more of antipyretic, corticosteroid or antihistamine

  • Subcutaneous infusion

Mild and transient
Intravascular acute hemolysis during infusion and lasting up to 3 d after infusion< 0.1
  • High-dose infusion

  • Blood group other than type O

  • Multiparous women

  • Higher titers of anti-A or anti-B IgG antibodies

  • Passive transfer of antibodies (isohemagglutinins) against antigens of ABO and Rh

  • Underlying inflammatory state

  • Blood type cross-matching

  • Determination of anti-A and anti-B antibody titer before infusion

  • Post-transfusion testing for hemolysis within 36 h in patients with anemia

Moderate (should not require transfusion)
Acute aseptic meningitis within 48–72 h after infusion< 0.1
  • Fast infusion rate

  • History of migraine

  • Release of inflammatory cytokines

  • Presence of ANCA-like immunoglobulins

  • Anti-inflammatory agents and pain killers

Moderate and transient
Arterial or venous thromboembolic event (transient ischemic attack, stroke or peripheral deep thromboembolism) starting within 24 h after infusion< 0.1
  • First infusion of IVIg

  • Age > 60 yr

  • High dose

  • Previous thrombotic event and thrombophilia

  • Risk factors for cardiovascular events (e.g., dyslipidemia, hypertension, diabetes)

  • Autoimmune disease or cancer

  • Rheological properties of IVIg leading to hyperviscosity

  • Contamination with clotting factors

  • Vasospasm secondary to release of vasoactive molecules

  • Formation of platelet–leukocyte aggregates

  • Prophylactic hydration

  • Slow infusion of IVIg

  • Early treatment of high-risk patients

  • Prophylactic anticoagulation

Moderate to severe
Hypertension and fluid overload during infusion and lasting up to 2 d after infusion< 1
  • Previous elevated plasma viscosity (e.g., polycythemia, paraproteinemia)

  • Previous heart and kidney failure

  • Hypergammaglobulinemia and viscosity

  • Adequate hydration

Moderate to severe
Acute renal failure (from transient mild alteration in renal function to renal failure requiring dialysis) starting within 1–10 d after infusion< 1
  • Age > 60 yr

  • Obesity and type 1 diabetes

  • Pre-existing renal disease

  • Sepsis

  • Paraproteinemia

  • Use of nephrotoxic agents

  • Direct toxicity on proximal renal tubular epithelial cells, osmotic tubular injury secondary to stabilizers used in IVIg preparation (sucrose, maltose, glucose)

  • Cryoglobulin precipitate

  • Adequate hydration

  • Monitoring of renal function before and after infusion

  • Use of sugar-free stabilizers

  • Avoidance of concomitant nephrotoxic therapy

  • Avoidance in cryoglobulinic-positive patients

Mild to severe
Non–IgE-mediated anaphylactic reaction (from tightness of throat or chest, chills and rigor to breathlessness, dizziness, fainting or collapse and death) starting early during infusion< 0.1
  • IgA deficiency (20% related to anti-IgA antibodies, particularly in patients with systemic lupus erythematosus or myasthenia)

  • Anti-IgA antibodies (IgG isotypes) reacting with IgA in IVIg preparations

  • Discontinuation of infusion and supportive treatment (intensive care unit)

  • Screening of IgA deficiency in patients before infusion

  • Use of IVIg preparation with lower concentration of IgA

Moderate to severe
Local reaction to subcutaneous immunoglobulin (swelling, redness, itching or burning sensation)8–50
  • Initiation of subcutaneous therapy

  • Local irritant effect

  • Symptomatic management

  • Monitoring to ensure no long-term changes such as fat necrosis or fibrosis

Mild to moderate
  • Note: ANCA = antineutrophil cytoplasmic antibodies, IVIg = intravenous immunoglobulin, SCIg = subcutaneous immunoglobulin.