Intravenous Immunoglobulin (IVIG) therapy is a medical treatment derived from the pooled plasma of thousands of healthy donors, containing a high concentration of antibodies, primarily Immunoglobulin G (IgG). This treatment is utilized for patients with primary immune deficiencies requiring replacement antibodies, or those with autoimmune and inflammatory conditions where the therapy modulates the immune system. The infusion of this massive quantity of external antibodies directly interferes with a broad spectrum of laboratory tests. The presence of these non-patient-produced proteins necessitates careful interpretation of results to avoid diagnostic errors and inappropriate clinical decisions.
How IVIG Elevates Immunoglobulin Levels
IVIG preparations are composed of more than 90% human IgG antibodies, introducing a large protein load into the bloodstream. The primary therapeutic effect is a rapid and significant elevation of the patient’s total serum IgG level, which is the intended outcome. Following infusion, the total IgG concentration can increase several-fold, peaking shortly after treatment is completed. This spike causes temporary hyperproteinemia, an increase in total protein measured in the blood. The half-life of these passively transferred antibodies is approximately 21 to 28 days, meaning elevated levels persist for several weeks. This high protein concentration can also interfere with basic chemistry panels, sometimes leading to pseudohyponatremia (a false low reading of serum sodium levels).
Impact on Antibody Screening and Blood Typing
The most significant interference occurs in blood bank testing, which detects antibodies that might cause a transfusion reaction. IVIG contains a wide variety of donor antibodies, including passively acquired alloantibodies (antibodies against other people’s red blood cell antigens). These external antibodies can bind to a patient’s red blood cells or react with test reagents, complicating pre-transfusion screening. The presence of these non-patient antibodies frequently causes a false-positive result on the Direct Antiglobulin Test (DAT), also known as the Direct Coombs Test. The DAT detects antibodies attached to the patient’s red blood cells, and the IVIG-derived antibodies can mimic an autoimmune hemolytic process. Similarly, the Indirect Antiglobulin Test (IAT) or antibody screen, which detects unbound antibodies in the patient’s plasma, may also turn positive. Such results can lead to incompatible cross-matches, making it difficult to safely provide blood transfusions and potentially delaying care.
Interference with Specific Clinical Markers
Beyond basic protein and blood typing tests, IVIG can disrupt the accurate measurement of many diagnostic markers used to identify disease. Since IVIG is pooled from thousands of donors, it often contains trace amounts of protective antibodies against common pathogens. The passive transfer of these antibodies can result in transient false-positive findings on serology tests for infectious diseases. For instance, patients may test positive for antibodies against viruses like Hepatitis C, Cytomegalovirus (CMV), or Human Immunodeficiency Virus (HIV), despite never having been infected. This can lead to unnecessary investigations for a non-existent infection. Furthermore, the high concentration of IgG can interfere with assays for autoimmune disorders, such as Antinuclear Antibody (ANA) tests, or create false “M-spikes” in Serum Protein Electrophoresis (SPEP), mimicking conditions like multiple myeloma.
Guidelines for Accurate Lab Testing
To mitigate the interference caused by IVIG, careful coordination and timing of blood collection are necessary. For tests monitoring the patient’s immune status, such as IgG levels, blood should be drawn immediately before the next scheduled infusion, known as a trough level. This timing provides the most accurate reading of the patient’s antibody status at its lowest point. For serology tests, particularly those for infectious diseases or specific autoimmune markers, the body needs time to clear the passively transferred donor antibodies. Clinicians recommend delaying these diagnostic tests for a significant period, often 6 weeks to 4 months. The laboratory and ordering physician must be informed of the exact date and dose of the last IVIG infusion to ensure proper interpretation of results.