Can Recent Multiple Transfusions Cause False Positive Coombs Test?
Yes, recent multiple blood transfusions can cause false positive Direct Antiglobulin Test (DAT/Coombs) results, and this is a well-recognized pitfall in immunohematology practice that requires careful interpretation and timing of repeat testing.
Mechanism of False Positivity After Transfusion
Transfused donor red blood cells carrying antibodies can create a positive DAT result that does not reflect the patient's own immune status, as the test detects antibodies coating any red cells in circulation—whether the patient's own or transfused donor cells 1
Passive transfer of antibodies from blood products, including IVIg infusion, can coat the patient's red cells and produce false-positive results 2
Mixed cell populations in recently transfused patients create diagnostic challenges, as serological phenotyping becomes unreliable when donor and recipient cells coexist in circulation 3
Clinical Timing for Repeat Testing
Wait at least 7 days after the last transfusion before repeating Toxoplasma IgM or IgA testing when false positivity from blood products is suspected 2
For neonates with suspected maternal blood contamination, repeat testing should occur at least 5 days after birth for IgM (half-life of 5 days) and 10 days for IgA (half-life of 10 days) 2
Follow-up studies several days after a suspected hemolytic transfusion reaction may clarify the diagnosis, as antibodies responsible for reactions may not be clearly demonstrable immediately post-transfusion 4
Diagnostic Approach in Transfused Patients
Genotyping is more reliable than phenotyping in transfusion-dependent patients, as molecular methods demonstrate fewer false results compared to serological testing when recent transfusions are present 3
Recent transfusions represent a major cause of discrepancies between serological phenotyping and genotyping, particularly in sickle cell disease patients and other chronically transfused populations 3
The direct Coombs test may be negative immediately post-transfusion even when a hemolytic reaction is occurring, limiting its diagnostic utility in the acute setting 4
Common Pitfalls to Avoid
Do not interpret a positive DAT as definitive evidence of autoimmune hemolytic anemia in recently transfused patients without considering the timing of transfusions and waiting the appropriate interval for repeat testing 1
Avoid transfusing additional blood products during the investigation period when a hemolytic transfusion reaction is suspected, as this will further complicate serological interpretation 4
False-positive and false-negative reactions exist for both serological and molecular methods, requiring investigation when predicted phenotypes are inconsistent with known antibodies or clinical history 3
Chronic antigenic stimulation from multiple transfusions causes immunologic abnormalities including depressed natural killer cell function and elevated HLA-DR expression on T cells, though this represents a different phenomenon from false-positive DAT results 5