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Causes of panagglutination on the pretransfusion antibody screen

Causes of panagglutination on the pretransfusion antibody screen
Cause of panagglutination Findings Approach to identifying crossmatch compatible blood
Alloantibody to a high-frequency antigen
  • History of previous exposure to allogeneic RBCs*
  • Negative autocontrol
  • Similar intensity of reactivity to all panel RBCs
  • Extended phenotype (or genotype) of patient RBCs
  • If a high-frequency antigen is suspected based on RBC phenotype/genotype, test with panel cells lacking that antigen
Multiple alloantibodies
  • History of previous exposure to allogeneic RBCs*
  • Negative autocontrol
  • Variable intensity of reactivity to different panel RBCs
  • Extended phenotype (or genotype) of patient RBCs
  • Enzyme treatment (papain or ficin)
  • Adsorption and elution
Autoantibodies
  • Known history of AIHA
  • Positive autocontrol
  • Direct antiglobulin (direct Coombs) test
Treatment with a therapeutic monoclonal antibody
  • Anti-CD38
  • Anti-CD47
  • Documentation of treatment by history or medical record
  • May cause positive autocontrol
  • Type and screen before starting therapeutic monoclonal antibody
  • For daratumumab, certain in vitro reagents can be used to decrease interference (refer to UpToDate for details)
Panagglutination refers to an antibody screen (indirect antiglobulin test; indirect Coombs test) in which the patient's serum/plasma reacts with all reagent RBCs on the test panels. The autocontrol determines whether the panagglutinin is present in the patient's serum/plasma. A key concern with autoantibodies is that there may also be alloantibodies that are not detected due to panagglutination caused by the autoantibodies. Intravenous immune globulin (IVIG) and anti-RhD do not cause panagglutination since they only contain certain antibodies.

RBCs: red blood cells; AIHA: autoimmune hemolytic anemia.

* The two most common types of exposure are prior transfusion and pregnancy. Rarely, an individual may be exposed via sharing of needles or other types of exposure.

¶ RBC genotyping may not be available in all centers. When available, it is most helpful when commercial reagents are unavailable to test a specific antigen or when RBC phenotyping is inconclusive or especially complex.
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