Positive direct and indirect antiglobulin tests associated with oxaliplatin can be due to drug antibody and/or drug-induced nonimmunologic protein adsorption.
BACKGROUND
Two patients were suspected of having immune hemolytic anemia (IHA) due to oxaliplatin. A related drug, cisplatin, is known to cause nonimmunologic protein adsorption (NIPA). Studies were performed to determine the presence of oxaliplatin-dependent antibodies in addition to oxaliplatin-induced NIPA.


METHODS
Sera and eluates from the two patients were tested against red blood cells (RBCs) treated with oxaliplatin, cisplatin, and carboplatin (another platinum drug). Sera were also tested against untreated RBCs in the presence of the same drugs. Testing with pooled normal sera and anti-human albumin was used to demonstrate the presence of NIPA. Oxaliplatin-treated RBCs sensitized with the patients' sera and pooled normal sera were tested by a monocyte monolayer assay (MMA) to determine potential clinical significance.


RESULTS
Both patients had high-titer antibodies to oxaliplatin in their sera that reacted with oxaliplatin-treated RBCs and with untreated RBCs in the presence of oxaliplatin. RBCs treated with oxaliplatin, cisplatin, and carboplatin all demonstrated NIPA (pooled normal sera and anti-human albumin were reactive to low titers). NIPA was also detected in tests with untreated RBCs in the presence of oxaliplatin and cisplatin. Lower-titer reactivity of both patients' sera with cisplatin may have been due to NIPA and/or cross-reactivity of anti-oxaliplatin with cisplatin. MMAs were weakly positive due to NIPA and more strongly positive due to oxaliplatin antibodies.


CONCLUSIONS
Two patients with IHA were demonstrated to have oxaliplatin-dependent antibodies. Oxaliplatin was also shown to cause NIPA. The drug-dependent antibody and/or the drug-induced NIPA could have contributed to the patients' hemolytic anemia.
Arndt
Patricia
P
American Red Cross Blood Services, Southern California Region, 100 Red Cross Circle, Pomona, CA 91768, USA. arndtp@usa.redcross.org
Garratty
George
G
Isaak
Edahn
E
Bolger
Michael
M
Lu
Qun
Q
D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D000327:Adsorption; D000368:Aged; D000744:Anemia, Hemolytic, Autoimmune / Q000097:blood / Q000139:chemically induced; D000906:Antibodies / Q000097:blood*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000097:blood / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D003298:Coombs Test / Q000379:methods*; D004347:Drug Interactions; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology* / Q000493:pharmacokinetics*; D000077150:Oxaliplatin; D011506:Proteins / Q000187:drug effects / Q000378:metabolism*
D000906:Antibodies; D009944:Organoplatinum Compounds; D011506:Proteins; D000077150:Oxaliplatin