Tan Ngoc Nguyen1, Elodie Maenulein1, Valentine Fihman2, Isabelle Vinatier1, Julia Moh Klaren1. 1. Etablissement Français du Sang, Laboratoire de Biologie Médicale, Site Saint-Antoine, Paris, France. 2. Etablissement Français du Sang, Laboratoire de Biologie Médicale, Site Ivry, 122-130 rue Marcel Hartmann, 94200 Ivry-sur-Seine, France.
Abstract
BACKGROUND: Oxaliplatin, a third-generation platinum derivative is commonly used in combination treatment of metastatic colorectal cancer. Since 2008, it is the second most common cause of drug-induced immune hemolytic anemia (DIIHA) investigated in our laboratory. STUDY DESIGN AND METHODS: Samples from fifteen patients including nine (60%) with intravascular hemolysis, suspected of having DIIHA were studied for the presence of anti-oxaliplatin. Direct antiglobulin tests (DATs) and tests with oxaliplatin-treated red blood cells (RBCs) or untreated and enzyme-treated RBCs in the presence of oxaliplatin were performed. A pool of normal AB sera with no unexpected antibodies was used as a control for nonimmunologic protein adsorption (NIPA). RESULTS: Eleven (73%) of the fifteen patients had antibodies to oxaliplatin that reacted with drug-treated RBCs and untreated RBCs in the presence of drug by tube and/or gel method. Lower-titer reactivity (<20) obtained with four patients' sera and the corresponding pooled normal sera was most likely due to NIPA. Eighty seven percent (13/15) of the patients had positive DAT either with anti-IgG only (33%), IgG + C3d (40%), or C3d only (13%). Two patients had a negative DAT. No directly agglutinating antibody was observed with the pools of normal donor's sera in the presence of oxaliplatin. CONCLUSION: Anti-oxaliplatin can cause severe intravascular hemolysis. Complement can usually be detected on the patient's RBCs and anti-oxaliplatin can be detected in the patient's serum. RBC-bound albumin detection with anti-human albumin needs to be performed to confirm NIPA which could have contributed to the patient's hemolytic anemia.
BACKGROUND:Oxaliplatin, a third-generation platinum derivative is commonly used in combination treatment of metastatic colorectal cancer. Since 2008, it is the second most common cause of drug-induced immune hemolytic anemia (DIIHA) investigated in our laboratory. STUDY DESIGN AND METHODS: Samples from fifteen patients including nine (60%) with intravascular hemolysis, suspected of having DIIHA were studied for the presence of anti-oxaliplatin. Direct antiglobulin tests (DATs) and tests with oxaliplatin-treated red blood cells (RBCs) or untreated and enzyme-treated RBCs in the presence of oxaliplatin were performed. A pool of normal AB sera with no unexpected antibodies was used as a control for nonimmunologic protein adsorption (NIPA). RESULTS: Eleven (73%) of the fifteen patients had antibodies to oxaliplatin that reacted with drug-treated RBCs and untreated RBCs in the presence of drug by tube and/or gel method. Lower-titer reactivity (<20) obtained with four patients' sera and the corresponding pooled normal sera was most likely due to NIPA. Eighty seven percent (13/15) of the patients had positive DAT either with anti-IgG only (33%), IgG + C3d (40%), or C3d only (13%). Two patients had a negative DAT. No directly agglutinating antibody was observed with the pools of normal donor's sera in the presence of oxaliplatin. CONCLUSION: Anti-oxaliplatin can cause severe intravascular hemolysis. Complement can usually be detected on the patient's RBCs and anti-oxaliplatin can be detected in the patient's serum. RBC-bound albumin detection with anti-human albumin needs to be performed to confirm NIPA which could have contributed to the patient's hemolytic anemia.