<i>Ex vivo</i> antigen preparation for the serological detection of drug‐dependent antibodies in immune haemolytic anaemias

Salama, Abdulgabar; Mueller‐Eckhardt, C.; Kissel, Karin; Pralle, H.; Seeger, Werner

doi:10.1111/j.1365-2141.1984.tb04000.x

Cited by 47 publications

(11 citation statements)

References 11 publications

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“…DIIHA should be suspected when there is positive DAT and an eluate that is non‐reactive or with disproportionately weaker reactions than the DAT against an RBC panel 7. If initial studies with native drug are negative then metabolites of the drug (plasma and/or urine) should be tested 9.…”

Section: Discussionmentioning

confidence: 99%

Trimethoprim-induced immune hemolytic anemia in a pediatric oncology patient presenting as an acute hemolytic transfusion reaction

Gupta

Piefer

Fueger

et al. 2010

Pediatr. Blood Cancer

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A 10-year-old male with acute leukemia presented with post-chemotherapy anemia. During red cell transfusion, he developed hemoglobinuria. Transfusion reaction workup was negative. Drug-induced immune hemolytic anemia was suspected because of positive direct antiglobulin test, negative eluate, and microspherocytes on smear pre- and post-transfusion. Drug studies using the indirect antiglobulin test were strongly positive with trimethoprim and trimethoprim-sulfamethoxazole but negative with sulfamethoxazole. The patient recovered after discontinuing the drug, with no recurrence in 2 years. Other causes of anemia should be considered in patients with worse-than-expected anemia after chemotherapy. Furthermore, hemolysis during transfusion is not always a transfusion reaction.

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Section: Discussionmentioning

confidence: 99%

Trimethoprim-induced immune hemolytic anemia in a pediatric oncology patient presenting as an acute hemolytic transfusion reaction

Gupta

Piefer

Fueger

et al. 2010

Pediatr. Blood Cancer

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“…One of the major reasons for false-negative results is the number of ddab reacting with RBCs only in the presence of the drug metabolites, but not with the native drug. Trace metabolites as immunogenic agents have been described for different drugs in DIHA, such as buthiazide, nomifensine [ 46 ], 5-FU [ 47 ], anti-infective drugs [ 48 ], ceftriaxone [ 24 ] and some non-steroidal anti-inflammatory drugs [ 21 , 49 , 50 ]. In our study, 17 (23%) of the ddab reacted only with ex vivo metabolites and would have been overlooked if analysis was performed only in the presence of the native drug.…”

Section: Discussionmentioning

confidence: 99%

Variability of Findings in Drug-Induced Immune Haemolytic Anaemia: Experience over 20 Years in a Single Centre

Mayer

Bartolmäs

Yürek

et al. 2015

Transfus Med Hemother

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Background: Drug-induced immune haemolytic anaemia (DIHA) is difficult to diagnose, and its true incidence remains obscure. Here, we present cases of DIHA identified at our institute over the last two decades. Methods: Serological tests were performed according to standard procedures. Detection of drug-dependent antibodies was performed in the presence and absence of the relevant drug and/or their ex vivo antigens. Results: Over the last 20 years, 73 patients have been identified with DIHA in our institute, which was related to 15 different drugs. The most common single drugs identified were diclofenac (n = 23), piperacillin (n = 13), ceftriaxone (n = 12) and oxaliplatin (n = 10). As far as data were available, haemolysis was acute in all patients, and signs of intravascular haemolysis were present in 90% of the cases. Haemolysis resulted in death in 17 patients (23%). The remaining patients recovered, but haemolysis was complicated by transitory renal and/or liver failure or shock in 11 patients. Upon initial evaluation, the antibody screening test was positive in 36 cases. A positive direct antiglobulin test (DAT) at least with anti-C3d was found in 65 cases, with anti-IgG only in 6 cases, and with anti-IgA only in 1 case. Conclusion: DIHA is a rare but potentially life-threatening disorder that should be considered if a patient develops haemolysis under drug treatment. The main serological finding is a positive DAT, primarily with anti-C3d.

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“…Antibodies of this type can sometimes be detected on the basis of drug‐dependent binding of antibody to target RBCs, 7 but results are often negative. In such cases, positive reactions are sometimes obtained when serum 8,9 or urine 10 from a person taking the implicated medication is substituted for the primary drug, which indicates that the sensitizing agent is probably a drug metabolite formed in vivo.…”

mentioning

confidence: 99%

Immune hemolytic anemia caused by sensitivity to a metabolite of etodolac, a nonsteroidal anti‐inflammatory drug

et al. 2000

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This patient appears to have experienced acute, severe immune hemolytic anemia on two occasions because of sensitivity to the glucuronides of etodolac and 6-OH etodolac. In patients suspected of having drug-induced immune hemolytic anemia, RBC-reactive antibodies can sometimes be detected by using urine from an individual taking the implicated medication as the source of drug metabolites in in vitro reactions. For patients who present with acute immune hemolysis, a careful history of drug exposure should be taken, and, where indicated, confirmatory testing should be performed to identify the sensitizing drug and prevent inadvertent reinduction of hemolysis at a later time.

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Ex vivo antigen preparation for the serological detection of drug‐dependent antibodies in immune haemolytic anaemias

Cited by 47 publications

References 11 publications

Trimethoprim-induced immune hemolytic anemia in a pediatric oncology patient presenting as an acute hemolytic transfusion reaction

Trimethoprim-induced immune hemolytic anemia in a pediatric oncology patient presenting as an acute hemolytic transfusion reaction

Variability of Findings in Drug-Induced Immune Haemolytic Anaemia: Experience over 20 Years in a Single Centre

Immune hemolytic anemia caused by sensitivity to a metabolite of etodolac, a nonsteroidal anti‐inflammatory drug

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