One center's experience: the serology and drugs associated with drug-induced immune hemolytic anemia--a new paradigm.
BACKGROUND
Drug-induced immune hemolytic anemia (DIIHA) is an uncommon finding characterized by a sudden decrease in hemoglobin after treatment with the putative drug. The full range of drugs causing DIIHA and the initial serologic presentation are not fully appreciated. This work identifies additional drugs associated with DIIHA and offers additional insights about diagnosis.


METHODS
A 20-year retrospective review of testing in one laboratory was performed. Patient sex, age, medication history, initial direct antiglobulin test (DAT) and indirect antiglobulin test, method of drug-dependent antibody (DDA) detection, and specificity were reviewed.


RESULTS
Seventy-one patients with 73 DDAs to 23 different drugs were identified. The following DDA specificities were identified: cephalosporins (37), penicillin and/or penicillin derivatives (12), nonsteroidal anti-inflammatory drugs (NSAIDs) (11), quinine and/or quinidine (7), and others (6). Fifty-two percent (37) were due to cephalosporins with 27 cefotetan-dependent antibodies detected. Four NSAIDs required urinary metabolite for detection. DAT was strongly positive, at least 2+, in 75 percent (51/68) of patients with a positive DAT. Initial eluate was negative in 52 patients, weak positive (<2+) in 14 patients, and strong positive (>or=2+) in 2 patients. Serologic results showed characteristics of warm autoimmune hemolytic anemia (AIHA) in 22 or 31 percent of all cases and cold-reactive AIHA in 2 cases.


CONCLUSIONS
It is important to consider DIIHA when a patient serologically presents as either warm- or cold-type AIHA to avoid erroneous diagnosis. Based on these findings, the strength of the initial DAT is much stronger than previously reported for all types of drug-induced immune hemolysis. This report is also unique in the number of NSAIDs reported. A new classification of categorizing DDA is proposed.
Johnson
Susan T
ST
BloodCenter of Wisconsin, Inc., Immunohematology Reference Laboratory, Milwaukee, Wisconsin 53201-2178, USA. sue.johnson@bcw.edu
Fueger
Judith T
JT
Gottschall
Jerome L
JL
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000744:Anemia, Hemolytic, Autoimmune / Q000097:blood / Q000139:chemically induced / Q000175:diagnosis*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D015313:Cefotetan / Q000009:adverse effects; D002511:Cephalosporins / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D003298:Coombs Test / Q000379:methods; D064420:Drug-Related Side Effects and Adverse Reactions / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010406:Penicillins / Q000009:adverse effects; D011802:Quinidine / Q000009:adverse effects; D011803:Quinine / Q000009:adverse effects; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D012698:Serologic Tests / Q000379:methods
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002511:Cephalosporins; D010406:Penicillins; D015313:Cefotetan; D011803:Quinine; D011802:Quinidine