Ceftriaxone causes drug-induced immune thrombocytopenia and hemolytic anemia: characterization of targets on platelets and red blood cells.
BACKGROUND
Ceftriaxone, a third-generation cephalosporin, has been reported to occasionally cause fatal drug-induced immune hemolytic anemia (DIHA). A clinical and serologic analysis of the first two patients with severe drug-induced thrombocytopenia (DITP) due to ceftriaxone and one patient with fatal DIHA is reported.


METHODS
Sera were assessed by the IAT, EIA, glycoprotein (GP)-specific immunoassay, flow cytometry, and immunoprecipitation using transfectants expressing GPIIb/IIIa and GPIb/IX and with different cephalosporins.


RESULTS
Sera from Patients 1 and 2 reacted strongly with PLTs in the presence of the drug, but not with RBCs. The binding sites of the drug-dependent antibodies (DDAbs) could be localized to GPIIb/IIIa and GPIb/IX, respectively. Inhibition studies indicated that DDAbs recognized epitopes residing on the GPIIb/IIIa complex and on the GPIX subunit, respectively. No cross-reactivity was observed with other cephalosporin derivatives. Serum 3 showed strong agglutination with RBCs of Rh(null) phenotype in the presence of ex-vivo metabolites of ceftriaxone, but no cross-reactivity with PLTs.


CONCLUSIONS
The first two cases of severe DITP and a third patient with DIHA are reported. DDAbs from all patients showed individual reaction patterns and clear cell lineage specificity. In addition, the DDAbs were dependent on the substitution at position 3 of the ceftriaxone molecule. Epitopes on GPIIb/IIIa and GPIX were involved on PLTs. The Rh protein was not the only target of DDAbs on RBCs.
Grossjohann
Beatrice
B
Institute for Immunology and Transfusion Medicine, Ernst Moritz Arndt University Greifswald, Germany.
Eichler
Petra
P
Greinacher
Andreas
A
Santoso
Sentot
S
Kroll
Hartmut
H
D000293:Adolescent; D000368:Aged; D000743:Anemia, Hemolytic / Q000139:chemically induced*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D001792:Blood Platelets / Q000187:drug effects*; D016466:CHO Cells; D002443:Ceftriaxone / Q000009:adverse effects*; D002648:Child; D006224:Cricetinae; D004912:Erythrocytes / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000276:immunology; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000276:immunology; D013921:Thrombocytopenia / Q000139:chemically induced*
D000900:Anti-Bacterial Agents; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019038:Platelet Glycoprotein GPIb-IX Complex; D002443:Ceftriaxone