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Ceftriaxone causes drug‐induced immune thrombocytopenia and hemolytic anemia: characterization of targets on platelets and red blood cells
Author(s) -
Großjohann Beatrice,
Eichler Petra,
Greinacher Andreas,
Santoso Sentot,
Kroll Hartmut
Publication year - 2004
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/j.1537-2995.2004.03378.x
Subject(s) - epitope , ceftriaxone , hemolytic anemia , platelet , serology , medicine , antibody , immunology , antibiotics , chemistry , biochemistry
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. STUDY DESIGN AND METHODS: Sera were assessed by the IAT, EIA, glycoprotein (GP)‐specific immunoassay, flow cytometry, and immunoprecipitation using trans‐fectants 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.