Ceftriaxone causes drug-induced immune thrombocytopenia and hemolytic anemia: characterization of targets on platelets and red blood cells
Article first published online: 28 JUN 2004
Volume 44, Issue 7, pages 1033–1040, July 2004
How to Cite
Großjohann, B., Eichler, P., Greinacher, A., Santoso, S. and Kroll, H. (2004), Ceftriaxone causes drug-induced immune thrombocytopenia and hemolytic anemia: characterization of targets on platelets and red blood cells. Transfusion, 44: 1033–1040. doi: 10.1111/j.1537-2995.2004.03378.x
- Issue published online: 28 JUN 2004
- Article first published online: 28 JUN 2004
- Received for publication November 25, 2003; revision received February 3, 2004, and accepted February 10, 2004.
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 Rhnull 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.