Glycoprotein Ib/IX complex is the target in rifampicin‐induced immune thrombocytopenia

Abstract

Summary. Thrombocytopenia is a major adverse effect of several drug treatments. Rifampicin has been recognized as a cause of immune thrombocytopenia during intermittent high-dose therapy. We characterized the antibody of a patient who presented with purpura and thrombocytopenia during treatment of tuberculosis with rifampicin. Drugdependent binding of the antibody to platelets was demonstrated by flow cytometry. In a glycoprotein-specific immunoassay, the binding epitope of the IgG antibody was found in the glycoprotein Ib/IX complex, using four different monoclonal antibodies (mAbs) against various epitopes on the GPIb/IX complex, as well as mAbs against GPIIb/IIIa, GPIa/IIa and GPIV. By immunoprecipitation of biotinlabelled platelets, reactivity of the antibody with GPIb/IX was found only in the presence of the drug. These findings clearly demonstrate that rifampicin induces the formation of drug-dependent antibodies capable of causing thrombocytopenia. The binding site of the rifampicin-dependent antibody, located in the GPIb/IX complex, seems to be a favoured target for antibodies induced by different drugs.

A Case of Isoniazid-Induced Thrombocytopenia: Recovery with Immunoglobulin Therapy

“…This finding correlates with previous studies reporting that intermittent drug administration is likely to result in a more severe and rapid adverse reaction. RFP-induced thrombocytopenia mostly developed in patients who were either on intermittent-dose regimens or were re-administered RFP after an interval (5,7,9,10).…”

Flow cytometry in the diagnosis of drug‐induced thrombocytopenia: Two illustrative cases

“…Drug binding to platelet surface can form a new epitope or cause the exposure of a neo-epitope. Glycoprotein Ib-IX and GP IIb/IIIa are most frequently involved in drug binding, which leads to the formation of new epitopes that appear to be very specific for each different drug [6][7][8][9][10][11][12][13][14]. The development of drug-dependent antiplatelet antibodies may thus cause accelerated platelet clearance in vivo and induce severe thrombocytopenia.…”

“…An immunological mechanism is postulated for many drugs, but so far there is clear evidence of drugdependent antiplatelet antibodies only for a few of them (rifampicin, abciximab, quinine, ranitidine, vancomycin, teicoplanin, sulfonamide, tamoxifene, heparin, and few others) [2,[6][7][8][9][10][11][12][13][14][15][16]. Drug binding to platelet surface can form a new epitope or cause the exposure of a neo-epitope.…”

Not So Innocent: Thrombocytopenia After One Dose of Rifampicin

“…İntermittan tedavi alan olgularda, ilaç alınmayan dönemlerde oluşan antikorların, ilacın tekrar alımı sonrasında alerjik reaksiyon oluşturduğu gösterilmiştir [5] . İlaca bağlı oluşan antikorların trombosit membran proteini olan glikoprotein Ib-IX ile etkileşime geçerek immün trombositopeniye neden oldukları bazı çalışmalarda gösterilmiştir [6,7] . İleri laboratuvar testler sonucunda ilaca bağlı gelişen antikorları saptamak mümkündür.…”