Could abciximab (ReoPro) induce refractory thrombocytopenia, if so, what is the proper therapy?/nTh

Fråga: Could abciximab (ReoPro) induce refractory thrombocytopenia, if so, what is the proper therapy?

The question relates to a 56-year-old male who was transferred for coronary angiography after an acute myocardial infarction. He was treated with clopidogrel (Plavix) and with abciximab infusion (20 mg bolus dose iv + 8 mg 12h infusion). He was previously also on acetylsalicylic acid (Trombyl) 75 mg/d and simvastatin (Zocord) 20 mg/d. On the 4:th day after abciximab infusion the thrombocyte concentration decreased from 211x 10E9/L to 23x 10E9/L. Clopidogrel treatment was stopped. The thrombocyte concentration was normalised on the 8:th day 225x 10E9/L. The next day the patient was again transferred for coronary angiography and received a second 20 mg bolus dose of abciximab followed by infusion. One hour after initiation of abciximab the thrombocyte concentration was 46x 10E9/L and the infusion was discontinued. A few hours later the thrombocyte concentration was further decreased to 8x 10E9/L. Repeated thrombocyte transfusions and treatment with prednisolone (Deltison) 50 mg x2 were without effect.

Sammanfattning: Thrombocytopenia is a well known adverse reaction to abciximab. In most cases the patients recover within 6-8 days. There is no data in the literature regarding repeated exposure to abciximab and thrombocytopenia. The main treatment of profound thrombocytopenia following abciximab therapy, is platelet transfusion. If there are no clinical signs of active bleeding and platelet transfusion is considered, pseudothrombocytopenia should be ruled out. In cases where heparin was used heparin induced thrombocytopenia should also be ruled out before platelet transfusion.

Svar: Thrombocytopenia is a well known adverse reaction to abciximab (1) and is also reported for clopidogrel and acetylsalicylic acid (2). The mechanism underlying the abciximab induced thrombocytopenia is not well understood but seems to be of immunological origin (3). Abciximab is the F(ab) fragment of a chimeric mouse/human monoclonal immunoglobulin G antibody against the platelet GP IIb/IIIa receptors and blocks the binding of fibrinogen and thus inhibits platelet aggregation(5). Of the nine reported cases in the Swedish drug information system (Swedis) almost all patients recovered within 6-8 days. In one case it took 4 weeks to reach full recovery (2). In the present case, the patient was also on other drugs known to cause thrombocytopenia and the overall effect might be a more pronounced and/or prolonged thrombocytopenia.

We could not find any data in the literature about the possible consequences of repeated exposure to abciximab regarding thrombocytopenia. The treatment of profound thrombocytopenia following abciximab therapy was recently reviewed in an article by Jubelirer et al (3). In conclusion, abciximab should be discontinued immediately and platelet transfusion should be given if active bleeding is present. IgG can be considered in addition to to platelet transfusion, but its therapeutic effect is unknown. If platelet transfusion is considered in the absence of clinical signs of bleeding, pseudothrombocytopenia due to platelet clumping should be ruled out (3,4). Heparin induced thrombocytopenia should also be ruled out in cases where heparin was administered (6). 1 Summary product characteristics (SPC) Reopro 2 Swedis (The Swedish Drug Information System) 3 Jubelirer SJ, Koening BA, Bates MC. Acute profound thrombocytopenia following C7E3 Fab (abciximab) therapy: case reports, review of the literature and implications for therapy. Am J Hematol 1999; 61: 205-8 4 Holmes MB, Kabbani S, Watkins MW, Battle RW, Schneider DJ. Abciximab-associated pseudothrombocytopenia. Circulation 2000; 101: 938-9 5 Kozak M, Dove T, Rozman P, Blinc A. A case of pseudothrombocytopenia after infusion of abciximab in vivo and anticoagulant-independent plateletc clumping after rechallenge with abciximab in vitro. Wien Klin Wochenschr 2000; 112: 138-41 6 Davidson SJ, Turner JR. Oldershaw PJ, Burman JF. The importance of differentiating ReoPro (c7E3 abciximab) induced thrombocytopenia from heparin-induced thrombocytopenia. Thromb Haemost 1999; 82: 1560-1