Abciximab thrombocytopenia with

Doses and contraindications to glycoprotein Ilb/IIIa receptor blockers are described in Table 5-2. Major bleeding and rates of transfusion are increased with administration of a glycoprotein Ilb/IIIa receptor inhibitor in combination with aspirin and an anticoagulant,30 but there is no increased risk of intracranial hemorrhage in the absence of concomitant fibrinolytic treatment. The risk of thrombocytopenia with tirofiban and eptifibatide appears lower than that with abciximab. Bleeding risks appear similar between agents. 

The bleeding potential is similar among the agents. However, thrombocytopenia, particularly profound thrombocytopenia (platelet count <50,000 mrrT3) occurs with a two-to four-fold higher frequency with abciximab (0.4— 1.0%) compared with eptifibatide (0-0.2%) or tirofiban (0,1 —0.3%) (6), The exact mechanism of this difference is not clear, However, immune complex-mediated reaction (due to an anamnestic response to the humanized chimeric antibody) may contribute to rapid precipitation of thrombocytopenia with abciximab (6), Platelet counts should, therefore, be measured early (within the first one to four hours) after administration of these agents and followed for the duration of therapy. Platelet transfusion should be considered for profound thrombocytopenia with or without serious bleeding (6). 

The main concern with the use of Gp llb/llla inhibitors is the risk of hemorrhage and thrombocytopenia. On meta-analysis, major hemorrhage was significantly more likely with abciximab than with either tirofiban (standard regimen) or eptifibatide (33), The TARGET trial demonstrated abciximab to predispose to thrombocytopenia when compared to tirofiban (35), Regardless, thrombocytopenia (platelet count <20,000/ jJ) is rare (<3%) and can often be treated conservatively, without the need for platelet transfusions,... 

During postmarketing surveillance of the first 4000 patients treated with abciximab in France, 25 cases of thrombocytopenia (0.6%) were reported, with five severe cases (0.15%) and three acute profound forms (0.08%). In all cases reported, the role of heparin must be taken into account. The thrombocytopenia associated with abciximab differs with that associated with heparin by its rapid onset (within 24 hours), its reversal after platelet transfusion, and its possible association with hemorrhage but not with thrombosis. 

E3 monoclonal antibody to GPIIb/llla (abciximab) is very useful as an antiplatelet drug in high-risk ACSs and PCI, It can be used in conjunction with reduced levels of heparin and with aspirin (Table I), Patients may uncommonly experience sudden severe thrombocytopenia within the early hours of treatment as a side effect. 

Abciximab STEMI (27), unstable angina (28),elective PCI (29) 0.25mg/kg followed by 0.125 xg/kg/min infusion Benefit in low/intermediate risk patients following clopidogrel pretreatment debated (39,40) Significant benefit (27-29) especially with respect to mortality (27) and reinfarction (27,28) Increased risk of major bleeding and thrombocytopenia compared to other Gp Ilb/IIIa inhibitors (33)... 

Adverse effects. Haemorrhage occurs but is less of a problem with low doses of heparin it remains a particular risk in patients treated after failed fibrinol5 c therapy for acute myocardial infarction. Platelet transfusion after cessation of abciximab is necessary for refractory or life threatening bleeding. After transfusion, the antibody redistributes to the transfused platelets, reduces the mean level of receptor blockade and improves platelet function. Thrombocytopenia may occur from 1 hour to days after commencing treatment in up to 1% of patients. This necessitates platelet counts at 2-4 hours and then daily if severe, therapy must be stopped and, if necessary, platelets transfused. EDTA-induced pseudothrombocytopenia has been reported and a low platelet count should prompt examination of a blood film for agglutination before therapy is stopped. 

The other significant risk associated with abciximab is thrombocytopenia. Data pooled from three major trials showed that thrombocytopenia (under 100 x 10 /1) was significantly more frequent in those who received a bolus dose of abciximab followed by an infusion than in placebo recipients (3.7 versus 2%). Severe thrombocytopenia (under 50 x 10 /1) was also more frequent with abciximab (1.1 versus 0.5%) (18). Very acute and profound thrombocytopenia (under 20 x 10 /1) within 24 hours after administration has been observed in 0.3-0.7% of patients treated with abciximab for the first time (15,18-20). 

Positive human anti-chimeric antibodies have been detected in 6% of patients (generally in low titers) but were not associated with hypersensitivity or allergic reactions. Preliminary data indicate that abciximab can be safety readministered, although a greater incidence of thrombocytopenia after administration has been reported with a lesser efficacy of platelet transfusion (12). 

A 65-year-old woman with type 2 diabetes mellitus and coronary artery disease received a 0.25 mg/kg bolus of abciximab at the time of intervention followed by an infusion of 10 micrograms/minute for 12 hours. Her baseline platelet counts were 286 x 10 /1 before use, 385 X 10 /1 at 2 hours, and 296 x 10 /1 at 18 hours. On day 7 she developed petechiae over her legs and her platelet count was 1 x 10 /1. Coagulation tests were normal and there was no evidence of heparin-induced thrombocytopenia. She received 10 units of single-donor platelets and recovered slowly over the next 4 days. The platelet count was 114 x 10 /1 on day 12. 

In another case of profound thrombocytopenia after abciximab there was a delayed onset (6 days after therapy) (22). The authors speculated that preceding treatment with methylprednisolone may have delayed the onset of thrombocytopenia.The mechanism of severe thrombocjdopenia associated with abciximab is unclear. Further administration should be avoided, but other glycoprotein Ilb/IIIa inhibitors (eptifibatide and tirofiban)... 

Thrombocytopenia after a second exposure to abciximab in nine patients showed that each had a strong immunoglobulin IgG antibody that recognized platelets sensitized with abciximab (23). Five patients also had IgM antibodies. Thrombocytopenia occurred four times as often as after the first exposure. The mechanism is not understood, but these findings suggest that it may be antibody-mediated. These antibodies were also found in 77 of 104 healthy patients, but in the patients the antibodies were specific for murine sequences in abciximab, causing the hfe-threatening thrombocytopenia. 

Because of its antigenic potential, there are theoretical concerns about the readministration of abciximab, and this has been studied in 1342 patients, who underwent percutaneous coronary interventions and received abciximab at least twice (25). There were no cases of anaphylaxis, and there were only five minor allergic reactions, none of which required termination of the infusion. There was clinically significant bleeding in 31 patients, including one with intracranial hemorrhage. There was thrombocytopenia (platelet count below 100 X 10 /1) in 5% and profound thrombocytopenia (platelet count below 20 x 10 /1) in 2%. In patients who received abciximab within 1 month of a previous treatment (n = 115), the risks of thrombocytopenia and profound thrombocytopenia were 17 and 12% respectively. Human chimeric antibody titers before... 

Schell DA, Ganti AK, Levitt R, Potti A. Thrombocytopenia associated with c7E3 Fab (abciximab). Ann Hematol 2002 81(2) 76-9. 

E Discontinue abciximab, aspirin, and heparin and give a platelet transfusion. Because abciximab is associated with thrombocytopenia, platelet counts should be monitored carefully. The manufacturer recommends that a platelet count be obtained prior to initiation of abciximab, 2 to 4 hours following the bolus dose, and 24 hours after discontinuing abciximab or prior to patient discharge. If thrombocytopenia is verified, then the following should be employed (see Table A-14). 

Rare cases of acute profound thrombocytopenia (i.e., platelet count <20,000/mm ) have been reported with the glycoprotein Ilb/IIIa receptor antagonist abciximab. ° Although the mechanism is unknown, it is thought that abciximab binding to the glyco-... 

Because abciximab is coadministered with heparin, it is important to distinguish between abciximab-induced and heparin-induced thrombocytopenia. Performing a heparin-induced platelet aggregation study is helpful in making this differentiation. 

Pseudothrombocytopenia, defined as in vitro platelet aggregation in blood anticoagulated with ethylenediaminetetraacetic acid (EDTA), is clinically insignificant, but it must also be differentiated from thrombocytopenia induced by abciximab. In this case, microscopic examination of a peripheral blood smear, along with repeated platelet counts in citrate-anticoagulated blood samples, makes the distinction possible. ... 

The major side effect is bleeding, as is the case with abciximab. The frequency of major bleeding in trials was about 10%, compared with about 9% in a placebo group, which included heparin. Thrombocytopenia has been seen in 0.5 to 1% of patients. 

Curtis BR, Divgi A, Garritty M, Aster RH (2004) Delayed thrombocytopenia after treatment with abciximab a distinct clinical entity associated with the immune response to the drag. J Thromb Haemost 2 985-992... 

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