Glycoprotein IIb/IIIa inhibitors in unstable angina

During the last ten years we have considerably update our knowledge about the pathogenesis of unstable angina or acute coronary syndromes. The platelet activity have in this settings the central role in development of the thrombotic process. Platelet glycoprotein IIb/IIIa inhibitors block fibrinogen binding to platelets, and the effect of this on the final common pathway of platelet aggregation makes these compounds extremely potent antiplatelet drugs. Three intravenous IIb/IIIa receptor antagonists are approved for clinical use, and this class of therapy has update our pharmacologic armatarium to avoid ischemic complication in the settings of percutaneous coronary revascularization at first and now in medical treatment of acute coronary syndromes. Results of large trials using this drugs suggest that this agents are effective in patient with unstable angina particularly in those presenting a high score of risk for acute ischemic events and those requiring coronary intervention.     

Glycoprotein IIb/IIIa Receptor Inhibition in Interventional Cardiology

Journal of Thrombosis and Thrombolysis -     

Platelet Glycoprotein IIb/IIIa Integrin Blockade in Coronary Artery Disease: Current State of the Art

Platelets have been shown to play an important role in the pathogenesis of atherosclerosis, acute coronary syndromes, and ischemic complications after percutaneous coronary intervention. Fibrinogen binding via platelet surface glycoprotein (GP) IIb/IIIa receptors constitutes the "final pathway" in platelet aggregation leading to thrombus formation. The GP IIb/IIIa receptor inhibitors, a new class of antiplatelet agents that have emerged in recent years, show great promise in reducing complications of coronary angioplasty and acute coronary syndromes. This review will examine the biology of platelet GP IIb/IIIa receptors, the various classes of GP IIb/IIIa receptor antagonists, the results of the latest clinical trials, and their implications in current clinical practice.     

Impact of Glycoprotein IIb/IIIa Inhibitors Use on Outcomes After Lower Extremity Endovascular Interventions From Nationwide Inpatient Sample (2006–2011)

• Anticoagulant and antiplatelet medications are necessary in peripheral endovascular intervention, but a standardized approach has not yet been established.
• Glycoprotein IIb/IIIa inhibitor use in endovascular lower extremity interventions decreased overall amputation rates.
• Glycoprotein IIb/IIIa inhibitor use in endovascular lower extremity interventions increased postprocedural bleeding and complications requiring intervention.

     

Glycoprotein IIb/IIIa autoantigenic repertoire in chronic idiopathic thrombocytopenic purpura

Summary. The objective of the present study was to further disclose the autoantigenic repertoire carried by the platelet glycoprotein (GP) IIb/IIIa complex. IgG-F(ab')₂ fragments were prepared from two prototype ITP patients, and their ability to block the binding of GPIIb/IIIa reactive antibodies derived from other patients with ITP was evaluated using a modified MAIPA assay; a P1^A1 alloantiserum and 20 normal sera were included as controls. It was found that the two prototype IgG-F(ab')₂ fragments were each able to significantly block the binding of serum IgG to GPIIb/IIIa in six (55%) and seven (64%) out of 11 patients with chronic ITP, respectively. No significant blocking effect was observed for IgG-F(ab')2 fragments prepared from normal subjects. Also, the binding of the P1^A1 alloantiserum to its epitope on GPIIIa was not affected by any of the blocking IgG-F(ab')2 fragments exploited in the study. These data substantiate that in chronic ITP at least half of the GPIIb/IIIa reactive sera bind to homogenous autoepitopes.     

Glycoprotein IIb/IIIa inhibitors: questioning indications and treatment algorithms

Glycoprotein inhibitors (GPI) are viewed as beneficial adjunctive pharmacotherapy agents for percutaneous coronary interventions (PCIs). The major benefit of GPI is derived from the reduction of ischemic events (mostly non-Q-wave myocardial infarctions) during PCI. There is no single randomized clinical trial demonstrating that any of these agents significantly reduces mortality in any clinical subset of patients. Studies of sustained oral GPI resulted in excessive death and myocardial infarctions. Reduction of ischemic end points was counteracted by excessive bleeding, vascular complications, and thrombocytopenia. These complications bear considerable medical and economic impact. The Acute Catheterization and Early Intervention Triage Strategy trial demonstrated that GPI, when added to heparin, enoxaparine, or bivalirudin, do not reduce mortality or ischemic events but significantly increase bleeding complications. Major bleeding resulted in threefold mortality at 1 year. In view of available data, the use of GPI should be limited to moderate-risk to high-risk PCI patients with low bleeding propensity. Protocols of abbreviated GPI administration and careful bleeding surveillance, in conjunction with lower doses of unfractionated heparin or new and possibly safer antithrombins, can potentially improve patient safety.     

Glycoprotein IIb/IIIa complex is the target in mirtazapine-induced immune thrombocytopenia

Mirtazapine (MW 265.36), a tetracyclic antidepressant of the piperazine-azapine group which augments central noradrenergic and serotonergic activity, is currently used as an oral antidepressant. We report a case of severe thrombocytopenia in a 66-year-old patient occurring after mirtazapine administration, suggesting an immune mechanism. This report documents the first case of mirtazapine-induced immune thrombocytopenia. The patient's serum was screened for drug-induced anti-platelet antibody with the chromium(51) (Cr(51)) platelet lysis technique. The drug-dependent antibody was characterized using flow cytometry, the monoclonal antibody immobilization of platelet antigens assay (MAIPA assay), and immunoprecipitation. By the Cr(51) platelet lysis technique, we obtained an equivocal result for the detection of mirtazapine-induced antibody. However, the patient's serum tested positive for mirtazapine-induced antibody by flow cytometry. The results showed that the binding ratio of 5.7 (mean fluorescence intensity) in the presence of the patient's serum and mirtazapine in a final concentration of 1.0 mmol/L was strongly positive. The antibody was found to bind the glycoprotein (GP) IIb/IIIa complex by MAIPA assay by using five different monoclonal antibodies against GP complexes Ib/IX, GPIIb/IIIa, or GPIa/IIa. Immunoprecipitation studies showed that the GPIIb/IIIa complex was precipitated by antibody in the presence, but not in the absence, of mirtazapine. These findings provide evidence that immune thrombocytopenia can be caused by sensitivity to the antidepressant mirtazapine. This is the first well-documented case of mirtazapine-induced immune thrombocytopenia.     

Glycoprotein IIb/IIIa receptor blockade with coronary stent placement.

GP IIb/IIIa blockade for stenting offers almost complete inhibition of platelet aggregation and can bridge the delayed onset of action of ticlopidine. In the EPISTENT trial, GP IIb/IIIa blockade with abciximab reduced the 30-day cardiac event rate after stenting by more than 50% compared to placebo. Economic constraints may demand to restrict the use of GP IIb/IIIa blockade to subgroups that benefit most. Bail-out stenting constitutes one of these subgroups. Another group are patients with acute myocardial infarction. Moreover, the exquisitely high risk of residual dissection after stenting suggests to always employ GP IIb/IIIa blockade in this instance.     

Glycoprotein IIb/IIIa inhibitors in acute ST segment elevation myocardial infarction

Limitations in the standard treatment of acute myocardial infarction have focused attention on inhibition of platelet activity by its final common pathway of activation, the glycoprotein IIb/IIIa receptor. Animal studies have suggested that a glycoprotein IIb/IIIa inhibitor could accelerate thrombolysis and prevent reocclusion after successful thrombolysis. Studies evaluating the use of a glycoprotein IIb/IIIa inhibitor alone without thrombolysis or percutaneous transluminal coronary revascularization do not suggest that isolated use of glycoprotein IIb/IIIa inhibitors restores TIMI 3 flow in a sufficient proportion of patients. Clinical studies evaluating the combination of thrombolytic therapy and glycoprotein IIb/IIIa inhibitors appear most promising, with evidence of improved angiographic outcomes. Reducing the dose of thrombolytic agents may result in reduction in bleeding risk. Current and future trials will investigate reduced-dose reteplase with abciximab and eptifibatide with reduced-dose alteplase. Available evidence suggests that glycoprotein IIb/IIIa inhibition may facilitate thrombolysis, thus adding a new element to future reperfusion regimens.     

Glycoprotein IIb/IIIa inhibitor-associated thrombocytopenia: clinical predictors and effect on outcome

Glycoprotein IIb/IIIa inhibitors are used as an adjunct to antiplatelet therapy in percutaneous coronary intervention to reduce postprocedural enzyme elevations. Previous studies have shown a risk for thrombocytopenia that is associated with these agents. We sought to evaluate the incidence and outcomes of glycoprotein IIb/IIIa inhibitor-associated thrombocytopenia in an unselected series of patients undergoing percutaneous coronary intervention. We reviewed 984 interventions performed on 908 subjects over a specific time period. Glycoprotein IIb/IIIa inhibitors were used in 58.8% of cases. Their use increased from 38 to 82% during the study period (p < 0.0001). The incidence of glycoprotein IIb/IIIa inhibitor-associated thrombocytopenia was 5.4%. The occurrence of thrombocytopenia was not associated with higher age, gender or ethnicity. The preprocedural platelet count was not associated with induced thrombocytopenia (237 +/- 76 vs. 209 +/- 68 x 10(3), p > 0.05). The occurrence of thrombocytopenia was not associated with increased in-hospital mortality, 1-year mortality, myocardial infarction or revascularization, but was associated with a hospital stay twice as long as in those patients without thrombocytopenia (5.6 +/- 11.3 vs. 2.1 +/- 2.2 days, p < 0.001). Of the 5.4% of patients who developed thrombocytopenia, only 2 patients (7.1%) required platelet or blood cell transfusion.