Effects of anti-platelet glycoprotein Ib and /or IIb/IIIa autoantibodies on the size of megakaryocytes in patients with immune thrombocytopenia

Abstract: To determine whether anti-platelet autoantibodies react with megakaryocytes, as well as with platelets, in immune thrombocytopenia (ITP), 38 ITP patients were studied. They were classified into four groups; anti-platelet glycoprotein lb-positive (group A, n> = 5), anti-platelet glycoprotein II/b/IIIa-positive (group B, n = 2), positive to both antibodies (group C, n = 3), and negative to both antibodies (group D, n = 28). The number and size of megakaryocytes in each group were compared. The number of megakaryocytes in groups A, B, C, and D was 12.8 ± 8.9, 75.2, 29.1, and 17.0 ± 21.7/mm², respectively. The mean cytoplasmic area of megakaryocytes in groups A, B, C, and D was 1001 ± 26.3, 1621, 1109, and 1311 ± 235.6/μm², respectively. This finding indicated that, in the presence of anti-platelet glycoprotein Ib, megakaryocytes were not increased in number and were small in size, whereas, in the presence of anti-platelet glycoprotein Ilb/IIIa, megakaryocytes were increased in number and in cytoplasmic area. Our study suggested that anti-platelet glycoprotein Ib may impair platelet production by megakaryocytes in ITP.     

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.     

Intravenous immunoglobulin inhibits anti-glycoprotein IIb-induced platelet apoptosis in a murine model of immune thrombocytopenia

We have previously shown that injection of anti-glycoprotein (GP) IIb induces murine immune thrombocytopenia (ITP) and that intravenous immunoglobulin (IVIg) ameliorates ITP. We hypothesise that murine ITP may be associated with platelet apoptosis, which is upregulated by anti-GPIIb and downregulated by IVIg. The current study demonstrated that anti-GPIIb injection induced three critical apoptosis manifestations in platelets: (i) mitochondrial inner transmembrane potential (delta psi m) depolarisation; (ii) caspase-3 activation; and (iii) phosphatidylserine (PS) exposure. IVIg administration inhibited caspase-3 activation and PS exposure, but not delta psi m-depolarisation, in anti-GPIIb-treated platelets, demonstrating that IVIg ameliorates thrombocytopenia concomitantly with inhibiting late, but not early mechanisms of platelet apoptosis.     

Efficacy and safety of argatroban with or without glycoprotein IIb/IIIa inhibitor in patients with heparin induced thrombocytopenia undergoing percutaneous coronary intervention for acute coronary syndrome

Background There is limited experience with the use of argatroban in combination with glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitor in acute coronary syndrome (ACS) patients with heparin-induced thrombocytopenia (HIT) undergoing percutaneous coronary intervention (PCI). Materials and methods This single-center, retrospective study evaluated the efficacy (composite of death, myocardial infarction, or urgent revascularization) and safety (evaluated by TIMI major bleeding) of the argatroban with or without a GPIIb/IIIa inhibitor during PCI. Among 102 consecutive ACS patients (71.6% unstable angina or NSTEMI and 28.4% STEMI) who received argatroban (239 ± 104 μg/kg bolus, followed by a 17 ± 11 μg/kg/min infusion) for confirmed or suspected HIT during PCI, 52 patients (51%) received a GPIIb/IIIa inhibitor simultaneously (86% integrilin, 10% tirofiban, 4% abciximab) and 50 patients (49%) did not. Results There was no difference between the groups in the efficacy endpoint, which occurred in nine patients (17.3%) who received GPIIb/IIIa inhibitor and in eight patients (16%) who did not (P = 0.70). TIMI major bleeding occurred in three (5.8%) patients in the GPIIa/IIIb inhibitor group versus 0 (0%) patients in the argatroban alone group (P = 0.085). Conclusion In patients with suspected or confirmed HIT undergoing PCI for ACS, argatroban with or without GPIIb/IIIa appears to provide adequate anticoagulation and is well tolerated with a low rate of bleeding.     

Use of ICHOR-platelet works to assess platelet function in patients treated with GP IIb/IIIa inhibitors.

Platelet glycoprotein GP IIb/IIIa inhibitors have been recently approved for use in treating patients with acute coronary syndromes and those undergoing PCI. The purpose of this study was to assess the feasibility of using a new device, the ICHOR platelet works, to detect platelet inhibition in patients undergoing PCI and treated with abciximab or tirofiban. The study was conducted at Baylor College of Medicine, Houston, Texas. Thirty patients undergoing PCI and treated with abciximab (n = 10) or tirofiban (n = 20) are included. Blood samples were obtained before, at 30 min, at 4 hr, and at 12 hr after starting the GP IIb/IIIa inhibitors and 2 hr after discontinuation. Baseline studies revealed > 95% platelet aggregability in all patients after exposure to ADP (20 microM). After starting tirofiban, 82%, 83%, and 82% of platelets were inhibited at 30 min, 4 hr, and 12 hr. Platelet inhibition decreased to 43% 2 hr after discontinuation of tirofiban. Similarly, ICHOR platelet works detected 91%, 92%, and 85% platelet inhibition at 30 min, 4 hr, and 12 hr after starting abciximab, respectively. Platelet inhibition decreased to 73% 2 hr after discontinuation. The ICHOR platelet works is a promising, simple, and rapid bedside method that may have clinical utility in assessing platelet inhibition in patients treated with GP IIb/IIIa inhibitors. Cathet Cardiovasc Intervent 2001;53:346-351.     

The failure of orally administered glycoprotein IIb/IIIa inhibitors to prevent recurrent cardiac events

PURPOSE: Despite the success of intravenous glycoprotein IIb/IIIa antagonists, oral formulations have failed to show benefit and have been associated with increased mortality. To understand these findings, we performed a meta-analysis of results from four phase 3 trials. SUBJECTS AND METHODS: Trials were identified by MEDLINE search; review of abstracts from American College of Cardiology, European Society of Cardiology, and American Heart Association scientific sessions; or querying investigators in the field. Published, phase 3, randomized, placebo-controlled trials involving more than 1000 patients with coronary artery disease that compared an oral glycoprotein IIb/IIIa antagonist with or without background aspirin versus aspirin, and that had a planned follow-up of > or =30 days, were included. Four trials met these criteria. Odds ratios (ORs) and 95% confidence intervals (CIs) were generated from results, and combined using an empirical Bayes random-effects model. RESULTS: Among 33,326 patients, oral glycoprotein IIb/IIIa agents were associated with 31% increased mortality (OR = 1.31; 95% CI: 1.12 to 1.53; P= 0.0001). Results were similar whether the agent was added to (OR = 1.38; 95% CI: 1.15 to 1.67) or substituted for (OR = 1.37; 95% CI: 1.00 to 1.86) aspirin. Ischemic events or sudden death (OR = 1.22; 95% CI: 0.91 to 1.63) were also more common. Among patients with acute coronary syndromes, the incidence of myocardial infarction was increased (OR = 1.16; 95% CI: 1.03 to 1.29). CONCLUSION: Oral glycoprotein IIb/IIIa inhibitor therapy is associated with increased mortality and myocardial infarction. No single explanation for these findings is satisfactory; the problem is likely to be multifactorial.     

Role of oral blockade of platelet glycoprotein IIb/IIIa on neutrophil activation in patients with acute coronary syndromes

Orbofiban is a unique antiplatelet agent that inhibits the binding of fibrinogen to gycoprotein (GP) IIb/IIIa integrin receptors and thus prevents platelet aggregation induced by various agents. However, recent studies indicate that treatment with orbofiban does not reduce the incidence of recurrent ischemic events. The mechanisms underlying the lack of benefit of orbofiban in patients with acute coronary syndromes are not completely clear. The purpose of this study was to characterize the effects of orbofiban on cellular activation (neutrophil superoxide generation) and surface expression of adhesion molecules of circulating neutrophils (CD18, CD11b, and L-selectin) and platelets (P-selectin and GP IIb/IIIa) in patients with acute coronary syndromes. After 5–7 days, orbifiban (50 mg BID) did not reduce PMN adhesion molecule expression and ex vivo-stimulated PMN superoxide generation—as was observed in the placebo group, without orbofiban. In contrast, orbofiban induced marked reductions in GP IIb/IIIa and P-selectin expressions after 5–7 days of treatment. The sustained neutrophil activation observed with orbofiban may have a role on the recurrent thrombotic events observed with orbofiban treatment in the OPUS-TIMI 16 trial.     

Association of autoantibodies against platelet glycoproteins Ib/IX and IIb/IIIa, and platelet-reactive anti-HIV antibodies in thrombocytopenic narcotic addicts

The levels of platelet-associated Igs (PAIgs) and plasma circulating antiplatelet antibodies were evaluated by a flow cytometric immunofluorescence assay (FCIFA), an enzyme-linked immunoassay (ELISA), and a platelet radioactive antiglobulin test (PRAT), in a group of 45 human immunodeficiency virus (HIV)-infected intravenous drug users (IVDUs), with or without thrombocytopenia (TCP). Direct tests demonstrated an increased amount of PAIgs in 40% of the patients, irrespective of their platelet count. These PAIgs were mainly of IgG class and could not be eluted with ether. Plasma IgG with antiplatelet activity was found in 70% of the thrombocytopenic individuals, whereas it was detected in only one patient without TCP. The relative frequencies of antibodies against the platelet glycoproteins (GPs) Ib/IX and IIb/ IIIa were assessed in plasma from all patients by means of the monoclonal antibody-specific immobilization of platelet antigens assay (MAIPA). Plasmas from all non-thrombocytopenic patients were negative when tested by indirect MAIPA. In contrast, 10/23 plasmas from thrombocytopenic patients reacted with either GP IIb/IIIa, GP Ib/IX, or both GPs. Finally, aiming to investigate whether HIV antibodies from these patients are reactive with normal platelets, we performed absorption-elution experiments, followed by evaluation of HIV antibodies in the indirect eluates by ELISA and Western blot. Interestingly, we detected anti-HIV antibodies that bind to normal platelet antigens in 50% of the ether eluates prepared from control platelets sensitized with plasma from patients with TCP, but in only 5% of eluates obtained from platelets sensitized with plasma from non-thrombocytopenic patients. The present study provides direct evidence that specific autoantibodies against platelet membrane GPs Ib/IX and IIb/IIIa are common in HIV positive thrombocytopenic individuals. The finding in these patients of HIV antibodies cross-reactive with normal platelets, suggests that mimicry of human antigens by HIV could play a key role in the pathophysiology of the HIV-related TCP.     

Facilitated reperfusion with prehospital glycoprotein IIb/IIIa inhibition: predictors of complete ST-segment resolution before primary percutaneous coronary intervention in the On-TIME 2 trial: Correlates of reperfusion before primary PCI

Objective

The objective of this study is to evaluate the incidence, predictors, and outcome of complete ST-segment resolution (STR) during transportation after pretreatment with dual or triple antiplatelet therapy in the Ongoing Tirofiban in Myocardial Infarction Evaluation (On-TIME) 2 trial.

Methods

Patients with ST-segment elevation myocardial infarction were randomized in the ambulance to pretreatment with high-dose tirofiban (HDT) or to a control pretreatment (placebo or no HDT) on top of 600-mg clopidogrel, 500-mg aspirin, and 5000-IU unfractionated heparin. Complete STR was defined as ≥70% STR on the electrocardiogram obtained before percutaneous coronary intervention (PCI) as compared with the inclusion electrocardiogram.

Results

Complete STR before PCI occurred in 16.8% (n = 188/1121) and more frequently in the HDT group (19.0% vs 14.6%, P = .05). Independent predictors for complete STR before PCI were younger age (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.70-0.96, P = .01 per 10 year increase), fast diagnosis (OR, 0.97; 95% CI, 0.97-1.0, P = .004 per 15-minute increase time from symptom onset to diagnosis), longer pretreatment time (OR, 1.09; 95% CI, 1.03-1.16, P = .003 per 15-minute increase time start study medication to angiography), and randomization to HDT (OR, 1.39; 95% CI, 1.0-1.9, P = .05). Complete STR before PCI was associated with very low 30-day (0.5% vs 2.8%, P = .07) and 1-year (1.1% vs 5.0%, P = .019) mortality.

Conclusions

Dual or triple antiplatelet pretreatment in the ambulance results in complete STR before PCI in 17% of patients. Fast ST-segment elevation myocardial infarction diagnosis, prehospital initiation of pretreatment early after symptom onset, and HDT independently predicted STR before PCI. Complete STR is associated with improved clinical outcome.     

Effects of glycoprotein IIb/IIIa inhibition on clinical stabilization parameters in patients with unstable angina and non-Q-wave myocardial infarction

Glycoprotein IIb/IIIa receptor inhibition prevents the major cardiac events and improves the prognosis of patients with acute coronary syndromes. The purpose of the study was to evaluate the effects of tirofiban on clinical stabilization parameters in patients with unstable angina (UA) and non-Q-wave myocardial infarction (MI). Eighty-three patients presenting with prolonged ongoing chest pain and ST segment depression were included in the study. Forty-two patients were randomized to aspirin and heparin therapy, and 41 patients to tirofiban therapy in addition to the aspirin and heparin therapy. The interval between the initiation of the treatment and the disappearance of angina, recovery time of ST segment depression, creatine kinase-MB (CK-MB) levels, onset of decrease and normalization of CK-MB, and frequency of in-hospital major cardiac events were compared. The interval between initiation of the treatment and the disappearance of angina was significantly shorter in the tirofiban group (3.5 ± 4.2 vs 9.1 ± 8.6h, P 0.001). Recovery time of ST depression was also significantly shorter in the tirofiban group (5.1 ± 7.3 vs 12.3 ± 11.5h, P 0.05). The peak CK-MB values were significantly lower in the non-Q-wave MI and UA subgroups of tirofiban than in the heparin group (P = 0.04 for both). The onset of the CK-MB decrease was significantly earlier in the tirofiban group (15 ± 14 vs 24 ± 15h, P = 0.02). The normalization time of the CK-MB was relatively shorter in the tirofiban group but without statistical significance (50 ± 22 vs 60 ± 25h). The tirofiban group had a lower frequency of total major cardiac events (26% vs 54%, P = 0.01), acute MI (2.4% vs 19%, P = 0.03), and recurrent angina (26% vs 50%, P = 0.04). The frequency of death and urgent revascularization did not differ between the groups. Tirofiban, in addition to heparin, provides earlier clinical stability and prevents major in-hospital cardiac events in patients with UA and non-Q-wave MI as compared to heparin therapy alone.     

Bleeding complications associated with glycoprotein IIb/IIIa inhibitors in patients 80 years of age and older undergoing percutaneous coronary intervention

BACKGROUND:

Treatment of symptomatic coronary artery disease with percutaneous intervention requires antithrombotic therapy. Patients with elevated thromboembolic risk benefit from therapy with glycoprotein IIb/IIIa inhibitors. The safety and effectiveness of glycoprotein IIb/IIIa inhibition have been well documented in clinical trials. Drug-induced bleeding complications in elderly patients have not been specifically addressed.

METHODS:

Between 2006 and 2009, a total of 439 unselected patients 80 years of age and older undergoing percutaneous intervention for symptomatic coronary artery disease were included in the present nonrandomized retrospective study. In one-half of the patients, glycoprotein IIb/IIIa inhibitors were administered peri-interventionally. The in-hospital occurrence of bleeding complications (access site, gastrointestinal and cerebral) were analyzed in the groups with and without glycoprotein IIb/IIIa inhibitors.

RESULTS:

The mean age of the patients was 84 years. Nearly all patients (95%) received dual antiplatelet therapy. Patients treated with glycoprotein IIb/IIIa inhibitors had more complex coronary lesions and bypass graft interventions, and a tendency toward more access site bleeding complications than patients without inhibitors, which included femoral hematomas (4.6% versus 2.3%, respectively; P not significant) and femoral pseudoaneurysms (6% versus 3.2%, respectively; P not significant). The rate of blood transfusion was equal in both groups (0.9%). Major hemorrhagic events did not occur. Vessel closure devices were used more often in patients without glycoprotein inhibition.

CONCLUSIONS:

An increase in minor bleedings must be expected when using glycoprotein IIb/IIIa inhibitors in patients 80 years of age and older. However, this issue must not prevent this treatment option from being offered to elderly patients. There appears to be no elevated risk for major bleeding complications. Broadened use of vascular closure devices in this specific patient population may lower the rate of access site complications.     

Combined thrombectomy and intracoronary administration of glycoprotein IIb/IIIa inhibitors improves myocardial reperfusion in patients undergoing primary percutaneous coronary intervention: a meta-analysis

Background Suboptimal myocardial reperfusion is common in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). Furthermore, it results in increased infarct size and mortality rates. We performed a meta-analysis to evaluate the role of aspiration thrombectomy (AT) combined with intracoronary administration of glycoprotein IIb/IIIa inhibitors (GPI) in the improvement of myocardial reperfusion and clinical outcomes. Methods PubMed, Embase, Web of Science, and CENTRAL databases were searched for randomized controlled trials (RCTs) investigating combined AT and intracoronary GPI treatment versus AT alone. Outcomes of interest were thrombolysis in myocardial infarction myocardial perfusion grade (TMPG), infarct size (IS) assessed by cardiac magnetic resonance imaging, left ventricular ejection fraction (LVEF), major adverse cardiac events (MACE) at short-term (≤ 1 month) and long-term (6?12 months) follow-up, and bleeding complications during the hospital stay. Results Eight trials involving 923 patients were included. Compared with AT alone, combined AT and intracoronary GPI significantly increased TMPG 3 flow (RR: 1.15, 95% CI: 1.04 to 1.26), reduced IS [mean difference (MD): ?3.46, 95% CI ?5.18 to ?1.73], and improved LVEF (MD: 1.44, 95% CI: 0.54 to 2.33). Furthermore, GPI use decreased the risk of MACE at long-term follow-up (RR: 0.60, 95% CI: 0.37 to 0.98). There was no significant difference between the two groups in the incidence of minor and major bleeding complications. Conclusions Our findings showed that compared with AT alone, combined AT and intracoronary GPI treatment resulted in improved myocardial reperfusion, better cardiac function, and MACE-free survival benefits at the long-term follow-up for patients with STEMI undergoing PPCI.     

Drug-induced thrombocytopenia and thrombosis: Evidence from patients receiving an oral glycoprotein IIb/IIIa inhibitor in the Orbofiban in Patients with Unstable coronary Syndromes- (OPUS-TIMI 16) trial

Objective: To assess etiology and impact of thrombocytopenia in a large oral glycoprotein (GP) IIb/IIIa inhibitor trial. Background: Heparin is known to cause thrombocytopenia, and in some of these patients thrombosis. GP IIb/IIIa inhibitors are also associated with thrombocytopenia. Methods: The Orbofiban in Patients with Unstable Coronary Syndromes (OPUS-TIMI 16) Trial randomized 10,392 patients with ACS to the oral GP IIb/IIIa inhibitor orbofiban or placebo. Patients were followed for a minimum of ten months. Thrombocytopenia was defined prospectively as a platelet count < 80,000. Results: Thrombocytopenia was rare in the OPUS-TIMI 16 trial (0.68% at Day 30 and 0.80% at 1 year), but more common in patients treated with orbofiban (0.92%) compared with those treated with placebo (0.2%), p < 0.001. Patients who developed thrombocytopenia had higher rates of death (11.6% vs. 1.7%, p < 0.001), recurrent MI (12.1% vs. 2.8%, p < 0.001), intracranial hemorrhage (2.9% vs. 0.0%, p < 0.001), and major or severe bleeding (19.0% vs. 2.0%, p < 0.001) at 30 days (with similar results at one year). Conclusion: Thrombocytopenia, though uncommon, was associated with orbofiban use and an increased risk of bleeding, but also death and MI. This study provides further evidence that drugs that lead to thrombocytopenia are, in a significant proportion of patients associated with thrombotic events.     

Outcome of access site in patients treated with platelet glycoprotein IIb/IIIa inhibitors in the era of closure devices.

The most consistent procedural predictor of vascular access site complications thus far has been the intensity and duration of anticoagulant therapy during and after percutaneous coronary interventions (PCI). Several devices have been developed to aid in the closure of the femoral arteriotomy. This report describes the clinical outcome of unsuccessful deployment of femoral closure devices in a cohort of 285 consecutive patients who underwent PCI and were treated with platelet glycoprotein (GP) IIb/IIIa inhibitors. Manual femoral artery compression was used in 123 patients, Perclose in 123 patients, and AngioSeal in 39 patients. Successful homeostasis was achieved in 98.4% of patients who received manual compression, in 91.9% of the Perclose-sealed arteriotomy, and in 84.6% of patients who received the AngioSeal closure device (P = 0.004). The incidence of vascular complications after successful deployment was 9%. Patients not achieving hemostasis with closure device or 1 degrees manual compression developed complications in the majority of cases (> 80%; P < 0.05). By multivariate analysis (with adjustment for baseline differences), the use of AngioSeal closure device was found to be an independent risk factors leading to primary deployment failure and all access site complications (OR 2.97; 95% CI 1.5-6.0; P = 0.006). In summary, failed hemostasis by artery closure devices in patients undergoing PCI who are treated with GP IIb/IIIa inhibitors is associated with significant vascular complications. AngioSeal may be associated with a higher failure rate, while manual compression and Perclose seem to be more effective with a lower complication rate.     

Safety and efficacy of Bivalirudin with Glycoprotein IIb/IIIa for high-risk percutaneous coronary intervention

AimsThe aim of the study was to assess the safety and efficacy of Bivalirudin + Glycoprotein (Gp) IIb/IIIa inhibitor as compared to unfractionated Heparin (UFH) + Gp IIb/IIIa inhibitor in high risk patients undergoing elective percutaneous coronary intervention (PCI). The primary end point was time to sheath removal and ambulation where as peri-procedure myocardial damage, access site bleeding and major adverse cardiac events (MACE) rates were secondary end points.MethodsOne hundred and one high risk patients undergoing elective PCI were randomly assigned to either Bivalirudin + GpIIb/IIIa inhibitor or UFH + Gp IIb/IIIa inhibitor. PCI was performed by standard technique and activated clotting time was monitored immediately on arrival to recovery area and every 60 min thereafter. Sheath were pulled out once ACT was below 150 seconds and patients were mobilized 6hrs after sheath were removed. Peri-procedure myocardial damage was assessed by serial Trop I levels.ResultsPatient assigned to Bivalirudin + Tirofiban has significantly reduced time to sheath removal and ambulation as compared to those who received UFH + tirofiban (p < 0.0001) although peak Act did not differ in the groups. Peak Trop I levels were significantly lower in Bivalirudin + Tirofiban group (p = 0.023) and peri-procedure Trop I elevation occurred in significantly lower number of patients treated with Bivalirudin + Tirofiban (p = 0.029).ConclusionsThe combination of Bivalirudin + Tirofiban was safe and effective as compared to UFH + Tirofiban in high risk patients undergoing elective PCI.     

An audit of the use and complications of glycoprotein IIb/IIIa inhibitors in percutaneous coronary intervention against national UK standards

Coronary thrombosis is a pivotal event in the pathogenesis of acute coronary syndromes and ischemic complications resulting from coronary intervention. Activation of the platelet glycoprotein (GP) IIb/IIIa receptor is the final common pathway leading to platelet aggregation, coronary thrombus formation, and myocardial ischemia. Inhibitors of platelet GP IIb/IIIa are potent agents to prevent progression to myocardial infarction and death.

We prospectively surveyed the indications, frequency, and complications associated with the use of GP IIb/IIIa inhibitors in percutaneous coronary intervention in a tertiary center setting.

A total of 170 patients underwent screening over a period of 6 weeks. One hundred four (61%) had coronary intervention, out of which eight (8%) had failed intervention. Glycoprotein IIb/IIIa inhibitors were used in 57 (55%) patients; 47 (45%) did not have any agent periprocedure. Eptifibatide was the most commonly used agent in 35 (33%), followed by abciximab in 19 (18%) and tirofiban in 3 (3%).

Out of 57 patients in whom GP IIb/IIIa agents were used, 22 (38%) had visible intracoronary thrombus, 22 (38%) had diffuse disease, 8 (14%) had complex intervention, and 5 (9%) had diabetes.

The overall incidence of complications was not increased by the use of GP IIb/IIIa inhibitors; serious complications were rare with the use of GP IIb/IIIa agents; no stroke, thrombocytopenia, gastrointestinal bleed, or death was recorded. The overall use in emergency settings was not associated with increased complications. Bradycardia and vomiting were more common with abciximab group, whereas puncture site pain was commoner in eptifibatide group.     

Vascular access site complications with the use of closure devices in patients treated with platelet glycoprotein IIb/IIIa inhibitors during rescue angioplasty.

The objective of this study was to evaluate the effectiveness of two different closure devices in patients undergoing rescue percutaneous coronary intervention (PCI) using IIb/IIIa inhibitors and to compare it with patients undergoing elective PCI. One hundred sixty-two patients undergoing rescue PCI treated with IIb/IIIa inhibitors underwent vascular access site closure (6 Fr Perclose, n = 92, or 6 Fr Angioseal, n = 70). Vascular complications were compared with a sex- and age-matched group (n = 100) of patients undergoing manual compression after sheath removal and a similar group of patients undergoing elective PCI (n = 196). The incidence of access site complications was not significantly different between the three groups undergoing rescue PCI and was not higher than in patient receiving GP IIb/IIIa inhibitors without fibrinolysis (RR = 0.95; 95% CI = 0.88-1.01). In patients undergoing rescue PCI and receiving IIb/IIIa inhibitors, closure devices allow early sheath removal and are associated with similar outcomes compared with manual compression and elective PCI regardless of the type of closure device used.     

A critical appraisal of platelet glycoprotein IIb/IIIa inhibition

Despite the success of abciximab in preventing ischemic events after percutaneous coronary interventions, attempts to develop intravenous, small-molecule glycoprotein IIb/IIIa antagonists and diversify the clinical indications for these agents have produced varied results. The 30-day ischemic event reduction in the percutaneous coronary intervention trials has ranged by over three-fold (16% to 56%) and is greater among the acute coronary syndrome trials. The phase III trials exploring the role of oral glycoprotein IIb/IIIa inhibition have been consistently disappointing, with evolving evidence of increased mortality. Mechanisms contributing to these heterogeneous results may include normal variation in platelet or receptor number, differences in receptor activity, interpatient variation in pharmacological dose-response and the possibility of prothrombotic or nonglycoprotein IIb/IIIa effects. Plausibility of “suboptimal” effect is suggested by several recent studies. Trials investigating the role of intravenous small-molecule IIb/IIIa antagonists highlight the importance of effective dosing. The increase in bleeding and mortality observed in the oral glycoprotein IIb/IIIa studies indicate the consequences of suboptimal dosing on safety on one hand, while raising the possibility of important prothrombotic, counterregulatory or other sudden cardiac events. This article will undertake a review of the relevant platelet biology, discuss the mechanisms that may contribute to suboptimal antiplatelet efficacy with these agents and examine insights from the clinical trials supporting these concepts.