Glycoprotein IIb-IIIa Receptor Research Articles

Role of platelets aggregation in the process of ductus arteriosus closure of newborn pups

To investigate the role of platelets aggregation in the developing process of ductus arteriosus closure of newborn pups, and the effect of platelet membrane glycoprotein IIb-IIIa (GPIIb-IIIa) receptor antagonist (tirofiban). Four 24-month-old Beagle bitches were selected and numbered 1, 2, 3, and 4 respectively, and their pups were removed by cesarean section in two batches 1-2 days before the expected date of delivery. Bitches 1 and 2 were the first batch. Eighteen newborn pups were removed after cesarean section as the control group. They were divided into three subgroups: 1-hour subgroup, 4-hour subgroup, and 12-hour subgroup according to postnatal time point, with 6 pups in each subgroup. The newborn pups were injected with normal saline 10 mL/kg via jugular vein immediately after birth. Bitches 3 and 4 were the second batch. Nineteen newborn pups were removed by cesarean section as tirofiban group. They were also divided into three subgroups: 1-hour subgroup (n = 6), 4-hour subgroup (n = 6), and 12-hour subgroup (n = 7) according to the postnatal time point. The newborn pups were injected with tirofiban hydrochloride injection 10 mL/kg (10 mL injection including 2.5 mg of tirofiban) via jugular vein immediately after birth. The diameter of ductus arteriosus was measured by echocardiography. Ductus arteriosus was removed by surgical dissection and divided into two parts. Western blotting and immunohistochemistry were used to detect the expression of platelet membrane GPIIb-IIIa, respectively. In the control group, 1 newborn pup died at 0.5 hour after birth in the 1-hour subgroup. The experiment was completed by 19 in the tirofiban group. Ductus arteriosus of all pups were not closed in 1-hour subgroups of the two groups, and there was no significant difference in the diameter of ductus arteriosus between the control group and the tirofiban group (mm: 1.72±0.08 vs. 1.70±0.11, P > 0.05). Ductus arteriosus of 1 newborn pup in 4-hour subgroup of the control group was closed, but the ductus arteriosus of all the newborn pups in 4-hour subgroup of the tirofiban group were not closed. The diameter of ductus arteriosus of the tirofiban group was significantly larger than that of the control group (mm: 1.52±0.15 vs. 0.95±0.48, P < 0.05). Ductus arteriosus of all pups were closed in 12-hour subgroup of the control group, but the ductus arteriosus of 2 pups of the tirofiban group were still not closed, with the diameter of ductus arteriosus of 1.0 mm and 1.1 mm, respectively. Western blotting showed that at 1-hour, 4-hour and 12-hour after birth, the expression of platelet membrane GPIIb-IIIa was gradually increased in ductus arteriosus of newborn pups of the two groups. The expression of GPIIb-IIIa in 1-hour subgroup of the tirofiban group was significantly lower than that in the control group (GPIIb-IIIa/β-actin: 0.67±0.07 vs. 0.84±0.16, P < 0.05). The expression of GPIIb-IIIa in 4-hour and 12-hour subgroups of the tirofiban group were slightly lower than those in the control group (GPIIb-IIIa/β-action: 0.85±0.12 vs. 0.95±0.11 in 4-hour subgroup, 1.04±0.16 vs. 1.09±0.17 in 12-hour subgroup, both P > 0.05). Immunohistochemistry showed that the change trend of platelet membrane GPIIb-IIIa in ductus arteriosus of newborn pups in both groups was similar to the results of Western blotting. The ductus arteriosus of newborn pups begin to close 1-4 hours after birth, and all closed at 12 hours after birth. The expression of platelet membrane GPIIb-IIIa in ductus arteriosus increase gradually after birth, and the platelet aggregation may participate in and promote ductus arteriosus closure to some extent. Tirofiban, a platelet membrane GPIIb-IIIa receptor antagonist, may delay ductus arteriosus closure of newborn pups to some extent by inhibiting platelet aggregation.

Continuous clopidogrel dose modification after platelet function testing improves clinical outcome in acute coronary syndrome treated with percutaneous coronary intervention and initially determined high on-treatment platelet reactivity

Introduction: High on-treatment platelet reactivity (HTPR) on clopidogrel correlates with adverse clinical outcomes in patients with acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI)1 . Whether HTPR on clopidogrel is a modifiable risk factor for ischemic events is not clear. We sought to evaluate the effect of the serial clopidogrel dose tailoring after platelet function testing (PFT) on a clinical outcome of the patients with determined HTPR after successful PCI in ACS. Patients and Methods: We screened 461 consecutive ACS patients. Exclusion criteria was present in 120 patients (continuous postinterventional glycoprotein (GP) IIbIIIa receptor inhibitor perfusion, thrombocytopenia ( 200 µmol/L), anemia (Htc 80 years of age). Patients without exclusion criteria (341) underwent PFT 1224 hours following PCI. Patients with determined HTPR on Proπireni saaeetak / Extended abstract

TCTAP A-132 Impact of Periprocedural Glycoprotein IIbIIIa Receptor Inhibitors on TIMI Flow and 1 Month Major Clinical Outcomes Following Primary Percutaneous Coronary Intervention in Diabetic Patients

TCTAP A-132 Impact of Periprocedural Glycoprotein IIbIIIa Receptor Inhibitors on TIMI Flow and 1 Month Major Clinical Outcomes Following Primary Percutaneous Coronary Intervention in Diabetic Patients

IMPACT OF PERIPROCEDURAL GLYCOPROTEIN IIBIIIA RECEPTOR INHIBITORS ON TIMI FLOW AND 1 MONTH MAJOR CLINICAL OUTCOMES FOLLOWING PRIMARY PERCUTANEOUS CORONARY INTERVENTION IN DIABETIC PATIENTS

Glycoprotein (Gp) IIbIIIa receptor inhibitors are known to reduce mortality, target vessel revascularization but not re-infarction in ST elevation myocardial infarction (STEMI) patients. We investigated the impact of Gp IIbIIIa receptor inhibitors on the post procedure TIMI flow and 1 month major

Glycoprotein IIb-IIIa inhibitors for acute ischaemic stroke

Glycoprotein (GP) IIb-IIIa inhibitors are antiplatelet agents that act by antagonising GP IIb-IIIa receptors on the platelet surface and block the final common pathway to platelet aggregation by preventing the binding of fibrinogen molecules that form bridges between adjacent platelets. Thus, GP IIb-IIIa inhibitors could favour endogenous thrombolysis by reducing thrombus growth and preventing thrombus re-formation through competitive inhibition with fibrinogen and, due to their mechanism of action, are likely to have a more profound antiplatelet effect with more rapid onset than conventional antiplatelet agents, such as aspirin or clopidogrel. Currently used in clinical practice for the treatment of individuals with acute coronary syndromes and during coronary angioplasty, GP IIb-IIIa inhibitors could also be useful for the treatment of people with acute ischaemic stroke. To assess the use of GP IIb-IIIa inhibitors in people with acute ischaemic stroke to evaluate whether such treatments (1) reduce the proportion of patients who die or remain dependent, and (2) are sufficiently safe for general use. We wished to examine the effects GP IIb-IIIa inhibitors alone or in combination with thrombolytic agents. We searched the Cochrane Stroke Group trials register (last searched 10 June 2013), MEDLINE (1966 to June 2013), EMBASE (1980 to June 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 5, 2013), and major ongoing clinical trials registers (June 2013). We also searched reference lists and contacted trial authors and pharmaceutical companies. We aimed to analyse unconfounded randomised controlled trials (RCTs) of GP IIb-IIIa inhibitors in the treatment of people with acute ischaemic stroke. Only individuals who started treatment within six hours of stroke onset were included. We independently selected trials for inclusion, assessed trial quality and extracted the data. We included four trials involving 1365 participants. Three trials compared the intravenous GP IIb-IIIa inhibitor Abciximab with intravenous placebo (1215 participants) and one trial compared the intravenous GP IIb-IIIa inhibitor Tirofiban with intravenous aspirin (150 participants). Treatment with either of these GP IIb-IIIa inhibitors did not significantly reduce long-term death or dependency (odds ratio (OR) 0.97, 95% confidence interval (CI) 0.77 to 1.22, for the comparison between Abciximab and placebo; OR 1.00, 95% CI 0.52 to 1.92, for the comparison between Tirofiban and aspirin) and had no effect on deaths from all causes (OR 1.08, 95% CI 0.77 to 1.53, for the comparison between Abciximab and placebo; OR 1.00, 95% CI 0.35 to 2.82, for the comparison between Tirofiban and aspirin). Abciximab was associated with a significant increase in symptomatic intracranial haemorrhage (OR 4.6, 95% CI 2.01 to 10.54) and with a non-significant increase in major extracranial haemorrhage (OR 1.81, 95% CI 0.96 to 3.41), whereas the only small trial comparing Tirofiban with aspirin showed no increased risk of bleeding complications with Tirofiban (OR 0.32, 95% CI 0.03 to 3.19, for symptomatic intracranial haemorrhage; OR 3.04, 95% CI 0.12 to 75.83, for major extracranial haemorrhages). There was no significant inconsistency across the studies. The available trial evidence showed that, for individuals with acute ischaemic stroke, GP IIb-IIIa inhibitors are associated with a significant risk of intracranial haemorrhage with no evidence of any reduction in death or disability in survivors. These data do not support their routine use in clinical practice. The conclusion is driven by trials of Abciximab, which contributed 89% of the total number of study participants considered.

Prevention and Treatment of Thrombosis in Pediatric and Congenital Heart Disease

Thrombosis has long been recognized as a potentially life-threatening complication in children with congenital heart disease (CHD), children with acquired heart disease, and in adults with CHD. High-risk groups include patients with shunt- dependent single ventricles (shunt thrombosis, 8%–12%; 4%

Early and late outcomes after primary percutaneous coronary intervention by radial or femoral approach in patients presenting in acute ST-elevation myocardial infarction and cardiogenic shock

Although radial approach is increasingly used in percutaneous coronary interventions (PCIs) including in acute myocardial infarction (MI), patients with cardiogenic shock have been excluded from comparisons with femoral approach. The aim of our study was to compare clinical outcomes in patients undergoing primary PCI with cardiogenic shock by radial and femoral approach. From 2,663 patients presenting with ST-elevation MI in 2 large volume radial centers, we identified 197 patients (7.4%) with signs of cardiogenic shock immediately before undergoing primary PCI. Radial approach was used in 55% of cases when at least 1 radial artery was weakly palpable, either spontaneously or after intravenous noradrenaline bolus. Patients in the radial group were older (69 ± 12 vs 64 ± 12 years, P = .010), had less diabetes (13% vs 26%, P = .028), and required less often intubation prior PCI (42% vs 66%, P = .0006) or intraaortic balloon pump (36% vs 55%, P = .0096). Mortality at 1 year was 44% in the radial group and 64% in the femoral group (P = .0044). Independent predictors of late mortality included radial approach (hazard ratio [HR] 0.65, 95% CI 0.42-0.98, P = .041), the use of glycoprotein IIb-IIIa receptor inhibitors (HR 0.63, 95% CI 0.40-0.96, P = .032), baseline creatinine ≥110 μmol/L (HR 3.34, 95% CI 2.20-5.12, P < .0001), initial glycemia >200 mg/dL (HR 2.02, 95% CI 1.34-3.11, P = .0008), and age >65 years (HR 1.80, 95% CI 1.18-2.79, P = .006). Radial approach was safe and feasible in more than half of the patients with ST-elevation MI and cardiogenic shock treated by primary PCI. After adjustment for baseline and procedural characteristics, radial approach remained associated with better survival. However, prognosis of patients undergoing primary PCI in cardiogenic shock remains poor.

Antiplatelet Therapy in the Prevention of Coronary Syndromes: Mode of Action, Benefits, Drawbacks

Blood platelets play a key role in normal hemostasis but also in atherothrombosis due to their ability of thrombus formation at site of a ruptured atherosclerotic plaque. Platelets are also involved in vascular inflammation due to interactions with endothelial cells, leukocytes, and smooth muscle cells that may result in an excessive fibroproliferative response after vessel dilatation. This review article describes both, the current status of standard anti-platelet drug therapy using acetylsalicylic acid, adenosine diphosphate or glycoprotein IIb-IIIa receptor antagonists in the prevention of cardiovascular events as well as drawbacks like non-responsiveness or increased bleeding rates leading to enhanced reintervention and transfusion rates, both responsible for adverse clinical outcomes after coronary interventions.

Abstract 4017: Safety of Intra-Arterial Bolus and Intravenous Infusion of Eptifibatide as an Adjunct to Intravenous Alteplase in Acute Ischemic Stroke: A Prospective Registry

Background and Purpose: Eptifibatide, a competitive platelet glycoprotein IIb-IIIa receptor inhibitor with high selectivity for platelet glycoprotein IIb-IIIa receptors and a short half-life, has been shown to reduce the risk of ischemic events associated with coronary interventions. However, its role in conjunction with full dose intravenous alteplase in neurointerventional procedures needs to be determined. We report the results of an open-label prospective registry to evaluate the safety (in terms of avoiding hemorrhagic complications) and effectiveness (in terms of recannalization rates and clinical improvement) of administering eptifibatide. Method: Patients data was prospectively maintained at a University-affiliated community hospital from January 2010 to June 2011. Consecutive patients with moderate to severe stroke who received intravenous Alteplase and failed to improve were studied. Femoral artery access was established and site of cerebral occlusion crossed with microcatheter. Each patient was administered 135 mcg/kg intraarterial bolus followed by intravenous eptifibatide infusion (0.5-microg/kg/min) for 20 hours. The outcome analysis was done to look at recannalization rates, clinical improvement within 24 hours and mRS at discharge. The primary safety end point was symptomatic intracranial or major extra-cranial bleeding. Result: Sixteen patients (Mean Age 72.7, Range 30-93, Male-5(31.25%), Female-11(68.75%)) underwent treatment with this strategy. Recannalization was achieved in 93.75%(n=16)(Complete Recannalization in 43.75%, Partial Recannalization in 50%). There was immediate clinical improvement in 68.75% and good outcomes in 31.25%. One symptomatic and one asymptomatic intracerebral hemorrhage occurred during the follow-up period. Minor femoral site bleeding without requiring transfusion occurred in one patient. Conclusions: In conclusion, eptifibatide administered as an adjunct to thrombectomy for bridging after intravenous Alteplase appears to be safe and promotes recannalization in patients with acute ischemic stroke. Further studies are required to analyze eptifibatide efficacy after intravenous alteplase and its role in neurointerventional procedures.

Intra-Arterial Tirofiban Infusion for Partial Recanalization with Stagnant Flow in Hyperacute Cerebral Ischemic Stroke

Early reocclusion is a major concern associated with poor clinical outcomes in patients with an ischemic cerebral stroke. This occurs most frequently in patients with partial initial recanalization. This study focuses on partial recanalization with stagnant antegrade flow after intravenous (IV) tPA or spontaneously, treated with the administration of intra-arterial (IA) tirofiban. Three patients with initial M1 occlusion on diagnostic studies had an occluded segment that was recanalized with stagnant flow after IV tPA or spontaneously. In all cases, IA tirofiban was administrated. We evaluated the distal blood flow and the degree of vascular narrowing in the pre and post-procedure angiography and at follow-up in addition to the clinical status. In all patients, severe vascular narrowing with stagnation of blood flow was detected in the initial M1. After infusion of IA tirofiban, improvement of the distal blood flow was achieved rapidly within 40 minutes in all patients. The severe vascular narrowing resolved rapidly in two patients without residual stenosis. In one patient, moderate vascular narrowing was still present. The median baseline National Institutes of Health Stroke Scale (NIHSS) scores were 18 and the median post-procedural NIHSS scores were 2 at two weeks. No intracerebral hemorrhage occurred in any of the patients. Treatment with IA tirofiban was safe and effective in patients with partial initial recanalization. It can be suggested that detection of any partial recanalization is time for administration of glycoprotein IIb-IIIa receptor inhibitor in hyperacute ischemic stroke.

Glycoprotein IIb‐IIIa Inhibitors

Platelets play a pivotal role in the pathogenesis of coronary artery disease and myocardial infarction. Therefore, great interests have been focused in the last decades on improvement in antiplatelet therapies, that currently are regarded as main pillars in the prevention and treatment of coronary artery disease, with special attention to glycoprotein IIb-IIIa (GP IIb-IIIa) receptors, that mediates the final stage of platelet activation. GP IIb-IIIa inhibitors, especially abciximab, have been shown to improve clinical outcome in patients undergoing primary angioplasty for STEMI. Upstream administration cannot routinely recommended, but may potentially be considered among high-risk patients within the first 4 h from symptoms onset. In case of periprocedural administration of antithrombotic therapy, Bivalirudin should be considered, especially in patients at high risk for bleeding complications. Among high-risk patients with acute coronary syndromes, an early invasive strategy with selective downstream administration of GP IIb-IIIa inhibitors is the strategy of choice, whereas bivalirudin should be considered in patients at high risk for bleeding complications. Among patients with unstable angina GP IIb-IIIa inhibitors should be considered only in case of evidence of intracoronary thrombus or in case of thrombotic complications (as provisional use). Further, randomized trials are certainly needed in the era of new oral antiplatelet therapies, and with strategies to prevent bleeding complications such as larger use of radial approach, mechanical closure devices, bivalirudin, or postprocedural protamine administration to promote early sheat removal.

Bleeding Risk Comparing Targeted Low-Dose Heparin With Bivalirudin in Patients Undergoing Percutaneous Coronary Intervention

Prior randomized trials have shown reduced bleeding with bivalirudin compared with unfractionated heparin (UFH) in patients undergoing percutaneous coronary intervention (PCI). However, it is not known if this benefit is also present when UFH doses are more tightly controlled (as measured by activated clotting time, ACT). Patients enrolled in the EVENT (Evaluation of Drug-Eluting Stents and Ischemic Events) registry, were divided into 3 groups, based on the antithrombotic drug used during PCI (UFH monotherapy, UFH+glycoprotein IIb-IIIa receptor inhibitor [GPI], or bivalirudin alone). Propensity score matching was used to adjust for measured covariates (89 variables) and to compare bivalirudin versus UFH monotherapy and bivalirudin versus UFH+GPI groups. The UFH groups were stratified based on ACT achieved (optimal ACT defined as 250-300 for UFH monotherapy and 200-250 when GPI was also used). The primary bleeding outcome was in-hospital composite bleeding, defined as events of access site bleeding, Thrombolysis In Myocardial Infarction major/minor bleeding, or transfusion. Primary (in-hospital death/myocardial infarction) and secondary ischemic outcomes (death/MI/unplanned repeat revascularization at 12 months) were also evaluated. Propensity score matching yielded 3022 patients for the UFH monotherapy versus bivalirudin comparison and 3520 patients for the UFH+GPI versus bivalirudin comparison. Bivalirudin use was associated with numerically lower bleeding rates at all categories of achieved ACT when compared with UFH (low, optimal, high ACT: 2.5% versus 4.7%, 1.9% versus 6.0%, 3.1% versus 4.8%, respectively) or heparin+GPI groups (low, optimal, high ACT: 0.0% versus 2.7%, 2.7% versus 5.2%, 2.4% versus 6.1%, respectively) and was not associated with any statistically significant increase in either primary or secondary ischemic outcomes. Among unselected patients undergoing PCI, bivalirudin use during PCI was associated with a lower risk of bleeding at all comparator ACT levels without an increase in ischemic outcomes.

Intelligent Platelet Inhibitors Are on the Horizon

Hemostasis is a tightly regulated physiological sequence of events that maintains vascular integrity and imminent blood loss after vessel injury. Platelets play a critical role in primary hemostasis and in regulation of coagulation. Under physiological conditions, hemostasis and thrombosis are in a fragile equilibrium. Uncontrolled platelet activation leads to intravascular thrombosis and organ failure. In patients with cardiovascular diseases such as coronary artery disease or stroke, antiplatelet therapy has substantially improved morbidity and mortality. To date, several antiplatelet inhibitors, including acetyl salicylic acid, P2Y12 inhibitors, and glycoprotein (GP) IIb-IIIa (integrin αIIbβ3) receptor blockers, are available to prevent or treat arterial thrombosis in affected patients.1 However, all current antiplatelet drugs inhibit both resting and activated platelets resulting in inhibition of hemostasis. Thus, current antiplatelet therapy is associated with enhanced risk of bleeding. Novel antiplatelet strategies are warranted to control undesired platelet activation without disrupting hemostasis and risking life-threatening bleeding complications. See accompanying article …

Stent assisted coiling of the ruptured wide necked intracranial aneurysm

BackgroundStent assisted coiling of unruptured wide necked intracranial aneurysms require antiplatelets to prevent stent thrombosis. The effect of the loading dose of antiplatelets prior to the stent coiling procedure in...

Could Iron Deficiency Also Affect Platelet‐Related Hemostasis Impairment in Hemodialysis Patients?

time) and iron deficiency (measured by hypochromic red cells) in hemodialysis patients, and which speculated that the hemostasis impairment might affect (functional) iron deficiency, most likely by facilitating excessive blood loss (1). This explanation is plausible, but we would like to say that iron deficiency itself could also affect platelet-related hemostasis impairment. Although not as yet extensively studied, Caliskan et al. showed that collagenor adenosine diphosphate-induced platelet aggregation was decreased in patients with iron deficiency anemia (2), and Pati et al. also demonstrated that the rate and degree of platelet aggregation with all agonists (except the lowest concentration of adenosine diphosphate) were significantly lower in anemic patients than in control and post-iron therapy subjects (P < 0.05–0.001) (3). Although it has been reported that uremic patients have decreased shear-induced platelet aggregation mediated by the decreased availability of glycoprotein IIb-IIIa receptors (4), and defective platelet aggregation in uremia is transiently worsened by hemodialysis (5), iron deficiency itself might also cause additional platelet-related hemostasis impairment in hemodialysis patients. However, further studies will be necessary to evaluate whether iron therapy could reverse defective platelet aggregation due to iron deficiency or reduce excessive blood loss in hemodialysis patients in the future.

Abciximab or eptifibatide in percutaneous coronary intervention: in-hospital outcomes and costs and six-month results

Inhibition of platelet aggregation with glycoprotein (GP) IIb-IIIa receptor blockers has been shown to reduce ischemic complications in patients with acute coronary syndromes (ACS) and in those undergoing percutaneous coronary intervention (PCI) in multiple placebo-controlled, randomized clinical trials. The effect of pharmacologic and cost differences between abciximab and eptifibatide, the only GP IIb-IIIa inhibitors indicated for PCI, on clinical outcomes and total hospital costs for patients undergoing PCI remain to be defined. To determine the rate of clinical events and costs associated with the use of abciximab vs eptifibatide at our centers, we retrospectively reviewed data for the cohort of 188 consecutive patients who underwent PCI and were treated with either abciximab (n = 85) or eptifibatide (n = 103) in the period between January 1998 and June 1999. The choice of a GP IIb-IIIa inhibitor was based on the preference of the interventional cardiologist. In-hospital events evaluated included death, major bleeding, minor bleeding, and hematoma. Additionally, the duration of hospital stay and total in-hospital costs were also assessed. Clinical events at 6 months included combined incidence of death, acute myocardial infarction (MI), or unstable angina (UA), as well as the incidence of hospital readmissions. In-hospital complications were generally more common with abciximab (death: 4.7% vs 0% with eptifibatide; major bleeding: 7.1% vs 4.8%, respectively; minor bleeding: 9.4% vs 5.7%, respectively; hematoma: 21.2% vs 21.4%, respectively), although none of these differences reached statistical significance. However, abciximab therapy was associated with a significantly longer mean duration of hospitalization (4.17 ± 0.48 days vs 2.85 ± 0.26 days with eptifibatide; P = 0.017) and a significantly higher mean total in-hospital costs ($31,396 ± 2,111 vs $25, 135 ± 815; P = 0.007). At six-month follow-up, the combined incidence of death, acute MI, or UA was also significantly higher in the abciximab group (32.9% vs 15.5%; P = 0.01). Additionally, hospital readmissions related to acute coronary syndromes at 6 months occurred significantly more often in the abciximab group (36.7% vs 16.5% with eptifibatide; P = 0.014). Our retrospective analysis of 188 patients undergoing PCI indicates that the use of eptifibatide instead of abciximab is associated with significantly lower in-hospital costs, significantly shorter duration of index hospitalization, and significantly reduced rates of ischemic complications and cardiovascular readmissions at 6-month follow-up. These differences were seen despite the fact that the baseline characteristics of patients in the two groups were generally similar. Therefore, eptifibatide provides a clinically effective and economically more attractive alternative to abciximab.

170 Does atrial differences in endothelium damage, leukocyte and platelet activation contribute to chamber specific thrombogenic status in patients with atrial fibrillation?

In atrial fibrillation (AF), the reasons why most of the thrombi form in the left atrium are mainly unknown. In the vasculature, endothelial damage together with platelet activation and inflammation contribute to initiation of blood coagulation and thrombus growth. The purpose of this study was to investigate whether atrial-specific differences in endothelial damage, leukocyte activation, platelet stimulation occur in patients with AF. Twenty patients (15 men, 5 women; age 55 ± 8 years, 15 paroxystic AF, 5 persistent AF) with AF undergoing ablation were investigated. Blood samples from the left and right atrium were obtained at the start of the procedure. Procoagulant microparticles (MPs), reliable markers of vascular damage were measured by capture assays. Their procoagulant abilities were quantified by functional prothrombinase assay and their cellular origin were determined (endothelium, platelet, leukocyte). In addition, platelet reactivity was evaluated by whole blood flow cytometry for expression of platelet Pselectin (CD62P), active glycoprotein IIbIIIa receptor (PAC-1). Platelet aggregation was evaluated using Arachidonic acid (AA), ADP, TRAP and collageninduced whole blood aggregometry. No atrial-specific differences in the levels of total procoagulant MP, leukocyte-derived-MP and platelet-derived MP could be evidenced. Conversely, endothelial-derived MPs (CD105+) were slightly elevated in the right atrium (RA 0.96 ± 0.53 vs. LA 0.80 ± 0.45 nm PhtdSer Eq.; p = 0.041). Likewise, collagen-induced platelet aggregation was evidenced in the right atrium (Collagen 1 mg/l RA: 48 ± 33% vs LA 37 ± 29%; p 0.035; collagen 2,5 mg/l RA: 76 ± 25% vs LA: 60 ± 29%; p = 0.001). In patients with AF, endothelial damage and collageninduced platelet aggregation appear slightly more pronounced in the right atrium. Our data did not substantiate the view that chamber specific enhanced thrombogenic status could be a reliable explanation for the increased propensity for thrombus formation observed in the left atrium in AF patients.

169 Does atrial differences in endothelium damage, leukocyte and platelet activation contribute to chamber specific thrombogenic status in patients with atrial fibrillation?

In atrial fibrillation (AF), the reasons why most of the thrombi form in the left atrium are mainly unknown. In the vasculature, endothelial damage together with platelet activation and inflammation contribute to initiation of blood coagulation and thrombus growth. The purpose of this study was to investigate whether atrial-specific differences in endothelial damage, leukocyte activation, platelet stimulation occur in patients with AF. Twenty patients (15 men, 5 women; age 55 ± 8 years, 15 paroxystic AF, 5 persistent AF) with AF undergoing ablation were investigated. Blood samples from the left and right atrium were obtained at the start of the procedure. Procoagulant microparticles (MPs), reliable markers of vascular damage were measured by capture assays. Their procoagulant abilities were quantified by functional prothrombinase assay and their cellular origin were determined (endothelium, platelet, leukocyte). In addition, platelet reactivity was evaluated by whole blood flow cytometry for expression of platelet Pselectin (CD62P), active glycoprotein IIbIIIa receptor (PAC-1). Platelet aggregation was evaluated using Arachidonic acid (AA), ADP, TRAP and collageninduced whole blood aggregometry. No atrial-specific differences in the levels of total procoagulant MP, leukocyte-derived-MP and platelet-derived MP could be evidenced. Conversely, endothelial-derived MPs (CD105+) were slightly elevated in the right atrium (RA 0.96 ± 0.53 vs. LA 0.80 ± 0.45 nm PhtdSer Eq.; p = 0.041). Likewise, collagen-induced platelet aggregation was evidenced in the right atrium (Collagen 1 mg/l RA: 48 ± 33% vs LA 37 ± 29%; p 0.035; collagen 2,5 mg/l RA: 76 ± 25% vs LA: 60 ± 29%; p = 0.001). In patients with AF, endothelial damage and collageninduced platelet aggregation appear slightly more pronounced in the right atrium. Our data did not substantiate the view that chamber specific enhanced thrombogenic status could be a reliable explanation for the increased propensity for thrombus formation observed in the left atrium in AF patients.

Two hour bivalirudin infusion after PCI for ST elevation myocardial infarction

The standard of care for STEMI PCI for the past decade has been aspirin, clopidogrel, heparin, and a glycoprotein IIbIIIa receptor inhibitor (GPI). A bivalirudin strategy was shown to be superior to a GPI strategy in the HORIZONS AMI trial for net adverse clinical events (combined MACE and bleeding). An increased risk of acute stent thrombosis in the bivalirudin arm may have prevented broader adoption of bivalirudin for this indication. We hypothesized that acute stent thrombosis risk could be ameliorated by a 2 h infusion of bivalirudin following STEMI PCI. We implemented a multicenter, prospective registry for all STEMI patients in Vermont treated at a single PCI center. Each patient was routinely pre-loaded with dual antiplatelet therapy and 75% received an unfractionated heparin bolus prior to PCI. The utilization of bivalirudin bolus and continued 2 h infusion after PCI was routine with GPI bailout optional. 128 consecutive STEMI patients underwent primary PCI from October 1, 2008 to September 30, 2009. 92% of primary PCI patients received bivalrudin during and after the procedure with a 9% rate of bail out GPI. There was one case of probable or definite acute stent thrombosis (0.7%), and this single case occurred despite use of bailout GPI. Despite the prolonged infusion of bivalirudin, major bleeding occurred in only 1.7% of STEMI patients. In conclusion, prolonging bivalirudin for 2 h after STEMI PCI may be a promising method to alleviate acute stent thrombosis risk without losing the bleeding complication benefit of the bivalirudin strategy.

Antithrombotic therapy in patients with coronary artery disease and with type 2 diabetes mellitus

Diabetes mellitus (DM) is a life-threatening disease. Patients with DM have a 2- to 4-fold higher risk of developing cardiovascular disease compared to their non-diabetic counterparts. Several drugs are available for the treatment of stable coronary artery disease (CAD) and acute coronary syndrome (ACS). Among oral antiplatelet agents (acetylsalicylic acid, ticlopidine, clopidogrel, and prasugrel), prasugrel has shown the highest efficacy in patients with DM and ACS. The use of glycoprotein IIb-IIIa receptor inhibitors in diabetic subjects with ACS undergoing percutaneous coronary intervention (PCI) reduces adverse clinical events in a greater extent than in non-diabetics. Several direct and indirect antithrombins are recommended for the treatment of ACS such as unfractionated heparin (UFH), enoxaparin, fondaparinux, and bivalirudin. Enoxaparin and bivalirudin have been shown to be superior to UFH among patients with ST-elevation MI (STEMI) and non-ST elevation MI (NSTEMI) also in diabetic subgroup analyses.