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Patients undergoing early surgery after coronary stent implantation are at increased risk for mortality from ischemic and hemorrhagic complications. The optimal antiplatelet strategy in patients who cannot discontinue dual antiplatelet therapy (DAPT) before surgery is unclear. Current guidelines, based on surgical and clinical characteristics, provide risk stratification for bridging therapy with intravenous antiplatelet agents, but management is guided primarily by expert opinion. This review summarizes perioperative risk factors to consider before discontinuing DAPT and reviews the data for intravenous bridging therapies. Published reports have included bridging options such as small molecule glycoprotein IIb/IIIa inhibitors (eptifibatide or tirofiban) and cangrelor, an intravenous P2Y12 inhibitor. However, optimal management of these complex patients remains unclear in the absence of randomized controlled data, without which an argument can be made both for and against the use of perioperative intravenous bridging therapy after discontinuing oral P2Y12 inhibitors. Multidisciplinary risk assessment remains a critical component of perioperative care.

Cardiovascular disease remains one of the world's leading causes of death. Myocardial infarction (heart attack) is triggered by occlusion of coronary arteries by platelet-rich thrombi (clots). The development of new anti-platelet drugs to prevent myocardial infarction continues to be an active area of research and is dependent on accurately modelling the process of clot formation. Occlusive thrombi can be generated in vivo in a range of species, but these models are limited by variability and lack of relevance to human disease. Although in vitro models using human blood can overcome species-specific differences and improve translatability, many models do not generate occlusive thrombi. In those models that do achieve occlusion, time to occlusion is difficult to measure in an unbiased and objective manner. In this study we developed a simple and robust approach to determine occlusion time of a novel in vitro microfluidic assay. This highlighted the potential for occlusion to occur in thrombosis microfluidic devices through off-site coagulation, obscuring the effect of anti-platelet drugs. We therefore designed a novel occlusive thrombosis-on-a-chip microfluidic device that reliably generates occlusive thrombi at arterial shear rates by quenching downstream coagulation. We further validated our device and methods by using the approved anti-platelet drug, eptifibatide, recording a significant difference in the "time to occlude" in treated devices compared to control conditions. These results demonstrate that this device can be used to monitor the effect of antithrombotic drugs on time to occlude, and, for the first time, delivers this essential data in an unbiased and objective manner., Lab on a Chip, 21 (21), ISSN:1473-0197, ISSN:1473-0189

Acute ischemic vertebrobasilar stroke (AIVBS) is usually associated with poor outcome and prognosis and in case of basilar artery occlusion (BAO) with high mortality. Intravenous thrombolysis (IVT), as a standard recanalization therapy of acute ischemic stroke (IS) within first 4.5 h, can be administrated beyond this therapeutic time window in case of symptomatic BAO. Repeated IVT is generally contraindicated in case of early recurrent IS, despite a risk of poor outcome or death after recurrent IS. The aim was to present 2 cases of repeated IVT for recurrent AIVBS and discuss specific situations where repeated IVT may be considered. Up to now, repeated IVT has been reported only in recurrent stroke in anterior circulation.

Objective: To determine and compare the incidence of in-hospital and 30-day hemorrhagic complication and major adverse cardiac events (MACEs) as evidence of safety and efficacy using three different anti- thrombotic strategies using Bivalirudin, Heparin plus Eptifibatide (GPI: GP IIb/IIIa inhibitor), and Unfractionated Heparin (UFH) monotherapy in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) in a tertiary care cardiac hospital. Background: UFH or Heparin plus Eptifibatide or Bivalirudin is the most commonly used antithrombotic regimen to improve peri and post-PCI clinical outcomes in a patient undergoing PCI for ACS. Among them, the most effective and optimal antithrombotic regimen for preventing ischemic complications while limiting bleeding risk in ACS patients undergoing PCI is still far from being clear. Methods: 324 ACS patients ( age >18 years and ≤75 years) who underwent PCI from May 2018 to May 2019 at UCC, BSMMU, Dhaka were consecutively enrolled in the study and were divided into three groups according to antithrombotic. The choice of Anti-thrombotic strategy was at the discretion of the operator(s) and the patient’s affordability. Group-A: 107 patients received Bivalirudin as intravenous (I/V) bolus of 0.75 mg/ kg, followed by an infusion of 1.75 mg/kg/hr up to 4 hours. Group-B: 111 patients received UFH as an I/ V bolus of 70-100 U/kg (targeted ACT: 250-300 s). Group-C: 106 patients were administered UFH plus Eptifibatide as per the standard hospital guidelines. Dual antiplatelet (DAPT) loading as Aspirin 300 mg plus P2Y12 inhibitors ( Clopidogrel 600 mg or Prasugrel 60 mg or Ticagrelor 180 mg) was given in all patients before the procedure. The maintenance dose of DAPT was continued for at least one month and patients were followed telephonically up to 30 days. The outcome measures were in-hospital and 30-day hemorrhagic complication and MACEs [death, MI, stroke, stent thrombosis and target-vessel revascularization (TVR)] Results: In-hospital outcome: Patients treated with Bivalirudin as compared with UFH had a significantly lower incidence of QMI lesions (0% vs.6%; p=0.038) and major bleeding (0% vs. 7%; p=0.021). The bleeding rate was also significantly lower in Bivalirudin arm as compared with Heparin plus GPI arm (0% vs. 6%; p=0.038). However, the incidence of cardiac death, stent thrombosis, TVR were no differences among the three groups. 30-day outcome: There was only one NQMI in the bivalirudin group as opposed to 8% in the heparin group (p=0.041). No other adverse effects were found significantly different among the study groups. Conclusion: In this perspective, observational study of ACS patients undergoing PCI in a single-center showed that Bivalirudin monotherapy is safer than other contemporary antithrombotic strategies. In terms of efficacy, Bivalirudin is non inferior to Heparin plus Eptifibatde but superior to UFH monotherapy. University Heart Journal Vol. 17, No. 2, Jul 2021; 91-98

Objective: The objective of the present study is to develop a stability-indicating reverse-phase high-performance liquid chromatography (RP-HPLC) method for qualitative and quantitative determination of Eptifibatide and its impurities in bulk and pharmaceutical dosage forms. Methods: The chromatographic separation was carried on Phenomenex Luna C18 column (250 mm×4.6 mm; 5µ id) as stationary phase, methanol and phosphate buffer at pH 6.4 in the ratio of 65:45 (v/v) as mobile phase at flow rate of 1.0 ml/min, Ultra Violet (UV) detection was carried at the wavelength of 236 nm and the analysis was completed with a run time of 15 min. Results: In the developed conditions, the retention time of Eptifibatide and its impurities 1 and 2 were found to be 3.35, 4.93 and 8.18 min, respectively. The method was validated for system suitability, range of analysis, precision, specificity, stability and robustness. Spiked recovery at 50%, 100% and 150% was carried for both standard and impurities and the acceptable % recovery of 98-102 was observed for Eptifibatide and both impurities studied and the % Relative standard deviation (RSD) in each spiked level was found to be less than 2. Stability tests were done through the exposure of the analyte solution to five different stress conditions i. e expose to 1N Hydrochloric acid (HCl), 1 N Sodium hydroxide (NaOH), 3% Hydrogen peroxide (H2O2), 80 °C temperature to UV radiation. In all the degradation conditions, standard drug Eptifibatide was detected along with both the impurities studied and the degradation products were successfully separated. In the formulation analysis, there is no other chromatographic detection of other impurities and formulation excipients. Conclusion: The developed method was found to be suitable for the quantification of Eptifibatide and can separate and analyse impurities 1 and 2.

Eptifibatide is a glycoprotein (GP) IIb/IIIa receptor antagonist, used for the treatment of acute coronary syndrome with high-risk features or ongoing ischemia. Several case reports have described thrombocytopenia as a rare side effect of eptifibatide administration. The exact mechanism remains unclear but may be due to immune destruction of circulating platelets in the peripheral blood. We present the case of acute-onset severe thrombocytopenia in a 76-year-old female undergoing percutaneous coronary intervention.

Few data are available on procedural complications of percutaneous coronary intervention (PCI) in the setting of acute coronary syndrome in the contemporary era.We sought to describe the prevalence of procedural complications of PCI in a non-ST-segment elevation acute coronary syndrome (NSTE ACS) cohort, and to identify their clinical characteristics and association with clinical outcomes.Patients randomized in TAO (Treatment of Acute coronary syndrome with Otamixaban), an international randomized controlled trial (ClinicalTrials.gov Identifier: NCT01076764) that compared otamixaban with unfractionated heparin plus eptifibatide in patients with NSTE ACS who underwent PCI, were included in the analysis. Procedural complications were collected prospectively, categorized and adjudicated by a blinded Clinical Events Committee, with review of angiograms. A multivariable model was constructed to identify independent clinical characteristics associated with procedural complications.A total of 8656 patients with NSTE ACS who were enrolled in the TAO trial underwent PCI, and 451 (5.2%) experienced at least one complication. The most frequent complications were no/slow reflow (1.5%) and dissection with decreased flow (1.2%). Procedural complications were associated with the 7-day ischaemic outcome of death, myocardial infarction or stroke (24.2% vs. 6.0%, odds ratio 5.01, 95% confidence interval 3.96-6.33; P0.0001) and with Thrombolysis In Myocardial Infarction major and minor bleeding (6.2% vs. 2.3%, odds ratio 2.79, 95% confidence interval 1.86-4.2; P0.0001). Except for previous coronary artery bypass grafting, multivariable analysis did not identify preprocedural clinical predictors of complications.In a contemporary NSTE ACS population, procedural complications with PCI remain frequent, are difficult to predict based on clinical characteristics, and are associated with worse ischaemic and haemorrhagic outcomes.

BACKGROUND AND PURPOSE: Maintaining carotid patency and avoiding symptomatic intracranial hemorrhage are competing concerns in tandem occlusions. This study provides data regarding the safety and efficacy of eptifibatide in stroke from tandem occlusion of the extracranial carotid artery and the intracranial carotid or middle cerebral artery. MATERIALS AND METHODS: This is a retrospective analysis of 58 consecutive patients who received low-dose eptifibatide (135-mcg/kg bolus, 1-mcg/kg/min infusion) during treatment of tandem occlusions. Brain imaging and carotid sonography were performed at 24–36 hours. mRS was documented at 90 days, and carotid sonography, at 30–60 days. RESULTS: The median age and NIHSS score were 64 years and 15, respectively. Twenty-five patients (43%) received tPA. ASPECTSs were 8–10 in 47 (81%) and 5–7 in 11 (19%) patients. Thirty-eight patients had angioplasty/stent placement acutely; 20 had angioplasty alone. Symptomatic intracranial hemorrhage occurred in 1 patient (2%). TICI 2b or higher was achieved in 56 patients (96%). Fifty-seven of 58 patients had clinical follow-up at 90 days (1 lost to follow up). The 90-day mRS was 0–2 in 42 patients (72%). There were 4/58 (7%) re-occlusions within 24–36 hours, all originally treated with stent placement. Forty-nine of 53 surviving patients had carotid sonography at 30–60 days, with 3 delayed re-occlusions, 2 with stents and 1 with angioplasty alone. The overall carotid patency at 30–60 days was 42/49 (86%). Carotid re-occlusion was not associated with clinical decline. CONCLUSIONS: Low-dose eptifibatide seemed to be safe in tandem occlusions (symptomatic intracranial hemorrhage, 2%), although asymptomatic cervical carotid artery re-occlusions still occurred in 14% of patients.

Acute ischemic stroke (AIS) is a time sensitive medical emergency and a leading cause of morbidity and mortality worldwide. Intravenous (IV) recombinant tissue plasminogen activator (IV alteplase) is currently the only proven effective medication for the treatment of AIS with promising adjuvant medications currently under investigation. Recent advances in endovascular thrombectomy have broadened therapeutic options in specific patient populations, with modern treatment strategies utilizing advanced imaging modalities to extend the window for treatment. In all cases, rapid treatment remains a priority. The future of IV alteplase and the changing standard for treatment of AIS remain unwritten with the increasing evidence for imaging selection for both endovascular thrombectomy and IV alteplase, while novel adjuncts are under investigation. In this article, we review the history of IV alteplase investigations for stroke, evidence for thrombectomy as an adjunct to IV alteplase, and the potential of novel adjuvant therapeutics currently under investigation.

We have developed a microfluidic system to perfuse whole blood through a flow channel with an upstream stenotic region and a downstream protein capture region. This flow-based system was used to assay how effectively antiplatelet agents suppress shear-induced platelet adhesion and activation downstream of the stenotic region. Microcontact printing was used to covalently attach one of three platelet binding proteins [fibrinogen, collagen, or von Willebrand factor (vWf)] to the surface of the downstream capture region. Whole blood with an antiplatelet agent was transiently exposed to an upstream high wall shear rate (either 4860 s-1 or 11 560 s-1), and subsequently flowed over the downstream capture region where the platelet adhesion was measured. Several antiplatelet agents (acetylsalicylic acid, tirofiban, eptifibatide, anti-vWf, and anti-GPIbα) were evaluated for their efficacy in attenuating downstream adhesion. Following antibody blocking of vWf or GPIbα, downstream platelet activation was also assessed in perfused blood by flow cytometry using two activation markers (active GPIIb/IIIa and P-selectin). Acetylsalicylic acid demonstrated its inability to diminish shear-induced platelet adhesion to all three binding proteins. GPIIb/IIIa inhibitors (tirofiban and eptifibatide) significantly reduced platelet adhesion to fibrinogen. Antibody blocking of vWf or GPIbα effectively diminished platelet adhesion to all three capture proteins as well as platelet activation in perfused blood, indicating an essential role of vWf-GPIbα interaction in mediating shear-induced platelet aggregation.

The glycoprotein IIb/IIIa inhibitor eptifibatide, administered as bolus followed by infusion, is an adjunctive antithrombotic treatment during primary percutaneous coronary intervention (PCI) in selected patients with ST-segment elevation myocardial infarction (STEMI). Whether both bolus and infusion are necessary to improve outcomes is unknown. We hypothesized that primary PCI with eptifibatide bolus only is non-inferior to the conventional treatment (bolus and infusion) with regard to infarct size, while reducing bleeding complications. We analyzed 720 consecutive STEMI patients receiving eptifibatide bolus only or conventional treatment in an observational case-control study utilizing propensity score matching of clinical and intervention-specific confounders. Infarct size was estimated based on myocardial bound creatine kinase, creatine kinase (CK), and CK area under the curve values, with a prespecified non-inferiority margin of 20%. Major bleeding was defined as type 2, 3, or 5 on the Bleeding Academic Research Consortium classification. Eptifibatide bolus only was administered to 147 patients (20%), which were matched 1:1 to patients receiving conventional treatment. Based on peak myocardial bound creatine kinase, CK and CK area under the curve values, infarct size was -8.4% (95% CI [-31.2%, 14.4%]), -11.6% (95% CI [-33.5%, 10.3%]), and -13.9% (95% CI [-34.1%, 6.2%]) after eptifibatide bolus, respectively, reaching prespecified noninferiority compared with conventional treatment. Bolus treatment significantly reduced major bleeding complications (OR 0.48, 95% CI [0.30, 0.79]). In conclusion, eptifibatide given as abbreviated bolus only to selected STEMI patients who underwent primary PCI was noninferior regarding infarct size and resulted in less bleeding complications compared with conventional bolus and infusion treatment.

Background: Ticks puncture the skin of their hosts and secrete saliva, containing antiplatelet proteins, into the blood. Here, we studied disagregin, a potent platelet-inhibiting protein derived from the salivary glands of Ornithodoros moubata, an African soft tick. Whereas conventional alpha IIb beta 3 antagonists contain an Arg-Gly-Asp (RGD) sequence for platelet integrin binding, disagregin contains an Arg-Glu-Asp (RED) sequence, hypothesizing a different mode of inhibitory action.Objectives: We aimed to compare the inhibitory effects of disagregin and its RGD variant (RGD-disagregin) on platelet activation and to unravel the molecular basis of disagregin-alpha IIb beta 3 integrin interactions.Methods: Disagregin and RGD-disagregin were synthesized by tert-butyloxycarbonyl -based solid-phase peptide synthesis. Effects of both disagregins on platelet aggregation were assessed by light transmission aggregometry in human platelet-rich plasma. Whole-blood thrombus formation was investigated by perfusing blood over collagen I with and without tissue factor at a high wall-shear rate (1000 s(-1)) in the presence of disagregin, RGD-disagregin, or eptifibatide.Results: Disagregin showed inhibition of collagen- and ADP-induced platelet aggregation with half maximal inhibitory concentration values of 64 and 99 nM, respectively. This resembled the complete antiaggregatory effect of eptifibatide. Multiparameter assessment of thrombus formation showed highly suppressed platelet adhesion and aggregate formation with both disagregins, in contrast to eptifibatide treatment, which incompletely blocked aggregation under flow. Fibrin formation under flow was delayed by both disagregin and RGD-disagregin (P Conclusions: Both alpha IIb beta 3-blocking disagregins have a strong potential to suppress collagen-tissue factor-mediated platelet adhesion, thrombus formation, and fibrin formation. Both disagregins can be seen as potential new alpha IIb beta 3 inhibitors.

Acute stent thrombosis may complicate neonatal arterial duct stenting for reduced pulmonary blood flow. Thrombolytic agents recanalise the clot but may cause bleeding around the vascular sheaths and other sites. Since early thrombus is platelet mediated, intravenous platelet glycoprotein inhibitor like eptifibatide is likely to be effective, but rarely utilised in neonates. Ductal stent thrombosis treated with eptifibatide is reported.

BACKGROUND Fibrin-specific fibrinolytics are preferred when they used in STEMI patients (pharmaco-invasive approach). However, streptokinase is still the most common used thrombolytic agent in Egypt because of its cheaper cost. METHODS 266 STEMI patients were randomly assigned to undergo PPCI or pharmacoinvasive (using streptokinase). Primary end point (death, shock, congestive heart failure, or reinfarction up to 30 d) and secondary end point (ischemic stroke, intracranial hemorrhage, or nonintracranial bleeding) were followed for 30 days after reperfusion. In pharmaco-invasive arm, urgent coronary angiography was performed in case of failed reperfusion. Based on the reperfusion time from symptoms onset, patients in both arms were divided into; early (≤3 hrs) and late reperfusion (>3 hrs). RESULTS No statistical significant difference regarding left ventricular ejection fraction, end diastolic and end systolic diameter in both arms. Early PPCI (≤3 hrs) had highest ejection fraction values (56.9 ± 7.5). Myocardial wall preservation was best achieved in early pharmaco-invasive (≤3 hrs).There was no statistical significant difference in TIMI flow results between all subgroups (early and late of both arms) (P = 0.750). Suction devices and IV Eptifibatide were less frequently used in the pharmaco-invasive comparing to PPCI arm; (P = 0.000 and P = 0.006) subsequently. No statistical significant difference regarding complication incidence in both arms (P = 0.518). Radial access was more commonly used in the pharmaco-invasive arm (P = 0.015). CONCLUSION Utilizing streptokinase in early re-perfused patients by PI approach (≤3 hrs) seems safe and efficient when PPCI delay (>120 min from symptom onset) is the other option.

Objective To compare the antiplatelet effect and major adverse cerebrovascular events of Pipeline for intracranial aneurysms using glycoprotein IIb/IIIa antagonists (GPI) eptifibatide and tirofiban. Methods Retrospective analysis of relevant data of patients using GPIs combined with oral antiplatelet therapy in Nanfang Hospital of Southern Medical University from December 2017 to December 2019. The study was approved by the ethics Committee of Nanfang Hospital of Southern Medical University. According to the random use of GPIs drugs, they were assigned to the eptifibatide group and tirofiban group. Basic data, platelet inhibition rates at baseline, 24h and 72h after administration, short-term major adverse cerebrovascular events, and bleeding complications were compared between the two groups. Results A total of 47 patients were included in this study, including 24 patients in eptifibatide group and 23 patients in tirofiban group. There was no significant difference in average age (53.75 vs. 53.91 years) and body mass index (BMI) (24.39 vs. 22.73 ​kg/m2) between eptifibatide group and tirofiban group. There was no significant difference in coagulation factor function (R), fibrinogen function (K), fibrinolysis function (EPL), comprehensive coagulation index (Cl), arachidonic acid pathway inhibition rate (AA%) and adenosine diphosphate inhibition rate (ADP%). However, the baseline level of residual platelet function MA (ADP) in eptifibatide group was significantly higher than that in tirofiban group (50.79 vs. 35.29 ​mm, P ​= ​0.0026). There was a statistical difference in the platelet aggregation function MA (65.38 vs. 62.54 ​mm, p ​= ​0.0442), the rate of spontaneous hemorrhagic stroke (4.3% vs. 0%) and the rate of asymptomatic minor bleeding (26.08% vs. 4.1%) in the two groups (P ​ Conclusion Both eptifibatide and tirofiban can effectively inhibit platelets, but the effect of etifeptide is better than that of tirofiban in preventing intracranial microhemorrhage and asymptomatic cerebral infarction.

The development of endovascular treatment for intracranial aneurysms has established new techniques such as balloon and stent-assistance, flow diversion and endosaccular occlusion devices. Antiplatelet treatment is an important aspect to reduce risk of thrombus formation on microcatheters and implanted devices when utilizing these methods. It is particularly relevant for flow diverting stents to prevent early and late stent thrombosis. Consideration of platelet physiology and appropriate selection of antiplatelet medication is important as platelet dysfunction drives many of the pathological processes and complications of neurointerventional procedures. Part one of this review focuses on basic platelet physiology, pharmacology of common antiplatelet medications and future directions and therapies. Part two focuses on clinical applications and evidence-based therapeutic regimens.

Recently, there has been a positive trend to reduce mortality from myocardial infarction. One of the reasons for such dynamics is the development of angiographic service in our country and the increase in the number of primary percutaneous coronary interventions. One of the most serious complications of endovascular interventions affecting the prognosis is the development of the phenomenon of slow or unrecoverable blood flow (≪slow/no-reflow≫ phenomenon). The reason for the development of this phenomenon is associated, first of all, with distal embolization by thrombotic masses and fragments of atherosclerotic plaque. In order to prevent this complication, manual thromboextraction was developed – the aspiration of thrombotic masses from the infarct-related artery. The manual thrombus aspiration has not been proven effective in a number of large randomized trials. In addition to the lack of influence on the prognosis, the method of manual thrombus aspiration significantly more often led to the development of ischemic strokes and currently should not be routinely carried out. Another method of preventing the phenomenon of delayed or unrecoverable blood flow is the use of glycoprotein IIb/IIIa receptor inhibitors which is, in contrast to the instrumental method, effective and relatively safe. According to a number of large randomized trials, drug treatment of this complication influences life expectancy in patients with ST-elevation myocardial infarction. At a time when there is already a meta-analysis on the routine use of glycoprotein IIb/IIIa receptor inhibitors during primary percutaneous coronary intervention and their positive impact on survival, in our country, unfortunately, the importance of these drugs is underestimated and according to the register they are used only in 3% of patients with ST-segment elevation myocardial infarction. This review presents studies and comparisons of glycoprotein IIb/IIIa receptor inhibitors existing on the market.

Background Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare coagulation disorder reported after administration of COVID-19 adenovirus-vectored vaccines. VITT is mediated by anti-platelet factor 4 (PF4) antibodies activating platelets through the Fcγ-receptor II (FcγRII), and it is associated with strong fibrin turnover. The complement system is involved in several other immunothrombotic entities, but its impact on VITT is not established. Objective To assess antibodies in interaction with the activation of platelets and complement triggered by VITT. Methods Antibodies against adenovirus type 2 hexon protein, ChAdOx1 adenoviral vector-specific IgG and PF4 were analyzed by enzyme immunoassays from VITT patients (n = 5). The EDTA plasma samples of the patients and controls were used to measure both terminal complement complexes (TCC) by ELISA and aggregation of healthy donor platelets. We studied the effects of human immunoglobulin (IVIG) and glycoprotein IIb/IIIa inhibitor (GPIIb/IIIa) on spontaneous and collagen-induced platelet aggregation supplemented with VITT plasma. Results None of the patients had experienced a COVID-19 infection. Antibody analyses confirmed the immunogenicity of the adenovirus-vectored ChAdOx1 vaccine. Moreover, VITT plasma had anti-PF4 antibodies and elevated TCC levels as a sign of complement activation. In isolated healthy donor platelets, VITT patient plasma caused marked, spontaneous aggregation of platelets, which was abolished by eptifibatide and high-dose therapeutic IVIG. Conclusions Our findings suggest that VITT is triggered by antibodies against adenovirus vector and PF4-polyanion complexes which strongly co-activate complement and platelets. The spontaneous platelet aggregation was suppressed by IVIG or eptifibatide, indicating that besides FcγRII, also GPIIb/IIIa receptor exerts platelet procoagulant role in VITT., Graphical abstract Unlabelled Image

Background. Eptifibatide is a glycoprotein IIb/IIIa (GP IIb/IIIa) receptor inhibitor which prevents platelet activation. The mechanism in which eptifibatide causes profound thrombocytopenia is poorly understood. One hypothesis suggests antibody-dependent pathways which cause thrombocytopenia upon subsequent reexposure to eptifibatide. This case reports acute profound thrombocytopenia ( platelets < 20 × 10 3 / m m 3 ) within 24 hours of administration. Alveolar hemorrhage occurred during a second eptifibatide infusion 5 days after initial asymptomatic eptifibatide treatment. Case Presentation. A 50-year-old male presenting with a STEMI was treated with eptifibatide during cardiac catheterization. Twelve hours posttreatment, the patient encountered profound thrombocytopenia and hemoptysis. The patient was briefly intubated for airway protection. The patient was stabilized after receiving platelet transfusion and fully recovered. Conclusion. This is one of several cases reported on eptifibatide causing acute profound thrombocytopenia and subsequent alveolar hemorrhage. This case supports the theory in which antibodies contribute to eptifibatide-induced thrombocytopenia.

Cells transmit piconewton forces to receptors to mediate processes such as migration and immune recognition. A major challenge in quantifying such forces is the sparsity of cell mechanical events. Accordingly, molecular tension is typically quantified with high resolution fluorescence microscopy, which hinders widespread adoption and application. Here, we report a mechanically-triggered hybridization chain reaction (mechano-HCR) that allows chemical amplification of mechanical events. The amplification is triggered when a cell receptor mechanically denatures a duplex revealing a cryptic initiator to activate the HCR reaction in situ. Importantly, mechano-HCR enables direct readout of pN forces using a plate reader. We leverage this capability and measured mechano-IC(50) for aspirin, Y-27632, and eptifibatide. Given that cell mechanical phenotypes are of clinical importance, mechano-HCR may offer a convenient route for drug discovery, personalized medicine, and disease diagnosis.

Guidelines recommend adjunct glycoprotein IIb/IIIa inhibitors (GPIs) only in selected patients with acute ST-segment elevation myocardial infarction (STEMI). This study aimed to evaluate routine GPI use in STEMI treated with primary percutaneous coronary intervention.Online databases were searched for randomized controlled trials of routine GPI vs control therapy in STEMI. Data from retrieved studies were abstracted and evaluated in a comprehensive meta-analysis. Twenty-one randomized controlled trials with 8585 patients were included: 10 trials randomized tirofiban, 9 abciximab, 1 trial eptifibatide, and 1 trial used abciximab+tirofiban; only 1 trial used dual antiplatelet therapy with prasugrel/ticagrelor.Routine GPI use was associated with a significant reduction in all-cause mortality at 30 days (2.4% [GPI] vs 3.2%; risk ratio [RR], 0.72; P = 0.01) and 6 months (3.7% vs 4.8%; RR, 0.76; P = 0.02), and a reduction in recurrent myocardial infarction (1.1% vs 2.1%; RR, 0.55; P = 0.0006), repeat revascularization (2.5% vs 4.1%; RR, 0.63; P = 0.0001), thrombolysis in myocardial infarction flow3 after percutaneous coronary intervention (5.4% vs 8.2%; RR, 0.61; P0.0001), and ischemic stroke (RR, 0.42; P = 0.04). Major (4.7% vs 3.4%; RR, 1.35; P = 0.005) and minor bleedings (7.2% vs 5.1%; RR, 1.39; P = 0.006) but not intracranial bleedings (0.1% vs 0%; RR, 2.7; P = 0.37) were significantly increased under routine GPI.Routine GPI administration in STEMI resulted in a reduction in mortality, driven by reductions in recurrent ischemic events-however predominantly in pre-prasugrel/ticagrelor trials. Trials with contemporary STEMI management are needed to confirm these findings.

The role of glycoprotein IIb/IIIa inhibitors (GPI) in primary percutaneous coronary intervention (PPCI) remains uncertain. Previous analyses compare PPCI outcomes with clopidogrel plus GPI, versus without GPI. This does not reflect modern contemporary PPCI practice with ticagrelor or prasugrel. Nor does it answer the important question faced daily by PPCI operators: should GPI be used routinely or selectively? We aim to determine whether a strategy of routine use of GPI in contemporary PPCI practice is superior to selective GPI use. A total of 110,327 consecutive PPCIs performed in England were prospectively recorded in the British Cardiovascular Intervention Society Database (2009 to 2015). The cohort was divided into routine and selective GPI usage groups based on the PPCI operator's strategy, defined as GPI used in75% and25% PPCIs, respectively. Overall, GPI use declined from 73.1% to 43.3% of PPCIs. Routine compared with selective GPI usage was associated with lower all-cause 1-year mortality: 9.7% versus 11.0%, p 0.001. There was a consistent survival benefit for routine GPI usage as compared with selective GPI usage: univariable analysis (hazard ratio = 0.88 [95% confidence interval 0.83 to 0.93], p 0.001), multivariable analysis (hazard ratio = 0.82 [0.77 to 0.88], p 0.001). For survival, there was no interaction between GPI usage and the type of P2Y12-inhibitor used. In conclusion, a strategy of routine GPI usage in patients who underwent PPCI was associated with lower all-cause mortality as compared with selective GPI usage. This benefit was maintained despite 44.3% of patients receiving prasugrel or ticagrelor.

Introduction: Carotid angioplasty and stenting (CAS) represents an effective procedure for treating carotid artery disease. The acute in-stent thrombosis is an extremely rare complication of CAS especially when it occurs postprocedurally during the first 24 hours. Improper antiplatelet therapy or poor response to antiplatelet medications is known to be associated with a higher risk of in-stent thrombosis during early postprocedural period following a successful intervention. Material and Methods: A patient who experienced acute carotid in-stent thrombosis in early postprocedural period is described. He had been taking dual antiplatelet therapy for 2 weeks before undergoing a successful CAS. Moreover, pharmacogenetics studies showed the patient to be a clopidogrel ultrarapid metabolizer, which theoretically confers hyperresponsivity to medication. Alongside the report itself, a brief literature review of relevant sources pertinent to the case has been conducted. Results: According to the available literature, this is the first case report describing an ultrarapid clopidogrel metabolizer who underwent an uneventful CAS but experienced acute carotid in-stent thrombosis in early postprocedural period. A rescue procedure included an endovascular intervention consisting of thrombectomy and local alteplase application, followed by postprocedural administration of intravenous eptifibatide. At discharge, patient’s dual antiplatelet therapy included ticagrelor instead of clopidogrel. Conclusion: Acute carotid in-stent thrombosis is a highly unexpected complication of CAS and can occur despite ultrarapid clopidogrel metabolism trait.

Background Wide-necked intracranial aneurysms present unique treatment challenges in the setting of subarachnoid hemorrhage. New generations of endoluminal devices (stents) have expanded our ability to treat complex aneurysms. The PulseRider Aneurysm Neck Reconstruction Device (PulseRider [Cerenovus, Irvine, California, USA]) is new to the U.S. market after receiving Food and Drug Administration approval in June 2017. Official recommendation for use of the PulseRider is with dual antiplatelet therapy (DAPT). Its design has been hypothesized to carry a lower risk of thromboembolic complications in the circumstance that DAPT needs to be discontinued. Methods Between March and June 2018, we treated 4 cases of ruptured wide-necked basilar tip aneurysms at the University of Colorado Hospital, Aurora, Colorado, with PulseRider-assisted coil embolization. Imaging and chart reviews were performed retrospectively on each of these patients. Results All 4 aneurysms were successfully treated with PulseRider-assisted coil embolization. There were no periprocedural hemorrhages and no postprocedural reruptures. Two patients developed nonocclusive thrombi in the posterior cerebral arteries at the time of coiling, which was resolved with intra-arterial glycoprotein IIb/IIIa receptor antagonists. Two patients developed external ventricular drain-associated hemorrhages, only one of which developed after the administration of DAPT. All patients were eventually discharged to home. Conclusions The PulseRider device represents a novel design for stent-assisted coil embolization. We report a small but promising series of its successful use in the acute treatment of wide-necked, ruptured basilar artery aneurysms. Additional experience is needed to determine if this device has a place in our armamentarium for treatment of ruptured aneurysms.

Background Eptifibatide (Integrilin®) is a hepta-peptide drug which specifically prevents the aggregation of activated platelets. The peptide drugs are encapsulated into nanolipisomes in order to decreasing their side effects and improving their half-life and bioavailability. Objectives In this study, the in vitro cytotoxicity and hemocompatibility of RGD-modified nano-liposomes (RGD-MNL) encapsulated a highly potent antiplatelet drug (eptifibatide) was investigated. Material and methods RGD-MNL encapsulated eptifibatide was prepared using lipid film hydration and freeze/thawing method. The morphology and size distribution (about 90 nm) of RGD-MNL were characterized using transmission electron microscopy (TEM). The in-vitro cytotoxicity of nano-liposomes was examined using the MTT, LDH release and reactive oxygen species (ROS) generation assays. The effect of RGD-MNL on red blood cells (RBC) was investigated using hemolysis and LDH release assays. Results The results revealed that RGD-MNL had no significant cytotoxic effect on HeLa and HUVEC cell lines, and also no ROS generation increase in the cells. In addition, the adverse effect of RGD-MNL on LDH release and membrane integrity of RBC was not observed. Conclusions In conclusion, the recommended RGD-MNL formulations have not any significant cytotoxicity on normal cells or RBC and have potential for protecting and enhancing the activity of antiplatelet drugs.

Background.Eptifibatide achieves high local concentration via direct intracoronary (I/V) injection as it promotes clot disaggregation, but it remains unclear if it is of superior benefit than the routine intravenous (I/V) administration. Aim. The current study aimed to examine the safety and efficacy of I/C vs I/V bolus regimen dose of eptifibatide during primary percutaneous coronary intervention (PPCI).Material and methods. Prospective, controlled, randomized study enrolled 100 patients with acute anterior ST-segment elevation myocardial infarction (STEMI) eligible for PPCI equally divided into 2 groups (group A received bolus I/C eptifibatide and group B received it I/V) followed by 12-hour continuous I/V infusion. Features related to of myocardial salvage in the form of TIMI flow grade 3, myocardial blush grade 3, ST segment resolution and left ventricular systolic function were evaluated with short-term follow up for 1 month.Results. Mean age of the study population was 50.95±8.45years, there was statistically insignificant difference between both groups regarding baseline characteristics in age (p=0.062), gender (p=0.488), coronary artery disease risk factors (p>0.05), time from onset of pain to admission (p=0.86) or door to balloon (p=0.12). Group A achieved statistically significant better myocardial blush grade 3 (42% vs 10%, p=0.005), ejection faction 30 days after PPCI (46.11±7.81% vs 40.88±6.26%, p=0.005) but statistically insignificant TIMI flow grade 3 (p=0.29) and ST resolution (p=0.34). Incidence of complications in the hospital and 30 days after discharge was statistically insignificant (p>0.05).Conclusion. Both regimens were safe and effective in STEMI patients undergoing PPCI and regimen of I/C bolus eptifibatide achieved better myocardial blush grade and systolic function.

Integrins are a family of transmembrane glycoprotein signaling receptors that can transmit bioinformation bidirectionally across the plasma membrane. Integrin αIIbβ3 is expressed at a high level in platelets and their progenitors, where it plays a central role in platelet functions, hemostasis, and arterial thrombosis. Integrin αIIbβ3 also participates in cancer progression, such as tumor cell proliferation and metastasis. In resting platelets, integrin αIIbβ3 adopts an inactive conformation. Upon agonist stimulation, the transduction of inside-out signals leads integrin αIIbβ3 to switch from a low- to high-affinity state for fibrinogen and other ligands. Ligand binding causes integrin clustering and subsequently promotes outside-in signaling, which initiates and amplifies a range of cellular events to drive essential platelet functions such as spreading, aggregation, clot retraction, and thrombus consolidation. Regulation of the bidirectional signaling of integrin αIIbβ3 requires the involvement of numerous interacting proteins, which associate with the cytoplasmic tails of αIIbβ3 in particular. Integrin αIIbβ3 and its signaling pathways are considered promising targets for antithrombotic therapy. This review describes the bidirectional signal transduction of integrin αIIbβ3 in platelets, as well as the proteins responsible for its regulation and therapeutic agents that target integrin αIIbβ3 and its signaling pathways.

Introduction: Glycoprotein (Gp) IIb/IIIa is a platelet receptor participating in platelet aggregation. According to ESC guidelines, glycoprotein IIb/IIIa inhibitors might be considered during percutaneous coronary interventions in patients with the acute coronary syndrome. Purpose: A case study of profound thrombocytopenia in 80-year-old man with the acute coronary syndrome. Case presentation: An 80-year-old, medicationnaive man with acute coronary syndrome was admitted to the Department of Invasive Cardiology. Due to the unsuccessful invasive strategy, an intracoronary bolus of Gp IIb/IIIa inhibitor – eptifibatide - was administered. During the following intravenous infusion, large subcutaneous hematomas were observed. Eptifibatide infusion was discontinued. Drop in platelet count to 1 thou/μL without significant anemia was registered. A control sample in sodium citrate showed similarly low platelet count - 2 thou/uL. Acetylsalicylic acid and clopidogrel were discontinued, steroids were introduced. Neither PLT nor FFP transfusion were necessary. Consecutive lab tests showed the gradual increase of PLT up to 35 thou/μL at discharge. A week later, the patient did not complain of any cardiovascular or bleeding symptoms; hematomas resented significant involution. Laboratory findings were normal. During follow-up visit 30 days after the discharge, the patient presented no cardiovascular symptoms. Conclusions: There are patients at risk of druginduced thrombocytopenia, especially those with impaired kidney function and the elderly. In such cases, decisions concerning anti-platelet and antithrombotic therapy should be taken cautiously. Because of its rare occurrence, every case of severe thrombocytopenia in ACS patients should be reported. Moreover, such patients should be followed-up to minimalize risk of similar adverse events in the future.

Background Eptifibatide is used in acute coronary syndromes to reversibly block platelet aggregation by inhibiting the platelet glycoprotein IIb/IIIa receptor. A serious adverse effect of eptifibatide is a profound drop in platelet count, termed eptifibatide-induced thrombocytopenia (EIT). Objective To provide insight into the types of complications and management of EIT. Methods Cases of EIT submitted to the Food and Drug Administration adverse event reporting system were evaluated. Data analyses included management of EIT, complications of thrombocytopenia, initial platelets, and platelet nadir following eptifibatide. Results 103 cases of EIT were reported from January 2010 to 2019; 57 cases met the Naranjo scale and were included. Only 37 of those cases contained information on how EIT was managed. Eptifibatide administration was withheld in all 37 of those cases. Platelet transfusions were administered in 20 cases (54%). Two cases were managed with steroids (5.4%), and 1 case used intravenous immunoglobulin G to reverse EIT (2%). The median initial platelet count prior to administration of eptifibatide was 207 000 cells/mm3 (SD = 69 000; n = 27), and median platelet nadir was 9000 cells/mm3 (SD = 19 000; n = 35) The majority of complications of EIT included bleeding events (16/28, 57%). Delayed procedures, prolonged stay, allergic reactions, and thrombosis were each reported in 3 patients (10.75%). Conclusion and Relevance Most cases of EIT were managed by withholding eptifibatide with platelet transfusion if necessary. The majority of complications included bleeding. However, significant procedure delays, prolonged hospital stay, thrombosis, and allergic reactions were also reported.

Background A tracheo-innominate fistula is a rare but life-threatening complication of tracheostomy and has a mortality rate of 100% without therapy. The underlying cause is an acquired fistula between the brachiocephalic trunk and the trachea, induced by a tracheostomy cannula’s mechanical impact. Case presentation A 25-year-old female was admitted with pulsatile bleeding from a tracheostomy. The cause of the bleeding was a tracheo-innominate artery fistula, which was difficult to recognize. Said fistula was treated with implantation of a self-expanding stent-graft. The bleeding stopped immediately after the implantation of the stent-graft. Dual antiplatelet medication with aspirin IV and ticagrelor PO, bridged with a bolus of eptifibatide IV, was started right after the stent deployment. Conclusions Endovascular self-expanding stent-graft implantation is a viable treatment option for tracheo-innominate artery fistulae, especially in hemorrhagic emergencies.

Primary hemostasis, secondary hemostasis, and fibrinolysis (anticoagulant biological system) are the three distinct-yet-interlinked components of the in vivo hemostatic mechanism. The primary hemostasis is characterized by platelet response resulting in the formation of a ‘temporary/soft’ hemostatic plug and the secondary hemostasis is the incitement of the coagulation cascade ultimately transforming the clot to a ‘definitive/hard’ hemostatic plug. Antiplatelets, anticoagulants, and fibrinolytics are drugs that aid in maintaining this intricate biological process of hemostasis by preventing either excessive pathological thrombus formation or excessive pathological bleeding. The chapter includes discussion on the various antiplatelet drugs—including, aspirin, clopidogrel, prasugrel, ticagrelor, cangrelor, abciximab, eptifibatide, tirofiban, vorapaxar, dipyridamole, and cilostazol; the anticoagulant drugs—including, heparins, fondaparinux, warfarin, dabigatran, rivaroxaban, apixaban, and edoxaban; and the fibrinolytic drugs—including, streptokinase, alteplase, reteplase, and tenecteplase. The approved therapeutic application with the dosing guidelines for these drugs is also elucidated.

A growing industrial interest toward the peptide drug market fueled the need for the development of effective and cGMP compliant manufacturing methods for these complex molecules. Solid-phase strategies are considered methods of election for medium-length peptide syntheses not only on the research scale but for multigram-scale production, as well. The possibility to use microwave-assisted technology on the multigram scale, recently introduced, prompted us to evaluate the possibility to conveniently set up a safe and fully cGMP-compliant pilot process to produce eptifibatide, a generic peptide active pharmaceutical ingredient. Accordingly, we developed an optimized process on the laboratory scale (1-5 mmol), which was subsequently successfully scaled up to 70 mmol, obtaining all the information required by regulatory agencies to validate the process and qualify the pilot scale plant. The process consists of 5 steps: (1) automated microwave-assisted solid-phase synthesis of eptifibatide linear precursor; (2) cleavage from the resin with concomitant amino acid side-chains deprotection; (3) disulfide-bond formation in solution; (4) purification by flash column chromatography; (5) ion-exchange solid-phase extraction. Since the direct scale-up of a multigram-scale cGMP compliant peptide API production procedure is a challenge that requires an accurate understanding of each involved step, we initially performed a quality management risk assessment, which enabled a smooth and effective achievement of a successful final result.

We investigated several strategies, based on the use of microwave-assisted solid-phase peptide synthesis (MW-SPPS) and scalable to kilogram-scale manufacturing, for the preparation of Eptifibatide, a disulfide-bridged cyclo-heptapeptide drug approved as an antithrombotic agent. Following the very fast microwave-assisted Fmoc/tBu synthesis of the linear precursor, we explored both the solution (off-resin) and the solid-phase (on-resin) disulfide formation. In order to optimize the oxidation in solution, we focused our attention on the mild disulfide formation procedure based on the use of air, observing some drawbacks, such as the formation of unwanted oxidation byproducts, such as dimers, or the use of large volumes of an environmentally unfriendly solvent (CHCN). In order to overcome these difficulties, we studied four different on-resin strategies, with the final aim to develop a fully automated, single reactor procedure, exploring different strategies to protect the thiol side-chain functional group on the C-terminal Cys residue and to form the Eptifibatide ring. The main difference among these strategies is represented by the final cyclization mode that was obtained either by direct formation of an S-S disulfide bridge or by head to MPA on cysteine side-chain amide bond formation. In conclusion, the optimization of the latter strategy enabled us to devise an optimized scalable fully automated solid-phase microwave-assisted cGMP-ready process to prepare Eptifibatide.

During metastatic progression multiple players establish competitive mechanisms, whereby cancer cells (CCs) are exposed to both pro- and anti-metastatic stimuli. The early metastatic niche (EMN) is a transient microenvironment which forms in the circulation during CC dissemination. EMN is characterized by the crosstalk among CCs, platelets, leukocytes and endothelial cells (ECs), increasing CC ability to extravasate and colonize secondary tissues. To better understand this complex crosstalk, we designed a human "EMN-on-a-chip" which involves the presence of blood cells as compared to standard metastases-on-chip models, hence providing a microenvironment more similar to the in vivo situation. We showed that CC transendothelial migration (TEM) was significantly increased in the presence of neutrophils and platelets in the EMN-on-a-chip compared to CC alone. Moreover, exploiting the EMN-on-chip in combination with multi-culture experiments, we showed that platelets increased the expression of epithelial to mesenchymal transition (EMT) markers in CCs and that the addition of a clinically approved antiplatelet drug (eptifibatide, inhibiting integrin beta3) impaired platelet aggregation and decreased CC expression of EMT markers. Inhibition of integrin beta3 in the co-culture system modulated the activation of the Src-FAK-VE-cadherin signaling axis and partially restored the architecture of inter-endothelial junctions by limiting VE-cadherinY658 phosphorylation and its nuclear localization. These observations correlate with the decreased CC TEM observed in the presence of integrin beta3 inhibitor. Our EMN-on-a-chip can be easily implemented for drug repurposing studies and to investigate new candidate molecules counteracting CC extravasation.

Background: The benefits and risks of blood transfusion in patients with acute myocardial infarction who are anemic or who experience bleeding are debated. We sought to study the association between blood transfusion and ischemic outcomes according to haemoglobin nadir and bleeding status in patients with NST-elevation myocardial infarction (NSTEMI).Methods: The TAO trial randomized patients with NSTEMI and coronary angiogram scheduled within 72h to heparin plus eptifibatide versus otamixaban. After exclusion of patients who underwent coronary artery bypass surgery, patients were categorized according to transfusion status considering transfusion as a timevarying covariate. The primary ischemic outcome was the composite of all-cause death or MI within 180 days of randomization. Subgroup analyses were performed according to pre-transfusion hemoglobin nadir and bleeding status.Results: 12,547 patients were enrolled. Among these, blood transfusion was used in 489 (3.9%) patients. Patients who received transfusion had a higher rate of death or MI (29.9% vs. 8.1%, p 9.0 g/dl (HR 4.01; p-interaction 9.0g/dl. This suggests possible harm of transfusion in those groups. (C) 2020 Elsevier B.V. All rights reserved.

Introduction: Platelets activation and aggregation play a major role in thrombosis formation of coronary arteries in patients with Acute Coronary Syndrome (ACS) and is responsible for most ischemic complications during PCI. There is little information on the benefits and side effects of intracoronary and intravenous injection of Eptifibatide ,a potent antiplatelet agent; therefore, this study was performed with aim to compare coronary blood flow velocity by measurement of TIMI frame count in intravenous versus intracoronary bolus administration of Eptifibatide during PCI in ACS patients. Methods: This non-randomized clinical trial study was performed on 103 patients with acute coronary syndromes who referred to the cardiac emergency ward of Ghaem hospital, Mashhad University of Medical Sciences, and were candidates for urgent coronary angiography and PCI. 48 cases received intracoronary bolus Eptifibatide and 55 intravenous Eptifibatide. TIMI Frame Count and Corrected TIMI Frame Count were used to compare the effect of these two methods on coronary blood flow velocity. Data were analyzed by SPSS software (version 22). To compare the quantitative variables in the two groups, according to the distribution of variables, the T test was used if it was normal or the Mann-Whitney test was used if it was not normal. Chi-square test was also used to compare qualitative variables in two groups. P

Purpose According to most guidelines, medical protocol for carotid stenting includes the administration of oral Aspirin and Clopidogrel at least four days before the procedure, with intraprocedural intravenous (IV) heparin. Some publications have also reported the safety of adding glycoprotein 2b/3a inhibitors to the protocol. In this retrospective study, we evaluate the safety of a new medication protocol that includes IV aspirin and intra-arterial Eptifibatide (glycoprotein 2b/3a inhibitor) during carotid stenting. All patients who underwent carotid stenting at Soroka University Medical Center between January 2015 and May 2020 were included (emergent cases were excluded). We divided patients into two groups—patients treated under the standard protocol, and patients treated under the new protocol. In the latter, patients received both the standard protocol regimen, as well as 150 mg IV aspirin immediately before stenting, and a slow intra-arterial injection of 2–3 mg Eptifibatide (glycoprotein 2b/3a antagonist) immediately after stenting. Forty-four patients were treated according to the standard protocol (group 1), and 41 patients were treated according to the new protocol (group 2). In group 1, six patients had complications, while in group 2, no complications of any kind were noted (p = 0.027). The safety and possible efficacy of this novel protocol was preliminarily demonstrated in the present study. Future studies are needed to prove the safety and efficacy of a specific drug regimen that will further reduce the complication rates of carotid stenting.

Introduction Even in the era of stent-retrievers, complete recanalization is often not achieved. Methods In this multi-institutional effort, we retrospectively evaluated 101 consecutive patients across 6 centers who underwent placement of a self-expanding stent during thrombectomy, either as a rescue strategy for intracranial recanalization or for tandem extracranial/intracranial occlusion. We aimed to evaluate recanalization, complications, clinical outcomes, and antithrombotic regimens in these patients. Results Occlusive thrombus was located in the internal carotid artery (ICA) in 23.8%, in the middle cerebral artery in 59.4% and in the vertebro-basilar circulation in 16.8% of cases. Indications for stenting included persistent occlusion/failed recanalization in 42.6% of cases, tandem occlusions with proximal flow limiting stenosis in 19.8%, vessel reocclusion after initial recanalization in 14.9%, vessel dissection in 15.8% cases, and underlying intracranial stenosis in 6.9% patients. 48.5% of patients had a stent deployed intracranially, 41.6% of stents were deployed within the extracranial ICA/vertebral artery while 9.9% extended from an extracranial to an intracranial vascular segment. Multiple stents were deployed in 9.9% of cases. Successful recanalization (TICI 2b/3) was obtained in 91.1% following stenting. Symptomatic intracranial hemorrhage occurred in 13 patients (12.9%), only two of which had received tPA. Significant in-stent stenosis/thrombosis occurred in 7 cases (6.9%). 54.9% had a favorable mRS score at 90 days (0–3) and 90-day mortality occurred in 15.8%. The primary factor associated with complications was placement of multiple stents (P=0.018). 71.3% of patients were loaded with antiplatelet agents intraoperatively prior to stent placement, most commonly with aspirin/Plavix ± eptifibatide or Tirofiban, followed by maintenance on dual antiplatelet treatment. There were no significant differences in outcomes between different antithrombotic regimens. Conclusion Stent placement as a rescue strategy for thrombectomy failure and for tandem configurations offers a high rate of recanalization and favorable outcome without an increase in the hemorrhage risk regardless of antithrombotic regimen and tPA status. Disclosures B. Daou: None. A. Sweid: None. S. Koduri: None. P. Jabbour: None. A. Ringer: None. P. Kan: None. G. Rajah: None. M. Bining: None. A. Pandey: None.

Background Applying of stents for endovascular treatment of cerebral aneurysms in the acute period of intracranial hemorrhage remains a debatable topic at present time. In this work we reflected our experience in treatment of acute aneurysms, Materials and Methods January 2011 through December 2019, 186 patients with 204 cerebral aneurysms were treated in our department in the acute period of hemorrhage: 27 patients had multiple aneurysms (2 to 5). Patients were 20 to 78 years old (47.2 years mean). Operations were performed in the period from 0 to 19 days after the rupture of the aneurysm. Results The most frequent localization of aneurysms in our series is the supraclinoid part of the internal carotid artery - 40.2%, ACA aneurysms - 25.8%, bifurcation of the middle cerebral artery - 17.5%; posterior circulation was in 12.4% of cases.Coiling without assistance was used in 44.7% of aneurysms; 33.6% of aneurysms required the use of balloons; 21.5% of aneurysms required stent assistance.Stent implantation in the acute period of subarachnoid hemorrhage was used after transvenous administration of Eptifibatide (Integrilin); after the procedure patients received oral antiplatelet agents.No perioperative complications were reported in our series. General disability is 6.3%, mortality - 2.1%. Conclusion Coiling with intracranial stents is effective for complex aneurysms with a wide neck in the acute period of intracranial hemorrhage, and it allows achieving a good result without increasing the risk of surgical treatment. Disclosures V. Berestov: None. K. Orlov: None. N. Strelnikov: None. M. Demyanovskaya: None.

This is a case report of a 60‐year‐old male, without any cardiovascular risk factor and no cardiac history admitted to hospital with a diagnosis of interstitial pneumonia caused by coronavirus disease 2019 (COVID‐19). After 7 days, the blood tests showed a significant rise of inflammatory and procoagulant markers, along with a relevant elevation of high‐sensitivity Troponin I. Electrocardiogram and transthoracic echocardiogram (TTE) were consistent with a diagnosis of infero‐posterolateral acute myocardial infarction and the patient was transferred to the isolated Cath Lab for primary percutaneous coronary intervention (PCI). The angiography showed an acute massive thrombosis of a dominant right coronary artery without clear evidence of atherosclerosis. Despite the optimal pharmacological therapies and different PCI techniques, the final TIMI flow was 0/1 and after 3 hr the clinical condition evolved in cardiac arrest for pulseless electric activity. Acute coronary syndrome–ST‐elevation myocardial infarction is a relevant complication of COVID‐19. Due to high levels of proinflammatory mediators, diffuse coronary thrombosis could occur even in patients without cardiac history or comorbidities. This clinical case suggests that coronary thrombosis in COVID‐19 patients may be unresponsive to optimal pharmacological (GP IIb–IIIa infusion) and mechanical treatment (PCI).

Introduction Tandem intracranial/extracranial occlusion presents a challenge due to the coincident risks of symptomatic intracranial hemorrhage (SICH) and carotid re-occlusion. Various anti-thrombotic regimens have been reported with mixed results for SICH, but infrequent analysis of cervical carotid patency. We present a single center, retrospective analysis of tandem occlusion patients treated with low dose eptifibatide, with emphasis on rates of hemorrhage and rigorous reporting of cervical carotid artery patency. The work is unique due to the completeness of vessel imaging follow-up. Materials and Methods N=58 patients were administered a low dose perioperative eptifibatide regimen (135 mcg/kg bolus, 1 mcg/kg/min infusion) during intracranial thrombectomy and extracranial carotid angioplasty ± stent placement. A prospective database was reviewed retrospectively for patient characteristics, clinical and imaging outcomes. Determination of SICH was per the SITS-MOST definition. Management of the intracranial occlusion by direct aspiration (ADAPT) or combination therapy (CAPTIVE) was per physician choice, as was management of the extracranial lesion with stenting or angioplasty alone. Patients were converted to dual oral anti-platelet therapy with aspirin and clopidogrel or ticagrelor if the 24 hour ultrasound and CT demonstrated carotid patency and no significant hemorrhage. Results The average age and NIHSS were 64 and 16, respectively, with tPA use in 43% of cases. ASPECTS scores were 8–10 in N=47 (81%) and 5–7 in N=11 (19%). N=38 patients had stenting acutely, while N=20 had angioplasty alone, 6 of whom had delayed endarterectomy or stenting within the first week. All patients had brain imaging within 24–36 hours. Any evidence of intracranial hemorrhage was present in n=18 (29%), mostly petechial or small subarachnoid hemorrhage, with only one case of SICH (2%). Technical success (TICI 2B or 3) was achieved in N=56 (96%). 90 day MRS was documented by phone or in person in 57/58 patients (one patient lost to follow up). 90 day MRS of 0–2 was achieved in N=42 (72%), with MRS of 6 in N=5 (9%). All patients had duplex within 36 hours. There were N=4 (7%) acute re-occlusions, all in patients originally treated with stenting. N=49 patients had carotid imaging at 30–60 days (5 deceased, 3 not done, 1 lost to follow up), with an additional N=3 re-occlusions (6%), two of whom had stents and one angioplasty alone. Carotid artery patency at 30–60 days for patients imaged was 86% (42/49). No acute or delayed carotid occlusion was associated with clinical decline, and 5/7 (71%) had 90 day MRS of 0–2. Conclusion Within this cohort, low dose eptifibatide in the tandem occlusion population seemed to be safe with a low incidence of SICH. Cervical carotid artery re-occlusions did occur with an overall 30–60 day patency of 86%. Re-occlusion was not associated with clinical decline in any patient. In the absence of a control arm, it is unknown whether cervical carotid patency is improved with low dose eptifibatide compared to any other regimen. All conclusions are limited by the small sample size, retrospective nature of the study, and lack of core lab adjudication of outcomes. Disclosures A. Jost: None. C. Roels: None. M. Brown: None. R. Janjua: None. D. Heck: 2; C; Stryker.

International audience; Drug-induced immune thrombocytopenia (DITP) is a life-threatening clinical syndrome that is under-recognized and difficult to diagnose. Many drugs can cause immune-mediated thrombocytopenia, but the most commonly implicated are abciximab, carbamazepine, ceftriaxone, eptifibatide, heparin, ibuprofen, mirtazapine, oxaliplatin, penicillin, quinine, quinidine, rifampicin, suramin, tirofiban, trimethoprim-sulfamethoxazole, and vancomycin. Several different mechanisms have been identified in typical DITP, which is most commonly characterized by severe thrombocytopenia due to clearance and/or destruction of platelets sensitized by a drug-dependent antibody. Patients with typical DITP usually bleed when symptomatic, and biological confirmation of the diagnosis is often difficult because detection of drug-dependent antibodies (DDabs) in the patient's serum or plasma is frequently not possible. This is in contrast to heparin-induced thrombocytopenia (HIT), which is a particular DITP caused in most cases by heparin-dependent antibodies specific for platelet factor 4, which can strongly activate platelets in vitro and in vivo, explaining why affected patients usually have thrombotic complications but do not bleed. In addition, laboratory tests are readily available to diagnose HIT, unlike the methods used to detect DDabs associated with other DITP that are mostly reserved for laboratories specialized in platelet immunology.