Expert position paper on the management of antiplatelet therapy in patients undergoing coronary artery bypass graft surgery

Sousa-Uva, Miguel; Storey, Robert F.; Huber, Kurt; Falk, Volkmar; Leite‐Moreira, Adelino F.; Amour, Julien; Attar, Nawwar Al; Ascione, Raimondo; Taggart, David P.; Collet, Jean‐Philippe

doi:10.1093/eurheartj/ehu158

Cited by 77 publications

(61 citation statements)

References 88 publications

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“…6 This ‘treatment-devoid’ phase leaves these high-risk patients defenseless against recurrent ischemic events and any means to shorten this vulnerable period would be of clinical value. Platelet transfusions are advised and frequently employed to deal with bleeding complications during CABG surgery in patients on antiplatelet therapy, 7, 8 and could potentially be used for the earlier restoration of hemostasis in DAPT treated patients, thereby shortening their waiting time for operation. However, the degree to which the newly infused platelets restore patients’ hemostatic function, and its relationship to the quantity of platelets infused, is unknown.…”

Section: Introductionmentioning

confidence: 99%

Impact of Timing on the Functional Recovery Achieved With Platelet Supplementation After Treatment With Ticagrelor

Zafar

Smith

Baber

et al. 2017

Circ: Cardiovascular Interventions

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Background ACC/AHA guidelines advise waiting 5-7 days before operating on P2Y12 inhibitor-treated ACS patients, to allow dissipation of its antiplatelet effects. Platelet transfusion is often used to restore hemostasis during operations but its effectiveness and optimal timing are unclear. We investigated the degree of functional gains obtained from platelet-supplementation after loading and maintenance dual antiplatelet therapy [DAPT]with ticagrelor, and the influence of timing on this strategy. Methods and Results Following baseline platelet testing (Multiplate® Analyzer and VerifyNow®), CVD patients (n=20, 56.9±7.9 years, 65% male, 75% diabetic) received DAPT as a single loading-dose [LD: ticagrelor 180mg plus aspirin 325mg] and as daily/maintenance treatment for 5-7 days [MT: ticagrelor 90mg b.i.d. plus aspirin 81mg q.d.]. At 4-, 6-, 24- and 48-hours from (last) dosing, patients’ blood samples were supplemented with concentrated platelets from healthy donors in vitro, raising platelet counts by 0% (un-supplemented ‘control’), 25%, 50% and 75%, and the function retested. Reactivity in supplemented samples was compared with respective 0% sample and with the pre-treatment baseline. Results under LD and MT regimens were nearly identical. Platelet reactivity was higher (p<0.05) in nearly all supplemented samples vs. respective controls. Aggregations with supplementation were 59%-79% of baseline at 24-hours, and equal to baseline at 48-hours. Conclusions Platelet reactivity of ticagrelor-treated patients can be restored using concentrated platelets after a loading-dose/maintenance-therapy in a time-dependent manner under in vitro testing. Although statistically significant improvements are evident 6 hours after (last) dosing, up to 24 hours maybe needed for clinically meaningful restoration in platelet function.

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Section: Introductionmentioning

confidence: 99%

Impact of Timing on the Functional Recovery Achieved With Platelet Supplementation After Treatment With Ticagrelor

Zafar

Smith

Baber

et al. 2017

Circ: Cardiovascular Interventions

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“…[217][218][219] European investigators clarified, in particular, the role of altered platelet formation versus platelet destruction in thrombocytopenia and of in vivo platelet activation, platelet "exhaustion", altered nitric oxide signaling, and enhanced nitric oxide formation in platelet dysfunction. Similarly, the role of uremic toxins and enhanced generation of nitric oxide in uremic platelet dysfunction have been shown by European investigators.…”

Section: European Research Contributionsmentioning

confidence: 99%

“…218 The bleeding risk associated with drug-induced platelet dysfunction in patients undergoing surgery and its management has been the object of position statements from European experts. 219 Finally, several studies have documented the strong and independent negative prognostic value of thrombocytopenia in critically ill patients. 220 Mechanisms causing pathogen-induced thrombocytopenias, including decreased platelet production by megakaryocyte invasion and/or enhanced platelet consumption by direct interaction with platelet receptors or by antiplatelet antibodies or immune complexes, have been described by European researchers.…”

Section: European Research Contributionsmentioning

confidence: 99%

The European Hematology Association Roadmap for European Hematology Research: a consensus document

et al. 2016

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T he European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at €23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.

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“…The guidelines proposed treatment for bleeding includes platelet transfusion (PT) based on the hypothesis that replacing the dysfunctional platelet population with functional donor platelets could result in overall improved hemostasis, and indeed this strategy is commonly used in clinical practice. 8,9 However, the evidence for the efficacy of such a strategy is limited to ex vivo studies with no single evaluation looking at the biological effect of restoration of platelet reactivity after PT in patients who are bleeding in the operative or nonoperative setting, whatever the underlying dual antiplatelet therapy (DAPT) is. [10][11][12][13][14] Furthermore, no single study has directly compared the effect of transfusion between all 3 P2Y 12 RI: clopidogrel, prasugrel, and ticagrelor.…”

Section: O'connor Et Al Restoration Of Platelet Function With Platelementioning

confidence: 99%

Efficacy of Ex Vivo Autologous and In Vivo Platelet Transfusion in the Reversal of P2Y ₁₂ Inhibition by Clopidogrel, Prasugrel, and Ticagrelor

O’Connor

Amour

Mercadier

et al. 2015

Circ: Cardiovascular Interventions

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T he addition of P2Y 12 receptor inhibiting drugs to aspirin therapy has resulted in improved clinical outcome secondary to reduced recurrent ischemic events in patients with acute coronary syndromes (ACS) or after percutaneous coronary intervention (PCI).1-3 The ischemic benefit is offset by significant morbidity and mortality associated with major bleeding complications in the both coronary artery bypass graft 4 and the nonoperative setting. 5 Indeed, the clinical benefit of systematic pretreatment with P2Y 12 receptor inhibitors (RI) has been recently challenged because of an increase in major Background-Allogenic platelet transfusions (PT) are administered to treat excessive bleeding in patients on P2Y 12 receptor inhibitors (RI). We assessed the effect of ex vivo and in vivo PT on platelet activation and aggregation in patients on dual antiplatelet therapy. Methods and Results-In the Antagonize P2Y 12 Treatment Inhibitors by Transfusion of Platelets in an Urgent or DelayedTiming After Acute Coronary Syndrome or Percutaneous Coronary Intervention Presentation-Acute Coronary Syndrome (APTITUDE-ACS) study, patients presenting with acute coronary syndrome or for elective percutaneous coronary intervention, receiving loading doses of clopidogrel (600 mg, n=13 or 900 mg, n=12), prasugrel 60 mg (n=10), or ticagrelor 180 mg (n=10) were included. PT was performed ex vivo by mixing platelet-rich plasma from blood sampling performed at baseline in increasing proportions with platelet-rich plasma sampled 4 hours after loading dose. The percentage restoration of residual platelet aggregation achieved with 80% proportion PT (residual platelet aggregation 80% PT mix/ residual platelet aggregation baseline×100) significantly decreased with increasing potency of P2Y 12 RI (83.9±11%, 73±14%, 66.3±15%, 40.9±19% for clopidogrel 600 mg, clopidogrel 900 mg, prasugrel, and ticagrelor, respectively; P for trend <0.0001). In the APTITUDE-Coronary Artery Bypass Graft (APTITUDE-CABG) study, vasodilator-stimulated phosphoprotein-platelet reactivity index, a specific marker of the P2Y 12 RI drug-effect, was assessed before and after in vivo PT administered for excessive bleeding in patients undergoing cardiac surgery while on a maintenance dose of aspirin and clopidogrel (n=45), prasugrel (n=6), or ticagrelor (n=3). When compared with baseline, there was a significant relative increase of 23.1% in platelet activation after PT transfusion (42.2±23.6% versus 56.6±18.2%; P=0.0008). Conclusions-PT restores platelet reactivity in patients with acute coronary syndrome/percutaneous coronary intervention and in patients undergoing cardiac surgery on P2Y 12 RI while bleeding with a less effect with increasing potency of P2Y 12 inhibition. Clinical Trial Registration

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Expert position paper on the management of antiplatelet therapy in patients undergoing coronary artery bypass graft surgery

Cited by 77 publications

References 88 publications

Impact of Timing on the Functional Recovery Achieved With Platelet Supplementation After Treatment With Ticagrelor

Impact of Timing on the Functional Recovery Achieved With Platelet Supplementation After Treatment With Ticagrelor

The European Hematology Association Roadmap for European Hematology Research: a consensus document

Efficacy of Ex Vivo Autologous and In Vivo Platelet Transfusion in the Reversal of P2Y ₁₂ Inhibition by Clopidogrel, Prasugrel, and Ticagrelor

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Expert position paper on the management of antiplatelet therapy in patients undergoing coronary artery bypass graft surgery

Cited by 77 publications

References 88 publications

Impact of Timing on the Functional Recovery Achieved With Platelet Supplementation After Treatment With Ticagrelor

Impact of Timing on the Functional Recovery Achieved With Platelet Supplementation After Treatment With Ticagrelor

The European Hematology Association Roadmap for European Hematology Research: a consensus document

Efficacy of Ex Vivo Autologous and In Vivo Platelet Transfusion in the Reversal of P2Y 12 Inhibition by Clopidogrel, Prasugrel, and Ticagrelor

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Efficacy of Ex Vivo Autologous and In Vivo Platelet Transfusion in the Reversal of P2Y ₁₂ Inhibition by Clopidogrel, Prasugrel, and Ticagrelor