The effectiveness of platelet supplementation for the reversal of ticagrelor-induced inhibition of platelet aggregation

Martin, Anne-Céline; Berndt, Célia; Calmette, Leyla; Philip, Ivan; Decouture, Benoit; Gaussem, Pascale; Gouin‐Thibault, Isabelle; Samama, Charles‐Marc; Bachelot‐Loza, Christilla; Godier, Anne

doi:10.1097/eja.0000000000000348

Cited by 51 publications

(42 citation statements)

References 24 publications

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“…If bleeding occurs during surgery, platelet transfusion has been shown to effectively counteract ASA effects. [166][167][168] This finding further supports the possibility of continuing ASA throughout the perisurgical period as ASA allows direct antiplatelet effect reversal if clinically indicated. The increased risk of bleeding complications if ASA and other antithrombotic drugs are not discontinued should be weighed against the potentially increased risk of thrombotic complications during the pre-operative cessation period.…”

Section: 157supporting

confidence: 53%

2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS

Valgimigli¹,

Bueno²,

Byrne³

et al. 2017

European Heart Journal

2,357

484

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Section: 157supporting

confidence: 53%

2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS

Valgimigli¹,

Bueno²,

Byrne³

et al. 2017

European Heart Journal

2,357

484

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“…10 The possibility of normalizing platelet reactivity after ticagrelor therapy has also been investigated in a few small studies with mixed outcomes, ranging from no recovery at all, 11, 12 to some restoration of function. 13 Clopidogrel and prasugrel are members of thienopyridine class, binding irreversibly to the P2Y 12 receptor and exerting long acting inhibitory effects, whereas ticagrelor is the first member of the cyclo-pentyl-triazolo-pyrimidine class, with reversible binding and short-acting effects, hence the twice-daily administration.…”

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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“…Although the authors observed a partial restoration of platelet aggregation in patients on maintenance treatment with these drugs, other studies and case reports provided conflicting data. 6,7,[9][10][11] The complete inefficacy of platelet transfusions to reverse the antiplatelet action of ticagrelor was nicely highlighted in a case report of a patient with intracranial hemorrhage, where platelet reactivity levels remained virtually unchanged despite transfusion of 17 U of platelets. 7 Other reports provided similar results.…”

Section: Sibbing and Massberg Restoring Platelet Function On Antiplatmentioning

confidence: 99%

“…As long as this is not the case, we have to take the data coming from (in vitro) studies such as APTITUDE 5 and others [6][7][8][9][10] as the best available evidence for guidance of patient treatment. Second, the comparatively low sample size for prasugrel-treated patients (n=6) and ticagrelor-treated patients (n=3) in the APTITUDE-CABG cohort precludes from drawing definite conclusions on the feasibility of immediate and sustained platelet restoration after platelet transfusion with these 2 agents.…”

Section: Sibbing and Massberg Restoring Platelet Function On Antiplatmentioning

confidence: 99%

“…7 Other reports provided similar results. 6,9 Furthermore, for APTITUDE-CABG, the authors merged prasugrel-and ticagrelor-treated patients into 1 group within their study. Such an approach, however, is debatable because it was shown in previous studies that their properties in terms of platelet function recovery may differ because of their specific pharmacological properties.…”

Section: Sibbing and Massberg Restoring Platelet Function On Antiplatmentioning

confidence: 99%

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Restoring Platelet Function in Patients on P2Y ₁₂ Receptor Inhibitor Treatment

Sibbing

Maßberg

2015

Circ: Cardiovascular Interventions

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Dual antiplatelet therapy (DAPT) with aspirin and a P2Y 12 receptor inhibitor is the current mainstay of pharmacological treatment in both patients with stable coronary artery disease and acute coronary syndrome managed invasively by percutaneous coronary intervention (PCI). 1 The primary goal of DAPT is to reduce the risk of ischemic events including (re)-infarction and stent thrombosis. Contrary, this well-recognized ischemic benefit of DAPT is cut down by an increased on-treatment bleeding risk including major and fatal bleeding in both a nonoperative and operative setting like coronary artery bypass grafting (CABG).2,3 Bleeding risks differ for the currently available oral P2Y 12 receptor inhibitors. On the basis of the results of large-scale clinical trials and the clinical experience in recent years, we considered that the risk of bleeding to be modest for the second-generation thienopyridine clopidogrel, whereas more potent platelet inhibition, such as it is delivered by the third-generation thienopyridine prasugrel or the cyclo-pentyl-triazolo-pyrimidine ticagrelor, comes along with a substantially higher risk of bleeding. 2-4Immediate and sustained restoration of platelet function in patients on DAPT may become mandatory in a nonoperative setting with acute bleeding (eg, intracranial bleeding) or during cardiac and noncardiac surgery. From a pharmacological point of view, the ability to restore platelet function may differ for the irreversibly acting P2Y 12 receptor inhibitors clopidogrel and prasugrel when compared with the directacting reversibly binding antiplatelet agent ticagrelor. This is because of the circumstance that active metabolites of both clopidogrel and prasugrel exhibit a short plasma half-life and their binding to the P2Y 12 receptor is irreversible. Hence, transfused allogeneic platelet concentrates remain uninhibited in patients on thienopyridine maintenance treatment. In contrast and because of its pharmacological properties, ticagrelor and its active metabolite may inhibit fresh platelets after allogeneic platelet transfusion. ) and in an in vivo setting with allogeneic platelet transfusion in cardiac surgery patients on DAPT who had excessive bleeding during surgery (APTITUDE-CABG). As a key result of the APTITUDE-ACS study (n=59 patients), the authors were able to show that the level of restoration of platelet function by ex vivo administration of autologous platelet-rich plasma significantly decreased with increasing potency of the antiplatelet agent. In clopidogrel-treated patients, platelet function restoration was highest, whereas restoration was lower in prasugreltreated subjects and by comparison lowest in the subgroup of ticagrelor-treated patients. In APTITUDE-CABG (n=52 patients), platelet transfusion resulted in a significant 23% relative increase (42.2±23.6% platelet reactivity index [PRI] before transfusion versus 56.6±23.6% PRI after transfusion; P=0.008) of the VASP PRI and the primary study end point was met. Of note, for the merged subgroup of patients (n=9) treat...

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The effectiveness of platelet supplementation for the reversal of ticagrelor-induced inhibition of platelet aggregation

Abstract: Platelet supplementation restored platelet aggregation in aspirin-spiked but not in ticagrelor-spiked samples. These results do not support the use of platelet transfusion to reverse the effects of ticagrelor.

Cited by 51 publications

References 24 publications

2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS

2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS

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

Restoring Platelet Function in Patients on P2Y ₁₂ Receptor Inhibitor Treatment

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The effectiveness of platelet supplementation for the reversal of ticagrelor-induced inhibition of platelet aggregation

Abstract: Platelet supplementation restored platelet aggregation in aspirin-spiked but not in ticagrelor-spiked samples. These results do not support the use of platelet transfusion to reverse the effects of ticagrelor.

Cited by 51 publications

References 24 publications

2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS

2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS

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

Restoring Platelet Function in Patients on P2Y 12 Receptor Inhibitor Treatment

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Product

Resources

About

Restoring Platelet Function in Patients on P2Y ₁₂ Receptor Inhibitor Treatment