Lethal cerebral hemorrhage after ticagrelor intoxication: a specific antidote is urgently needed

Willeman, Théo; Marlu, Raphaël; Böhle, Holger; Francony, Gilles; Jourdil, Jean-François; Fonrose, Xavier; Stanke‐Labesque, Françoise

doi:10.1080/15563650.2018.1480026

Cited by 10 publications

(12 citation statements)

References 12 publications

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“…This observation confirms that platelet transfusion, as already well documented, readily and promptly corrects aspirin effects. On the contrary, high-dose platelet transfusion is inefficient to reverse ticagrelor, as previously reported in a few case reports 15 16 17 18 19 and a small case series. 3 Indeed, circulating ticagrelor and its active metabolite, present at high plasma concentrations, immediately inhibit the transfused platelets.…”

mentioning

confidence: 55%

Successful Use of Recombinant Activated Factor VII to Reverse Ticagrelor-Induced Bleeding Risk: A Case Report

Godiér

Dupont

Desilles

et al. 2018

TH Open

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Management of ticagrelor-associated bleeding is challenging, especially in neurosurgery. Platelet transfusion is inefficient and no antidote is currently available. We report here the first case of recombinant activated factor VII (rFVIIa) use to bypass ticagrelor-induced platelet inhibition. A woman treated with ticagrelor and requiring emergent neurosurgery for an intracranial hematoma received preoperative high-dose platelet transfusion and 60 μg/kg rFVIIa. Laboratory monitoring demonstrated that platelet transfusion failed to reverse ticagrelor-induced platelet inhibition while rFVIIa improved hemostasis by shortening the thromboelastometric clotting time. Neurosurgery occurred without any bleeding event but the patient presented with a postoperative pulmonary embolism. In conclusion, rFVIIa may decrease ticagrelor-induced bleeding risk but careful assessment of the benefit-risk balance is warranted before using rFVIIa to reverse ticagrelor effects.

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mentioning

confidence: 55%

Successful Use of Recombinant Activated Factor VII to Reverse Ticagrelor-Induced Bleeding Risk: A Case Report

Godiér

Dupont

Desilles

et al. 2018

TH Open

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“…High plasma concentrations of TCG and ARC124910XX were found. The authors suggest that fatal cases have not previously been reported and documented related to TCG administration and emphasize the need for a specific antidote to manage such complications resulting from a TCG overdose (Willeman et al, ). The analytical characteristics of the above‐cited HPLC methods are presented in brief in Table .…”

Section: Methodsmentioning

confidence: 99%

“…TCG administration and emphasize the need for a specific antidote to manage such complications resulting from a TCG overdose (Willeman et al, 2018). The analytical characteristics of the above-cited HPLC methods are presented in brief in Table 2.…”

Section: Liquid Chromatography-mass Spectrometrymentioning

confidence: 99%

Analytical methodologies for the determination of ticagrelor

Kelemen

Hancu

Papp

2019

Biomedical Chromatography

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Ticagrelor is an orally administered platelet aggregation inhibitor with a cyclopentyl‐triazolopyrimidine structure; it is a selective reversible P2Y12 receptor antagonist, which prevents P2Y12‐mediated and ADP‐mediated platelet activation and aggregation. It is used to reduce the rate of cardiovascular death, myocardial infarction and stroke in patients with acute coronary syndrome or history of myocardial infarction. Several analytical methods have been published for the determination of ticagrelor in pharmaceuticals and biological materials by spectrophotometry, high‐performance liquid chromatography with ultraviolet detection and liquid chromatography coupled with tandem mass spectrometry. The purpose of the current review is to provide a systematic survey of the analytical techniques used for the determination of ticagrelor since its introduction in therapy until today.

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“…The reversibility of ticagrelor's inhibition of P2Y12 allows unbound ticagrelor and its active metabolite to inhibit fresh platelets (8). Reports highlight platelet transfusions, even at high-doses, have been unsuccessful in patients with intracranial hemorrhage previously treated with ticagrelor (9,10). In vitro studies have suggested that while pooled platelets are ineffective, platelet-rich plasma (PRP) may be more effective (8).…”

Section: Current Strategies For Ticagrelor Reversalmentioning

confidence: 99%

Targeting ticagrelor: a novel therapy for emergency reversal

et al. 2019

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Newer P2Y12 inhibitors are prescribed in place of clopidogrel for patients with acute coronary syndrome (ACS) and are associated with significant bleeding risks. Currently, limited options exist for the management of life-threatening bleeding or acute reversal for patients on P2Y12 inhibitor therapy, specifically ticagrelor. Various interventions, including platelet transfusion and desmopressin, have been studied for ticagrelor reversal demonstrating limited success. PB2452 is a novel monoclonal antibody which binds to both ticagrelor and its active metabolite resulting in a rapid return of platelet aggregation. PB2452 has been studied in animal models and, most recently, in a Phase I trial in healthy volunteers. In animal models, PB2452 displayed rapid reversal of ticagrelor and its metabolites and return to near normal levels of platelet aggregation within 60 min. In healthy human volunteers, cohorts that received higher dose bolus and infusions of PB2452 over 12-16 h resulted in maximal and sustained reversal of ticagrelor inhibition of platelet aggregation. While it is currently not US Food and Drug Administration approved, future Phase 2 and 3 studies are currently underway that may lead to new directions for patients on ticagrelor therapy who require urgent reversal.

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Lethal cerebral hemorrhage after ticagrelor intoxication: a specific antidote is urgently needed

Abstract: To the best of our knowledge, no prior fatal cases have been reported and documented with both ticagrelor and AR-C124910XX concentrations. Our findings highlight the need for a specific antidote to manage such complications resulting from ticagrelor overdose.

Cited by 10 publications

References 12 publications

Successful Use of Recombinant Activated Factor VII to Reverse Ticagrelor-Induced Bleeding Risk: A Case Report

Successful Use of Recombinant Activated Factor VII to Reverse Ticagrelor-Induced Bleeding Risk: A Case Report

Analytical methodologies for the determination of ticagrelor

Targeting ticagrelor: a novel therapy for emergency reversal

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