Conservative Management of Intentional Massive Dabigatran Overdose

Mumoli, Nicola; Fiorini, Marcello; Pennati, Paolo; Testa, Sophie; Dentali, Francesco

doi:10.1111/jgs.13684

Cited by 6 publications

(8 citation statements)

References 10 publications

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“…13,14,18,19,50–61 Stevenson et al reported that between January 2011 and July 2013, there were 49 calls to a single poison control center regarding dabigatran and rivaroxaban. 18 Of these, only 4 cases were a result of self-harm, and only mild bleeding was reported in 1 case.…”

Section: Management Of Patients On Noacs Who Are At Risk For Bleedingmentioning

confidence: 99%

Management of Patients on Non–Vitamin K Antagonist Oral Anticoagulants in the Acute Care and Periprocedural Setting: A Scientific Statement From the American Heart Association

Raval¹,

Cigarroa²,

Chung³

et al. 2017

Circulation

224

147

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Non–vitamin K oral anticoagulants (NOACs) are now widely used as alternatives to warfarin for stroke prevention in atrial fibrillation and management of venous thromboembolism. In clinical practice, there is still widespread uncertainty on how to manage patients on NOACs who bleed or who are at risk for bleeding. Clinical trial data related to NOAC reversal for bleeding and perioperative management are sparse, and recommendations are largely derived from expert opinion. Knowledge of time of last ingestion of the NOAC and renal function is critical to managing these patients given that laboratory measurement is challenging because of the lack of commercially available assays in the United States. Idarucizumab is available as an antidote to rapidly reverse the effects of dabigatran. At present, there is no specific antidote available in the United States for the oral factor Xa inhibitors. Prothrombin concentrate may be considered in life-threatening bleeding. Healthcare institutions should adopt a NOAC reversal and perioperative management protocol developed with multidisciplinary input.

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Section: Management Of Patients On Noacs Who Are At Risk For Bleedingmentioning

confidence: 99%

Management of Patients on Non–Vitamin K Antagonist Oral Anticoagulants in the Acute Care and Periprocedural Setting: A Scientific Statement From the American Heart Association

Raval¹,

Cigarroa²,

Chung³

et al. 2017

Circulation

224

147

View full text Add to dashboard Cite

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“…Several cases of massive rivaroxaban overdose have been managed successfully without bleeding and without administration of blood products or reversal agents, attributed in part to the saturation of gastrointestinal absorption at dosages above 50 mg . Cases involving apixaban and dabigatran have likewise been conservatively managed with success . While blood products and idarucizumab have also been administered safely in some overdose cases, their impact on clinical outcomes is unclear …”

Section: Guidancementioning

confidence: 99%

Reversal of direct oral anticoagulants: Guidance from the Anticoagulation Forum

Cuker

Burnett

Triller³

et al. 2019

American J Hematol

269

263

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Two specific reversal agents for direct oral anticoagulants (DOACs) have been approved in the United States: idarucizumab for dabigatran reversal and andexanet alfa for apixaban and rivaroxaban reversal. Non‐specific prohemostatic agents such as prothrombin complex concentrate (PCC) and activated PCC have also been used for DOAC reversal. The goal of this document is to provide comprehensive guidance from the Anticoagulation Forum, a North American organization of anticoagulation providers, regarding use of DOAC reversal agents. We discuss indications for reversal, provide guidance on how the individual reversal agents should be administered, and offer suggestions for stewardship at the health system level.

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“…イダルシズマブはダビガトランに高い親和性で結合するヒトモノクローナル抗体フラグメントである 2), 3)。イダルシズマブは，本邦で2016年より，重大な出血が予想される観血的処置施行時，または止血困難な出血の発現時の，ダビガトラン抗凝固作用の中和に対して使用可能となった。しかしダビガトラン過量内服例に対する，イダルシズマブの使用経験は限られている。また，ダビガトラン過量内服において，イダルシズマブ投与前後で，血漿中ダビガトラン濃度および血液凝固能がどのように変化するか，詳細に検討した報告は少ない 4), 5), 6), 7), 8), 9)。今回我々は，ダビガトランを大量内服した邦人女性にイダルシズマブを投与し，血漿中ダビガトラン濃度，血液凝固能を記録したため報告する。…”

Section: はじめにunclassified

“…2022年6月にPubMed ® を使用して，期間および言語の制限を設けずに“dabigatran overdose”の用語でMEDLINE databaseを検索した。この検索で，自殺企図目的にダビガトランを過量内服した6例を抽出した 4), 5), 6), 7), 8)。これらの論文の引用文献からcross referenceを行い，さらに1例追加した 9)。これらに自験例を加えた8症例のダビガトラン内服用量（mg），血漿中ダビガトラン濃度（ng/mL），治療，転帰などの比較をTable 1に示す。本症例の血漿中ダビガトラン濃度4,217ng/mLは，治療域 10)の10～40倍であり，既報では最も高かった。これら8例のうち，イダルシズマブを投与したのは，本症例を含めて3例あり 4), 5)，いずれもイダルシズマブ投与後速やかに血漿中ダビガトラン濃度が低下した（Fig. 2A）。ダビガトラン投与に関連する有害事象は，これら3例のいずれも起きなかった。これは，イダルシズマブは，治療域 10)の10～40倍高い血漿中濃度であっても，安全かつ迅速にダビガトランを中和できることを示す。…”

Section: 考　　察unclassified

ダビガトラン過量服薬に対するイダルシズマブの静脈内投与：血漿中ダビガトラン濃度と血液凝固能の関連性(Intravenous idarucizumab for dabigatran overdose: association between plasma dabigatran concentration and coagulation profile)

圭介

雄康

勇輔

et al. 2023

Nihon Kyukyu Igakukai Zasshi: Japanese Journal of Japanese Asso

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要旨ダビガトランは直接トロンビンを阻害することで抗凝固作用を示す経口抗凝固薬であり，近年処方機会が急増している。過量内服症例における，血漿中ダビガトラン濃度および血液凝固能の推移に関するデータは不足している。腎機能障害のない，非弁膜症性心房細動をもつ71歳邦人女性が近医より処方されていたダビガトランを合計7,480mg自殺目的に過量内服し，当院に搬送された。過量内服4時間後の血漿中ダビガトラン濃度は4,217ng/mL（治療域濃度100～400ng/mL）であり，APTTは160.3秒，PT–INRは9.46であった。イダルシズマブ5g経静脈投与後，血漿中ダビガトラン濃度は経時的に低下し，それに伴いAPTTとPT–INRも正常化した。血漿中ダビガトラン濃度とAPTT（R2=0.9898），およびPT–INR（R2=0.9998）との間には強固な関連性が認められた。本症例は第9病日に後遺症なく独歩退院した。治療域の40倍の血漿中濃度を示すダビガトラン大量内服症例において，イダルシズマブは血漿中ダビガトラン濃度を安全に，かつ効果的に低下させた。また，血液凝固能は，血漿中ダビガトラン濃度を強固に反映した。本症例により，一般的な血液凝固能検査を用いることで，ダビガトランの血中薬物動態を推定できる可能性が示された。

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Conservative Management of Intentional Massive Dabigatran Overdose

Cited by 6 publications

References 10 publications

Management of Patients on Non–Vitamin K Antagonist Oral Anticoagulants in the Acute Care and Periprocedural Setting: A Scientific Statement From the American Heart Association

Management of Patients on Non–Vitamin K Antagonist Oral Anticoagulants in the Acute Care and Periprocedural Setting: A Scientific Statement From the American Heart Association

Reversal of direct oral anticoagulants: Guidance from the Anticoagulation Forum

ダビガトラン過量服薬に対するイダルシズマブの静脈内投与：血漿中ダビガトラン濃度と血液凝固能の関連性(Intravenous idarucizumab for dabigatran overdose: association between plasma dabigatran concentration and coagulation profile)

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