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Review
. 2018 Dec 3;11(1):55.
doi: 10.1186/s12245-018-0215-6.

The impact of prothrombin complex concentrates when treating DOAC-associated bleeding: a review

Maureane Hoffman  1 , Joshua N Goldstein  2 , Jerrold H Levy  3
Affiliations
Review

The impact of prothrombin complex concentrates when treating DOAC-associated bleeding: a review

Maureane Hoffman et al. Int J Emerg Med. .

Abstract

Background: Bleeding complications are a risk associated with all anticoagulants. Currently, the treatment options for the management of direct oral anticoagulant (DOAC)-associated bleeding are limited. Prothrombin complex concentrates (PCCs) have been proposed as a potential therapeutic option, and evidence regarding their use is increasing.

Review: Many studies supporting PCC have used preclinical models and healthy volunteers; however, more recently, observational studies have further improved insight into current DOAC reversal strategies. Multiple clinical practice guidelines now specifically suggest use of PCCs for this indication. Specific reversal agents for Factor Xa inhibitors may become available in the near future, but data on their efficacy are still emerging.

Conclusions: Ultimately, a multimodal approach may be the optimal strategy to restore haemostasis in patients presenting with DOAC-associated coagulopathy.

Keywords: Anticoagulant reversal; Anticoagulants; Apixaban; Dabigatran; Edoxaban; Haemorrhage; Non-vitamin K antagonist oral anticoagulants; Prothrombin complex concentrates; Rivaroxaban.

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Conflict of interest statement

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

M Hoffman received research funding from CSL Behring, Novo Nordisk and Boehringer Ingelheim and served as consultant for CSL Behring and Novo Nordisk. JH Levy serves on scientific advisory boards for CSL Behring, Boehringer Ingelheim, Octapharma, Instrumentation Labs, and Merck. JN Goldstein received research funding from Pfizer and Portola, and served as a consultant to CSL Behring and Octapharma.

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Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Effect of DOACs on the coagulation cascade. Figure legend: F, factor; Ca; calcium; HK, high-molecular-weight kininogen; DOAC, non-vitamin K antagonist oral anticoagulant; PL, phospholipid; PK, prekallikrein; TF, tissue factor
Fig. 2
Fig. 2
Treatment of DOAC-associated bleeding. Figure legend: aPCC, activated prothrombin complex concentrate; DOAC, non-vitamin K antagonist oral anticoagulant; PCC, prothrombin complex concentrate
Fig. 3
Fig. 3
DOAC-induced anticoagulation and the proposed effect of PCCs. Figure legend: Direct inhibitors of FXa or thrombin (FIIa) affect both initiation and propagation of thrombin generation. FIIa inhibitors (e.g. dabigatran) directly inhibit the FIIa that is formed (a), while FXa inhibitors (e.g. rivaroxaban, edoxaban, apixaban) reduce the amount of thrombin generated by FXa (b). PCCs are thought to mitigate the anticoagulant effect of FXa or FIIa inhibitors, by increasing the levels of non-activated clotting factors (c), predominantly FII, FIX and FX, which can be activated in case of an active bleed. F, factor; FGN, fibrinogen; DOAC, non-vitamin K antagonist oral anticoagulant; PCC, prothrombin complex concentrate; TF, tissue factor; vWF, von Willebrand factor
See this image and copyright information in PMC

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