Is Thrombin Time useful for the assessment of dabigatran concentrations? An in vitro and ex vivo study

Lessire, Sarah; Douxfils, Jonathan; Baudar, Justine; Bailly, Nicolas; Dincq, Anne-Sophie; Gourdin, Maximilien; Dogné, Jean Michel; Châtelain, Bernard; Mullier, François

doi:10.1016/j.thromres.2015.07.018

Cited by 28 publications

(19 citation statements)

References 19 publications

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“…This recommendation has not been universally embraced, and the current recommendations for TT testing seems to be limited to excluding drug presence with a normal result 65,68 or use to assess low concentrations (<50 ng/mL) of drug. 50 A previous report mentioned that concentration as high as 86 ng/mL could provide TT results below 60 seconds. This has been observed in laboratories where Siemens reagents (i.e., Siemens Thrombin or Thromboclotin) were used.…”

Section: Thrombin Timementioning

confidence: 97%

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Laboratory Assessment of Direct Oral Anticoagulants

Douxfils

Gosselin

2017

Semin Thromb Hemost

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Oral vitamin K anticoagulation (warfarin, Coumadin, coumarin) has long been used for long-term treatment and prophylaxis in a variety of clinical settings. Given the unpredictable pharmacokinetic and food impact of warfarin, episodic monitoring is required. Since the early 2000s, direct oral anticoagulants (DOACs) entered into clinical trials as a potential alternative strategy to oral vitamin K antagonists for long-term anticoagulation. As these drugs have predictable pharmacokinetics and pharmacodynamics, there was no requirement for episodic or routine monitoring. However, shortly after their introduction into clinical use, it became apparent that certain emergent or acute situations may require some capacity to measure these drugs, especially in a bleeding patient with DOAC exposure. The scramble for literature and data to support or suggest laboratory methods which can rapidly and accurately quantify or estimate DOAC concentration soon began. This review describes the literature to date, and recommendations for laboratories to provide tests that will assure either the presence/absence of DOAC or the capacity to quantify DOAC using rapid methods that could be implemented on most clinical laboratory instruments.

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Section: Thrombin Timementioning

confidence: 97%

“…If this is not possible, samples should be rapidly stored at 4°C to be tested within the next 24 hours (the stability results of this study do not go beyond 24 hours). 50…”

Section: Sample Collection and Stabilitymentioning

confidence: 99%

Laboratory Assessment of Direct Oral Anticoagulants

Douxfils

Gosselin

2017

Semin Thromb Hemost

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“…These tests can provide qualitative information regarding the presence or absence of clinically significant drug levels (ie, typical on‐therapy or above‐therapy levels). For example, the thrombin time (TT) is very sensitive to the presence of any dabigatran and a normal TT likely excludes clinically significant levels of dabigatran . The sensitivity of aPTT for detecting dabigatran is variable, but a prolonged aPTT suggests clinically significant dabigatran levels (especially if using a sensitive assay) .…”

Section: Preparing For Reversal: Are Clinically Significant Doac Levementioning

confidence: 99%

“…For example, the thrombin time (TT) is very sensitive to the presence of any dabigatran and a normal TT likely excludes clinically significant levels of dabigatran. [19][20][21] The sensitivity of aPTT for detecting dabigatran is variable, but a prolonged aPTT suggests clinically significant dabigatran levels (especially if using a sensitive assay). 22 The most accurate and reliable tests for measuring dabigatran levels are the dilute thrombin time (dTT), ecarin clotting time (ECT), and ecarin chromogenic assay (ECA).…”

Section: Coagulation Testingmentioning

confidence: 99%

Pharmacological reversal of the direct oral anticoagulants—A comprehensive review of the literature

Shaw

Siegal

2018

Research and Practice in Thrombosis and Haemostasis

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Essentials There remains clinical concern regarding the optimal management of direct oral (DOAC) anticoagulant effect for emergencies such as bleeding or urgent surgery/procedures.Idarucizumab is the preferred agent for urgent reversal of dabigatran for severe bleeding or urgent surgeries/procedures.There are currently no commercially available specific reversal agents for direct Xa inhibitors.Evidence for prothrombin complex concentrate (PCC), activated PCC (aPCC), and recombinant VIIa (rVIIa) is limited primarily to animal bleeding models and studies in human volunteer subjects.PCC, aPCC, or rVIIa may contribute to hemostasis for severe bleeding or urgent surgery/procedures in patients receiving factor Xa inhibitors, or dabigatran if idarucizumab is unavailable but benefits and harms are uncertain. The direct oral anticoagulants (DOACs) are used for stroke prevention in atrial fibrillation (SPAF) and the prevention and treatment of venous thromboembolic disease (VTE). Although DOAC‐associated bleeding events are less frequent as compared to vitamin K antagonists, there is significant concern surrounding physicians’ ability to evaluate and manage DOAC‐associated bleeding when it does occur. Idarucizumab is a specific reversal agent for dabigatran and is the agent of choice for dabigatran reversal in the setting of major bleeding or urgent surgery/procedures. There are no commercially available specific reversal agents for the direct Xa inhibitors. Although they have not been rigorously studied in DOAC‐treated patients requiring urgent anticoagulant reversal, limited evidence from in vitro studies, animal bleeding models, human volunteer studies (in vivo and in vitro) and case series suggest that coagulation factor replacement with prothrombin complex concentrate (PCC) and activated PCC (FEIBA) may contribute to hemostasis. However, the safety and efficacy of these agents and the optimal dosing strategies remain uncertain.

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“…Also an inhibitor against Factor I (fibrinogen) seemed to be unlikely, since fibrinogen levels were measured above the RR, using the Clauss method. Based on normal TT values a clinically relevant FII inhibitor could also be excluded [3,4]. Finally, based on the fact that other inhibitors of FX, such as heparin or rivaroxaban, alter values of the anti-factor-Xa assays, we used a negative anti-factor-Xa result as surrogate marker to exclude the presence of FX antibodies [5].…”

mentioning

confidence: 99%