Dabigatran Plasma Measurement to Guide the Management of Acute Bleeding and Thrombotic Complications

摘要

Oral anticoagulant therapy is recommended for the prevention and treatment of venous thromboembolism and to prevent stroke in non-valvular atrial fibrillation. Until a few years ago, vitamin K antagonists were the only drugs available, but direct oral anticoagulants have recently been introduced into clinical practice for the same clinical indications. Unlike the situation with VKAs, fixed-dose administration was proposed for DOACs, without the necessity for routine laboratory monitoring. However, in clinical practice a high inter-variability in DOAC plasma levels, independently of the type of drug and patient characteristics, was observed and the importance of measuring DOAC anticoagulant activity to support treatment decisions has therefore been recognized. We describe two clinical cases in order to highlight the role and importance of dabigatran-specific measurements to guide patient management in case of major complications.LEARNING POINT class="unordered" style="list-style-type:disc">Direct oral anticoagulants (DOACs) have been used in clinical practice at fixed doses without laboratory monitoring.However, the importance of measuring DOAC anticoagulant activity to support treatment decisions, particularly in emergency conditions, has been recognized.The clinical value of DOAC measurement is highlighted in the two described cases where the anticoagulation level was taken into consideration when deciding on treatment. class="kwd-title">Keywords: DOACs, dabigatran, anticoagulant, plasma measurement, idarucizumab class="head no_bottom_margin" id="__sec2title">INTRODUCTIONOral anticoagulant therapy is recommended for the prevention and treatment of venous thromboembolism and to prevent stroke in non-valvular atrial fibrillation (NVAF)^[]. Until few years ago, vitamin K antagonists (VKAs) were the only drugs available, but recently direct oral anticoagulants (DOACs) were introduced into clinical practice for the same clinical indications. DOACs include two classes of molecules with a similar pharmacological profile but with different pharmacokinetic and pharmacodynamic characteristics: an anti-IIa selective inhibitor (dabigatran) and anti-Xa selective inhibitors (rivaroxaban, apixaban and edoxaban). Unlike the situation with VKAs, fixed-dose administration was proposed for DOACs, based on the results of phase III clinical trials performed on selected populations, without the necessity for routine laboratory monitoring. However, in clinical practice a high inter-variability in DOAC plasma levels, independently of the type of drug and patient characteristics (gender, age, renal and liver function, and body weight) was observed^[]. Therefore, the importance of measuring DOAC anticoagulant activity to support treatment decisions, particularly in emergency conditions, has been recognized^[]. Dabigatran is a specific, reversible inhibitor of both free and clot-bound thrombin and its antidote (idarucizumab, Praxbind^®) is available and recommended for patients who develop life-threatening or uncontrolled bleeding, or require an urgent surgical/invasive procedure. In these special clinical situations, the measurement of dabigatran plasma levels can guide^[–] antidote use in the setting of acute bleeding, thus avoiding expensive and useless treatment.We describe two clinical cases in order to highlight the role and importance of dabigatran-specific measurements to guide patient management in case of major complications.