Dabigatran Etexilate: Clinical Implications in Dermatologic Surgery

Abstract

The authors have indicated no significant interest with commercial supporters. D abigatran etexilate (Pradaxa, Boehringer-Ingelheim Pharmeceuticals, Ridgefield, CT) is a novel anticoagulant recently approved by the Food and Drug Administration for prevention of thrombi in patients requiring long-term anticoagulation. In dermatologic surgery, patients are frequently stratified for bleeding risk in the preoperative setting with questions concerning the use of anticoagulants, including platelet inhibitors and herbal supplements with known anticoagulant properties. Current data suggest that patients taking traditional anticoagulants (e.g., aspirin, warfarin, clopidogrel) may be at higher risk of baseline bleeding. The clinical decision to discontinue anticoagulants before surgery varies depending on other patient factors including age, comorbidities, and the specific dermatologic procedure performed, but this general set of guidelines was developed only with respect to traditional anticoagulants. There are no guidelines on preoperative cessation of dabigatran etexilate based on the experience of dermatologic surgeons. Dabigatran etexilate offers notable benefits over previous anticoagulants in that it may be administered orally, is rapidly reversible, provides a predictable dose-dependent response, and does not require regular monitoring. 1 Mechanism of ActionDabigatran etexilate is a direct competitive inhibitor of free and bound thrombin, preventing the conversion of fibrinogen to fibrin and subsequent thrombus formation. 2,3 It is a substrate of the Pglycoprotein (P-gp) transporter and is affected by inducers and inhibitors of the P-gp system, such as rifampin (inducer) and ketoconazole (inhibitor). The P-gp transporter is a member of the ATP-binding cassette superfamily and is also known as ABCB1 and CD243. It is an efflux pump encoded by the ABCB1 gene. Dabigatran etexilate is renally excreted, and the half-life ranges from 13 to 18 hours, based on creatinine clearance. The anticoagulant effects of dabigatran etexilate are most sensitively evaluated according to a prolongation of the ecarin clotting time (ECT), although partial thromboplastin time (aPTT) can be used as an approximation. The international normalized ratio (INR) is not recommended for evaluation. In some institutions and laboratory settings, including that of the authors, the ECT assay may not be readily available. 4 Clinical ImplicationsThe manufacturer of dabigatran etexilate recommends that it be discontinued before surgery but also cautions about risks for thromboembolic events in those who do so. 2 Caution should also be taken with patients who have low creatinine clearance, because they may require prolonged abstinence from dabigatran etexilate to effectively reduce bleeding risks. It is recommended that

A review of traditional and novel oral anticoagulant and antiplatelet therapy for dermatologists and dermatologic surgeons

“…Although drug interactions are limited (Table II), dabigatran is a substrate of the efflux transporter Pglycoprotein and is affected by inducers and inhibitors of this system. 25,26 Prothrombin complex concentrate and recombinant factor VIIa have been proposed as reversal agents for dabigatran, but clinical studies are limited. 27 Thrombin time and ecarin clotting time have been evaluated as monitoring assays but are not currently routinely used to monitor drug efficacy.…”

Complications With New Oral Anticoagulants Dabigatran and Rivaroxaban in Cutaneous Surgery

“…1 Although data suggest that patients taking aspirin, warfarin, or clopidogrel may be at slightly higher risk of minor bleeding from cutaneous surgery, these agents have not been associated with severe life-threatening hemorrhagic complications after cutaneous surgery. 2,3 In contrast, perioperative discontinuation of medically necessary aspirin and warfarin during cutaneous surgery has been associated with severe thrombotic complications (e.g., cerebrovascular accidents, transient ischemic attacks, myocardial infarctions, deep venous thromboses [DVT], pulmonary embolism [PE], retinal artery occlusion leading to blindness, and death). 4,5 The morbidity and magnitude of the potential hemorrhagic complications pale in comparison with these potential thrombotic events.…”