Management of dabigatraninduced bleeding expert

Authors: Dietmar Fries Alexander Giurea Manfred Gütl WalterMichael Halbmayer Sibylle KozekLangenecker Andreas Pachucki Franz Roithinger Barbara Steinlechner Heinrich Thaler Ansgar Weltermann

Publish Date: 2013/11/12

Volume: 125, Issue: 21-22, Pages: 721-729

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Abstract

The interdisciplinary group of experts has compiled a clinical guidance for manifest dabigatraninduced haemorrhage and envisaged invasive interventions on patients under dabigatran It recommends an escalation of treatment measures as summarized in a pocket guide see electronic supplementary material online and insert in the print issueDie interdisziplinäre Expertengruppe hat einen klinischen Leitfaden für das Vorgehen bei manifester Dabigatraninduzierter Blutung und bei anstehenden invasiven Eingriffen bei Patienten unter Dabigatran zusammengestellt Es wird ein eskalierendes Vorgehen vorgeschlagen und in einer Karte für die Manteltasche zusammengefasst siehe “Electronic supplementary material” online und Beilage in der PrintAusgabeNot least on account of demographic developments the number of patients receiving oral anticoagulants is constantly increasing 1 Accordingly in case of elective and semielective surgery there is an increasing need for a perioperative risk benefit assessment of whether anticoagulation should be continued discontinued or “bridged” parenterally In case of continued oral anticoagulation perioperatively and in case of acute surgery severe bleeding episodes may require rapid inhibition of the biological action of the anticoagulant reversal Emergency reversal may also be indicated after injuries and spontaneous nonsurgical bleeding Such measures should be taken in due consideration of the situation ie depending on the severity of the risk of haemorrhage and balancing the risks of haemorrhage and thrombosis in view of the preexisting indication for chronic anticoagulation For Vitamin K antagonists longstanding experience is available although at a low level of scientific evidence 2 3 Such experience and evidence on perioperative management and practical clinical bleeding management is however still lacking for the new oral anticoagulants NOACs more recently also referred to as direct oral anticoagulants DOACs Dabigatran etexilate is the longeststanding NOAC registered for chronic application Accordingly the management of dabigatraninduced haemorrhagic complications is currently a frequent clinical and interdisciplinary challengeCurrently available expert statements permit only an incomplete insight into the complexity of the management of dabigatraninduced haemorrhages particularly in terms of the classification of haemorrhages according to acuity and severity as well as the escalating indication for multimodal therapies and the availability of therapy monitoring methods 4 Therefore the objective of the present interdisciplinary group of experts was to prepare recommendations for the management of dabigatraninduced bleeding in the course of daytoday clinical work The resulting expert opinion reflects the medical knowledge specific experience evaluations and opinions of the authors As with all expert statements each of these recommendations will have to be revised over time as new evidence and experience is gained It should also be noted that use of the proposed recommendations will not guarantee therapeutic success or the absence of complicationsThe present expert recommendation does not focus on presenting fundamental knowledge of the pharmacology of dabigatran and the research required for registration since such reviews are readily available 4 5 6 7 8 For this reason we merely recapitulate the facts relevant for prophylactic and therapeutic management of bleedingDabigatran is an oral reversible direct thrombin inhibitor DTI that inhibits both free and fibrinbound thrombin and thrombininduced platelet aggregation 5 6 After adsorption nonspecific plasma esterases transform the inactive prodrug dabigatran etexilate into the active substance in both plasma and liver Its mean terminal halflife has been stated to be 14–17 h but may be longer postoperatively 9 As the drug is primarily eliminated by the kidneys the halflife is significantly prolonged in patients with renal insufficiency 10 For this reason renal function should be monitored at regular intervals eg twice a year whenever dabigatran is used for longterm therapy 11 Contraindications against the use of dabigatran are a creatinine clearance  30 ml/min artificial heart valves allergies haemorrhages liver disease affecting survival spontaneous or pharmacologically induced impairment of haemostasis A dose reduction of Pradaxa® from 2 × 150 mg to 2 × 110 mg per os or from 220 mg to 150 mg per os is indicated in patients with a creatinine clearance of 30–50 ml/min concomitant administration of verapamil in the presence of thrombopathy/thrombopenia gastroesophageal reflux disease and in patients aged 80 years or olderOn account of its low tendency to bind to plasma proteins 62–68  of the active substance can be eliminated by haemodialysis within 2–4 h 4 It may be assumed that dabigatran can also be removed by haemofiltration and haemodiafiltration though elimination times are likely to be longer  4 h

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