The acute management of haemorrhage, surgery and overdose in patients receiving dabigatran

Abstract

Dabigatran is an oral direct thrombin inhibitor (DTI) licensed for stroke prevention in atrial fibrillation and likely to be soon approved in Europe for treatment of venous thrombosis. Predictable pharmacokinetics and a reduced risk of intracranial haemorrhage do not negate the potential risk of haemorrhage. Unlike warfarin, there is no reversal agent and measurement of the anticoagulant effect is not ‘routine’. The prothrombin time/international normalised ratio response to dabigatran is inconsistent and should not be measured when assessing a patient who is bleeding or needs emergency surgery. The activated partial thromboplastin time (APTT) provides a qualitative measurement of the anticoagulant effect of dabigatran. Knowledge of the time of last dose is important for interpretation of the APTT. Commercially available DTI assays provide a quantitative measurement of active dabigatran concentration in the plasma. If a patient receiving dabigatran presents with bleeding: omit/delay next dose of dabigatran; measure APTT and thrombin time (consider DTI assay if available); administer activated charcoal, with sorbitol, if within 2 h of dabigatran ingestion; give tranexamic acid (1 g intravenously if significant bleeding); maintain renal perfusion and urine output to aid dabigatran excretion. Dabigatran exhibits low protein binding and may be removed by dialysis. Supportive care should form the mainstay of treatment. If bleeding is life/limb threatening, consider an additional haemostatic agent. There is currently no evidence to support the choice of one haemostatic agent (FEIBA, recombinant factor VIIa, prothrombin complex concentrates) over another. Choice will depend on access to and experience with available haemostatic agent(s).

Point-of-Care Coagulation Testing for Assessment of the Pharmacodynamic Anticoagulant Effect of Direct Oral Anticoagulant

“…[12][13][14]31 However, the degree of overlap of the PT measured in seconds between maximum rivaroxaban concentrations and trough concentrations is still high. PTs analyzed by POCT in whole blood are usually directly derived from standard PTs performed on plasma and it remained unknown whether PTs measured by POCT might be less variable to rivaroxaban.…”

The Role of Renal Replacement Therapy in the Management of Pharmacologic Poisonings

“…Until recently, the management of bleeding in patients taking dabigatran was supportive [24]. However, recently, a monoclonal antibody, idarucizumab, has been shown to be effective in the management of patients with dabigatran related bleeding [25].…”

[Budget impact analysis of idarucizumab for the management of patients treated with dabigatran in emergency / urgent situations in Italy]

“…Sebbene l'esperienza clinica nell'utilizzo dell'emodialisi (emofiltrazione) per l'eliminazione di dabigatran sia limitata, in particolare, nelle situazioni di emergenza, essa risulta essere un'opzione da considerare poiché consente di ridurre le concentrazioni plasmatiche di dabigatran. Va sottolineato che, in un contesto di emergenza l'accesso alla procedura emodialitica potrebbe essere limitato [20][21][22][23]. Con la disponibilità di idarucizumab, è emerso che si eviterebbero i trattamenti con emodialisi in tutti i tipi di emorragie (intracranici, gastrointestinali, e altre) e negli interventi chirurgici di emergenza.…”