a 79 year old female returns to ED with left sided chest pain & dyspnoea. She was recently admitted following a fall with rib fractures (including a flail segment) and a small haemothorax.
Her past medical history includes AF, IHD & ischaemic cardiomyopathy. She has an AICD insitu.
On examination she is in marked respiratory distress with a SaO2 of 86%. You hear very little air entry on the left-side so order this chest x-ray…
- Metoprolol 50mg bd
- Frusemide 40mg bd
- Ramipril 5mg mane
… & Dabigatran 110mg bd – this was restarted upon discharge.
- A direct thrombin inhibitor.
- Predictable pharmacokinetics.
- Rapidly absorbed after oral administration
- Peak plasma concentration & maximal anticoagulation effect within 2-3 hours !
- 80% excreted through the kidneys unchanged.
Given that this drug is being used more and more, by general practitioners and cardiologists, we better get familiar with it !!
Measuring the effect of dabigatran.
- Response is inconsistent & insensitive.
- May be prolonged by supratherapeutic levels of dabigatran.
- Curvilinear dose response to increasing levels of plasma concentrations of dabigatran.
- If the APTT is prolonged by 2-3x at trough –> higher risk of bleeding.
- Time of last dose is important.
- Thrombin time:
- A measure of conversion of fibrinogen to fibrin (clot).
- Displays a linear time response to increasing plasma concentrations of dabigatran.
- Exquisitely sensitive to the presence of dabigatran.
- a normal TT indicates an absence of dabigatran (can be used to exclude dabigatran as cause of haemorrhage)
Haemorrhage! (on dabigatran) Now what ?!?
There are currently no antidotes available to reverse dabigatran.
Resuscitation & Supportive Care.
- Blood product replacement / Transfusion (1:1:1 ratio).
- Maintain renal perfusion [aids in dabigatran elimination].
- Plasma concentrations can reduced by 50-60% after 4 hours of dialysis.
- Significant logistical implications.
Prothrombin Complex Concentrates.
- Whilst not directly affecting the action of dabigatran; thought to provide more substrate to increase thrombin generation.
- Some positive animal studies.
- Enables generation of thrombin, independently of Factor VIII.
- Case report of use of low-dose FEIBA (Factor Eight Inhibitor Bypassing Activity).
- 26 U/kg.
- Caution: too much can lead to DIC.
Recombinant factor VIIa
- Is able to directly activate factors IX & X resulting in burst thrombin generation.
- Reduced bleeding time in rat-tail models.
- Prolonged aPTT in healthy volunteers on dabigatran.
- There is increased risk of thrombotic complications.
- Utility is not firmly established.
- Tranexamic Acid.
- Inhibition of fibrinolysis.
- Used as an adjunct for bleeding with dabigatran on-board
- little evidence to support this use however.
- Activated charcoal.
- Recommended for dabigatran overdose (when ingestion is < 2 hours)
- NIV was applied and markedly improved her oxygenation & work of breathing.
- Concern was raised due to her elevated INR & aPPT.
- Decision made for HDU admission & NIV overnight for support, allowing some ‘time’ for her anticoagulant effect to wear off.
- A left sided pig-tail catheter is placed on Day 2 of her re-admission with litres of blood stained fluid drained.
on the morning of drain insertion…
- Connolly S, Ezekowitz M, Yusuf S, et al. the RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009;361:1139–51.
- van Ryn J. Dabigatran etexilate – a novel, reversible, oral direct thrombin inhibitor: Interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost 2010; 103: 1116–1127.
- Alikhan R, et al. The acute management of haemorrhage, surgery and overdose in patients receiving dabigatran. Emerg Med J 2013
- Dager WE, Gosselin RC, Roberts AJ. Reversing dabigatran in life-threatening bleeding occurring during cardiac ablation with factor eight inhibitor bypassing activity. Crit Care Med. 2013 May;41(5):e42-6.
- Eerenberg ES et al. Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects. Circulation. 2011 Oct 4;124(14):1573-9
- Avecilla ST, et al. Plasma-diluted thrombin time to measure dabigatran concentrations during dabigatran etexilate therapy. Am J Clin Pathol. 2012 Apr;137(4):572-4.
and more on this from the #FOAMed community…