Is thrombolysis contraindication not needed in the era of DOAC reversal?

Stroke treatment guidelines should be re-written to remove DOAC recent use as a contraindication to thrombolysis, Australian neurologists say.

Dr Geoffrey Herkes and Dr Chee Hoou Loh make the recommendation in their report of a patient with acute ischaemic stroke who had rapid reversal of dabigatran with idarucizumab (Praxbind) prior to successful thrombolysis.

The 77-year old man with a history of atrial fibrillation presented at the Royal North Shore Hospital with suspected stroke symptoms (acute onset left sided weakness and slurred speech) and told doctors he had just taken a single dose of 110mg dabigatran in response to the symptoms.

After investigations including  a CT brain scan, a decision was made to proceed with alteplase treatment as his NIHSS score was 8 and he was still within the 4.5 hour thrombolysis time window after symptom onset.

Initially his INR was 1.1 and his anti Xa dabigatran level was less than 35ng/ml. In consultation with a haematologist, the anticoagulation was reversed with idarucizumab (two vials of 2.5g each by rapid IV infusion).

The patient was then given a total dose of 75mg alteplase, at 195 minutes after onset of symptoms. His repeat anti-Xa dabigatran level was less than 35ng/ml on repeat testing at two hours after thrombolysis.

Subsequent post-thrombolysis CT brain scans showed stable appearances of left cerebellar hemisphere infarction with no haemorrhagic transformation.

Further investigations including troponin levels led the clinicians to diagnose a non-ST elevation myocardial infarction complicated by a left ventricular thrombus causing an embolic stroke.

The patient had a favourable outcome and was discharged after seven days.

Writing in BMJ Case Reports, the authors said the patient’s outcome after dabigatran reversal and thrombolysis was in line with favourable outcomes reported in many cases and case series in the literature.

However they noted that most clinical guidelines are not in favour of recommending stroke thrombolysis in patients who have recently taken DOACs.

A thrombin time (TT)-based protocol for thrombolysis has been proposed for selected patients on dabigatran with a serum level of less than 10 ng/mL and TT of less than 38 s, “but this remains to be validated in a large clinical trial and still not widely adopted in clinical practice,” they wrote.

“Most clinicians are still conservative in their approach and would not consider thrombolysis in the context of recent anticoagulation,” they added.

But in light of the emerging evidence of good outcomes associated with stroke thrombolysis after dabigatran reversal, they recommended that current contraindication guidelines for recent DOACs be reconsidered.

“Given the increasingly common use of dabigatran for atrial fibrillation, the use of idarucizumab to reverse of dabigatran is a novel treatment that should be considered as an important adjunct to facilitate thrombolysis for ischaemic strokes and minimise haemorrhagic complications,” they concluded.

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