ISCHEMIC STROKE / ACUTE THERAPY

Recanalization therapy in anticoagulated patients

Created 11/11/2021, last revision 25/04/2023

Intravenous thrombolysis

in general, intravenous thrombolysis (IVT) is contraindicated in patients who are effectively anticoagulated (due to the presumed increased risk of ICH)
with the use of DOACs, this contraindication has become somewhat relative

Warfarin

INR ≤ 1.7 ⇒ IVT can be performed (ESO guidelines, 2021)
- 2 larger studies and data from the registry of nearly 24 000 patients have not shown an increased risk of bleeding among warfarin-treated patients with baseline INR ≤1.7 [Xian, 2012]
INR > 1.7 or unknown INR ⇒ no IVT (ESO guidelines, 2021)
NR > 1.7 + administration of 4F-PCC followed by thrombolysis ⇒ may be safe based on small studies; randomized trials are not available
- prothrombin complex concentrates may enhance coagulation with worsening of neurological deficits
- no clear recommendation can be made [Chausson, 2018]

Heparin / LMWH

prophylactic doses of LMWH are not a contraindication; IVT appears to be safe and is not associated with an increased risk of sICH (Cooray, 2019]
contraindications to IVT:
- aPTT above the upper limit of normal (> 40s)
- full (therapeutic) dose of LMWH administered in < 24h
not much data on the safety of IVT after protamine administration; there is a risk of ischemia progression ⇒ prefer direct MT

Dabigatran (PRADAXA)

intravenous thrombolysis (IVT) in patients with acute ischemic stroke is possible with dabigatran therapy if aPTT + TT, ECT, or HEMOCLOT values do not exceed the upper limits of normal (AHA/ASA 2013 III/C)
- normal aPTT alone is not sufficient; it does not completely rule out an elevated TT [Kermer, 2017] [Hankey, 2014]
- IVT may be considered in patients with normal TT or TT <60 s and normal APTT (ESO guidelines 2021)
  - expert opinion, insufficient evidence to make an evidence-based recommendation
- Hemoclot – a dabigatran level < 50 ng/ml > 6h after the last dose of the drug indicates the absence of anticoagulant activity
administration of thrombolysis after prior neutralization of the effect of dabigatran with the antidote PRAXBIND is possible (IVT is an emergency procedure)
- according to expert consensus, the combination of idarucizumab and IVT is suggested for patients with acute ischemic stroke of <4.5 h duration (ESO guidelines 2021) [Diener, 2017]
- according to registry data, administration of the antidote PRAXBIND in patients with acute stroke followed by thrombolysis is effective, safe, and easy to perform [Kermer, 2017]

Xabans (ELIQUIS, XARELTO, LIXIANA)

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since the shift from vitamin K antagonists (VKAs) to DOACs, it is estimated that every sixth patient with a stroke otherwise eligible for IVT uses DOACs
guidelines recommend to exclude stroke patients with recent use of DOACs (< 48 hours) from receiving IVT (except for dabigatran, where idarucizumab can be used)
- this recommendation was based on the presumption of an increased risk of symptomatic intracranial hemorrhage (sICH)
recent data suggest that IVT may also be safe in patients taking DOACs
- according to both a cohort study and a meta-analysis, IVT does not lead to an increased incidence of sICH in selected patients taking DOACs (Kam, 2022) (Shahjouei,2019)
- DOAC-IVT trial (2023) also showed insufficient evidence of excess harm associated with off-label IVT in selected ischemic stroke patients with recent DOAC use

the use of anticoagulants or thrombocytopenia is no contraindication to mechanical thrombectomy (MT); the benefit is clear for proximal occlusions
- MT may be performed in patients on DOACs without antidote administration [Diener, 2017]
some data suggest that patients on warfarin (not DOACs) have a higher risk of sICH and increased mortality [Meinel, 2020]
MT should not be combined with IA thrombolysis in patients on anticoagulant therapy