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
  • 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]
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Intravenous thrombolysis in DOAC-treated patients

  • 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

Mechanical recanalization (thrombectomy)

  • 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
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Recanalization therapy in anticoagulated patients