Table 2

American Heart Association/American Stroke Association absolute and relative contraindications to treatment of acute ischaemic stroke with alteplase

Absolute contraindicationsComments regarding alteplase (rtPA) use
Systolic blood pressure >185 mmHg or diastolic blood pressure >110 mmHgTreatment recommended if blood pressure can be lowered
International normalised ratio (INR) >1.7Must be tested if the patient is taking Warfarin, rapid point of care testing can be used in the hyperacute setting.
Direct oral anticoagulant (DOAC) use within 48 hoursSafety of thrombolysis in patients on DOACs is not well studied. Direct factor Xa assays may become a fast and reliable method for measuring direct factor Xa inhibitor activity (apixaban and rivaroxaban) and dilute thrombin time is sensitive to the presence of dabigatran activity, but more research is required.*
Platelets <100 000/mm3Serum platelet level not required before rtPA unless low platelet count is suspected.
Active internal bleedingLow bleeding risk in those with past (>21 days) gastrointestinal bleeding.
Intracranial or intraspinal surgery or severe head trauma within 3 monthsNo high-quality evidence. but the location of potential surgical site bleeding may limit benefits of rtPA compared to general surgical patients.
Intracerebral vascular malformationsIncluding cavernous angioma, capillary telangiectasia, developmental venous anomalies and arteriovenous malformations. Insufficient data and large variation in haemorrhage risk.
Intracranial malignancyrtPA should be safe with extra-axial but not recommended in those with intra-axial malignancy.
Previous intracerebral haemorrhage‘Recent’ history of previous intracerebral haemorrhage in recent FDA label. Limited data but increased risk of developing symptomatic intracerebral haemorrhage seems related to volume of encephalomalacia from the previous haemorrhage, same vascular territory as ischaemic event and how recent. Cerebral microbleeds have not been shown to increase risk of symptomatic intracerebral haemorrhage.
Ischaemic stroke within 3 monthsLimited data to suggest increased risk of adverse events. Contraindication removed from updated FDA licence.
Arterial puncture at non-compressible site within 7 daysIncluding subclavian or jugular catheterisation.
Infective endocarditisCerebral infarcts caused by septic emboli are prone to haemorrhagic transformation due to septic arteritis.
Relative contraindications
Rapidly improving symptomsrtPA recommended if symptom improvement but remains disabled.
Pregnancy and early postpartum (<14 days)Insufficient data, case-by-case risk decision with obstetric team.
Unruptured intracranial aneurysmSmall (<10 mm) unsecured unruptured intracranial aneurysm should not preclude rtPA, insufficient data on larger unruptured intracranial aneurysms.
Seizure at onsetConcerns of diagnostic uncertainty (post-ictal neurological deficits).
Major extracranial trauma within 14 daysLimited data. One small meta-analysis of rtPA use in cervical artery dissection (including some trauma-related) reported no safety concerns.
Major surgery within 14 days or gastrointestinal or genitourinary surgery within 21 daysIncluding coronary artery bypass grafting, organ biopsy or childbirth and relates to increased risk of surgical site haemorrhage. Limited data, so not an absolute contraindication, but case-by-case risk decision.
Acute myocardial infarction (MI) within 3 monthsrtPA recommended if concurrent myocardial infarction and ischaemic stroke. If history of myocardial infarction within the last 3 months, rtPA is reasonable if non-STEMI or right/inferior myocardial STEMI. Lower class of evidence for left anterior myocardial STEMI.
  • Abridged from Demaerschalk et al66.

  • NSTEMI, non-ST-elevation myocardial infarction; rtPA= recombinant tissue-type plasminogen activator (alteplase); STEMI, ST-elevation myocardial infarction.

  • *The European Heart Rhythm Association recommends considering thrombolysis if DOAC plasma level is below the lower limit of detection (or <30 ng/mL for Xa inhibitors if >4 hours after intake) or last dose within 24–48 hours and normal renal function.67 One meta-analysis has indicated no increased risk of sICH with prior DOAC use patients treated with IVT and reports successful thrombolysis after dabigatran reversal with idarucizumab.68 Andexanet alfa is FDA-approved for Xa inhibitor reversal but is not currently licensed in the UK.

  • FDA, Food and Drug Administration; IVT, intravenous thrombolysis; NSTEMI, non-ST-elevation myocardial infarction; rtPA, recombinant tissue-type plasminogen activator (alteplase); sICH, symptomatic intracranial hemorrhage; STEMI, ST-elevation myocardial infarction.