Thrombolysis in Stroke

Thrombolysis in Stroke Fifteen–Twenty High-Yield Points Principle

The introduction of intravenous alteplase (rt-PA) transformed acute stroke care. Its benefit is tempered by the risk of precipitating intracranial haemorrhage and by strict licensing conditions.

The rationale is the ischaemic penumbra — an under-perfused but potentially salvageable area of brain surrounding the infarct core. The higher the residual perfusion, the longer ischaemia is tolerated before electrical failure, ion pump failure and cell death.

NINDS rt-PA Stroke Study: patients under 80 with carotid or vertebrobasilar territory stroke, not comatose, treated within 3 hours. Intracranial haemorrhage occurred in 6.4% of thrombolysed patients within 36 hours versus 0.6% with placebo, but treated patients were about 30% more likely to have minimal or no disability at three months.

ECASS-3 confirmed that alteplase can be given safely to patients under 80 between 3 and 4.5 hours after onset, with a small overall benefit.

IST-3 included patients over 80. Pooled analysis with NINDS and other trials confirmed that intravenous thrombolysis significantly reduces death or dependency, with a linear relationship between time to treatment and benefit, extending up to six hours from onset. Age alone is not a contraindication.

Absolute: haemorrhage on pre-treatment imaging; suspected subarachnoid haemorrhage; any history of intracranial haemorrhage; known arteriovenous malformation or aneurysm; active bleeding from any site.

Imaging-based: visible infarction involving more than one-third of the MCA territory — a clearly delineated hypodensity indicates established infarction with blood-brain barrier breakdown and a high haemorrhage risk.

Haematological: platelet count below 100 × 109/L; recent heparin with raised APTT; recent warfarin with elevated INR.

Recent events: major surgery or trauma within 14 days; gastrointestinal or urinary tract haemorrhage within 21 days; neurosurgery, serious head trauma or previous stroke within 3 months; recent myocardial infarction with pericarditis; recent arterial puncture at a non-compressible site; recent lumbar puncture.

Physiological: blood pressure persistently above 185 mmHg systolic or 110 mmHg diastolic; blood glucose below 3 or above 20 mmol/L (roughly <55 or >360 mg/dL); active pancreatitis; suspected or known pregnancy.

Clinical: symptoms only minor or rapidly improving; epileptic seizure at stroke onset.

Hypertension above 180/110 mmHg should be treated cautiously before giving thrombolysis. Aspirin is contraindicated within the first 24 hours after rt-PA because of an increased risk of death.

If intracranial haemorrhage occurs, stopping the ongoing infusion is mandatory. Send an urgent clotting profile, consider reversal agents such as cryoprecipitate, and obtain neurosurgical consultation for severe haemorrhage.

Service requirements: thrombolysis requires hyperacute stroke units (HASUs) with pathways giving urgent access to brain imaging and stroke expertise, aiming for a door-to-needle time under 30 minutes, and facilities for appropriate post-thrombolysis monitoring.

Imaging: non-contrast CT is the initial investigation; early signs are a hyperdense artery, loss of the insular ribbon and lentiform nucleus definition, sulcal effacement and mass effect. CT is normal in 30–40% of patients in the first few hours; DWI-MRI becomes abnormal within minutes and is far more sensitive.

CT angiography identifies intracranial occlusion, and CT perfusion assesses the extent of hypoperfusion, refining selection for thrombolysis or thrombectomy, particularly beyond six hours.

Mechanical thrombectomy improves functional outcome, increasing the proportion functionally independent at 90 days by around 20%. It has advantages over thrombolysis: greater efficacy in large-artery occlusion, a longer window, and usability in some patients with contraindications to thrombolysis.

Thrombectomy is indicated for proximal anterior circulation occlusion (intracranial carotid, M1 or proximal M2), NIHSS above 5, pre-morbid modified Rankin score below 3, and no major established ischaemic change — within 6 hours, or up to 12–24 hours where advanced imaging shows substantial salvageable tissue.

Benefit declines with time: independence at three months falls from 50% at 3 hours to 45% at 4.5 hours, 40% at 6 hours and 33% by 8 hours. The 'drip and ship' model — thrombolyse locally, then transfer — is one of two accepted service configurations.

Neuroprotective drugs have consistently failed in clinical trials. Tight control of physiological parameters — oxygenation, glucose, temperature and blood pressure — remains the only effective way to limit secondary damage.