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August 2003

Principal Developer: R. Cote
Secondary Developers: A. Roussin, P. Wells

Thrombolytic - Stroke

Background and Rationale:

Ischemic stroke is the most common type of stroke accounting for about 30,000 cases annually in Canada. In the great majority of cases, the cause is an acute occlusion of intracerebral arteries caused by thrombus originating either from proximal arterial atherothrombotic lesions or from an intracardiac source. Because thrombolytic therapy has been shown to restore vessel patency rapidly in different vascular beds, its use in acute cerebral ischemia appears reasonable as the brain is particularly sensitive to ischemia. Although several drugs (tissue plasminogen activator, urokinase, pro-urokinase, streptokinase) have been tested in this clinical context, only tissue plasminogen activator (t-PA) has been approved for treatment of acute ischemic stroke in Canada.

Indications:

  • Acute ischemic stroke within 3 hours of symptom onset and with a clinically meaningful neurologic deficit.
  • Baseline brain CT or other diagnostic imaging method (MRI) showing no evidence of intracranial hemorrhage.

Contra-Indications:

  • Minor or rapidly improving neurological symptoms or signs
  • Uncontrolled hypertension (systolic pressure >185mmHg and/or diastolic pressure >110mmHg).Aggressive treatment necessary to lower blood pressure.
  • Low platelet count (<100,000/mm3)
  • Major surgery or trauma in past 2 weeks
  • Seizure at stroke onset
  • Glycemia < 2.7 mmol/L or > 22.2 mmol/L
  • Active internal bleeding
  • Anticoagulant use with elevated activated partial thromboplastin time or INR >1.4
  • Presence of symptoms suggesting pericarditis
  • Pregnant or lactating women

Physicians using this treatment should be experienced in acute stroke management and CT scan interpretation and be treating patients in an appropriate hospital setting to closely monitor the neurological and hematological status of the patient.

Dose Regimen and Monitoring:

Based on favorable clinical evidence, the suggested dose of intravenous t-PA is 0.9mg/kg (maximum of 90mg) with 10% of the total dose given as an initial bolus and the remainder given over 60 minutes. Expert personnel (physicians, nurses), is required for clinical monitoring and management of potential complications. The risk of intracranial hemorrhage is increased approximately ten fold in patients treated with tPA within the first 36 hours. Doses of t-PA greater than 0.9mg/kg, uncontrolled hypertension (>185/110), severity of initial neurological deficit or evidence of early signs of infarction and mass effect on the pretreatment CT scan all may be associated with an increased risk of intracranial hemorrhage. Close clinical monitoring with regular and frequent neurological signs, as well as blood pressure monitoring (keep BP <180/105mmHg) and avoidance of any antithrombotic agents including antiplatelets in the first 24 hours after administration of t-PA is strongly suggested. Although no special hematological monitoring is required, a CBC, PT, PTT, INR, fibrinogen and brain CT are suggested between 24-36 hours post-administration. Presently, intravenous streptokinase is not recommended for treatment of acute ischemic stroke and intra-arterial thrombolytic therapy is still investigational.

 

Management of Bleeding Complications:

For suspected major bleeding or intracranial hemorrhage:

  • Stop infusion if still in progress
  • Stat fibrinogen, CBC w/platelet, PT, PTT, FDP
  • Type and cross 4 units PRBCs, 6 units cryoprecipitate, 2 units FFP, 1 unit platelets
  • Stat CT scan without contrast of head if intracranial hemorrhage suspected

See corresponding section in Thrombolytic Therapy for Venous Thromboembolic Disease (VTE) guidelines.

References:

  1. Adams HP, Brott TG, Furlan AJ et al. Guidelines for Thrombolytic Therapy for Acute Stroke: A supplement to the guidelines for the management of patients with acute ischemic stroke. Circulation 1996;94:1167-1174.
  2. Albers GW,Amarenco P, Easton JD et al. Antithrombotic and Thrombolytic Therapy for Ischemic Stroke. Chest 2001 (suppl);119:300S-320S www.chestjournal.org/content/vol114/issue5/.
  3. Norris JW, Buchan A, Côté R et al. Canadian Guidelines for Intravenous Thrombolytic Treatment in Acute Stroke. A consensus statement of the Canadian Stroke Consortium. The Canadian Journal of Neurological Sciences 1999;25:257-259.
  4. Lyden PD, Grotta JC, Levine SR et al. Intravenous Thrombolysis for Acute Stroke. Neurology 1997;49:14-29.
  5. Hacke W, Brott T, Caplan L. Thrombolysis in Acute Ischemic Stroke: Controlled trials and clinical experience. Neurology 1999;5(supp 4):S3-S14.