Neuroscience Clerkship

 
 

Indication and Value of Thrombolysis in Acute Ischemic Stroke

The use of thrombolytic therapy, specifically recombinant tissue plasminogen activator (rtPA), has revolutionized the management of acute ischemic stroke. However, extreme caution must be taken in selecting the appropriate patient for thrombolytics, as a high rate of complications, mainly intracranial hemorrhage can result from their use.
 

rtPA converts plasminogen to plasmin which subsequently degrades fibrinogen and fibrin, the mesh-like material which composes a blood clot. The resulting fibrin degradation and clot dissolution may restore blood flow to an ischemic area and reverse a stroke in progress. Please review the diagram above of the fibrinolytic pathway. Note that normally tPA is produced by the endothelium. This is in response to coagulation to help limit the extent of clotting.
 

Above: 2D representation of the tPA molecule.

Indications

tPA should be considered in any patient presenting with signs or symptoms of an ischemic stroke (see learning objectives for anterior and posterior circulation stroke)

The following eligibility requirements must be met to qualify for tPA:

• Age ≥ 18 years

• Clinical diagnosis of ischemic stroke causing a measurable neurological deficit as per the NIH stroke scale (NIHSS)

• Time of onset < 6 hours for intra-arterial tPA, or < 3 hours for IV tPA

Contraindications

• Symptoms minor (NIHSS < 4) or rapidly improving

• Seizure at onset of stroke

• Stroke of serious head trauma in the last 3 months

• Major surgery within the last 14 days

• Known history of intracranial hemorrhage

• Sustained systolic blood pressure > 185 mm Hg (see learning objective on the management of BP in acute ischemic stroke)

• Sustained diastolic blood pressure > 110 mm Hg

• Aggressive treatment necessary to lower blood pressure

• Symptoms suggestive of subarachnoid hemorrhage

• GI or urinary tract hemorrhage within 21 days

• Arterial puncture at non-compressible site within 7 days

• Received heparin within 48 hours and has elevated PTT

• PT > 15 sec or INR > 1.7

• Platelet count < 100,000 mL

• Serum glucose < 50 mg/dL, or > 400 mg/dL

In the NINDS study, the 90 day rate of death or disability was significantly lower in the rt-PA versus the control group (61% vs 74%, p < 0.001). The symptomatic or parenchymal hemorrhage rate was significantly higher in the rt-PA group compared to control group, (6.4% vs 0.3%, p < 0.001). These results paved the way for the use of rtPA in the setting of acute stroke. Note, however that even in patients who meet all the criteria still have a 6.4% chance of symptomatic or parenchymal hemorrhage. This highlights the need to pay special attention to the exclusion criteria.