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Anticoagulation in Acute Ischemic Stroke. TPA: Tissue Plasminogen Activator. 1995: NINDS study of TPA administration Design: randomized, double blind placebo-controlled study. N=624 Dosing: 0.9mg/kg (10% bolus, 90% given over 60 minutes)

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tpa tissue plasminogen activator
TPA: Tissue Plasminogen Activator

1995: NINDS study of TPA administration

Design: randomized, double blind placebo-controlled study.


Dosing: 0.9mg/kg (10% bolus, 90% given over 60 minutes)

Outcomes: At 12 months tpa patients were 30% more likely to have minimal or no disability.

1996: FDA approved TPA for acute stroke management.

Additional Studies: ECASS I/II and Atlantis: Concluded the earlier the better (< 3hrs) and there is improved outcome if no significant infarct on CT.

tpa tissue plasminogen activator1
TPA: Tissue Plasminogen Activator
  • Inclusion criteria:

**Clinical diagnosis of stroke with measurable deficit.

** Time: < 3 hours (based on the last time patient was seen normal)

** Previously independent functional status.

tpa tissue plasminogen activator2
TPA: Tissue Plasminogen Activator
  • Absolute Exclusion criteria


1. CVA or head trauma 3 months prior

2. Cerebral Aneurysm or known AVM.

3. MI in the 3 months prior

4. Any history of intracranial hemorrhage


1. spontaneously clearing stroke symptoms

2. BP >185 or diastolic >110.


1. Platelets <100,000

2. INR >1.7 on oral anticoagulants

**Radiology:Evidence of multi-lobar infarction with >33% cerebral involvement or hemorrhage or mass on CT

tpa tissue plasminogen activator3
TPA: Tissue Plasminogen Activator
  • Relative Exclusion criteria


1. Major surgery <14 days prior

2. GI or GU bleeding <21 days prior

3. LP <7 days prior.

4. Arterial puncture at non-compressible site <7 day prior.

**Labs: Glucose <50 or >400

aspirin therapy
Aspirin Therapy
  • Aspirin: Only therapy that has been evaluated with RCTs.
  • Aspirin therapy given within 48 hours of onset of acute ischemic stroke symptoms leads to a significant reduction in the risk of early stroke recurrence/mortality, and leads to improved long-term outcome (IST and CAST).
  • Recommended dose: Initial 325mg, thereafter 150mg -325mg/day. It may be used in assoc. with DVT prophylaxis.
  • Contraindications: Receiving TPA, IV heparin, or oral anticoagulants.
  • Alternatives: clopidogrel, ticlopidine, aggrenox.
ist international stroke trial
IST ( International Stroke Trial)
  • Design: Unblinded, randomized control trial.
  • N= 19,435; 467 hospitals in 36 countries.
  • Treatment arms:

1. no treatment

2. ASA 300mg

3. heparin 5000 units SQ BID

4. Heparin 5000 U SQ BID + ASA 300mg

5. Heparin 12,500 U SQ BID + ASA 300mg

6. Heparin 12, 500U SQ

ist international stroke trial1
IST ( International Stroke Trial)
  • Conclusions regarding ASA therapy :

>ASA led to significantly fewer recurrent ischemic stroke.

>ASA led to decreased death and dependence at 6 months.

>ASA was NOT associated with an excess of hemorrhagic strokes.

  • Combined analyst of the IST and CAST trial: Of 1000 patients, 9 deaths/recurrent stroke are prevented with ASA therapy in the first few weeks. 13 deaths/recurrent strokes are prevented at 6 months.
full anticoagulation with iv heparin and lmwh
Full anticoagulation with IV heparin and LMWH.
  • Use is not recommended by AHA/ASA and ACCP due to limited evidence of efficacy and increased risk of bleeding complications.
  • No clinical trial has yet to adequately evaluate full dose-anticoagulation in acute stroke.
  • The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator foracute ischemic stroke. N Engl J Med 1995; 333:1581–1587.
  • International Stroke Trial Collaborative Group. The International Stroke Trial (IST): a randomized trial of aspirin, subcutaneous heparin, both, or neither among 19,435 patients with acute ischemic stroke. Lancet 1997; 349:1569–1581.
  • ACP medicine Dale and Federman et Al. 2007 2206-2212
  • Anti-thrombotic and Thrombolytic Therapy for Ischemic Stroke: Chest 2001;119;300S-320S