Is Tissue-Specific Plasminogen Activator (TSPA) reliable?

Reliability of Tissue-Specific Plasminogen Activator (TSPA)

Tissue-Specific Plasminogen Activator (TSPA) has limited reliability for clinical use, with current evidence showing mixed results and significant safety concerns including bleeding complications.

Clinical Applications and Evidence

Use in Pleural Infections

• Intrapleural fibrinolytic drugs including tissue plasminogen activator (TPA) have been used to improve radiological outcomes in pleural infections 1
• While they improve radiological appearance, there is insufficient evidence that they reduce mortality or the need for surgery 1
• Patients who receive streptokinase should be given a streptokinase exposure card and should receive urokinase or TPA for subsequent indications due to immunological concerns 1

Safety Profile

• Significant safety concerns exist with intrapleural fibrinolytic therapy:
  • Isolated reports of local pleural hemorrhage and systemic bleeding 1
  • Reports of nose bleeds, pleural pain, and transient disorientation 1
  • One reported case of adult respiratory distress syndrome (ARDS) in a patient who received both streptokinase and urokinase for empyema drainage 1

Use in Acute Ischemic Stroke

• IV recombinant tissue plasminogen activator (rtPA) is recommended within 4.5 hours of symptom onset for acute ischemic stroke 2
• Standard dosing is 0.9 mg/kg (maximum 90 mg) over 60 minutes with 10% given as a bolus over 1 minute 2
• Symptomatic intracerebral hemorrhage occurs in approximately 6.4% of patients treated with tPA compared to 0.6% with placebo 3
• In the STARS study, 3.3% of patients experienced symptomatic intracerebral hemorrhage, with 7 fatalities among these patients 4

Comparative Effectiveness

Comparison with Other Thrombolytics

• For myocardial infarction, tPA showed a 30-day mortality of 6.3% compared to 7.3% with streptokinase, despite higher risk of intracranial hemorrhage 5
• The Cleveland area experience showed that only 1.8% of ischemic stroke patients received IV tPA, with 15.7% experiencing symptomatic ICH (higher than clinical trials) 6
• 50% of patients in the Cleveland study had deviations from national treatment guidelines, suggesting implementation challenges 6

Protocol Adherence Issues

• Protocol violations were reported in 32.6% of patients in the STARS study, including:
  • Treatment with tPA more than 3 hours after symptom onset (13.4%)
  • Treatment with anticoagulants within 24 hours of tPA administration (9.3%)
  • Administration despite systolic blood pressure exceeding 185 mm Hg (6.7%) 4

Clinical Decision Algorithm

1. Patient Selection:

   • Carefully evaluate contraindications before administering TSPA
   • For stroke patients: ensure treatment within 4.5 hours of symptom onset
   • Verify absence of recent surgery, head trauma, or bleeding history

2. Monitoring Requirements:

   • For stroke patients: neurological assessments every 15 minutes during and after infusion for 2 hours, then every 30 minutes for 6 hours, and hourly until 24 hours 2
   • Monitor blood pressure to maintain below 180/105 mmHg 2
   • Obtain follow-up imaging at 24 hours post-treatment before starting antiplatelet therapy 2

3. Risk Mitigation:

   • Do not administer antiplatelet agents until 24 hours post-thrombolysis and after confirming absence of hemorrhage 2
   • For patients with previous streptokinase exposure, use urokinase or TPA for subsequent indications 1

Common Pitfalls and Caveats

1. Protocol Adherence:

   • Strict adherence to treatment protocols is essential as deviations are associated with poorer outcomes
   • The Cleveland study showed 50% protocol deviation rate with higher mortality (15.7% vs. expected 7.9%) 6

2. Bleeding Risk:

   • Always assess bleeding risk before administration
   • Higher risk in elderly patients and those with severe stroke 1
   • Consider lower-risk alternatives for patients with bleeding predisposition

3. Timing Considerations:

   • Efficacy decreases and risk increases with time from symptom onset
   • The benefit from intravenous tPA decreases as a function of time from onset to treatment 1

4. Implementation Challenges:

   • Physician reluctance to use tPA due to fear of side effects and liability 1
   • Requires institutional commitment to acute stroke care with rapid provision of neurological and radiological expertise 1

In conclusion, while TSPA has established efficacy in specific clinical scenarios like acute ischemic stroke, its reliability is limited by significant safety concerns, strict timing requirements, and implementation challenges that affect real-world outcomes.