Can a patient with pulmonary embolism (PE) who is already on heparin (unfractionated heparin) receive a thrombolytic agent such as alteplase (tissue plasminogen activator, tPA)?

Thrombolytic Therapy in Pulmonary Embolism Patients on Heparin

Yes, a patient who has been started on heparin for pulmonary embolism can receive a thrombolytic agent such as alteplase, particularly in cases of massive pulmonary embolism with hemodynamic instability.

Indications for Adding Thrombolytic Therapy

Thrombolytic therapy should be administered in the following scenarios:

1. Massive PE with hemodynamic instability:

   • Hypotension (systolic BP <90 mmHg)
   • Cardiac arrest
   • Cardiogenic shock requiring vasopressors
   • Respiratory failure requiring mechanical ventilation

2. Submassive PE with evidence of right ventricular dysfunction (more controversial):

   • Right ventricular dysfunction on echocardiography
   • Elevated cardiac biomarkers
   • Severe hypoxemia
   • Extensive clot burden

Dosing and Administration Protocol

When adding thrombolytic therapy to a patient already on heparin:

• For stable patients with confirmed massive PE: Administer alteplase 100 mg intravenously over 2 hours 1
• For patients with cardiac arrest or deteriorating condition: Administer alteplase 50 mg as an intravenous bolus 2, 1
• During thrombolysis: Suspend heparin infusion during the 2-hour alteplase administration 1
• After thrombolysis: Restart heparin after 3 hours following completion of thrombolytic therapy 2, 1

Benefits of Adding Thrombolytics

• More rapid restoration of pulmonary perfusion (30-35% reduction in perfusion defect at 24 hours vs. no substantial improvement with heparin alone) 2, 1
• Reduction in right ventricular dysfunction 3
• Decreased risk of clinical deterioration requiring escalation of treatment 3
• Reduced risk of recurrent PE 2
• Potential reduction in development of chronic thromboembolic pulmonary hypertension 2

Risks and Contraindications

Major Contraindications:

• Prior intracranial hemorrhage
• Known structural intracranial cerebrovascular disease
• Active internal bleeding
• Recent stroke (within 3 months)
• Recent major surgery or trauma
• Known bleeding diathesis

Bleeding Risk:

• Major hemorrhage occurs more frequently with thrombolytics plus heparin compared to heparin alone (OR 2.84,95% CI 1.92 to 4.20) 4
• Hemorrhagic stroke is a serious but rare complication 4

Clinical Decision Algorithm

1. Assess hemodynamic status:

   • If cardiac arrest or shock present → immediate thrombolysis with 50 mg alteplase IV bolus 2
   • If deteriorating condition → immediate thrombolysis with 50 mg alteplase IV bolus 2
   • If stable but with massive PE → thrombolysis with 100 mg alteplase over 2 hours 1

2. Evaluate for contraindications:

   • Review absolute contraindications (intracranial hemorrhage, active bleeding, etc.)
   • Consider relative contraindications (recent surgery, trauma, etc.)

3. Manage heparin therapy:

   • Suspend heparin during alteplase administration
   • Resume heparin 3 hours after completion of thrombolysis 2, 1

4. Monitor closely for:

   • Bleeding complications (especially at vascular access sites)
   • Hemodynamic response
   • Oxygen saturation
   • Vital signs

Important Clinical Considerations

• The benefit of thrombolysis is greatest when administered early after symptom onset
• In submassive PE, the mortality benefit is less clear (OR 0.61,95% CI 0.37 to 1.02) 4, but there is evidence for reduction in clinical deterioration 3
• The decision to use thrombolytics in submassive PE should weigh the risk of bleeding against the risk of clinical deterioration
• Patients with right ventricular dysfunction but normal blood pressure may benefit from thrombolysis if they have low bleeding risk 2

Pitfalls to Avoid

• Delaying thrombolysis in massive PE with hemodynamic instability
• Continuing heparin infusion during alteplase administration (increases bleeding risk)
• Using thrombolytics in patients with absolute contraindications
• Failing to monitor closely for bleeding complications
• Not having a plan for managing bleeding if it occurs

Remember that while adding a thrombolytic to heparin increases bleeding risk, in massive PE the benefit of preventing death or clinical deterioration generally outweighs this risk.