When should anticoagulant therapy be given in relation to thrombolysis (intravenous clot dissolution)?

Timing of Anticoagulant Therapy in Relation to Thrombolysis

Anticoagulant therapy should be discontinued during thrombolytic treatment and resumed only after thrombolysis is completed, when the aPTT has decreased to less than twice the normal control value. 1

Anticoagulation Protocol During and After Thrombolysis

During Thrombolysis

• Adjuvant anticoagulant therapy is not recommended during thrombolytic treatment 1
• Any ongoing warfarin therapy should be discontinued during thrombolysis 1
• There is usually no need to reverse warfarin's effect with vitamin K 1

After Thrombolysis

• Heparin treatment without a loading dose should begin when:

  • The aPTT has decreased to less than twice the normal control (or baseline) value 1
  • This typically occurs 24-48 hours after stopping thrombolysis 1

• Initial heparin dosing:

  • Start with approximately 1,300 U/hour continuous infusion 1
  • Target aPTT of 1.5 to 2 times normal (55 to 80 seconds) 1, 2
  • Average dosage to achieve this effect is 20,000 to 40,000 U/24 hours 1

Monitoring After Thrombolysis

• Due to rapidly changing levels of fibrinogen and heparin binding proteins:
  • Check aPTT four times every 6 hours initially
  • Then three times every 8 hours
  • Then daily 1

Transitioning to Oral Anticoagulation

• Conversion to oral anticoagulant treatment is performed by starting warfarin simultaneously with heparin 1
• For patients with VTE, direct oral anticoagulants (DOACs) are recommended over vitamin K antagonists for the first 3 months of treatment 1
• For patients with cancer-associated thrombosis, LMWHs or direct oral anticoagulants are recommended as first-line treatment 1

Special Considerations

Thrombolysis in Venous Thromboembolism

• For most patients with acute DVT, anticoagulant therapy alone is recommended over interventional (thrombolytic) therapy 1
• For patients with acute PE not associated with hypotension, systemic thrombolytic therapy is not recommended 1
• For patients with acute PE associated with hypotension who do not have high bleeding risk, systemic thrombolytic therapy is suggested 1

Pediatric Patients

• The American Society of Hematology suggests against using thrombolysis followed by anticoagulation for pediatric patients with DVT or submassive PE 1
• For pediatric patients with PE with hemodynamic compromise, thrombolysis followed by anticoagulation is suggested 1

Potential Complications and Management

Bleeding Complications

• If major bleeding occurs during thrombolytic treatment, the infusion should be immediately terminated 1
• Bleeding can be reversed with fresh-frozen plasma or more rapidly with prothrombin complex concentrate 1

Cerebral Embolism

• If neurologic symptoms of stroke develop during thrombolytic treatment, the infusion should be discontinued immediately 1
• A CT scan of the brain should be urgently obtained to rule out hemorrhage 1
• If the stroke is non-hemorrhagic, anticoagulant treatment may be administered 1

Long-term Management

• After successful thrombolytic treatment, anticoagulation should target an INR of 2.5 to 3.5 1
• The addition of low-dose aspirin (81 to 100 mg daily) is strongly recommended 1
• Close follow-up of anticoagulant control is necessary 1

Remember that the timing of anticoagulation in relation to thrombolysis is critical for balancing the risks of thrombosis and bleeding. Premature administration of anticoagulants during thrombolysis can significantly increase bleeding risk, while delayed administration after thrombolysis may increase the risk of re-thrombosis.