Do patients with massive pulmonary embolism (PE) need to be started on a heparin drip after receiving tissue plasminogen activator (TPA)?

Heparin Administration After TPA for Massive Pulmonary Embolism

Yes, patients with massive pulmonary embolism should be started on a heparin drip after receiving TPA, with the heparin infusion initiated as soon as the APTT is less than twice the upper limit of normal. 1

Timing of Heparin Administration Post-Thrombolysis

Heparin therapy should be initiated following TPA administration according to this protocol:

• Monitor APTT closely after TPA administration
• Begin heparin infusion at 1280 IU/hour as a continuous infusion as soon as the APTT falls below twice the upper limit of normal 1
• Do not delay heparin administration, as it is essential to prevent recurrent thromboembolism

Dosing and Monitoring

1. Initial dosing:

   • Loading dose: 5,000-10,000 units IV bolus (if not already given before TPA)
   • Maintenance: 400-600 units/kg/day as continuous infusion 1, 2

2. Target anticoagulation:

   • Maintain APTT at 1.5-2.5 times the control value 1, 2
   • Check APTT 4-6 hours after starting treatment
   • Repeat APTT 6-10 hours after every dose change and at least daily thereafter 1

3. Duration:

   • Continue heparin for at least 5 days
   • Overlap with warfarin during the last 4-5 days of heparin therapy 1, 2

Rationale and Evidence

The rationale for post-thrombolytic heparin therapy is well-established:

• Thrombolysis dissolves the acute clot but does not address the underlying prothrombotic state
• Heparin prevents recurrent embolism while the body's natural anticoagulant mechanisms recover
• In studies of rtPA for massive PE, heparin was consistently administered after thrombolysis 1
• Failure to achieve adequate anticoagulation is associated with a high risk of recurrent venous thromboembolism 3

Special Considerations

1. Blood pressure management:

   • Monitor BP every 15 minutes for the first 2 hours after TPA, then every 30 minutes for 6 hours, then hourly for 16 hours 4
   • Maintain BP below 180/110 mmHg to reduce bleeding risk 4
   • In patients who were initially hypotensive, monitor for rebound hypertension as pulmonary vascular obstruction resolves 4

2. Bleeding risk:

   • Major bleeding occurs in approximately 14% of patients receiving thrombolytic therapy for PE 1
   • Monitor all access sites carefully, especially those used for invasive procedures 4
   • Consider weight-based heparin dosing to reduce APTT fluctuations and achieve therapeutic levels more quickly 1

3. Alternative to unfractionated heparin:

   • While unfractionated heparin has traditionally been preferred after thrombolysis, recent evidence suggests LMWH may be safe and effective after thrombolytic therapy 5
   • A 2016 study showed lower 30-day mortality with LMWH compared to UFH after thrombolysis (8.2% vs 17.3%) 5

Pitfalls to Avoid

1. Delayed anticoagulation: Failing to start heparin promptly after APTT normalizes can lead to recurrent thromboembolism

2. Inadequate monitoring: Insufficient APTT monitoring may result in subtherapeutic or excessive anticoagulation

3. Excessive fluid administration: Avoid aggressive fluid challenge in patients with right ventricular dysfunction as it may worsen RV distension 4

4. Concomitant antiplatelet drugs: Avoid administering antiplatelet medications in the first 24 hours after thrombolysis to reduce bleeding risk 4

5. Overlooking heparin resistance: An unexpectedly poor response to heparin may suggest pre-existing thrombophilia 1

By following these guidelines, clinicians can optimize outcomes in patients with massive PE who have received thrombolytic therapy.