Thrombolytic Therapy for Pulmonary Embolism

Introduction to Thrombolytic Therapy

The American Heart Association recommends rapidly reversing hemodynamic compromise, improving gas exchange, and reducing mortality in patients with massive pulmonary embolism using thrombolytic therapy, with a primary goal of improving patient outcomes 1

The American College of Cardiology suggests that single-bolus administration of thrombolytic therapy offers advantages over the 2-hour infusion required for alteplase, making it more practical in emergency situations 2
The FDA-approved standard dosing regimen for adults with pulmonary thromboembolism is 100 mg IV infused over 2 hours, according to the American College of Cardiology 3
Standard regimens involve 100 mg IV over 2 hours, while accelerated regimens involve 0.6 mg/kg IV over 15 minutes (maximum 50 mg) for severe cases, as recommended by the European Heart Journal 4

Alternative regimens include:

Medication	Dose
Alteplase (tPA)	0.6 mg/kg over 15 minutes (maximum 50 mg) [5]
Tenecteplase	weight-based IV bolus, with dosages ranging from 30 mg for patients <60 kg to 50 mg for patients ≥90 kg, as recommended by the American Heart Association and the American College of Cardiology [5, 6, 7]
Streptokinase	250,000 IU over 20-30 minutes followed by 100,000 IU/hour IV for up to 24 hours [5]

Absolute contraindications to thrombolysis include hemorrhagic stroke, recent major trauma/surgery, active bleeding, and others, while relative contraindications may be disregarded in life-threatening PE 8, 4, 6, 7, 9
Relative contraindications to thrombolysis include transient ischemic attack in preceding 6 months, oral anticoagulant therapy, pregnancy, and others 8, 4, 6
The American College of Cardiology advises against delaying thrombolysis in patients with massive pulmonary embolism and hemodynamic instability, using low molecular weight heparin concurrently with thrombolysis instead of unfractionated heparin, failing to monitor for bleeding complications, and not confirming pulmonary embolism diagnosis with imaging before administering thrombolytics when possible 2
The American Heart Association recommends against treating patients with undifferentiated cardiac arrest with fibrinolysis without confirmed pulmonary embolism diagnosis 2

Initial anticoagulation with unfractionated heparin (UFH) is recommended, with a dose of 80 units/kg IV bolus followed by 18 U/kg/h continuous infusion, as suggested by the British Thoracic Society and the European Society of Cardiology 9, 10
The target aPTT should be 1.5-2.5 times control value (46-70 seconds) for UFH, as recommended by the European Society of Cardiology 10
Low-Molecular-Weight Heparin can be substituted for Unfractionated Heparin in stable submassive pulmonary embolism patients, according to the European Society of Cardiology 10
Concurrent heparin administration with thrombolytics is recommended, with specific regimens varying by thrombolytic agent and clinical scenario, as recommended by the American College of Cardiology 11, 12

For bleeding complications, consider using tranexamic acid or aminocaproic acid, as suggested by the American College of Cardiology 3
Fresh frozen plasma or cryoprecipitate may be used, especially in cases of hypofibrinogenemia, according to the American College of Cardiology 3
Fibrinogen levels should be monitored during thrombolysis, and maintained >1.0 g/L 13
Major bleeding rate is approximately 13%, and intracranial/fatal hemorrhage rate is approximately 1.8%, as reported by the European Society of Cardiology 8
Increased risk of bleeding is associated with age and comorbidities, as reported by the European Society of Cardiology 14

The American Heart Association recommends transitioning to direct oral anticoagulants (DOACs) or vitamin K antagonists after initial stabilization (5-7 days), with a target INR of 2.0-3.0 for vitamin K antagonists, as recommended by the American Heart Association and the European Society of Cardiology 8, 2
Inferior vena cava (IVC) filters may be considered for patients with very poor cardiopulmonary reserve, but are not recommended for routine use as an adjuvant to anticoagulation in the treatment of acute PE, as stated by the American College of Cardiology 2

Surgical pulmonary embolectomy should be considered when thrombolysis is absolutely contraindicated or has failed, and can provide dramatic hemodynamic improvement, as recommended by the European Society of Cardiology 8
Surgical pulmonary embolectomy requires cardiopulmonary bypass but aortic cross-clamping should be avoided, as recommended by the European Society of Cardiology 8
Catheter-based interventions, including aspiration thrombectomy, thrombus fragmentation, and rheolytic thrombectomy, are alternative treatments for patients with contraindicated or failed thrombolysis, as recommended by the American Heart Association 1, 2