Low-Dose Systemic Alteplase (tPA) for the Treatment of Pulmonary Embolism

Objective: To review and evaluate the evidence regarding the use of low-dose regimens of alteplase (tPA) for the treatment of pulmonary embolism (PE). Data Sources: A PubMed search (1966-January 2015) was conducted using the search terms pulmonary embolism, drug therapy, thrombolytic therapy, fibrinolytic agents, and tissue plasminogen activator. Articles were cross-referenced for additional citations. Study Selection and Data Extraction: Clinical trials and case reports published in the English language assessing the use of low-dose systemic tPA for the treatment of PE were reviewed for inclusion. Data Synthesis: tPA is a thrombolytic agent indicated for the treatment of massive and submassive PE. Major bleeding complications of tPA are dose dependent and may occur in up to 6.4% of patients. Clinical trials have demonstrated safety and efficacy of low-dose tPA, particularly showing its benefit in patients with a low body weight (<65 kg) and right-ventricular dysfunction. Furthermore, case reports have safely used lower doses of tPA in patients at higher risk of bleeding, including elderly, pregnant, and surgical patients. Conclusions: The available data suggest that low-dose tPA may be a safe and effective treatment option for acute PE, particularly in patients at a high risk of bleeding. More studies are needed to determine the optimal dosing regimen of tPA for PE.