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

Ann Pharmacother. 2015 Jul;49(7):818-24. doi: 10.1177/1060028015579988. Epub 2015 Apr 9.


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.

Keywords: pulmonary embolism; thrombolytic therapy; tissue plasminogen activator.

Publication types

  • Review

MeSH terms

  • Fibrinolytic Agents / adverse effects
  • Fibrinolytic Agents / therapeutic use*
  • Hemorrhage / chemically induced
  • Humans
  • Pulmonary Embolism / drug therapy*
  • Risk
  • Thrombolytic Therapy
  • Tissue Plasminogen Activator / adverse effects
  • Tissue Plasminogen Activator / therapeutic use*
  • Treatment Outcome


  • Fibrinolytic Agents
  • Tissue Plasminogen Activator