Major bleeding in thrombolytic therapy for Acute Lower Limb Ischaemia: The value of laboratory tests for clinical decision making, 17 Years of Experience

Published:November 04, 2022DOI:
      This paper is only available as a PDF. To read, Please Download here.



      Regular measurement of fibrinogen as dose guidance in CDT for Acute Limb Ischaemia (ALI) has recently been dissuaded in European guidelines based on inconsistent literature. This study aimed to determine whether low fibrinogen- and high activated partial-thromboplastin time (APTT) levels are associated with an increased major bleeding risk during CDT.


      All consecutive patients treated with CDT for ALI in two Dutch hospitals between January 2004-April 2021 were retrospectively analysed. Patients were treated with two dosing regimens (low-dose: 50 000 IU/h; high-dose: 100 000 IU/h) of Urokinase (UK) and, after 2018 with a single low-dose regimen of Alteplase (rtPA) due to manufacturing problems of UK. The incidence of major bleeding and associated APTT and fibrinogen levels were reviewed from patient charts.


      Of the 443 cases included, 277 cases underwent CDT with UK and 166 with rtPA. The major bleeding incidence in the whole cohort was 7%. Cases with fibrinogen levels <1.0 g/L developed more major bleeding compared to cases in whom the fibrinogen level did not drop below 1.0 g/L (15% vs. 6%, p=.041). Systemic heparinization during CDT or high (>80 seconds) APTT were not significantly associated with major bleeding. Angiographic success (47% vs. 72%, p=.003) and 30-day amputation-free survival (53% vs. 82%, p=.000) were lower for cases with major bleeding. Increasing age (OR 1.06, 95% CI 1.02-1.11), cardiac history (OR 3.35, 95% CI 1.39-8.06), high-dose regimens (≥75,000 IU/hour UK; OR 2.67, 95% CI 1.18-6.04) and fibrinogen values lower than 1.0 g/L (OR 5.59, 95% CI 1.98-15.77) were independent predictors for major bleeding during CDT.


      High-dose thrombolytic regimens and fibrinogen levels of 1.0 g/L or less are associated with more major bleeding during thrombolytic therapy. Major bleeding significantly worsen clinical outcome. A prospective comparative study is needed to assess the benefit of monitoring fibrinogen levels.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to European Journal of Vascular and Endovascular Surgery
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect