Anticoagulation: no clear evidence for increased risk of recurrent venous thromboembolism with sub therapeutic aPTT levels.

Clinical bottom line (level 1a)

  1. There is no clear evidence to suggest that patients on intravenous heparin with sub therapeutic aPTT levels are at increased risk for recurrent venous thromboembolism.
Anand et al: Archives of Internal Medicine 1996; 156: 1677-1681
Expires June 2003

The study

Systematic review of clinical trials of
  • Patients: acute venous thromboembolism
  • Intervention: continuous iv heparin- typically received = 30,000 units/24 hours aPTT checked at 24-48 hours (therapeutic range 1.5 to 2.5)
  • Outcome: recurrent venous thromboembolism and fatal pulmonary embolism


    • Articles found in all using MEDLINE, 1966 to 1995 (search terms: heparin 'exploded' and combined with embolism or thrombosis or thromboembolism ) and bibliographies and Current Contents were also searched, authors and experts were contacted for unpublished studies or other relevant articles.

    Selection criteria: as above
    Appraisal criteria: selected by two independent reviewers using set criteria (detailed in text)
    Articles excluded if: starting infusion rate of iv heparin <30,000 U/ 24 hours, diagnosis of VTE not objective

    Five randomised controlled trials were included
    There was no significant heterogeneity.
  • Patients were followed for three months.

    • The evidence

    outcome time to outcome number of patients/total number %
    (95% CI)
    recurrent DVT/PE ? 31/445 6.97%
    (4.60% to 9.33%)
    fatal PE ? 2/445 0.45%
    (0.00% to 1.07%)

    prognostic factor for
    recurrent DVT/PE     		time to outcome control rate (%) adjusted OR
    (95% CI)    		 NNF+
    (95% CI)
    sub therapeutic aPTT 3 months 31/445
    (6.97%)     		0.89
    (0.20 to 4.04)     		139
    (-6 to 18)

    Comments

    1. Small numbers over all- could this miss a small harmful effect?
    2. Original paper demonstrating problems with sub therapeutic aPTT was a retrospective analysis on trial comparing iv and subcutaneous heparin. Do patients with subcutaneous heparin need therapeutic doses within 24 hours?

    Citation

    1. Anand S, Ginsberg JS, Kearon C, et al: The relation between activated partial thromboplastin time response and recurrence in patients with venous thrombosis treated with continuous intravenous heparin. Archives of Internal Medicine 1996; 156: 1677-1681
    Search Terms: anticoag* in Cochrane
    Contributor: Chris Ball and Clare Wotton, June 2000
    Reviewer:

    Clinical Question.
    Patient venous thromboembolism
    Intervention or Exposure continuous iv heparin
    Outcome recurrence