Deep vein thrombosis: tPA lysed clots, but may cause bleeds

Clinical bottom line (level 1b)

  1. In patients with DVT, tPA lysed at least 50% of a clot (NNT = at years) , though with possible increased risk of neurological problems and major bleeding.
  2. tPA alone may be as effective as combined with heparin, but heparin has proven value in preventing PE.
Goldhaber et al: American Journal of Medicine 1990; 88: 235-240
Expires May 2003

The study

Unblinded concealed randomised trial without intention-to-treat
Setting: ten hospitals, USA

64 patients (aged mean 50 years, 70% male) venographically proven deep vein thrombosis (symptomatic for <14 days)

Excluded if
  • major bleeding or chronic bleeding disorder
  • stroke
  • severe head or spinal trauma within three months
  • GU/GI bleeding within four weeks
  • trauma or major surgery within fourteen days
  • severe hepatic or renal disease
  • warfarin therapy
  • plt <100
  • lactation or pregnant
  • known hypersensitivity or other contraindication to contrast media
  • aged <18 or >75 years
  • diastolic blood pressure >100 mmHg


    • Control Group: (n = 12, 12 analysed): heparin 100 U/kg bolus then 1000 units/hr titred so aPTT 1.5 to 2.5
    Experimental Group: (n = 36, 36 analysed): recombinant tissue plasminogen activator 0.05 mg/kg/hr iv infusion over 24 hours to a maximum of 150 mg
    Experimental Group: (n = 17, 17 analysed): heparin plus r-tPA
    All patients had a repeat venogram within 36 hours of finishing infusion.
    100% followed for 2 days
    Outcome notes:
    • neurological complication : intracranial bleed, TIA

    The evidence

    heparin versus tPA plus heparin
    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    >50% clot lysis 2 days 0
    (0%)    		 5
    (29%)    		 %
    (% to %)    		 -29.4%
    (-51.1% to -7.75%)    		 -3
    (-13 to -2)

    heparin plus tPA versus tPA
    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    >50% clot lysis 2 days 5
    (29%)    		 10
    (28%)    		 6%
    (-130% to 62%)    		 1.63%
    (-24.5% to 27.8%)    		 61
    (NNT = 4 to infinity;
    NNH = 4 to infinity)
    neurological complication 2 days 0
    (0%)    		 1
    (2.78%)    		 %
    (% to %)    		 -2.78%
    (-8.15% to 2.59%)    		 -36
    (NNT = 39 to infinity;
    NNH = 12 to infinity)

    Comments

    1. What is the longterm effect on recurrent venous thromboembolism or post-phlebitic syndrome? Weighing this against any increased risk of bleeding is more important than clot lysis.
    2. The study is too small to demonstrate any increase in risk for major bleeding or neurological complications.

    Citation

    1. Goldhaber SZ, Meyerovitz MF, Green D, et al: Randomized controlled trial of tissue plasminogen activator in proximal deep vein thrombosis. American Journal of Medicine 1990; 88: 235-240
    Contributor: Chris Ball and Clare Wotton, May 2000
    Reviewer: Alex Gallus

    Clinical Question.
    Patient DVT
    Intervention or Exposure tPA
    Comparison heparin
    Outcome clot lysis