Deep vein thrombosis: systemic thrombolysis reduced post-thrombotic syndrome but increased major bleeding and pulmonary embolism

Clinical bottom line (level 1b)

  1. Patients with a DVT who received loco-regional thrombolysis compared with heparin alone were less likely to have post-thrombotic syndrome (NNT = 4 at 12 months) , but not clearly less likely to have severe post-thrombotic syndrome.
  2. There was no clear increase in the risk of major bleeding.
  3. Patients with a DVT who received systemic thrombolysis compared with heparin alone were less likely to develop post-thrombotic syndrome (NNT = 7 at 12 months) , or severe post-thrombotic syndrome (NNT = 4 at 12 months) .
  4. However patients on systemic thrombolysis were more likely to have a major bleed (NNH = 11 at 7 days) or pulmonary embolism (NNH = 11 at 7 days) .
Schweizer et al: Journal of the American College of Cardiology 2000; 36 : 1336-1343
Expires November 2003

The study

Single-blinded ?concealed randomised trial with intention-to-treat
Setting: 2 acute hospitals, Germany

250 patients (aged 22 to 63 mean 39, 57% female) with recent acute leg or pelvic thromboses (confirmed on venogram or ultrasound)

Excluded if
  • pregancy or lactation; delivery within last 20 days
  • history of cerebral disease
  • malignant disease
  • renal failure (creatinine > 350 micromol/L)
  • hepatic failure: AST > 100 U/l, prothrombin time > 50%)
  • haemorrhagic diathesis
  • DVT at one level only
  • existence of DVT for more than 9 days
  • previous DVT in same leg or thrombosis in calf veins only
  • urogenital or gastrointestinal bleeding
  • inflammatory bowel disease within last 12 months
  • acute pancreatitis
  • surgical intervention or cerebral trauma within last 3 months
  • intramuscular injection within last 10 days
  • arterial hypertension or diabetes (stage III to IV retinopathy)
  • clinical signs suggesting pulmonary embolism

    Control Group: (n = 50, 50 analysed): heparin
    Experimental Group: (n = 100, 100 analysed): loco-regional thrombolysis for 4 to 7 days using alteplase 20 mg over 4 hours daily and heparin 1000 units/hour continuously; or urokinase 100,000 units per hour continuously into a dorsal pedal vein
    Experimental Group: (n = 100, 100 analysed): systemic thrombolysis for 4 to 7 days using streptokinase 3000000 units over 6 hours and a continuous heparin infusion; or urokinase 5000000 units over 4 hours and a continuous infusion of unfractionated heparin
    All patients received anticoagulation and compression stockings for a year
    95% followed for 12 months
    Outcome notes:
    • major bleeding : requiring termination of thrombolysis
    • severe post-thrombotic syndrome : based on patient-reported clinical symptoms

    The evidence

    loco-regional thrombolysis v. heparin
    Outcome Time to outcome CER EER RRR
    (95% CI)    		 ARR
    (95% CI)    		 NNT
    (95% CI)
    major bleeding 7 days 0
    (0.0%)    		 3
    (3.00%)    		 %
    (% to %)    		 -3.00%
    (-6.34% to 0.344%)    		 -33
    (NNT = 16 to infinity;
    NNH = 290 to infinity)
    post-thrombotic syndrome 12 months 45
    (90.0%)    		 63
    (63.0%)    		 30%
    (17% to 41%)    		 27.0%
    (14.4% to 39.6%)    		 4
    (3 to 7)

    systemic thrombolysis v. placebo
    Outcome Time to outcome CER EER RRR
    (95% CI)    		 ARR
    (95% CI)    		 NNT
    (95% CI)
    major bleeding 7 days 0
    (0.0%)    		 9
    (9.00%)    		 %
    (% to %)    		 -9.0%
    (-14.6% to -3.39%)    		 -11
    (-29 to -7)
    pulmonary embolism 7 days 0
    (0.0%)    		 9
    (9.00%)    		 %
    (% to %)    		 -9.00%
    (-14.6% to -3.39%)    		 -11
    (-29 to -7)
    post-thrombotic syndrome 12 months 45
    (90.0%)    		 76
    (76.0%)    		 16%
    (2% to 27%)    		 14.0%
    (2.20% to 25.8%)    		 7
    (4 to 45)
    severe post-thrombotic syndrome 12 months 20
    (40.0%)    		 16
    (16.0%)    		 60%
    (30% to 77%)    		 24.0%
    (8.64% to 39.4%)    		 4
    (3 to 12)

    Comments

    1. There was no clear difference between controls and loco-regional thrombolysis for the rate of severe post-thrombotic syndrome.
    2. Patients who received systemic thrombolysis compared with loco-regional thrombolysis did not clearly have fewer closed venous segments after 12 months.
    3. The study was too small to show any difference between the various thrombolytic agents used.

    Citation

    1. Schweizer J, Kirch W, Koch R, et al: short- and long-term results after thrombolytic therapy for deep venous thrombosis. Journal of the American College of Cardiology 2000; 36 : 1336-1343
    Search Terms:
    Contributor: Chris Ball, November 2001
    Reviewer:

    Clinical Question.
    Patient deep vein thrombosis
    Intervention or Exposure thrombolysis
    Outcome post-thrombotic syndrome, major bleeding, pulmonary embolism