Anticoagulation and DVT: subtherapeutic aPTT after heparin increased risk of DVT.

Clinical bottom line (level 2b)

  1. Patients with deep vein thrombosis who had subtherapeutic levels of aPTT after 24 hours on iv heparin, were at increased risk for recurrent venous thromboembolism (NNF = 6 for 3 months) .
Hull et al: Archives of Internal Medicine 1997; 157: 2562-2568
Expires June 2003

The study

Retrospective cohort study with objective outcomes, adjusted for confounding factors, not validated in an independent set of patients.

Setting: university hospital, USA

528 patients (aged ?, ?% male) from three randomised controlled trials, with proximal deep vein thrombosis who received iv heparin (bolus of 5000 units and 30,000 units over 24 hours titred so that aPTT 1.5-2.5.

Factors studied:
  • recurrent DVT
  • subtherapeutic aPTT after 24 hours of heparin
  • subtherapeutic aPTT


    • All patients also received warfarin for three months with INR titred to 2.0-3.0, overlapped with heparin for 4-5 days.

    Cox proportional hazards model was used to adjust for confounding factors.

    100% followed for 3 months
    Outcomes studied:
  • recurrent DVT (s/c vs i/v) in 1986 RCT of subcutaneous heparin vs iv heparin
  • recurrent DVT (5d vs 10d and UFH vs LMWH) in 1990 RCT of 5 days heparin vs 10 days heparin, and 1992 RCT of iv heparin v LMWH

    • The evidence

    outcome time to outcome number of patients/total number %
    (95% CI)
    recurrent DVT (s/c vs i/v) 3 months 14/114 12.3%
    (6.26% to 18.3%)
    recurrent DVT (5d vs 10d and UFH vs LMWH) 3 months 28/414 6.76%
    (4.34% to 9.18%)

    prognostic factor for
    recurrent DVT (s/c vs i/v)     		time to outcome unadjusted RR
    (95% CI)    		 NNF+
    (95% CI)
    subtherapeutic aPTT after 24 hours of heparin 3 months 9.2
    (2.2 to 39)     		4
    (1 to 30)

    prognostic factor for
    recurrent DVT (5d vs 10d and UFH vs LMWH)     		time to outcome unadjusted RR
    (95% CI)    		 NNF+
    (95% CI)
    subtherapeutic aPTT 3 months 3.4
    (1.3 to 8.9)     		7
    (2 to 50)

    Comments

    1. Patients all followed standardised heparin dosing, ie. not weight-based. Therefore de facto some patients had subtherapeutic aPTT- a confounding factor that makes the study results less certain.
    2. Meta-analysis has shown no significant risk increase with subtherapeutic aPTT.
    3. All patients were selected for RCTs- what would risk be for a more general population.

    Citation

    1. Hull RD, Raskob GE, Brant RF, et al: Relation between the time to achieve the lower limit of the aPTT therapeutic range and recurrent venous thromboembolism during heparin therapy for deep vein thrombosis. Archives of Internal Medicine 1997; 157: 2562-2568
    Contributor: Chris Ball and Clare Wotton, June 2000
    Reviewer:

    Clinical Question.
    Patient proximal DVT
    Intervention or Exposure subtherapeutic aPTT
    Outcome recurrence