Heparin: :heparin-resistant patients: anti-factor Xa may no better than aPTT for monitoring dosing.

Clinical bottom line (level 1b-)

  1. In patients requiring large amounts of heparin, using anti-factor Xa heparin assay may be no better than aPTT for monitoring heparin dosing.
  2. Factor Xa monitoring may permit lower doses of heparin to be used for similar efficacy
  3. Patients who are heparin-resistant had a higher factor VIII level.
Levine et al: Archives of Internal Medicine 1994; 154: 49-56
Expires June 2003

The study

Unblinded concealed randomised trial with intention-to-treat
Setting: three university hospitals, Canada

153 patients (aged mean 57 years, 51% female) acute deep vein thrombosis, pulmonary embolism or arm vein thrombosis requiring at least 35,000 units of iv heparin during previous 24 hours (DVT diagnosed by venogram or impedance plethysmography; PE diagnosed by high probability ventilation-perfusion scan, pulmonary angiogram)

Excluded if
  • received thrombolytic therapy
  • had heparin for >72 hours
  • unable to be followed up


    • Control Group: (n = 66, 66 analysed): heparin adjusted by aPTT
    Experimental Group: (n = 65, 65 analysed): heparin adjusted by anti-factor Xa heparin assay
    All patients had 5000 units bolus and 33, 600 units/day adjusted by aPTT after 6 hours, range 1.5 to 2.5.
    100% followed for 3 months

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    recurrent DVT/PE 3 months 4
    (6.06%)    		 3
    (4.62%)    		 24%
    (-227% to 82%)    		 1.45%
    (-6.25% to 9.14%)    		 69
    (NNT = 11 to infinity;
    NNH = 16 to infinity)
    bleeding 3 months 4
    (6.06%)    		 1
    (1.54%)    		 75%
    (-121% to 97%)    		 4.52%
    (-1.97% to 11.0%)    		 22
    (NNT = 9 to infinity;
    NNH = 51 to infinity)

    Outcome Control Group
    (SD)    		 Experimental Group
    (SD)    		 Mean Difference
    (95% CI)
    factor VIII level/units heparin-resistant (n=114): 2.39
    (1.02)     		normal matched controls (n=35): 1.60
    (0.79)     		0.79
    (0.42 to 1.20)
    mean heparin dose (units/day): p<0.001 APTT group (n=66): 45 222
    (-)     		Factor Xa (n=65): 40 582
    (-)     		4640
    (- to -)

    Comments

    1. Patients did not start warfarin until D3-D5
    2. Patients were stratified by centre, presence or absence of underlying malignant neoplasm and duration of heparin therapy before randomisation.
    3. The study was not large enough to show any differences.

    Citation

    1. Levine MD, Hirsh J, Gent M, et al: Randomized trial comparing activated thromboplastin time with heparin assay in patients with acute venous thromboembolism requiring large daily doses of heparin. Archives of Internal Medicine 1994; 154: 49-56
    Contributor: Chris Ball and Clare Wotton, June 2000
    Reviewer: Alex Gallus

    Clinical Question.
    Patient DVT, PE or arm vein thrombosis
    Intervention or Exposure heparin adjusted by anti-factor Xa
    Comparison heparin adjusted by aPTT
    Outcome recurrence or major bleed