Anticoagulation: weight-adjusted heparin dosing was effective.

Clinical bottom line (level 1b)

  1. Using a weight-based nomogram for heparin dosing produced therapeutic levels or higher, sooner than the standard method (NNT = 2 at 6 hours) (NNT = 5 at 24 hours) .
  2. Using a weight-based nomogram was no better than the standard method for getting within therapeutic range for 24 hours.
  3. There was no clear difference in bleeding rates.
  4. Patients on the weight-based nomogram had fewer recurrent DVTs (NNT = 5 at 3 months) .
Raschke et al: Annals of Internal Medicine 1993; 119 (9): 874-881
Expires June 2003

The study

Double-blinded concealed randomised trial without intention-to-treat
Setting: two teaching hospitals, USA

115 patients (aged ?, ?% male) proven deep vein thrombosis or pulmonary embolism (85), unstable angina (25), acute peripheral arterial ischaemia (2), crescendo ischaemic attacks (2)

Excluded if
  • anticoagulated or thrombolysed in last seven days
  • active haemorrhage
  • acute major cerebrovascular accidents
  • history of heparin-induced thrombocytopenia
  • known heparin allergy


    • Control Group: (n = 53, 53 analysed): standard care nomogram- initially- 5000 unit bolus, then 100 units/hr: aPTT <1.2- 5000 unit bolus, then 200 units/hr: aPTT 1.2-1.5- 2500 units bolus, then 100 units/hr: aPTT 1.5-2.3- no change: aPTT 2.3-3.0- decrease rate by 100 units/hr: aPTT >3.0- stop infusion for one hour, then decrease rate by 200 units/hr
    Experimental Group: (n = 62, 62 analysed): weight-based nomogram- initially- 80 unit/kg bolus, then 18 units/kg/hr: aPTT <1.2- 60 units/kg bolus, then increase by 4 units/kg/hr: aPTT-1.2-1.5- 40 unit/kg bolus, then increase 2 units/kg/hr: aPTT 1.5-2.3- no change: aPTT 2.3-3.0- decrease rate by 2 units/kg/hr: aPTT >3.0- stop infusion for 1 hour, then decrease rate by 3 units/kg/hr
    Nurses performed dosing according to protocol- aPTT levels recorded six hours after every change. Warfarin was withheld for 48 hours. Patients and physicians were blinded to regimen used.
    100% followed for 3 months
    Outcome notes:
    • major bleed : overt bleed and: >2 g/dl drop; transfusion of two plus units; location of haemorrhage in retroperitoneum, cranium or prosthetic joint
    • minor discharge : overt bleed and none of the major bleed factors

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    first aPTT on treatment >1.5 x control 6 hours 17
    (32.1%)    		 53
    (85.5%)    		 -167%
    (-300% to -78%)    		 -53.4%
    (-68.7% to -38.1%)    		 2
    (1 to 3)
    aPTT >1.5 24 hours 41
    (77.4%)    		 60
    (96.8%)    		 -25%
    (-46% to -7%)    		 -19.4%
    (-31.5% to -7.32%)    		 5
    (3 to 14)
    aPTT 1.5-2.3 24 hours 40
    (75.5%)    		 55
    (88.7%)    		 -18%
    (-40% to 2%)    		 -13.2%
    (-27.3% to 0.77%)    		 8
    (NNT = 4 to infinity;
    NNH = 130 to infinity)
    major bleed unknown 2
    (3.77%)    		 2
    (3.23%)    		 15%
    (-486% to 88%)    		 0.55%
    (-6.21% to 7.31%)    		 180
    (NNT = 13 to infinity;
    NNH = 16 to infinity)
    minor discharge unknown 1
    (1.89%)    		 0
    (0.00%)    		 100%
    (% to %)    		 1.89%
    (-1.78% to 5.55%)    		 53
    (NNT = 18 to infinity;
    NNH = 56 to infinity)
    recurrent DVT 3 months 8
    (25.0%)    		 2
    (4.88%)    		 80%
    (14% to 96%)    		 20.1%
    (3.73% to 36.5%)    		 5
    (3 to 27)

    Outcome Control Group
    (SD)    		 Experimental Group
    (SD)    		 Mean Difference
    (95% CI)
    time to reach aPTT 1.5-2.3 22.3
    ()     		14.1
    ()     		p=0.003
    ( to )

  • For recurrent DVT, only 32 patients in the control group and 41 in the experimental group were available for analysis.

    • Comments

    1. The study is too small to show any effect on bleeding.

    Citation

    1. Raschke RA, Reilly BM, Guidry JR, et al: The weight-based heparin dosing nomogram compared with a 'standard care' nomogram: a randomized controlled trial. Annals of Internal Medicine 1993; 119 (9): 874-881
    Search Terms: anticoagulation in Best Evidence
    Contributor: Chris Ball and Clare Wotton, June 2000
    Reviewer:

    Clinical Question.
    Patient DVT or PE, unstable angina, acute peripheral arterial ischaemia, crescendo ischaemic attacks
    Intervention or Exposure weight-based nomogram
    Comparison standard care nomogram
    Outcome bleeding