Deep vein thrombosis: family history and previous DVT or PE increases the chance of thrombophilia.

Clinical bottom line (level 4)

  1. In aptients with DVT, thrombophilia conditions other than those associated with Factor V Leiden mutation are rare (~8%).
  2. These conditions are present in the population at a rate of ~2%
  3. Patients are more likely to have thrombophilia if they have:
    • a family history and a DVT or PE <41 yrs old (LR+3.1)
    • recurrent DVTs or PEs, a family history and a DVT or PE <41 yrs old (LR+4.7)
Heijboer et al: New England Journal of Medicine 1990; 323: 1512-1516
Expires September 2003

The study

Setting: academic medical clinic, Holland

277 patients (aged mean 56 years, 50% male) venographically confirmed deep vein thrombosis

Excluded if
  • long-term anticoagulation treatment
  • history of cancer
  • recurrent DVT
  • cirrhosis of the liver
  • vitamin K deficiency from malnutrition



    • Independent ?blinded reference standard, applied in all patients from a consecutive inappropriate spectrum.
    Reference standard:
    • AT, protein C, protein S and plasminogen activities
    Diagnostic test: history

    The evidence

    pre-test probability of DVT with any thrombophilia: 8%, (95% CI: 5% to 12%)
    pre-test probability of any thrombophilia (in community): 2%, (95% CI: 0.5% to 6%)
    pre-test probability of antithrombin III deficiency thrombophilia: 1%, (95% CI: 0% to 2%)
    pre-test probability of protein C deficiency thrombophilia: 3%, (95% CI: 1% to 5%)
    pre-test probability of protein S deficiency thrombophilia: 2%, (95% CI: 0% to 4%)
    pre-test probability of plasminogen deficiency thrombophilia: 1%, (95% CI: 0% to 2%)

    diagnostic test thrombophilia no thrombophilia LR+
    (95% CI)    		 post-test probability LR-
    (95% CI)    		 post-test probability
    previous PE or DVT 3 20 1.7
    (0.53 to 5.2)     		13% 0.94
    (0.80 to 1.1)     		8%
    first PE or DVT at <41 years old 10 73 1.5
    (0.91 to 2.5)     		12% 0.79
    (0.55 to 1.1)     		7%
    family history (first degree relative) 11 56 2.2
    (1.3 to 3.5)     		16% 0.67
    (0.45 to 1.0)     		6%
    family history and previous PE, DVT 3 17 1.9
    (0.62 to 6.2)     		15% 0.93
    (0.79 to 1.1)     		8%
    family history + first episode < 41 years old 6 21 3.2
    (1.4 to 7.0)     		22% 0.81
    (0.63 to 1.0)     		7%
    family history, first episode < 41 years old and previous PE, DVT 3 7 4.7
    (1.3 to 17)     		30% 0.89
    (0.76 to 1.1)     		7%
    total 23 254

    Comments

    1. This study was performed prior to the discovery of Factor V Leiden mutation. Koster et al found that about 20% of patients with a first DVT have Factor V Leiden.

    Citation

    1. Heijboer H, et al: Deficiencies of coagulation-inhibiting and fibrinolytic proteins in OP with DVT. New England Journal of Medicine 1990; 323: 1512-1516
    Contributor: Bob Phillips and Chris Ball, September 2000
    Reviewer: Alex Gallus

    Clinical Question.
    Patient first DVT
    Intervention or Exposure history
    Outcome diagnosis of thrombophilia