Venous thrombosis due to poor anticoagulant response to activated protein C: Leiden Thrombophilia Study

Lancet. 1993 Dec 18-25;342(8886-8887):1503-6. doi: 10.1016/s0140-6736(05)80081-9.

Abstract

We undertook a population-based case-control study to test the clinical importance of a hereditary abnormality in the coagulation system, characterised by poor anticoagulant response to activated protein C (APC), which is associated with familial thrombophilia. The abnormality was detected in 64 (21%) of 301 unselected consecutive patients younger than 70 years, with a first, objectively confirmed episode of deep-vein thrombosis and without underlying malignant disease. Among 301 healthy control subjects matched for age and sex, the frequency was 5% (14 subjects). Thus, there is a seven-fold increase in risk of deep-vein thrombosis in subjects with a poor response to APC (matched odds ratio 6.6 [95% CI 3.6-12.0]). In addition, there was a clear inverse relation between the degree of response to APC and thrombosis risk. In the families of the patients an autosomal dominant mode of transmission of the abnormality was confirmed. 9 of 10 thrombosis patients with a poor response to APC had 1 parent with a similar poor response, whereas 9 of 10 patients with normal tests had parents with equally normal tests. The abnormality was found in both parents of 1 patient with an extremely poor response to APC; this patient is probably homozygous for the abnormality. We conclude that the poor response to APC is the most important hereditary cause of venous thrombosis. Its high prevalence in a series of unselected patients will make testing of all thrombosis patients for this abnormality worth while.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Blood Coagulation / genetics
  • Blood Coagulation Tests
  • Case-Control Studies
  • Female
  • Heterozygote
  • Homozygote
  • Humans
  • Male
  • Middle Aged
  • Odds Ratio
  • Protein C / pharmacology*
  • Risk Factors
  • Thrombophlebitis / etiology*
  • Thrombophlebitis / genetics

Substances

  • Protein C