title: Venous thrombosis due to poor anticoagulant response to activated protein C: Leiden Thrombophilia Study.
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.
authors.affiliation: Department of Clinical Epidemiology, University Hospital, Leiden, Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: Koster
authors.forename: F R
authors.initials: FR
authors.lastname: Rosendaal
authors.forename: H
authors.initials: H
authors.lastname: de Ronde
authors.forename: E
authors.initials: E
authors.lastname: Briët
authors.forename: J P
authors.initials: JP
authors.lastname: Vandenbroucke
authors.forename: R M
authors.initials: RM
authors.lastname: Bertina
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001777:Blood Coagulation / Q000235:genetics; D001780:Blood Coagulation Tests; D016022:Case-Control Studies; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011486:Protein C / Q000494:pharmacology*; D012307:Risk Factors; D013924:Thrombophlebitis / Q000209:etiology* / Q000235:genetics
chemical_list: D011486:Protein C