VENOUS THROMBOSIS DUE TO POOR ANTICOAGULANT RESPONSE TO ACTIVATED PROTEIN-C - LEIDEN THROMBOPHILIA STUDY

We undertook a population-based case-control study to test the clinica l importance of a hereditary abnormality in the coagulation system, ch aracterised by poor anticoagulant response to activated protein C (APC ), which is associated with familial thrombophilia. The abnormality wa s 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 health y control subjects matched for age and sex, the frequency was 5% (14 s ubjects). Thus, there is a seven-fold increase in risk of deep-vein th rombosis 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 fam ilies of the patients an autosomal dominant mode of transmission of th e abnormality was confirmed. 9 of 10 thrombosis patients with a poor r esponse 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 extreme ly poor response to APC; this patient is probably homozygous for the a bnormality. We conclude that the poor response to APC is the most impo rtant hereditary cause of venous thrombosis. Its high prevalence in a series of unselected patients will make testing of all thrombosis pati ents for this abnormality worth while.