PREVALENCE OF PROTEIN-C DEFICIENCY IN THE HEALTHY POPULATION

Reported prevalence rates for protein C (PC) deficiency in the populat ion at large have varied widely. The differences presumably reflect th e existence of an apparently high number of clinically recessive forms of the deficiency. In an attempt to document more precisely the preva lence of PC deficiency in the healthy population we have measured PC a ctivity in just under 10,000 blood donors in the West of Scotland. Aft er repeat testing of donors with low results and then further observat ion and selection, 32 donors were identified who had individual mean P C activities below the age- and gender-specific study reference range. Assessment of available first degree relatives, and also PC gene anal ysis in 23 of these donors, allowed identification of at least 14 with an inheritable deficiency (8 by both family study and gene analysis, 3 by family study alone and 3 by gene analysis alone). Two recurring a nd seven unique point mutations, only one of which has been previously described, were identified. The observed prevalence of inherited PC d eficiency was 1.45 per 1000 (95% CI, 0.79/1000 to 2.43/1000). However after correcting for the possibility of missing some genuine inherited deficiencies we estimated the prevalence to be as high as 1 in 500. A ll cases of hereditary deficiency were asymptomatic with regard to thr ombosis and none had a strong family history of thrombosis. These find ings confirm the rather frequent occurrence of asymptomatic individual s with PC deficiency and support the hypothesis that additiorial defec ts in the anticoagulant pathways may be required to confer a high-thro mbotic-risk phenotype.