LAUSR

The Basques who live at the Western end of the Pyrenees demonstrate particular genetic characteristics thought to be related to very old ancestry and relative absence of mixing through the ages [1]. Interestingly, when studying genetic coagulation disorders in this population, we found a nearly absence of factor V Leiden [2] and a marked prevalence of factor XI deficiency in relation with a founding mutation [3]. Until the beginning of this century, no precise data were available regarding the geographical distribution of protein S (PS) deficiency. Some years ago, it has been suggested that PS deficiency seemed significantly more prevalent in Asia [4] than in Europe [5, 6]. These findings prompted us to evaluate, for the first time, the distribution of this genetic prothrombotic condition in a cohort of patients from the French Basque area. We reviewed the PS assay results obtained during a 57-month period (October 2011 and June 2016) from our laboratory registry, Centre Hospitalier de la Côte Basque, Bayonne. This public health structure includes a Department of Hematology which centralizes all the cases of blood disorders from the French Basque Country (about 270,000 inhabitants). The study cohort was composed of individuals explored for various thrombotic conditions: massive, repetitive or life-threatening venous thromboses, thrombosis in the young, familial history of thromboembolism or recurrent fetal loss. Total PS was measured by the STACLOT® chronometric assay (Stago, Asnières, France) and free PS using the LIATEST® immunoturbidimetric assay (Stago, Asnières, France). PS normal range was determined using the model of Dykes and coworkers integrating age, sex, hormone replacement therapy and contraceptive pill use [5]. Individuals combining low PS levels with the following conditions: acquired deficiency, coumarin treatment, pregnancy, severe liver failure or inflammatory disorder, were excluded from this analysis. The diagnosis of PS deficiency was always confirmed on repeated measurements (at least using two different samples). Autochthonous individuals were selected on the basis of a typical Basque surname which represents here a strong marker of origin. Family studies were performed in deficient cases. Both total and free PS measurements were available in 554 subjects during the above mentioned study period. There were 201 men and 353 women and their age ranged from 6 months to 87 years (median: 39). 319 females were premenopausal adults and 15 were below the age of puberty. 121 individuals (21.8%) were considered as autochthonous Basques. Basque and non-Basque subgroups were comparable regarding sex, age and underlying clinical conditions. Seventeen cases of PS deficiency were detected (3% of the entire cohort) in 3 men and 14 women aged between 3 and 63 years (median: 28). 16 of them had a personal and/ or a familial history of severe venous thrombosis. This deficiency was diagnosed incidentally in one case. Total and free PS levels varied between 13 and 62% and 14 and 70% respectively. Of note, all these deficient patients were of nonBasque origin. PS deficiency was statistically less prevalent among Basques than among non-autochthonous patients (p: 0.03, χ2 test). PS deficiency is usually found in 5% of thrombophilic patients and 1–2% of patients with a first episode of deep vein thrombosis [7]. The percentage obtained here from patients with miscellaneous thrombotic situations was within the range of these frequencies described in Caucasians. * Frédéric Bauduer [email protected]