title: No impact of factor IX Ala-10 mutations in acenocoumarol-treated southern Europeans.
abstract: Increased risk of bleeding during oral anticoagulant (OA) treatment may be related to mutations in the precursor of coagulation factor IX. Missense mutations at Ala-10 (Ala-10Thre and Ala-10Val) in the factor IX propeptide lead to impaired carboxylation of factor IX. When patients carrying these mutations are treated with coumarins, functional factor IX levels decrease significantly, leading to an excessively prolonged activated partial thromboplastin time (aPTT) and an increased bleeding risk. Mutations at Ala-10 have been described in northern-European patients, but it is not known whether geographical differences play a role in the prevalence of these mutations. We aimed to analyze the prevalence of mutations at Ala-10 in factor IX in southern-European patients on OA treatment. Patients attending the Oral Anticoagulant Unit of the Hospital Clinic were prospectively included. The aPTT was determined at their normal International Normalized Ratio (INR) control. When the aPTT was excessively prolonged for the INR value, determination of factor IX and genotyping for Ala-10 mutations was performed. A total of 2360 patients were included (1289 men, 1071 women; mean age, 70.5 +/- 12.1 years). Twenty-four patients (16 men, eight women; mean age, 61.0 +/- 16.2 years) had an aPTT over that expected for the INR. The mean aPTT was 69.6 +/- 16.2 s. Only one patient presented with a factor IX level lower than 10%. None of the 24 patients carried mutations at Ala-10. Mutations at Ala-10 in factor IX were non-existent in the southern-European population analyzed, and thus, do not represent a relevant cause of bleeding during OA treatment.
authors.affiliation: Hemotherapy and Hemostasis Department, Hospital Clinic and Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Spain. dtassies@clinic.ub.es
authors.forename: Dolors
authors.initials: D
authors.lastname: Tàssies
authors.forename: Joan
authors.initials: J
authors.lastname: Monteagudo
authors.forename: Santiago
authors.initials: S
authors.lastname: Maragall
authors.forename: Antoni
authors.initials: A
authors.lastname: Ordinas
authors.forename: Joan Carles
authors.initials: JC
authors.lastname: Reverter
mesh_terms: D000074:Acenocoumarol / Q000008:administration & dosage / Q000009:adverse effects*; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects*; D005164:Factor IX / Q000235:genetics*; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D011237:Predictive Value of Tests; D013030:Spain
chemical_list: D000925:Anticoagulants; D005164:Factor IX; D000074:Acenocoumarol