Factor X Friuli Coagulation Disorder: Almost 50 Years Later

Abstract

The story of factor X (FX) Friuli. Factor X Friuli was discovered in 1969 to 1970. However, the story of that disease was an international event since patients with this defect were studied in France and in Italy, and different diagnoses were reached—FVII; FX; combined prothrombin complex; and combined FII, FVII, and FX deficiencies. The diagnostic difficulties were due to the peculiar clotting pattern presented by these patients, namely, prolonged partial thromboplastin time, prolonged prothrombin time but normal Russell viper venom clotting time. Only suitable anti-FX antisera clarified the pattern. Altogether 12 homozygotes and 102 heterozygotes have been followed during 4 decades. Six homozygotes died, 2 of them due to HIV infection and 1 due to hepatitis B liver cirrhosis. The other 3 died of nontransfusion-related morbidity. Bleeding tendency has been moderate in agreement with the extrinsic or intrinsic system assay results—FX level of 4% to 5% is considered normal. Heterozygotes may present occasional bleeding manifestations usually during surgery or delivery. Molecular analysis have shown that the mutation responsible for the defect is a Pro343Ser substitution in exon 8. Chimeric FX Friuli mice have been useful in studying the effect of FX levels on embryonic or natal mortality of these animals. No new homozygote but several heterozygotes have been recently seen. The study of FX Friuli has revolutionized the diagnostic approach to FX deficiencies. The FX should be assayed by all assay systems. The FX Friuli has never been described in any other country, and all patients studied come from the Friuli Meduna River Valley.