Complex History of the Discovery and Characterization of Congenital Factor X Deficiency

Abstract

Factor X (FX) plays a pivotal role in blood coagulation. FX represents the point where all coagulation systems converge and, once activated, it converts prothrombin into thrombin. The discovery and definition of FX are based on the description between 1956 and 1957 about three patients and their families with a peculiar defect later demonstrated to be almost identical. These patients were an American (Mr. Stuart), a British (Ms. Prower), and a Swiss with Italian background (infant Delia B). We stated "almost identical" because immunological and molecular biology studies subsequently revealed that even though the basic clotting defect was identical, the FX protein level and the mutation were different in each case. Mr. Stuart had no FX protein in his plasma and the mutation was Val298Met (homozygote). Ms. Prower instead had a normal level of FX protein and the mutation was Arg287Trp + Asp282Asn (compound heterozygote). Unfortunately, the status of the Swiss patient in this regard is not known. Subsequent studies described a few major variants (FX Friuli, FX Melbourne, FX Padua, and other similar patients), which showed peculiar activation patterns (FX Friuli had a normal Russell viper venom clotting time; FX Melbourne was defective only in the intrinsic coagulation system; FX Padua, on the contrary, was defective only in the extrinsic coagulation system). All these studies have informed on the great heterogeneity and complexity of the FX defect. The story of the discovery and classification of FX deficiency has contributed considerably to our understanding of blood coagulation. The three original families and the families of the major variants, together with the researchers that discovered them, should be remembered with deep respect and gratitude.

Vitamin K-Dependent Coagulation Factors That May be Responsible for Both Bleeding and Thrombosis (FII, FVII, and FIX)

“…The condition was first described in 1956 to 1957 by British, Swiss, and American research. 13 During the past 60 years, several cases have been reported all over the world. However, the defect is still to be considered one of the rarest so far discovered.…”

Mutations Seen in Families with Factor X Deficiency Composed of Only Heterozygous Patients who Present a Bleeding Tendency

“…The bleeding tendency may be variable, but it is often severe with brain hemorrhage, hematomas, and hemarthrosis. [16][17][18] Heterozygotes for FX defects may present a mild bleeding tendency, particularly after tooth extraction, tonsillectomy, and other surgical procedures. [1,19] Easy bruising, epistaxis, and menorrhagia may also be present.…”