Download PDF
Semin Thromb Hemost 2015; 41(04): 359-365
DOI: 10.1055/s-0034-1544000
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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

Antonio Girolami
1   Department of Medicine, University of Padua Medical School, Padua, Italy
,
Elisabetta Cosi
1   Department of Medicine, University of Padua Medical School, Padua, Italy
,
Luisa Sambado
1   Department of Medicine, University of Padua Medical School, Padua, Italy
,
Bruno Girolami
2   Division of Medicine, Padua City Hospital, Padua, Italy
,
Maria Luigia Randi
1   Department of Medicine, University of Padua Medical School, Padua, Italy
› Author Affiliations
Further Information

Publication History

Publication Date:
14 April 2015 (online)

    Permissions and Reprints

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.

Keywords

factor X - deficiency - history - classification - variants
 

  • References

  • 1 Perry DJ. Factor X and its deficient states. Haemophilia 1997; 3 (3) 159-172
    CrossrefPubMedGoogle Scholar
  • 2 Uprichard J, Perry DJ. Factor X deficiency. Blood Rev 2002; 16 (2) 97-110
    CrossrefPubMedGoogle Scholar
  • 3 Menegatti M, Peyvandi F. Factor X deficiency. Semin Thromb Hemost 2009; 35 (4) 407-415
    Article in Thieme ConnectPubMedGoogle Scholar
  • 4 Girolami A, Molaro G, Lazzarin M, Scarpa R. Una nuova coagulopatia emorragica congenita probabilmente dovuta alla presenza di un fattore X abnorme. Studio preliminare. Minerva Med 1969; 60 (98) 4939-4949
    PubMedGoogle Scholar
  • 5 Girolami A, Molaro G, Lazzarin M, Scarpa R, Brunetti A. A “new” congenital haemorrhagic condition due to the presence of an abnormal factor X (factor X Friuli): study of a large kindred. Br J Haematol 1970; 19 (2) 179-192
    CrossrefPubMedGoogle Scholar
  • 6 Rabe F, Salomon E. Über Faserstoffmangel im Blute bei einem Falle von Hämophilie. Dtsch Arch Klin Med 1920; 132: 240-244
    PubMedGoogle Scholar
  • 7 Quick AJ. Congenital hypoprothrombinaemia and pseudo-hypoprothrombinaemia. Lancet 1947; 2 (6472) 379-382
    PubMedGoogle Scholar
  • 8 Pavlovsky A. Contribution to the pathogenesis of hemophilia. Blood 1947; 2 (2) 185-191
    PubMedGoogle Scholar
  • 9 Biggs R, Douglas AS, MacFarlane RG, Dacie JV, Pitney WR. , Merskey. Christmas disease: a condition previously mistaken for haemophilia. BMJ 1952; 2 (4799) 1378-1382
    CrossrefPubMedGoogle Scholar
  • 10 Aggeler PM, White SG, Glendening MB, Page EW, Leake TB, Bates G. Plasma thromboplastin component (PTC) deficiency; a new disease resembling hemophilia. Proc Soc Exp Biol Med 1952; 79 (4) 692-694
    CrossrefPubMedGoogle Scholar
  • 11 Owren PA. Parahaemophilia; haemorrhagic diathesis due to absence of a previously unknown clotting factor. Lancet 1947; 1 (6449) 446-448
    PubMedGoogle Scholar
  • 12 Alexander B, Goldstein R, Landwehr G, Cook CD. Congenital SPCA deficiency: a hitherto unrecognized coagulation defect with hemorrhage rectified by serum and serum fractions. J Clin Invest 1951; 30 (6) 596-608
    CrossrefPubMedGoogle Scholar
  • 13 Rosenthal RL, Dreskin OH, Rosenthal N. New hemophilia-like disease caused by deficiency of a third plasma thromboplastin factor. Proc Soc Exp Biol Med 1953; 82 (1) 171-174
    CrossrefPubMedGoogle Scholar
  • 14 Hathaway WE, Belhasen LP, Hathaway HS. Evidence for a new plasma thromboplastin factor. I. Case report, coagulation studies and physicochemical properties. Blood 1965; 26 (5) 521-532
    PubMedGoogle Scholar
  • 15 Ratnoff OD, Colopy JE. A familial hemorrhagic trait associated with a deficiency of a clot-promoting fraction of plasma. J Clin Invest 1955; 34 (4) 602-613
    CrossrefPubMedGoogle Scholar
  • 16 Owen CA, Bowie EJ, Thompson JH. The Diagnosis of Bleeding Disorders. Boston, MA: Little Brown and Company; 1975: 3
    Google Scholar
  • 17 Telfer TP, Denson KWE, Wright DR. A new coagulation defect. Br J Haematol 1956; 2 (3) 308-316
    CrossrefPubMedGoogle Scholar
  • 18 Hougie C, Barrow EM, Graham JB. Stuart clotting defect. I. Segregation of an hereditary hemorrhagic state from the heterogeneous group heretofore called stable factor (SPCA, proconvertin, factor VII) deficiency. J Clin Invest 1957; 36 (3) 485-496
    CrossrefPubMedGoogle Scholar
  • 19 Graham JB, Barrow EM, Hougie C. Stuart clotting defect. II. Genetic aspects of a new hemorrhagic state. J Clin Invest 1957; 36 (3) 497-503
    CrossrefPubMedGoogle Scholar
  • 20 Bachmann F, Duckert F, Flückiger P, Hitzig W, Koller F. Uber einen neuartigen kongenitalen Gerinnungsdefekt; Mangel an Stuart-Faktor. Thromb Diath Haemorrh 1958; 1 (1) 87-92
    PubMedGoogle Scholar
  • 21 Denson KWE. The discovery of factor X. J Thromb Haemost 2004; 2: 188-189
    CrossrefPubMedGoogle Scholar
  • 22 Bachmann F. The discovery of factor X: a personal reminiscence. Thromb Haemost 2007; 98 (1) 16-19
    PubMedGoogle Scholar
  • 23 Graham JB. Stuart Factor: discovery and designation as factor X. J Thromb Haemost 2003; 1 (5) 871-877
    CrossrefPubMedGoogle Scholar
  • 24 Hougie C. The discovery of factor X. J Thromb Haemost 2004; 2: 189-191
    CrossrefPubMedGoogle Scholar
  • 25 Lewis JH, Fresh JW, Ferguson JH. Congenital hypoproconvertinemia. Proc Soc Exp Biol Med 1953; 84 (3) 651-654
    CrossrefPubMedGoogle Scholar
  • 26 Venturelli R, Molaro GL, Camoretto R. Intervento chirurgico in soggetto affetto da deficit congenito del complesso protrombinico. Trasf Sangue 1961; 6: 34-35
    PubMedGoogle Scholar
  • 27 Chevallier P, Bernard J, Fiehrer A, Bilski-Pasquier G, Samama M, Cerf M. Deux cas d'hypoconvertinémie familiale. Sang 1955; 26 (7) 650-659
    PubMedGoogle Scholar
  • 28 Girolami A. The discovery of Factor X. J Thromb Haemost 2004; 2: 187-188
    CrossrefPubMedGoogle Scholar
  • 29 Denson KWE. Abnormal forms of factor X. Lancet 1969; 2 (7632) 1256
    PubMedGoogle Scholar
  • 30 Denson KW, Lurie A, De Cataldo F, Mannucci PM. The factor-X defect: recognition of abnormal forms of factor X. Br J Haematol 1970; 18 (3) 317-327
    CrossrefPubMedGoogle Scholar
  • 31 Fair DS, Edgington TS. Heterogeneity of hereditary and acquired factor X deficiencies by combined immunochemical and functional analyses. Br J Haematol 1985; 59 (2) 235-248
    CrossrefPubMedGoogle Scholar
  • 32 James HL, Girolami A, Fair DS. Molecular defect in coagulation factor XFriuli results from a substitution of serine for proline at position 343. Blood 1991; 77 (2) 317-323
    PubMedGoogle Scholar
  • 33 Chevallier P, Bernard J, Bilski-Pasquier G, De Grouchy J, Samama M. Déficience congénital et familiale en facteur Stuart. Sang 1959; 30: 525-530
    PubMedGoogle Scholar
  • 34 Parkin JD, Madaras F, Sweet B, Castaldi PA. A further inherited variant of coagulation factor X. Aust N Z J Med 1974; 4 (6) 561-564
    CrossrefPubMedGoogle Scholar
  • 35 Girolami A, Vicarioto M, Ruzza G, Cappellato G, Vergolani A. Factor X Padua: a ‘new’ congenital factor X abnormality with a defect only in the extrinsic system. Acta Haematol 1985; 73 (1) 31-36
    CrossrefPubMedGoogle Scholar
  • 36 Girolami A, Vianello F, Cabrio L, Lombardi AM. A new mutation (Arg251Trp) in the Ca2+ binding site of factor X protease domain appears to be responsible for the defect in the extrinsic pathway activation of factor X Padua. Clin Appl Thromb Hemost 2004; 10 (1) 5-8
    CrossrefPubMedGoogle Scholar
  • 37 Girolami A, Scarparo P, Scandellari R, Allemand E. Congenital factor X deficiencies with a defect only or predominantly in the extrinsic or in the intrinsic system: a critical evaluation. Am J Hematol 2008; 83 (8) 668-671
    CrossrefPubMedGoogle Scholar
  • 38 Girolami A, Vettore S, Scarparo P, Lombardi AM. Persistent validity of a classification of congenital factor X defects based on clotting, chromogenic and immunological assays even in the molecular biology era. Haemophilia 2011; 17 (1) 17-20
    CrossrefPubMedGoogle Scholar
  • 39 De Stefano V, Leone G, Ferrelli R, Hassan HJ, Macioce G, Bizzi B. Factor X Roma: a congenital factor X variant defective at different degrees in the intrinsic and the extrinsic activation. Br J Haematol 1988; 69 (3) 387-391
    CrossrefPubMedGoogle Scholar
  • 40 Peyvandi F, Menegatti M, Santagostino E , et al. Gene mutations and three-dimensional structural analysis in 13 families with severe factor X deficiency. Br J Haematol 2002; 117 (3) 685-692
    CrossrefPubMedGoogle Scholar
  • 41 Watzke HH, Lechner K, Roberts HR , et al. Molecular defect (Gla+14----Lys) and its functional consequences in a hereditary factor X deficiency (factor X “Vorarlberg”). J Biol Chem 1990; 265 (20) 11982-11989
    PubMedGoogle Scholar
  • 42 Zama T, Murata M, Watanabe R , et al. A family with hereditary factor X deficiency with a point mutation Gla32 to Gln in the Gla domain (factor X Tokyo). Br J Haematol 1999; 106 (3) 809-811
    CrossrefPubMedGoogle Scholar
  • 43 Cooper DN, Millar DS, Wacey A, Pemberton S, Tuddenham EG. Inherited factor X deficiency: molecular genetics and pathophysiology. Thromb Haemost 1997; 78 (1) 161-172
    PubMedGoogle Scholar
  • 44 Herrmann FH, Auerswald G, Ruiz-Saez A , et al; Greifswald Factor X Deficiency Study Group. Factor X deficiency: clinical manifestation of 102 subjects from Europe and Latin America with mutations in the factor 10 gene. Haemophilia 2006; 12 (5) 479-489
    CrossrefPubMedGoogle Scholar
  • 45 Girolami A, Allemand E, Scandellari R, Lombardi AM, Girolami B. The clinical and laboratory significance of cases of congenital FX deficiency due to defects in the Gla-domain. Hematology 2009; 14 (3) 177-181
    CrossrefPubMedGoogle Scholar
  • 46 Camire R, Ann Denchy R, Day III GA, Lanzano P, Sheth S, Brown S. Prenatal diagnosis of factor X deficiency using a combination of direct mutation detection and linkage analysis with an intragenic single nucleotide polymorphism. Prenat Diagn 2003; 23 (6) 457-460
    CrossrefPubMedGoogle Scholar
  • 47 van Dijk K, van der Bom JG, Fischer K, Grobbee DE, van den Berg HM. Do prothrombotic factors influence clinical phenotype of severe haemophilia? A review of the literature. Thromb Haemost 2004; 92 (2) 305-310
    PubMedGoogle Scholar
  • 48 Shetty S, Mota L, Ghosh K. Modulation of severity of clinical bleeding by co-inherited thrombophilia is also true for severe factor X deficiency. Clin Chim Acta 2010; 411 (3-4) 291
    CrossrefPubMedGoogle Scholar
  • 49 Girolami A, Randi ML, Tezza F, Molaro G, Girolami B. Unusual longevity in a patient with factor X Friuli coagulation disorder. Thromb Haemost 2005; 93 (2) 385-387
    PubMedGoogle Scholar
  • 50 Lewis JH, Bontempo FA, Spero JA, Ragni MV, Starzl TE. Liver transplantation in a hemophiliac. N Engl J Med 1985; 312 (18) 1189-1190
    PubMedGoogle Scholar
  • 51 McCarthy M, Gane E, Pereira S , et al. Liver transplantation for haemophiliacs with hepatitis C cirrhosis. Gut 1996; 39 (6) 870-875
    CrossrefPubMedGoogle Scholar
  • 52 Bang SH, Oh SH, Kim KM , et al. Successful liver transplantation for a child with life-threatening recurrent bleeding episodes due to congenital factor X deficiency: a case report. Transplant Proc 2012; 44 (2) 583-584
    CrossrefPubMedGoogle Scholar
  • 53 Chiossi G, Spero JA, Esaka EJ , et al. Plasma exchange in a case of severe factor X deficiency in pregnancy: critical review of the literature. Am J Perinatol 2008; 25 (3) 189-192
    Article in Thieme ConnectPubMedGoogle Scholar
  • 54 Girolami A, Ruzzon E, Tezza F, Scandellari R, Scapin M, Scarparo P. Congenital FX deficiency combined with other clotting defects or with other abnormalities: a critical evaluation of the literature. Haemophilia 2008; 14 (2) 323-328
    CrossrefPubMedGoogle Scholar
  • 55 Chilcott JL, Russell G, Mumford AD. Combined deficiency of factors VII and X: clinical description of two cases and management of spinal surgery. Haemophilia 2006; 12 (5) 555-558
    CrossrefPubMedGoogle Scholar
  • 56 Pfeiffer RA, Ott R, Gilgenkrantz S, Alexandre P. Deficiency of coagulation factors VII and X associated with deletion of a chromosome 13 (q34). Evidence from two cases with 46,XY,t(13;Y)(q11;q34). Hum Genet 1982; 62 (4) 358-360
    CrossrefPubMedGoogle Scholar
  • 57 Menegatti M, Karimi M, Garagiola I, Mannucci P, Peyvandi F. A rare inherited coagulation disorder: combined homozygous factor VII and factor X deficiency. Am J Hematol 2004; 77 (1) 90-91
    CrossrefPubMedGoogle Scholar
  • 58 Lohrmann J, Becker RC. New anticoagulants—the path from discovery to clinical practice. N Engl J Med 2008; 358 (26) 2827-2829
    CrossrefPubMedGoogle Scholar
  • 59 Ansell J, Askin D. New targets for anticoagulation and future perspectives. Curr Drug Discov Technol 2012; 9 (2) 150-155
    CrossrefPubMedGoogle Scholar
  • 60 Girolami A, Candeo N, Vettore S, Lombardi AM, Girolami B. The clinical significance of the lack of arterial or venous thrombosis in patients with congenital prothrombin or FX deficiency. J Thromb Thrombolysis 2010; 29 (3) 299-302
    CrossrefPubMedGoogle Scholar
  • 61 Giangrande PL. Six characters in search of an author: the history of the nomenclature of coagulation factors. Br J Haematol 2003; 121 (5) 703-712
    CrossrefPubMedGoogle Scholar
  • 62 Fair DS, Revak DJ, Hubbard JG, Girolami A. Isolation and characterization of the factor X Friuli variant. Blood 1989; 73 (8) 2108-2116
    PubMedGoogle Scholar
  • 63 Kim DJ, Girolami A, James HL. Characterization of recombinant human coagulation factor XFriuli. Thromb Haemost 1996; 75 (2) 313-317
    PubMedGoogle Scholar