The Prevalence of Moderate and Severe FXII (Hageman Factor) Deficiency among the Normal Population: Evaluation of the Incidence of FXII Deficiency among 300 Healthy Blood Donors

Summary

Factor XII (FXII) deficiency has been reported to be a risk factor for the development of arterial and venous thromboembolism. However, no data are available on the prevalence of FXII deficiency within the normal population. Measuring APTT and FXII activity, seven FXII deficiencies could be detected among 300 healthy blood donors. This corresponds to an incidence of FXII deficiency of 2.3%. On the basis of these data the prevalence of severe and mild FXTT deficiency in the normal population can be estimated to be 1.5-3.0%. Assessment of FXII antigen levels revealed, that all seven FXII deficient individuals had FXII antigen levels matching the activity. One presented a severe FXII deficiency (1/300, 0.3%) without detectable FXII activity and an APTT prolongation of more than 120 s. The remaining six FXII deficiencies (6/300, 2.0%) were moderate variations with FXII activities ranging from 20-45% and less prolonged APTTs. Among the 300 healthy donors 16 (5.3%) subjects with prolonged APTTs were identified. Causes for APTT-prolongation were FXII deficiency (7/16), lupus anticoagulant (6/16), mild FVIII deficiency (1/16) and hepatic disorder (1/16). In the remaining sample (1/16) the cause for the prolongation of the APTT remained unexplained. Although 8.7% (26/300) of the donors had a positive family-history of thromboembolism (TE-FH_X), none of the FXII deficient subjects were among those with positive TE-FH_X.

• References

• 1 Halbmayer W-M, Mannhalter C, Feichtinger C, Rubi K, Fischer M. The prevalence of factor XII deficiency in 103 orally anticoagulated outpatients suffering from recurrent venous and/or arterial thromboembolism. Thromb Haemostas 1992; 68: 285-90
• 2 Mannhalter C, Fischer M, Hopmeier P, Deutsch E. Factor XII activity and antigen concentrations in patients suffering from recurrent thrombosis. Fibrinolysis 1987; 1: 259-63
• 3 Goodnough LT, Saito H, Ratnoff OD. Thrombosis or myocardial infarction in congenital clotting factors abnormalities and chronic thrombocytopenias: A report of 21 patients and a review of 50 previously reported cases. Medicine 1983; 62: 248-55
• 4 Ratnoff OD, Busse RJ, Sheron R. The demise of John Hageman. New Engl J Med 1968; 279: 420-3
• 5 Rodeghiero F, Castaman G, Ruggieri M, Tosetto A. Thrombosis in subjects with homozygous and heterozygous factor XII deficiency. Thromb Haemostas 1992; 67: 590
• 6 Lammle B, Wuillemin WA, Huber I, Krauskopf M, Ziircher C, Pflugshaupt R, Furlan M. Thromboembolism and bleeding tendency in congenital factor XII deficiency – A study on 74 subjects from 14 Swiss families. Thromb Haemostas 1991; 65: 117-21
• 7 Saito H. Contact factors in health and disease. Semin Thromb Hemostas 1987; 13: 36-49
• 8 Saito H, Scott JG, Movat HZ, Scialla SJ. Molecular heterogeneity of Hageman trait (FXII deficiency). Evidence that two of 49 subjects are cross-reacting material positive (CRM+). J Lab Clin Med 1979; 94: 256-65
• 9 Saito H, Scialla SJ. Isolation and properties of an abnormal Hageman factor (factor XII) molecule in a cross-reacting material positive Hageman trait plasma. J Clin Invest 1981; 68: 1028-35
• 10 Berrettini M, Lammle B, Ciavarclla G, Ciavarella N. Functional and immunological studies of abnormal factor XII in a cross reacting material positive (CRM-F) factor XII deficiency. Thromb Haemostas 1985; 54: 120
• 11 Takahashi I, Saito H. A rapid purification with high recovery of factor XII (Hageman factor) on immunoaffinity column: application to an abnormal clotting factor XII (factor XII Toronto). J Biochem 1988; 103: 641-3
• 12 Miyata T, Kawabata SI, Iwanaga S, Takahashi I, Alving B, Saito H. Coagulation factor XII (Hageman factor) Washington DC: inactive factor Xlla results from Cys-571-Ser substitution. Proc Natl Acad Sci USA 1989; 86: 8319-22
• 13 Wuillemin WA, Huber I, Furlan M, Lammle B. Functional characterization of an abnormal factor XII molecule (FXII Bern). Blood 1991; 78: 997-1004
• 14 Wuillemin WA, Furlan M, Strieker H, Lammle B. Functional characterization of a variant factor XII (FXII Locarno) in a cross reacting material positive FXII deficient plasma. Thromb Haemostas 1992; 67: 219-25
• 15 Halbmayer W-M, Mannhalter C, Fischer M. Faktor-XII-Mangel und Thrombophilie. Haemostaseologie. 1993. in press
• 16 Halbmayer W-M, Haushofer A, Schratzberger W, Petera P, Duschet P, Fischer M. Assessment of lupus anticoagulants within the routine coagulation laboratory – Evaluation of 36 patients suffering from systemic lupus erythematosus. Med Klinik 1993; 88 (07) 417-22
• 17 Exner T, Papadopoulos G, Koutts J. Use of a simplified dilute Russell’s viper venom time (DRVVT) confirms heterogeneity among “lupus anticoagulants”. Blood Coag Fibrinolysis 1990; 1: 259-66
• 18 Czendlik C, Lammle B, Duckert F. Cold promoted activation and factor XII, prekallikrein and Cl-inhibitor. Thromb Haemostas 1985; 53: 242-4
• 19 Triplett DA. Screening for the lupus anticoagulant. Res Clin Lab 1989; 19: 379-89
• 20 Vilmar K, Gro Bklaus D, Rachmann KD. Richtlinien zur Blutgruppen-bestimmung und Bluttransfusion. Bundesgesundhbl 1992; 2: 96
• 21 Commission of the European Communities (eds.).. Richtlinien in der Blutgruppenserologie und Transfusionsmedizin. 29.10.1992 Brussels:
• 22 Thiagarajan P, Pengo V, Shapiro SS. The use of the dilute Russell viper venom time for the diagnosis of lupus anticoagulants. Blood 1986; 68: 869-74
• 23 Exner T, Triplett DA, Taberner D, Machin SJ. Guidelines for testing and revised criteria for lupus anticoagulants. SSC Subcommittee for the standardization of lupus anticoagulants. Thromb Haemostas 1991; 65: 320-2
• 24 Mancini G, Carbonara AT, Heremans JF. Immunochemical quantitation of antigens by single radial immunodiffusion. Immunochemistry 1965; 2: 235-8
• 25 Halbmayer W-M, Hopmeier P, Mannhalter C, Heuss F, Leodolter S, Rubi K, Fischer M. Cl-esterase inhibitor in uncomplicated pregnancy and mild and moderate preeclampsia. Thromb Haemostas 1991; 65: 134-8
• 26 Bruhn HD. Pathophysiology and diagnosis of prethrombosis. Lab Med 1993; 17: 158-64
• 27 Bick RL, Kunkel L. Hypercoagulability and thrombosis. Laboratory Medicine 1992; 23: 233-8
• 28 Heijboer H, Brandjes DP M, Biiller HR, Sturk A, Ten Cate JW. Deficiencies of coagulation-inhibiting and fibrinolytic proteins in outpatients with deep-vein thrombosis. N Engl J Med 1990; 323: 1512-6
• 29 Ben-Tal O, Zivelin A, Seligsohn U. The relative frequency of hereditary thrombotic disorders among 107 patients with thrombophilia in Israel. Thromb Haemostas 1989; 61: 50-4
• 30 Manoussakis MN, Tzioufas AG, Silis MP, Pange PJ E, Goudevenos J, Montsopoulos HM. High prevalence of anticardiolipin and other antibodies in a healthy elderly population. Clin Exp Immunol 1987; 69: 557-65
• 31 Cool DE, Edgell CI S, Louie GV, Zoller MJ, Brayer GD, MacGillivray RT A. Characterization of human blood coagulation factor XII cDNA. J Biol Chem 1985; 260: 13666-76
• 32 Bernardi F, Marchetti G, Patracchini P, del Senno L, Tripodi M, Fantoni A, Bartolai S, Vannini F, Felloni L, Rossi L, Panicucci F, Conconi F. Factor XII gene alteration in Hageman trait detected by TaqI restriction enzyme. Blood 1987; 69: 1421-4
• 33 Ruth S, Kempter B. Factor XII deficiency in a bavarian trait is not caused by a gene deletion, as proved by PCR double-exon-screening. Ann Hematol 1992; Suppl (Suppl. 64) A48
• 34 Kempter B, Ruth S, Lohse P. Investigations on the genetic basis of FXII deficiency. Ann Hematol 1992; Suppl (Suppl. 65) A77