Twenty-one patients (12 female and 9 male) with severe (homozygous) factor XII (FXII) deficiency and 58 (32 female and 26 male) with heterozygous FXII deficiency were observed for an average 16.2 years. No patient with homozygous FXII deficiency experienced myocardial infarction or any other arterial thrombosis. The same was true for heterozygotes. The cases of FXII deficiency and arterial thrombosis reported in the literature were evaluated. In every instance, associated risk factors were present that could justify the arterial thrombosis. Dyslipidemia, hypertension, smoking, and diabetes mellitus were the most frequent findings. The examination of the few papers that dealt with the prevalence of arterial thrombosis in patients with severe FXII deficiency showed that only 1 patient of 61 experienced myocardial infarction. In conclusion, it seems that the role of FXII deficiency in the pathogenesis of arterial thrombosis is minor.
Ratnoff OD, Colopy IE. A familial hemorrhagic trait associated with a deficiency of a clot-promoting fraction of plasma. J Clin Invest1955;34:602.
2.
Colman RW. Contact activation pathway: Inflammatory, fibrinolytic, anticoagulant, antiadhesive and antiangionenic activities. In: Colman RW, Hirsh J, Marden VJ, Clowes AW, Teorge JM, eds. Thrombosis and Haemostasis, 4th ed.Philadelphia: Lippincott, Williams and Wilkins, 2001.
3.
Girolami A, Maffei A, Brunetti A, Lazzarin M.Cholecystectomy in a patient with Hageman trait. Thromb Diath Haemorrh1970;23:449.
4.
Girolami A, De Marco L, Dal Bo Zanon R, Patrassi G, Cappellato MG. Rarer quantitative and qualitative abnormalities of coagulation. Clin Haematol1985;14:385.
5.
Ratnoff OD, Busse RJ, Shean RP. The demise of John Hageman. N Engl J Med1968;279:760.
6.
Goodnough LT, Saito H, Ratnoff OD. Thrombosis or myocardial infarction in congenital clotting factor abnormalities and chronic thrombocytopenias: A report of 21 patients and a review of 50 previously reported cases. Medicine (Baltimore)1983;62:248.
7.
Grant PJ. The genetics of atherothrombotic disorders: A clinician’s view. J Thromb Haemost2003;1:1381.
8.
Hellstern P, Kohler M, Schmengler K, Doenecke P, Wenzel E.Arterial and venous thrombosis and normal response to streptokinase treatment in a young patient with severe Hageman factor deficiency. Acta Haematol1983;69:123.
9.
Lämmle B, Wuillemin WA, Huber I, et al.Thromboembolism and bleeding tendency in congenital factor XII deficiency—a study on 74 subjects from 14 Swiss families. Thromb Haemost1991;65:117.
10.
Kitchens CS. The contact system. Arch Pathol Lab Med2002;126:1382.
11.
Egeberg O.New families with factor XII deficiency. Thromb Diath Haemorrh1970;24:441.
12.
McCain KF, Chernoff AI, Graham JB. Establisment of the inheritance of Hageman defect as an autosomal recessive trait. In: Brinkhous KM, ed. Hemophilia and other Hemorragic States. Chapel Hill, NC: UN Carolina Press, 1976:656.
13.
McPherson RA. Thromboembolism in Hageman trait. Am J Clin Pathol1977;68:420.
14.
Vroman L, quoted by Mossel ML. The contact system. In: Biggs R, ed. Blood Coagulation, Hemostasis and Thrombosis. Boston: Blackwell Scientific, 1976:113.
15.
Lodi S, Isa L, Pollini E, Bravo AF, Scalvini A.Defective intrinsic fibrinolytic activity in a patient with severe factor XII-deficiency and myocardial infarction. Scand J Haematol1984;33:80.
16.
Gluek HI, Roehill W Jr.Myocardial infarction in a patient with a Hageman (factor XII) defect. Ann Intern Med1966;64:390.
17.
Hoak JC, Swanson LW, Warner ED, Connor WE. Myocardial infarction associated with severe factor-XII deficiency. Lancet1966;22:884.
18.
Walsh PN. Platelet adhesiveness in Hageman trait. Lancet1970;2:575.
19.
Penny WJ, Colvin BT, Brooks N.Myocardial infarction with normal coronary arteries and factor XII deficiency. Br Heart J1985;53:230.
20.
Rodeghiero F, Castaman G, Ruggeri M, Cazzavillan M, Ferracin G, Dini E.Fibrinolytic studies in 13 unrelated families with factor XII deficiency. Haematologica1991;76:28.
21.
Sinakos Z, Sultan Y, Caen J, Bernard J.Le comportement des plaquethes dans les maladie hemorragique. Presse Ed1967;75:269.
22.
Schved JF, Gris JC, Neveu S, Mares P, Sarlat C.Variations of factor XII level during pregnancy in a woman with Hageman factor deficiency. Thromb Haemost1988;60:526.
23.
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 Haematol1970;19:179.
24.
Girolami A, Patrassi G, De Marco L, Cappellato G.Lack of factor XII antigen in factor XII deficiency as determined by electroimmunoassy. Blut1982;45:141.
25.
Girolami A, Simioni P, Scarano L, Girolami B, Zerbinati P.Symptomatic combined homozygous factor XII deficiency and heterozygous factor V Leiden. J Thromb Thrombolysis2000;9:271.
26.
Girolami A, Simioni P, Lazzaro AR, Cordiano I.Severe arterial cerebral thrombosis in a patient with protein S deficiency (moderately reduced total and markedly reduced free protein S): A family study. Thromb Haemost1989;61:144.
27.
Simioni P, Prandoni P, Lensing AW, et al.Risk for subsequent venous thromboembolic complications in carriers of the prothrombin or the factor V gene mutation with a first episode of deep-vein thrombosis. Blood2000;96:3329.
28.
Rees DC, Cox M, Clegg JB. World distribution of factor V Leiden. Lancet1995;346:1133.
29.
Rosendaal FR, Doggen CJ, Zivelin A, Arruda VR, Aiach M, Siscovick DS. Geographic distribution of the 20210 G to A prothrombin variant. Thromb Haemost1998;79:706.
30.
Girolami A, Randi ML, Gavasso S, Lombardi AM, Spiezia L.The occasional venous thromboses seen in patients with severe (homozygous) FXII deficiency are probable due to associated risk factors: A study of prevalence in 21 patients and review of the literature. J Thromb Thrombolysis2004;17:137.
31.
Halbmayer WM, Mannhalter C, Feichtinger C, Rubi K, Fischer M.Factor XII (Hageman factor) deficiency: A risk factor for development of thromboembolism. Incidence of factor XII deficiency in patients after recurrent venous or arterial thromboembolism and myocardial infarction. Wien Med Wochenschr1993;143:43.
32.
Koster T, Rosendaal FR, Briet E, Vandenbroucke JP. John Hageman’s factor and deep-vein thrombosis: Leiden thrombophilia study. Br J Haematol1994;87:422.
33.
Zeerleder S, Schloesser M, Redondo M, et al.Reevaluation of the incidence of thromboembolic complications in congenital factor XII deficiency—a study on 73 subjects from 14 Swiss families. Thromb Haemost1999;82:1240.
34.
Harris MG, Exner T, Rickard KA, Kronenberg H.Multiple cerebral thrombosis in Fletcher factor (prekallikrein) deficiency: A case report. Am J Hematol1985;19:387.
35.
Endler G, Mannhalter C, Sunder-Plassmann H, et al.Homozygosity for the C—>T polymorphism at nucleotide 46 in the 5’ untranslated region of the factor XII gene protects from development of acute coronary syndrome. Br J Haematol2001;115:1007.
36.
Kanaji T, Okamura T, Osaki K, et al.A common genetic polymorphism (46 C to T substitution) in the 5’-untranslated region of the coagulation factor XII gene is associated with low translation efficiency and decrease in plasma factor XII level. Blood1998;91:2010.
37.
Soria JM, Almasy L, Souto JC, et al.A quantitative-trait locus in the human factor XII gene influences both plasma factor XII levels and susceptibility to thrombotic disease. Am J Hum Genet2002;70:567.
38.
Kohler HP, Carter AM, Stickland MH, Grant PJ. Levels of activated FXII in survivors of myocardial infarction—association with circulating risk factors and extent of coronary artery disease. Thromb Haemost1998;79:14.
39.
Kohler HP, Futers TS, Grant PJ. FXII (46C→T) polymorphism and in vivo generation of FXII activity—gene frequencies and relationship in patients with coronary artery disease. Thromb Haemost1999;81:745.
40.
Girolami A, Agostino D, Cliffton EE. The effect of ellagic acid on coagulation in vivo. Blood1966;27:93.
41.
Girolami A, Cliffton EE. Hypercoagulable state induced in humans by the intravenous administration of purified ellagic acid. Thromb Diath Haemorrh. 1967;17:165.
42.
Winter M, Gallimore M, Jones DW. Should factor XII assays be included in thrombophilia screening?Lancet1995;346:352.
