Abstract
Twelve women with severe Factor XII (FXII) deficiency were under observation for an average period of about 16 years. During this time, these women had 19 pregnancies without any bleeding or thrombotic complications. The evaluation of the literature has shown that three patients manifested deep vein thrombosis during pregnancy. Five women also showed mild bleeding at delivery .The significance of these findings is not clear since thrombotic and bleeding complications may occur occasionally even in normal women. Five of our patients took oral contraceptive therapy during their fertile life for a variable period of time (2–10 years). No thrombosis was noted in any of these patients. From the scanty data gathered, in this respect, from the literature, it was shown that only three women with severe FXII deficiency took oral contraceptives and no thrombosis was noted. Altogether these results seem to indicate that the FXII deficiency does not play any significant role in the pathogenesis of bleeding and of thrombotic complications in pregnancy. However, the occurrence of deep vein thrombosis in 3 out of the 64 patients for whom sufficient data could be gathered indicates the need for further studies. This is more so if one considers that 3 out of the 6 cases of venous thromboses described altogether in the literature for females with severe FXII deficiency occurred during pregnancy or puerperium.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ratnoff OD, Colopy JE. A familial hemorrhagic trait associated with a deficiency of a clotting fraction of plasma. J Clin Invest 1955;34:602–608.
Ratnoff OD. A quarter of a century whith Hageman Factor. Thrombosis Haemostasis
Ratnoff OD, Busse RJ, Schean RP. The demise of J. Hageman. NEJ Med 1968;279:760–761.
Bauman R, Straub PW. Congenital deficiency of Hageman factors (clotting factor XII).Helv Med Acta 1968;34:313–316.
Condie RG. A serial study of coagulation factors XII, XI and X in plasma in normal pregnancy and in pregnancy complicated by pre-eclampsia. Brit J
Halbmayer WM, Mannhalter C, Feichtinger C, Rubi K, Fiscer M. FXII deficiency: A risk factor for development of thromboembolism. Incidence of FXII deficiency in patients after recurrent venous or arterial thromboembolism and miocardial infarction. Wien ME Wochenschr 1993;143:43–50.
Lammle B, Wuillemin WA, Huber I, Krenskop, Furlan M. Thromboembolism and bleeding tendency in congenital FXII deficiency- a study on 74 subjects from 14 Swiss families. Thromb Haemost 1991;65:117–121.
Koster T, Rosendaal FR, Briet EE, Vandenbroucke JP. John Hageman’s factor and deep-vein thrombosis:Leiden thrombophilia study. Br J Haematol 1994;87:422–424
Mannhalter C, Fischer M, Hopmaier P, Deutch E. Factor XII activity and antigen concentrations in patients suffering from recurrant thrombosis.
Zeeleder S, Schloesser M, Redondo M, Wuillemin WA, Engel W, Furlan M, Lämmle B. Revaluation of the incidence of thromboembolic complications in congenital factor XII deficiency. Thromb Haemost 1999;82:1240–1246.
Girolami A, Randi ML, Gavasso S, Lombardi AM, Spiezia L. The occasional venous thrombosis in patients wich severe homozygothes FXII deficiency are probably due to associated risk factors a study of prevalence in 21patients and review of the literature. J Thromb Thromb 2004;17:137–141.
Girolami A, Morello M, Girolami B, Lombardi AM, Bertolo C. Myocardial infarction and arterial thrombosis in severe, homozygons FXII deficiency: No apparent causative relation. Clin Appl Thromb Hemost (In press).
Eldor A. Thrombophilia, thrombosis and pregnancy. Thromb Haemost 2001;86:104–111.
Girolami A, Molaro G, Lazzarin M, Scarpa R, Brunetti A. A new congenital haemorrhagic condition due to the presence of an abnormal F X (factor X Friuli): Study of a large kindred. Br J Haematol 1970;19:179–192.
Girolami A, Simioni P, Lazzaro AR, Cordiano I. Severe arterial cerebral thrombosis in a patient with moderathely reduced total and markedly reduced free protein S: A family study. Thrombosis Haemost 1989;61:144–147.
Simioni P, Prandoni P, Lensing AW, Mangrin D, Tormene D, Gavasso S, Girolami B, Sardella C, Girolami A. Risk of subsequent venous thromboembolic complications in carriers of the prothrombin or the factor V gene mutation with a first episode of deep-vein thrombosis. Blood 2000;96:3329–3333.
Girolami A, Maffei A, Brunetti A, Lazzarin M. Cholecystectomy in a patient with Hageman trait. Thromb Diath Haemorrh 1970;23:449–454.
Girolami A, Simioni P, Scarano L, Girolami B, Zerbinati P. Symptomatic combined homozygous FXII deficiency and haterozygous factor V Leiden. J Thromb Thrombolysis 2000;9:271–275.
Girolami A, Patrassi G, De Marco L, Cappellato G, Lack of FXII antigen in FXII deficiency as determined by electroimmunoassy. Blut 1982;45:141–142.
Bigg R, Sharp AA, Morgolis J. Defects in the early stages of blood coagulation: A report of four cases. Brit J Haemat 1958;4:77–81.
Bonnar J, Prantice CRM, Mc Nicol GP, Douglas AS. Haemostatic mechanism in the uterine circulation during placental separation. Bri Med J 1970;2:564–568.
Didislein P. Hageman factor deficiency (Hageman trait).Arch Int Med 1962;110:170–174.
Lao TT, Lewinsky RM, Ohlsson A, Cohen H. Factor XII deficiency and pregnancy. Obstet Gynecol 1991;78:491–493.
Goodnough LT, Saito H, Ratnoff OD. Thrombosis or myocardial infarction in congenital clotting factor abnormalities and chronic thrombocytopenias: A report ao 21 patients and a review of 50 previously reported cases. Medicine 1983;62:248–255.
Gordon EM, Ratnoff OD, Saito H, Donaldson VH, Pensky J, Jones PK. Rapid fibrinolysis, augmented Hageman factor (Factor XII)titers, decreased C, esterase inhibitor titers in women taking oral contraceptives. J Lab Clin Med 1980;96:767–769.
Schved JF, Gris JC, Neven S, Mares P, Sarlat C. Variations of factor XII during pregnancy in a woman with Hageman factor deficiency. Thrombosis Haemostasis 1998;60:526–527.
Saidi P, Siegelman M, Mitchel VB. Effect of Factor XII deficiency on pregnancy and parturition. Thromb Haemost 41:523–528.
Yameda H, Kato EH, Ebina Y, Kishida T, Hoshi N, Kobashi G, Sakuragi N, Fujimoto, S. Factor XII deficiency in women with recurrent abortion. Gynecol Ostet Invest 2000;49:80–83.
Pauer HO, Burfeind P, Kostering H, Emons G, Hinney B. Factor XII deficiency in strongly associated with primary recurrent abortions. Fert steril 2003;80:590–594.
Matsuura T, Kobajashi T, Asahina T, Kanayama N, Terao T. Is factor XII deficiency related to recurrent miscarrige? Sem. Thromb Hemost 2001;27:115–120.
Egeberg O. New families with FXII deficiency. Thromb Diath Haemorr 1970;23:441-448.
Mangal AK, Naiman SC. Hageman factor deficiency and oral contraceptives. Lancet 1980;1:774.
Rees DC, Cox M, Cleeg JB. World distribution of factor V Leiden. Lancet 33) Rosendaal FR, Doggen CJ, Zivelin A, Arruda VR, Aiach M, Siscovick DS. Geographic distibution of the 20210 Gto A prothrombin variant. Thromb Haemost 1998;79:706–708.
Girolami A, Ruzzon E, Lombardi AM, Cabrio L, Randi ML. Thrombosis-free surgical procedures in severe (homozygote) factor XII deficiency: A report of four additional cases and review of the literature. Clin Appl Thromb Haemost (In press).
Rodeghiero F, Castaman G, Ruggeri M, Cazzavillan M, Ferracin G, Dini E. Fibrinolytic studies in 13 unselected families with FXII deficiency. Fibrinolisys 1991;76:28–32.
Haanen C, Hommes F, Benraad H, Morseet G. A case of Hageman-factor deficiency and a method to purify the factor. Thromb Diath Haemorrh 1961;5:2001–2005.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Girolami, A., Zocca, N., Girolami, B. et al. Pregnancies and Oral Contraceptive Therapy in Severe (Homozygons) FXII Deficiency: A Study in 12 Patients and Review of the Literature. J Thromb Thrombolysis 18, 209–212 (2004). https://doi.org/10.1007/s11239-005-0348-3
Issue Date:
DOI: https://doi.org/10.1007/s11239-005-0348-3