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

Abstract

SummaryFactor 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-FHX), none of the FXII deficient subjects were among those with positive TE-FHX.

Age-associated developmental changes in the activated partial thromboplastin time (APTT) and causes of prolonged APTT values in healthy Chinese children

“…Low factor XII is a common finding in otherwise normal individuals (28,36,38). This finding accounted for nearly half (7/16) of the prolonged APTT values seen in a healthy Austrian population (38). Plasma factor XII activity concentrations in Orientals are lower than those seen in Caucasians due to higher allele frequency of frequently occurring C--)T polymorphism in the factor XII promoter region at nucleotide (nt) 46 (25)(26)(27).…”

“…Decreased levels of FXII:C and FIX:C in children in this study are consistent with the results of Monagle et al (4), Andrew et al (6) and Gallistl et al (31). Low factor XII is a common finding in otherwise normal individuals (28,36,38). This finding accounted for nearly half (7/16) of the prolonged APTT values seen in a healthy Austrian population (38).…”

Subdural Hematoma in a Patient With Hageman Trait-Case Report-

“…8) In most cases, the deficiency is partial (due to heterozygous FXII gene defect) with FXII activities ranging from 25% to 50%, accounting for a mild APTT prolongation of 5-20% of the normal value. Severe (due to homozygous FXII gene defect) FXII deficiency, with FXII activity less than 1% and APTT prolongation of more than 120 sec, is detected only occasionally.…”

“…25) Hageman trait is an extremely rare disorder of blood coagulation transmitted in an autosomal recessive mode, usually with an asymptomatic course. 3,8,26,31) We treated a patient with severe FXII deficiency who presented with a subdural hematoma.…”

“…3,16,17,23) Congenital coagulation factor deficiencies of the contact system are extremely rare. 7,8) Such deficiencies manifest as significantly prolonged activated partial thromboplastin time (APTT) and normal prothrombin time in screening tests for coagulation. Congenital FXII deficiency was first described in 1955, and has since been known as Hageman trait, after the first patient identified with this deficiency.…”