We have studied plasmas of 49 individuals with homozygous
Hageman trait from 42 kindreds, all of which contained less than 1% of the
Hageman factor (
factor XII) clotting activity of pooled normal plasmas. Forty-seven plasmas contained less than 1% of
Hageman factor antigen. In two other, unrelated individuals with
Hageman trait, nonfunctional material immunologically indistinguishable from normal
Hageman factor was detected in plasma by radioimmunoassay at concentrations of 39% and 80%, respectively. These plasmas did not contain
circulating anticoagulants against
Hageman factor and, as in ordinary
Hageman trait, displayed impaired surface-mediated plasma reactions such as fibrinolysis and
kinin generation. Upon immunodiffusion against anti-
Hageman factor serum, these plasmas formed a single precipitin line of complete identity with normal plasma or purified
Hageman factor. Upon immunoelectrophoresis, the precipitin line had the same mobility as normal
Hageman factor. Nonfunctional
Hageman factor and normal
Hageman factor behaved identically on a
Sephadex G-150 column (apparent MW = 100,000) and on
sucrose density-gradient centrifugation (4.5S). Nonfunctional
Hageman factor was adsorbed to
kaolin as readily as normal
Hageman factor, suggesting that the binding site to negatively charged surfaces is different from functional sites. Antiserum raised against
Hageman factor-like material in a CRM+
Hageman trait plasma specifically inactivated
Hageman factor activity in normal plasma. The plasmas of three heterozygotes in these families contained approximately twice as much
Hageman factor antigen as
Hageman factor activity, whereas those of 16 heterozygotes in ordinary (CRM-)
Hageman trait families contained approximately equal amounts of activity and
antigen. The present study indicates that rarely homozygous
Hageman trait may be CRM+ and that this defect is genetically determined.