Summary
The plasma of a 68-year-old man with cross reacting material (CRM)-positive prekallikrein
(PK) deficiency was studied. PK clotting activity was <0.01 U/ml, and PK antigen was
0.1 U/ml. No circulating anticoagulant against PK was detectable. The abnormal PK
molecule, denoted as prekallikrein Zürich, was partially characterized by immunological
and functional studies on the propositus’ plasma. Immunobiotting analysis showed the
abnormal PK being a single chain molecule of the same M
r (80 kDa) as normal PK. Dextran sulfate activation of the propositus’ plasma did not
lead to proteolytic cleavage of the variant PK molecule, in contrast to dextran sulfate
activation of a mixture of 1 volume normal plasma and 9 volumes CRM-negative PK deficient
plasma. Agarose gel electrophoresis followed by immunoblotting demonstrated that PK
Zürich was complexed with high molecular weight kininogen similarly to PK in normal
plasma. Incubation of the propositus’ plasma with purified β-FXIIa resulted in impaired
cleavage of PK Zürich when compared with PK hydrolysis in a mixture of 10% normal
plasma and 90% CRM-negative PK deficient plasma. Moreover, proteolytically cleaved
PK Zürich showed no enzymatic activity against factor XII and high molecular weight
kininogen.
These studies show that the functional defect of prekallikrein Zürich is due to an
impaired cleavage by activated factor XII and probably the lack of enzymatic activity
of the cleaved variant molecule.
