A Novel Sensitive Assay for Functional Factor XII Based on the Generation of Kallikrein-C1-lnhibitor Complexes in Factor Xll-Deficient Plasma by Glass-Bound Factor XII

D M Dors; J H Nuijens; C C M Huijbregts; C E Hack

doi:10.1055/s-0038-1648516

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1992; 67(06): 644-648
DOI: 10.1055/s-0038-1648516

Original Articles

Schattauer GmbH Stuttgart

A Novel Sensitive Assay for Functional Factor XII Based on the Generation of Kallikrein-C1-lnhibitor Complexes in Factor Xll-Deficient Plasma by Glass-Bound Factor XII

Authors

D M Dors

The Central Laboratory of the Netherlands Red Cross Blood Transfusion Service and Laboratory for Experimental and Clinical Immunology, University of Amsterdam, Amsterdam, The Netherlands
J H Nuijens

The Central Laboratory of the Netherlands Red Cross Blood Transfusion Service and Laboratory for Experimental and Clinical Immunology, University of Amsterdam, Amsterdam, The Netherlands
C C M Huijbregts

The Central Laboratory of the Netherlands Red Cross Blood Transfusion Service and Laboratory for Experimental and Clinical Immunology, University of Amsterdam, Amsterdam, The Netherlands
C E Hack

The Central Laboratory of the Netherlands Red Cross Blood Transfusion Service and Laboratory for Experimental and Clinical Immunology, University of Amsterdam, Amsterdam, The Netherlands

Abstract

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Summary

We developed a very sensitive assay for functional factor XII. This assay is based on the property of glass-bound factor XII to activate prekallikrein (PK) into kallikrein in factor XH-deficient plasma, which is assessed by measuring the formation of kallikrein- C1 -inhibitor complexes in this plasma by radioimmunoassay.

Incubation of varying amounts of factor XII in glass tubes led to a dose-dependent increase in kallikrein-C1-inhibitor complexes in factor XH-deficient plasma with a lower limit of detection of ± 20 pg of factor XII. The specificity of the assay for factor XII was demonstrated by experiments with plasmas deficient for factor XII, PK or high molecular weight kininogen (HK) and by incubation of factor XII with Polybrene or with a monoclonal antibody that inhibits the amidolytic and procoagulant activity of factor XII. The high sensitivity of the assay appeared to be due to the inability of Cl-inhibitor to inhibit factor XII bound to glass, which resulted in a molar ratio of generated kallikrein to glass-bound factor XII of at least 100:1.

This assay for factor XII may be a feasible tool in studies on structural and functional aspects of (recombinant) factor XII species synthesized by cultured cells.

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References

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