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Thromb Haemost 1990; 63(03): 375-379
DOI: 10.1055/s-0038-1645050
Original Article
Schattauer GmbH Stuttgart

Hereditary Dysfunctional Protein C Molecules (Type II): Assay Characterization and Proposed Classification

Richard A Marlar
The Laboratory Service, Denver Veteran’s Administration Medical Center, Denver, Colorado, USA and the Department of Pathology, Department of Biochemistry, Biophysics and Genetics, Department of Pediatrics, University of Colorado Health Sciences Center, Denver, Colorado, USA
,
Dorothy M Adcock
The Laboratory Service, Denver Veteran’s Administration Medical Center, Denver, Colorado, USA and the Department of Pathology, Department of Biochemistry, Biophysics and Genetics, Department of Pediatrics, University of Colorado Health Sciences Center, Denver, Colorado, USA
,
Renée M Madden
The Laboratory Service, Denver Veteran’s Administration Medical Center, Denver, Colorado, USA and the Department of Pathology, Department of Biochemistry, Biophysics and Genetics, Department of Pediatrics, University of Colorado Health Sciences Center, Denver, Colorado, USA
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Publikationsverlauf

Received 31. Oktober 1989

Accepted after revision 09. Februar 1990

Publikationsdatum:
30. Juni 2018 (online)

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Summary

Protein C (PC) deficiency is among the increasing number of recognized causes of hereditary thrombotic disease. Two types of PC deficiency have been described: 1) Type I, which is characterized by a concomitant decrease in PC activity and antigen, and 2) Type II. characterized by disproportionately low activity compared to antigen (i.e. a dysfunctional molecule). To date, only a small number of Type II patients have been described. This study was undertaken to evaluate a number of dysfunctional PC molecules by comparing PC clotting and amidolytic activities with antigen levels. For these studies, an automated PTT-based clotting PC assay was developed. This assay was sensitive to 1% of a normal plasma pool, specific, accurate, and reproducible (± 12%). A good correlation (r = 0.918) of the clotting activity to antigen was found in normal individuals and Type I heterozygous and homozygous patients. To classify Type II PC deficient patients, the antigen, amidolytic and clotting PC levels were compared in ten affected families. The clotting activities were decreased in all affected members, whereas the antigen levels were within the normal limits. In four of the 10 families, the amidolytic activity was normal and similar to the antigen levels. This suggests that in certain families, defects in the PC molecule occur in regions not associated with amidolytic functions. From these studies, the molecular basis of Type II PC deficiency is varied and complex, involving different functional domains of the PC molecule. Therefore, we have suggested a nomenclature algorithm for Type II PC deficiency based on the location of the defect within the specific domains of the PC molecule.

 

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