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Thromb Haemost 1992; 68(05): 521-525
DOI: 10.1055/s-0038-1646311
Original Article
Schattauer GmbH Stuttgart

Congenital Deficiency of All Vitamin K-Dependent Blood Coagulation Factors Due to a Defective Vitamin K-Dependent Carboxylase in Devon Rex Cats

Berry A M Soute
1   The Department of Biochemistry, University of Limburg, Maastricht, The Netherlands
,
Magda M W Ulrich
1   The Department of Biochemistry, University of Limburg, Maastricht, The Netherlands
,
A David J Watson
2   The Department of Veterinary Clinical Sciences, The University of Sydney, Australia
,
Jill E Maddison
3   The Department of Pharmacology, The University of Sydney, Australia
,
Rob H M Ebberink
4   The Applied Biosystems, Maarssen, The Netherlands
,
Cees Vermeer
1   The Department of Biochemistry, University of Limburg, Maastricht, The Netherlands
› Author Affiliations
Further Information

Publication History

Received 13 April 1992

Accepted after revision 10 June 1992

Publication Date:
04 July 2018 (online)

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Summary

Two Devon Rex cats from the same litter, which had no evidence of liver disease, malabsorption of vitamin K or chronic ingestion of coumarin derivatives, were found to have plasma deficiencies of factors II, VII, IX and X. Oral treatment with vitamin K1 resulted in the normalization of these coagulation factors. After taking liver biopsies it was demonstrated that the coagulation abnormality was accompanied by a defective γ-glutamyl-carboxylase, which had a decreased affinity for both vitamin K hydroquinone and propeptide. This observation prompted us to study in a well-defined in vitro system the possible allosteric interaction between the propeptide binding site and the vitamin K hydroquinone binding site on carboxylase. It was shown that by the binding of a propeptide-containing substrate to γ-glutamylcarboxylase the apparent K M for vitamin K hydroquinone is decreased about 20-fold. On the basis of these in vitro data the observed defect in the Devon Rex cats can be fully explained.

 

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