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Thromb Haemost 1990; 63(02): 215-219
DOI: 10.1055/s-0038-1645197
Original Article
Schattauer GmbH Stuttgart

Familial Variant of Antithrombin III (AT III Bligny, 47Arg to His) Associated with Protein C Deficiency

M Wolf
*   The Laboratoire d’Hématologie and INSERM U 143, Briis-sour-Forges, France
,
C Boyer-Neumann
*   The Laboratoire d’Hématologie and INSERM U 143, Briis-sour-Forges, France
,
P Molho-Sabatier
**   Hôpital de Bicêtre, Le Kremlin-Bicêtre, the Centre de Recherche Claude Bernard sur les maladies vasculaires périphériques, Briis-sous-Forges, France
,
C Neumann
***   Hopital Broussais, Paris, and the CMC de Bligny, Briis-sous-Forges, France
,
D Meyer
*   The Laboratoire d’Hématologie and INSERM U 143, Briis-sour-Forges, France
,
M J Larrieu
*   The Laboratoire d’Hématologie and INSERM U 143, Briis-sour-Forges, France
› Author Affiliations
Further Information

Publication History

Received 10 May 1989

Accepted after revision 04 December 1989

Publication Date:
24 July 2018 (online)

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Summary

The association of a variant of antithrombin III (AT III Bligny) and protein C deficiency is described in a 36-year-old patient having suffered from severe thrombotic episodes. His mother has protein C deficiency and showed a single episode of thrombophlebitis following surgery. His father, sister and daughter have the variant AT III and are asymptomatic. The abnormal AT III was characterized in plasma by the discrepancy between a normal progressive activity and a reduced heparin cofactor activity. This variant AT III was purified, separated from the normal protein by heparin-Sepharose chromatography and was eluted with increased NaCI concentrations. At pH 7.4, the variant AT III eluted at lower (0.3 to 0.5 M) NaCI concentrations than normal (1 to 1.5 M) AT III, thus demonstrating a decreased affinity for heparin. At pH 6.0, however, the abnormal molecule bound more avidly to heparin-Sepharose and was eluted like normal AT III at pH 7.4. Similarly, the heparin enhancement of intrinsic fluorescence of the variant AT III, markedly reduced at pH 7.4, was normalized at pH 6.0. The abnormal AT III showed a normal antiprotease activity, a normal molecular weight by SDS-PAGE, but displayed only a partial immunological identity with the normal protein. Analysis of amplified genomic DNA from this patient by dot-blot demonstrates a heterozygous substitution of arginine by histidine at position 47.

 

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