Thrombosis from a prothrombin mutation conveying antithrombin resistance.
N Engl J Med
; 366(25): 2390-6, 2012 Jun 21.
Article
in En
| MEDLINE
| ID: mdl-22716977
ABSTRACT
We identified a novel mechanism of hereditary thrombosis associated with antithrombin resistance, with a substitution of arginine for leucine at position 596 (p.Arg596Leu) in the gene encoding prothrombin (called prothrombin Yukuhashi). The mutant prothrombin had moderately lower activity than wild-type prothrombin in clotting assays, but the formation of thrombin-antithrombin complex was substantially impaired. A thrombin-generation assay revealed that the peak activity of the mutant prothrombin was fairly low, but its inactivation was extremely slow in reconstituted plasma. The Leu596 substitution caused a gain-of-function mutation in the prothrombin gene, resulting in resistance to antithrombin and susceptibility to thrombosis.
Full text:
1
Database:
MEDLINE
Main subject:
Prothrombin
/
Point Mutation
/
Venous Thrombosis
/
Antithrombin Proteins
Type of study:
Prognostic_studies
Limits:
Adolescent
/
Female
/
Humans
/
Male
Language:
En
Year:
2012
Type:
Article