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Autoantibody against prothrombin aberrantly alters the proenzyme to facilitate formation of a complex with its physiological inhibitor antithrombin III without thrombin conversion.
- Source :
-
Blood [Blood] 2001 Jun 15; Vol. 97 (12), pp. 3783-9. - Publication Year :
- 2001
-
Abstract
- Acquired coagulation factor inhibitors include pathologic immunoglobulins that specifically bind to coagulation factors and either neutralize their procoagulant activity, accelerate their clearance from the circulation, or have proteolytic activity to degrade them into inactive polypeptides. Here, an autoantibody against prothrombin is described in a patient with serious hemorrhagic diatheses. The autoantibody exerts its influence by a previously unknown mechanism in which it inhibits coagulation through aberrant activation of the proenzyme in a catalytic manner. The antibody-bound prothrombin formed a stable stoichiometric complex with antithrombin III, consisting of intact prothrombin and an antithrombin III molecule cleaved at the (393)Arg-(394)Ser bond. The antibody dissociated from prothrombin after the complex formation with antithrombin III. Although the bound antibody elicited protease activity from prothrombin, the complex was not able to convert fibrinogen to fibrin or to activate protein C. Thus, this is the first description of an autoantibody that induces protease-like activity from a human proenzyme, permitting subsequent neutralization by its physiological inhibitor. (Blood. 2001;97:3783-3789)
- Subjects :
- Amino Acid Sequence
Autoantibodies pharmacology
Blood Coagulation Disorders immunology
Enzyme Activation drug effects
Epitopes analysis
Fibrinogen metabolism
Hematoma immunology
Humans
Kinetics
Male
Middle Aged
Protein Binding
Prothrombin metabolism
Retroperitoneal Space pathology
Serine Endopeptidases metabolism
Antithrombin III metabolism
Autoantibodies blood
Blood Coagulation Disorders etiology
Prothrombin immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0006-4971
- Volume :
- 97
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 11389017
- Full Text :
- https://doi.org/10.1182/blood.v97.12.3783