Anti-factor V auto-antibody in the plasma and platelets of a patient with repeated gastrointestinal bleeding.
Development of autoantibody against coagulation factor V (FV) is a rare clinical condition with hemorrhagic complications of varying severity. The aim of this study was to establish the pathomechanism of an acquired FV deficiency and characterize the FV inhibitor responsible for the clinical symptoms. A 78-year-old female was admitted to hospital with severe gastrointestinal bleeding. General clotting tests and determination of clotting factors were performed by standard methods. FV antigen and FV containing immune complexes were measured by ELISA. The FV molecule was investigated by Western blotting and by sequencing the f5 gene. The binding of patient's IgG to FV and activated FV (FVa) was demonstrated in an ELISA system and its effect on the procoagulant activity of FVa was tested in clotting tests and in a chromogenic prothrombinase assay. Localization of the epitope for the antibody was performed by blocking ELISA. FV activity was severely suppressed both in plasma and platelets. FV antigen levels were normal by ELISA using polyclonal anti-FV antibody or monoclonal antibody against the connecting region of FV, but depressed when HV1 monoclonal antibody against the C2 domain in the FV light-chain was used as capture antibody. The FV molecule was found intact. An IgG reacting with both FV and FVa was present in the patient's plasma and its binding to FV was inhibited by HV1 antibody. FV-containing immune complexes were detected in the patient's plasma and platelet lysate. The patient's IgG inhibited the procoagulant function of FVa. An anti-FV IgG was present in the patient's plasma and platelets. The autoantibody reacted with an epitope in the C2 domain of FV light chain and neutralized the procoagulant function of FVa.
Ajzner
E
E
Department of Clinical Biochemistry and Molecular Pathology, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary.
Balogh
I
I
Haramura
G
G
Boda
Z
Z
Kalmár
K
K
Pfliegler
G
G
Dahlbäck
B
B
Muszbek
L
L
D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D001780:Blood Coagulation Tests; D001792:Blood Platelets / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D005165:Factor V / Q000276:immunology*; D005166:Factor V Deficiency / Q000150:complications* / Q000175:diagnosis / Q000276:immunology; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000209:etiology / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology
D001323:Autoantibodies; D000939:Epitopes; D007074:Immunoglobulin G; D005165:Factor V