Inhibitory anti-factor V antibodies bind to the factor V C2 domain and are associated with hemorrhagic manifestations.
Factor V inhibitors may develop as spontaneous autoantibodies, as alloantibodies after exposure to bovine thrombin preparations, or in factor V-deficient patients after plasma therapy. Clinical manifestations range from asymptomatic laboratory abnormalities to life-threatening hemorrhage. We have characterized the anti-factor V antibodies from 12 patients diagnosed with factor V inhibitors. In 8 patients, hemorrhagic complications (5 autoantibodies and 3 bovine thrombin-induced alloantibodies) developed, and 4 were asymptomatic (2 autoantibodies and 2 alloantibodies). The IgG fractions from all 12 patients immunoprecipitated the factor Va light chain, but only the 8 IgG fractions associated with hemorrhage inhibited factor V activity in a prothrombinase assay. Nine IgG fractions, including the 8 patients with hemorrhage, immunoprecipitated the isolated second C-type domain (C2). The 8 IgG fractions from the symptomatic patients also immunoprecipitated recombinant chimeras containing only the N-terminal third of the factor V C2 domain, and isolated recombinant C2 domain abrogated the inhibitory effect of the antibodies. Five of the inhibitory IgG fractions blocked binding of factor V to phosphatidylserine. These results suggest that inhibitory anti-factor V antibodies are associated with hemorrhagic manifestations and frequently bind to a common region within the C2 domain, whether originating spontaneously or after exposure to bovine thrombin.
Ortel
T L
TL
Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Moore
K D
KD
Quinn-Allen
M A
MA
Okamura
T
T
Sinclair
A J
AJ
Lazarchick
J
J
Govindan
R
R
Carmagnol
F
F
Kane
W H
WH
D000293:Adolescent; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D002417:Cattle; D002648:Child; D002675:Child, Preschool; D003429:Cross Reactions; D018604:Epitope Mapping; D005165:Factor V / Q000276:immunology* / Q000378:metabolism; D005169:Factor VIII / Q000276:immunology / Q000378:metabolism; D005260:Female; D006474:Hemorrhagic Disorders / Q000276:immunology*; D006801:Humans; D007518:Isoantibodies / Q000276:immunology; D008297:Male; D008875:Middle Aged; D013917:Thrombin / Q000494:pharmacology
D001323:Autoantibodies; D007518:Isoantibodies; C035876:factor V clotting antigen; D005165:Factor V; D005169:Factor VIII; D013917:Thrombin