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Inhibitory Anti-Factor V Antibodies Bind to the Factor V C2
Domain and Are Associated With Hemorrhagic Manifestations
Thomas L. Ortel,
Karen D. Moore,
Mary Ann Quinn-Allen,
Takashi Okamura,
Allen J. Sinclair,
John Lazarchick,
Ramaswamy Govindan,
Françoise Carmagnol, and
William H. Kane
From the Departments of Medicine and Pathology, Duke University
Medical Center, Durham, NC; the First Department of Internal Medicine,
Kyushu University, Fukuoka 812, Japan; Twin Falls Clinic and Hospital,
Twin Falls, ID; the Department of Laboratory Medicine, Medical
University of South Carolina, Charleston; the Department of Internal
Medicine, Cook County Hospital, Chicago, IL; and the Laboratoire de
biologie, Cannes, France.
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.
Blood, Vol. 91 No. 11 (June 1), 1998:
pp. 4188-4196
© 1998 by The American Society of Hematology.
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