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Isolation and characterization of an acquired antithrombin antibody
JH Lawson, BJ Pennell, JD Olson and KG Mann
Department of Biochemistry, University of Vermont, College of Medicine,
Burlington.
A 68-year-old man, following mitral valve replacement, presented with a
low-grade chronic consumptive coagulopathy. Laboratory analysis showed mild
fibrinolysis, minimal effect of coumadin therapy, and a prolonged thrombin
time (greater than 150 seconds using bovine IIa). When purified human IIa
was used the thrombin time normalized to within 17 seconds of controls,
suggesting a possible inhibitor of bovine IIa. An anti-IIa antibody was
isolated by protein A-Sepharose (Sigma, St Louis, MO) chromatography
followed by affinity chromatography using a bovine IIa-Sepharose column.
The effects of this purified anti-IIa antibody on both bovine and human IIa
procoagulant and anticoagulant functions were studied. The isolated
immunoglobulin G (IgG) was observed to inhibit bovine IIa in all assays
tested. This IgG was also able to slightly prolong fibrinogen clotting by
human IIa. Using an enzyme-linked immunosorbent assay it was observed that
the IgG bound to bovine IIa, bovine II, human IIa, but not to human II.
Further, binding was detectable at approximately 50-fold lower
concentrations to bovine IIa (1 nmol/L IgG concentration) than to human IIa
(50 nmol/L IgG concentration). The effect of the antibody on the reaction
between IIa and AT III/heparin was investigated. Human IIa was found to be
protected from AT III/heparin neutralization in the presence of this
antibody. These results suggest that this patient developed an antibody
that strongly binds to and inhibits the bovine IIa in all assays tested.
However, the antibody only significantly affects human IIa neutralization
by AT III/heparin, and has little effect on the human IIa procoagulant
activity. These data suggest that the decreased effect of AT III/heparin on
this patient's IIa may have been a contributing factor in his coagulopathy.
The exact cause of this antibody development is unclear, but the role of
bovine topical thrombin used during cardiac valve replacement surgery is
suspect.
Volume 76,
Issue 11,
pp. 2249-2257,
12/01/1990
Copyright © 1990 by The American Society of Hematology
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