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Blood, Vol. 92 No. 5 (September 1), 1998:
pp. 1652-1660
Antiphospholipid Antibodies Accelerate Plasma Coagulation by
Inhibiting Annexin-V Binding to Phospholipids: A "Lupus
Procoagulant" Phenomenon
Jacob H. Rand,
Xiao-Xuan Wu,
Harry A.M. Andree,
J.B. Alexander Ross,
Elena Rusinova,
Mayra G. Gascon-Lema,
Cesare Calandri, and
Peter C. Harpel
From the Department of Medicine, the Divisions of Hematology and
Thrombosis, and the Department of Biochemistry, Mount Sinai School of
Medicine, New York, NY.
The antiphospholipid syndrome is a thrombophilic condition marked by
antibodies that recognize anionic phospholipid-protein cofactor
complexes. We recently reported that exposure to IgG fractions from
antiphospholipid patients reduces the level of annexin-V, a
phospholipid-binding anticoagulant protein, on cultured trophoblasts
and endothelial cells and accelerates coagulation of plasma exposed to
these cells. Therefore, we asked whether antiphospholipid antibodies
might directly reduce annexin-V binding to noncellular phospholipid
substrates. Using ellipsometry, we found that antiphospholipid IgGs
reduce the quantity of annexin-V bound to phospholipid bilayers; this
reduction is dependent on the presence of  2-glycoprotein
I. Also, exposure to plasmas containing antiphospholipid antibodies
reduces annexin-V binding to phosphatidyl serine-coated microtiter
plates, frozen thawed washed platelets, activated partial
thromboplastin time (aPTT) reagent and prothrombin time reagent and
reduces the anticoagulant effect of the protein. These studies show
that antiphospholipid antibodies interfere with the binding of
annexin-V to anionic phospholipid and with its anticoagulant activity.
This acceleration of coagulation, due to reduced binding of annexin V,
stands in marked contrast to the "lupus anticoagulant effect"
previously described in these patients. These results are the first
direct demonstration of the displacement of annexin-V and the
consequent acceleration of coagulation on noncellular phospholipid
surfaces by antiphospholipid antibodies.
© 1998 by The American Society of Hematology.
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