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Previous Volume 337:154-160 July 17, 1997 Number 3 Next

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ABSTRACT

Background The mechanisms of vascular thrombosis and pregnancy loss in the antiphospholipid-antibody syndrome are unknown. Levels of annexin V, a phospholipid-binding protein with potent anticoagulant activity, are markedly reduced on placental villi from women with this syndrome. Hypercoagulability in such women may therefore be due to the reduction of surface-bound annexin V by antiphospholipid antibodies. To test this idea, we studied how antiphospholipid antibodies affect levels of annexin V on cultured trophoblasts and human umbilical-vein endothelial cells and how they affect the procoagulant activity of these cells.

Methods We isolated IgG fractions from three patients with the antiphospholipid-antibody syndrome and from normal controls. These antibodies were incubated with cultured BeWo cells (a placental-trophoblast cell line), primary cultured trophoblasts, and human umbilical-vein endothelial cells. Annexin V on the cell surfaces was measured by an enzyme-linked immunosorbent assay. The coagulation times of plasma overlaid on the cells were also determined.

Results Trophoblasts and endothelial cells exposed to antiphospholipid-antibody IgG as compared with control IgG had reduced levels of annexin V (trophoblasts, 0.37±0.02 vs. 0.85±0.12 ng per well, P = 0.02; endothelial cells, 1.6±0.04 vs. 2.1±0.05 ng per well, P = 0.001). Also, trophoblasts and endothelial cells exposed to antiphospholipid-antibody IgG had faster mean (±SE) plasma coagulation times than cells exposed to control IgG (trophoblasts, 8.7±2.0 vs. 21.3±2.9 minutes, P = 0.02; endothelial cells, 9.8±0.8 vs. 14.2±1.2 minutes, P = 0.04).

Conclusions Antiphospholipid antibodies reduce the levels of annexin V and accelerate the coagulation of plasma on cultured trophoblasts and endothelial cells. The reduction of annexin V levels on vascular cells may be an important mechanism of thrombosis and pregnancy loss in the antiphospholipid-antibody syndrome.

Source Information

From the Department of Medicine, Divisions of Hematology (J.H.R., X.-X.W., P.C.H.) and Thrombosis (H.A.M.A.), and the Department of Obstetrics, Gynecology, and Reproductive Science (J.S.), Mount Sinai School of Medicine; and the Department of Obstetrics and Gynecology (C.J.L., S.G.) New York University School of Medicine — all in New York.

Address reprint requests to Dr. Rand at the Hematology Division, Mount Sinai Medical Center, Box 1079, 5 E. 98th St., New York, NY 10029.

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Antiphospholipid Antibodies, Annexin V, and Pregnancy Loss
Rote N. S., Cheng H.-M., Rand J. H., Harpel P., Lockwood C.
Extract | Full Text  
N Engl J Med 1997; 337:1630-1631, Nov 27, 1997. Correspondence

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