PREGNANCY LOSS IN THE ANTIPHOSPHOLIPID-ANTIBODY SYNDROME - A POSSIBLETHROMBOGENIC MECHANISM

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 reducti on 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 endotheli al cells and how they affect the procoagulant activity of these cells. Methods We isolated IgG fractions from three patients with the antiph ospholipid-antibody syndrome and from normal controls. These antibodie s were incubated with cultured BeWo cells (a placental-trophoblast cel l line), primary cultured trophoblasts, and human umbilical-vein endot helial 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 endothelia l cells exposed to antiphospholipid-antibody IgG as compared with cont rol 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 cel ls exposed to antiphospholipid-antibody IgG had faster mean (+/-SE) pl asma 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 antib odies 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 syndro me. (C)1997, Massachusetts Medical Society.