Reduction of circulating annexin A5 levels and resistance to annexin A5 anticoagulant activity in women with recurrent spontaneous pregnancy losses

Objective We investigated whether levels of annexin A5, evidence for resistance to annexin A5 activity, and levels anti–annexin A5 antibodies might be altered in women with a history of recurrent spontaneous pregnancy losses. Study design These annexin A5 parameters were assayed in 70 nonpregnant women with a history of ≥3 recurrent spontaneous pregnancy losses (cases) and 50 women without adverse pregnancy history (control subjects). Results Cases had significantly lower plasma annexin A5 levels than control subjects (median, 4.7 ng/mL [range, 0.3-40.4 ng/mL] vs 6.7 ng/mL [range, 0.7-56.0]; P = .01), significantly reduced anticoagulant ratios (188% [range, 119%-279%] vs 238% [range, 159%-286%]; P< .0001), and reduced binding of annexin A5 to phospholipid (6.3 ng/aliquot phospholipid [range, 1.5-16.4 ng/aliquot phospholipid] vs 9.7 ng/aliquot phospholipid (range, 3.5-17.0 ng/aliquot phospholipid]; P = .0002). There were no significant differences in anti–annexin A5 antibody levels. Conclusion Reduction of annexin A5 and interference with its anticoagulant and binding activities are associated significantly with a history of recurrent spontaneous pregnancy losses. These data support the concept of a significant role for annexin A5 in the maintenance of pregnancy.