Sera from habitual aborters induce monocyte procoagulant activity: a lymphocyte-dependent event

Placental thrombosis is a prominent feature in patients with unexplained recurrent fetal loss. To determine whether induction of monocyte procoagulant activity might be a relevant mechanism for unexplained recurrent fetal loss, peripheral blood mononuclear cells isolated from normal healthy controls were cocultured with (a) sera from normal healthy controls (n = 16), (b) sera from habitual aborters (n = 41), and (c) lipopolysaccharide as a positive control. Sera from three patients were fractionated on Sephracryl S-300 and the inducing molecule(s) characterized. Sera from normal healthy controls failed to induce procoagulant activity above basal levels of 21 +/- 4.6 mU/10(5) peripheral blood mononuclear cells. Of the sera from 41 habitual aborters examined 26 (63%) induced procoagulant to a mean value of 410 +/- 48 mU/10(5) peripheral blood mononuclear cells (P < 0.01). Sera from 15 patients failed to augment procoagulant activity. The induction of procoagulant activity was maximal after 6 hr of incubation and was lymphocyte dependent. Fractionation of serum from the three patients on Sepharcryl S300 revealed the procoagulant activity (PCA)-inducing factor(s) to have a molecular weight of between 300,000 and 800,000 Da. The serum factor was found to be heat, alkaline, and acid sensitive. Both anti-IgM and anti-IgA immunoabsorbents reduced the PCA-inducing factor. We conclude that IgM and IgA from some patients with unexplained recurrent fetal loss are capable of inducing procoagulant activity and could contribute to the development of placental microthrombi and infarction, prominent features of this syndrome.