Heparin and pregnancy in women with a history of repeated miscarriages

Many patients who experience recurrent spontaneous abortions (RSA) have high titered antibodies to trophoblast antigens and/or negatively charged phospholipids. Pregnancy success has been documented in some of these patients subsequent to heparin treatment. The effect of heparin on in vitro assays used to detect antibodies to phospholipids and trophoblast antigens has been investigated. We have found that complement-mediated detection of antibodies to trophoblast and lymphocyte antigens is inhibited by absorption of sera with solid-phase heparin. The data show that such inhibition involves an inhibitor and a heparin-sensitive regulator of the inhibitor. Heparin inhibits binding of antiphospholipid antibodies to phospholipids in solid-phase ELISA. The mechanism for this inhibition appears to involve an interaction between heparin and antibody to phospholipid. These findings reveal novel heparin-mediated reactions that bridge immunological and hematological interactions. The extent of heparin modulation of these antibody reactivities should be clarified in future clinical trials involving heparin treatment for RSA.