AUTOANTIBODY RELATED DISRUPTION OF KALLIKREIN-KININSYSTEM IN RECURRENT PREGNANCY LOSS

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Antiphospholipid antibodies (aPL) have been described in patients with thrombosis, thrombocytopenia, and recurrent pregnancy loss (RPL). We recently reported that a strong association between antiphosphatidylethanolamine antibodies (aPE) and RPL (Fertil Steril, 71, 1060, 1999). We also reported that certain aPE are not specific for phosphatidylethanolamine (PE) per se but are directed to PE-binding plasma proteins, such as kininogens (Blood, 86, 3083, 1995). Coagulation factor XII, prekallikrein and high molecular weight kininogen are known as plasma contact proteins in the intrinsic pathway of blood coagulation. However, deficiencies of these proteins are not associated with clinical bleeding despite marked prolongation of in vitro surface-activated coagulation time. Paradoxically, studies suggest that these proteins have anticoagulant, profibrinolytic functions in a physiologic milieu, on endothelial cells. Recently, surprisingly high prevalences of factor XII deficiency among patien … More ts with recurrent thrombosis and RPL have been reported. Since the presence of antibodies to factor XII in patients with lupus anticoagulant has been reported, we have now tested plasma samples from RPL patients for the factor XII activity, concentration of factor XII antigen and for the presence of autoantibodies to factor XII. One hundred ninety one patients with RPL were screened for factor XII activity. We found 34 (17.8%) patients with factor XII deficiency (activity<60%). Eighteen (52.9%) of these 34 patients were positive for aPL. Our data show that RPL are associated with factor XII deficiency (p=0.0028). We hypothesized that factor XII deficiency may be partly due to presence of antibodies to factor XII and tested plasma samples from patients with factor XII deficiency for the presence of antibodies to factor XII by immunoblot and biomolecular interaction analysis. We found that factor XII antibodies were present in a significant proportion of factor XII deficient patients with RPL. Less