Kininogen-dependent antiphosphatidylethanolamine antibodies and autoantibodies to factor XII in patients with recurrent pregnancy losses.

Factor XII, plasma prekallikrein and high-molecular-weight kininogen were first identified as coagulation proteins in the intrinsic pathway because patients deficient in these proteins had marked prolongation of in vitro surface-activated coagulation time. However, deficiencies of these proteins are not associated with clinical bleeding. Paradoxically, studies suggest that these proteins have anticoagulant and profibrinolytic activities. In fact, association between deficiencies of these proteins and thrombosis has been reported. Recently, autoantibodies to these proteins and antiphospholipid antibodies are frequent coagulation-related abnormalities found in unexplained recurrent aborters. Evidence has accumulated for the presence of the kallikrein-kininogen-kinin system in the fetoplacental unit. The contact system, or kallikrein-kininogen-kinin system, in the reproductive tract plays an essential roll in the regulation of thrombosis, hemostasis, angiogenesis and in the defense against invasive bacterial infection. Autoantibodies to these proteins may be associated with pregnancy losses due to disruption of this system. These possibilities will be reviewed, the functions of the individual components will be summarized, and their role in blood coagulation and pregnancy discussed.