Recent evidence shows that many antiphospholipid antibodies (aPL) to negatively-charged phospholipid (PL) do not target anionic PL per se, but are specific for anionic PL-binding plasma proteins, for example, β₂-glycoprotein I (β₂-GPI) and prothrombin. We also reported that certain antiphosphatidylethanolamine antibodies (aPE) are not specific for phosphatidylethanolamine (PE) per se, but are directed to PE-binding plasma proteins, high molecular weight kininogen (HK), and low molecular weight kininogen (LK). Additional studies have shown that certain aPE failed to recognize purified kininogens but continued to produce aPE ELISA reactivity in the presence of semipurified HK preparations containing the HK binding proteins, factor XI (FXI) and prekallikrein (PK). We therefore investigated if certain of these aPE recognized FXI and/or PK. In this study we observed that aPE can recognize contact proteins FXI and PK independently or in combination with HK. Since contact proteins such as HK, PK and factor XII (FXII) have anti-coagulant and profibrinolytic functions, the pathophysiological role of aPE has yet to be elucidated. We propose that aPE of different specificities may initiate or promote characteristics pathological conditions in patients with thrombosis or recurrent pregnancy losses.