ON THE ROLE OF PHOSPHATIDYLETHANOLAMINE IN THE INHIBITION OF ACTIVATED PROTEIN-C ACTIVITY BY ANTIPHOSPHOLIPID ANTIBODIES

Phosphatidylethanolamine (PE) is an important membrane component for s upporting activated protein C anticoagulant activity but has little in fluence on prothrombin activation. This difference constitutes a poten tial mechanism for selective inhibition of the protein C anticoagulant pathway by lupus anticoagulants and/or antiphospholipid antibodies. I n this study, we demonstrate that the presence of PE augments lupus an ticoagulant activity, In the plasma of some patients with lupus antico agulants, activated protein C anticoagulant activity is more potently inhibited than prothrombin activation. As a result, in the presence of activated protein C and PE, these patient plasmas clot faster than no rmal plasma, Patients with minimal lupus anticoagulant activity are id entified whose plasma potently inhibits activated protein C anticoagul ant activity. This process is also PE dependent. In three patient plas mas, these phenomena are shown to be due to immunoglobulins. The PE re quirement in the expression of activated protein C anticoagulant activ ity and the PE dependence of some antiphospholipid antibodies provide a mechanistic basis for the selective inhibition of the protein C path way. Inhibition of activated protein C function may be a common mechan ism contributing to increased thrombotic risk in certain patients with antiphospholipid antibodies.