On the role of phosphatidylethanolamine in the inhibition of activated protein C activity by antiphospholipid antibodies.
Phosphatidylethanolamine (PE) is an important membrane component for supporting activated protein C anticoagulant activity but has little influence on prothrombin activation. This difference constitutes a potential mechanism for selective inhibition of the protein C anticoagulant pathway by lupus anticoagulants and/or antiphospholipid antibodies. In this study, we demonstrate that the presence of PE augments lupus anticoagulant activity. In the plasma of some patients with lupus anticoagulants, 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 normal plasma. Patients with minimal lupus anticoagulant activity are identified whose plasma potently inhibits activated protein C anticoagulant activity. This process is also PE dependent. In three patient plasmas, these phenomena are shown to be due to immunoglobulins. The PE requirement in the expression of activated protein C anticoagulant activity and the PE dependence of some antiphospholipid antibodies provide a mechanistic basis for the selective inhibition of the protein C pathway. Inhibition of activated protein C function may be a common mechanism contributing to increased thrombotic risk in certain patients with antiphospholipid antibodies.
Smirnov
M D
MD
Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City 73104.
Triplett
D T
DT
Comp
P C
PC
Esmon
N L
NL
Esmon
C T
CT
D000925:Anticoagulants / Q000378:metabolism*; D001323:Autoantibodies / Q000276:immunology*; D001777:Blood Coagulation / Q000502:physiology; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D010714:Phosphatidylethanolamines / Q000276:immunology*; D010743:Phospholipids / Q000276:immunology*; D011486:Protein C / Q000378:metabolism*
D000925:Anticoagulants; D001323:Autoantibodies; D010714:Phosphatidylethanolamines; D010743:Phospholipids; D011486:Protein C