Summary
Dyslipoproteinemia involving low levels of high density lipoprotein (HDL) is linked
to venous thrombosis in young male adults and to recurrence of venous thrombosis in
patients who have experienced a previous unprovoked venous thrombosis episode. Plasma
cholesteryl ester transfer protein (CETP) modulates HDL metabolism and some lipoproteins
can affect blood coagulation reactions with either procoagulant or anticoagulant effects.
Hence, we evaluated relationships between the mass of CETP and blood coagulability
in plasma samples from 39 normal healthy adults. For clotting initiated by dilute
tissue factor or factor XIa,clotting times significantly correlated with CETP antigen
levels. Thus,coagulation initiated by either the extrinsic or intrinsic coagulation
pathway is positively correlated with CETP plasma levels. When added to plasma, a
recombinant CETP preparation dose-dependently shortened factor Xa-1-stage clotting
times, showing that it augmented procoagulant activity in plasma. In reaction mixtures
containing purified factors Xa and Va and prothrombin, the recombinant CETP preparation
dose-dependently increased prothrombin activation, suggesting it specifically enhances
prothrombinase activity. Thus, our data highlight a previously unknown positive relationship
between CETP plasma levels and blood coagulability that might relate to risks for
thrombotic events.
Keywords
CETP - coagulation factors - thrombosis - HDL