Summary
Inflammation often is considered a contributing factor to both thrombosis and disseminated
intravascular coagulation. The molecular mechanisms that dictate which of these clinical
manifestations will result from the inflammatory stimulus remain obscure. Bacterial
infection and certain tumors are common initiators of the disseminated intravascular
coagulant response. Complement activation resulting from bacterial infection shares
with selected tumors the capacity to generate or release membrane particles that lack
functional adhesion receptors and hence could circulate to amplify a disseminated
intravascular coagulant response. We developed a model of venous thrombosis that resulted
in localized thrombus formation without disseminated intravascular coagulation. The
model involves infusion of tumor necrosis factor, blockade of protein C and a partial
decrease in venous flow caused by ligation of the superficial femoral vein without
obstruction of the deep femoral vein. Infusion of phospholipid vesicles into this
model resulted in amplification of a localized thrombotic response into a consumptive
response.
Seven different groups of animals were studied. The first three groups established
the conditions necessary to produce deep vein thrombosis. The second four groups established
the conditions necessary to produce disseminated intravascular coagulation. The infusion
of phospholipid vesicles plus tumor necrosis factor and anti-protein C antibody resulted
in consumption of fibrinogen, the production of thrombin/antithrombin complexes, a
fall in platelet count, and venous thrombosis. Without ligation and catheterization
phospholipid vesicles failed to produce the consumptive response. We conclude, therefore,
that phospholipid vesicles can amplify a local thrombotic response into a consumptive
response, and that vesiculation accompanying inflammation is one means by which localized
coagulant activity may be amplified to produce disseminated intravascular coagulation.
