Summary
We have examined the relative contribution of stasis, activated coagulants, procoagulants
and vessel wall damage in the pathogenesis of experimental venous thrombosis. Using
a Wessler stasis model in rabbits, we found an inverse correlation between duration
of stasis and the amount of Contact Factor and Factor Xa required to produce a stasis
thrombus. However, the slope of the dose-response curve for producing thrombi was
different with these two coagulants. The infusion of Factor IX complex was also thrombogenic
in this model despite prolonged circulation prior to stasis, implying that high levels
of multiple procoagulants may be thrombogenic. In contrast, Factor VIII concentrates
or a purified Factor IX preparation did not give thrombi under these conditions.
When the vessel wall was crushed mechanically, followed by restored blood flow and
subsequent stasis, there was essentially no formation of thrombi over the time course
of the experiments. Scanning electron microscopy demonstrated that although the endothelium
was swollen and damaged, there was usually no exposure of sub-endothelium and no adherence
platelets. Where there was definite disruption of the endothelium, activated platelets
could be seen adhering to the vessel wall. However, the blood in the segments remained
fluid over a period of 30 min, despite the presence of adherent platelets.
Our experiments demonstrated that the combination of vessel wall damage and stasis
was relatively ineffective in producing venous thrombosis. In contrast, high levels
of zymogens or small amounts of activated clotting factors, combined with local stasis,
is a very effective thrombogenic stimulus in the venous system.
keywords
Experimental venous thrombosis - Factor Xa - Contact factor - IX complex - Vessel
wall
