Granulocyte thromboplastin as a mechanism of thrombosis in venous stasis

Human and dog granulocytes are both capable of producing thromboplastin when incubated in vitro. Granulocytes are also a prominent component of thrombi. Venous stasis in dogs causes massive sticking of granulocytes and an endothelial lesion (Stewart, et al, 1974). The present study was undertaken to investigate whether transient venous stasis would produce an accumulation of granulocytes producing thromboplastin. Conditioned dogs weighing between 10 and 15 kg were anesthetized and respired by a respirator and endotracheal tube. Jugular and femoral veins were dissected free and their side tributaries ligated and cut. Experimental veins were occluded by gentle digital pressure for 30 sec. The contralateral vein in the same dog was not occluded and served as a control. The skin incision was closed and normal flow allowed for 5 hr. The vein segment was then perfused with Tyrode's solution and opened. There was no visible accumulation on the endothelial surface. The surface was scraped with a spatula and the scrapings tested for clotting activity on recalcified dog plasma. Normal plasma clotted in 84 sec. Scrapings from experimental veins caused clotting in 35 to 54 sec. Scrapings from control veins prolonged clotting to 120 to 150 sec. Microscopic sections of the clots revealed many granulocytes. Sections of unscraped experimental veins showed massive granulocyte sticking absent from control with an occasional thrombus consisting mostly of granulocytes. It is concluded that venous stasis produces sticking of granulocytes to the vein wall. These granulocytes then produce thromboplastin which may be an intermediary mechanism of thrombosis in man.