THE NATURE AND MECHANISM OF THE HEMOSTATIC BREAKDOWN IN THE COURSE OF EXPERIMENTAL HEMORRHAGIC SHOCK*

Abstract

In 45 New Zealand rabbits significant changes in many clotting factors and in the overall blood-clotting mechanisms followed the removal of blood (40 ml kg body weight) rapid enough to induce reversible shock. The phemomena observed were divided in 3 major phases. During and in the 1st half hour following hemorrhage (early phase) the plasma fibrinogen level, the serum complement titer, and the labile factor (factor V) activity dropped rapidly. On the other hand, the number of platelets doubled and the speed of formation and the total yield of plasma thromboplastin were increased. The latter finding was apparently due to the development of a potent accelerator of clotting, since the addition of serum from the animal in shock to a system in vitro containing normal platelets and normal plasma resulted in a much more rapid formation and increased yield of plasma thromboplastin than when normal serum was used. Also an experiment in vivo was devised in which normal rabbits received homologous thrombin-free serum from 50 ml of blood. Only minor acceleration in the formation of plasma thromboplastin followed when the serum was from normal animals. The injection of serum from animals in hemorrhagic shock induced more rapid and complete formation of thromboplastin. As the shock deepened, even after arrest of bleeding and for as long as 12-24 hours afterwards, different findings developed (late phase). While the fibrinogen level continued to drop, platelets also became drastically reduced and the formation of thromboplastin was slow and incomplete. This phase was followed by a period of recovery of 2-3 days* duration, during which all factors returned to normal. Histologic sections taken between the 3d and the 72d hour showed deposition of material with the morphological and staining properties of fibrin into some of the venous vessels of the lungs, kidney and liver. Analytical study of the fibrinolytic system suggested activation in vivo in the early phase because of considerable increase in the titer of antifibrinolysin and sharp decrease in the activity of the profibrinolysin possibly consumed in vivo. In the later phase, on the other hand, the serum profibrinolytic activity rose and that of antifibrinolysin decreased, suggesting a return of the fibrinolytic mechanism to normal. Splenectomy within 3 weeks before hemorrhagic shock prevented most of the changes described or reduced their severity. No clot accelerator developed in the splenectomized animals during the early phases of shock. Thus, significant intravascular clotting occurs in the early phase of hemorrhagic shock. This statement is based on the findings of accelerated formation of thromboplastin because of the development of a clotting accelerator agent, appearance of thrombocytopenia, intravascular deposition of fibrin demonstrable by histologic technics, and activation of the fibrinolytic mechanism. Since changes were minor in splenectomized animals, the splenic contraction which accompanies severe hemorrhage may initiate intravascular clotting through the emission into the blood-stream of tissular thromboplastin or of thromboplastic material from the platelets lysed within the splenic sinusoids.