Heterotoxicity of Human Serum V.

Abstract

Intravenous injections of fresh human serum (FHS) with an operative alternative complement pathway (ACP) were toxic for mice. The toxic reaction was manifested by intravascular hemolysis, hemoglobinuria, and a slight prolongation in the mean activated thromboplastin time, prothrombin time and thrombin time. In moribund animals, this was followed by a profound thrombocytopenia and alterations in the leukocyte counts. Marked to slight leukopenia developed in animals dying relatively quickly, while leukocytosis was observed infrequently in animals dying after a protracted shock, and only in concurrence with hemoconcentration and thrombocytopenia. Although the latter sequence of events was not investigated extensively, it may have led to intravascular coagulation. During the acute phase of the reactions, the deposition of platelets mainly in the lungs, and erythrocytes mainly in the liver, was demonstrated by accumulation of radioactive labelling of platelets and erythrocytes, respectively. Histologic sections of the lung revealed hemorrhagic lesions and the accumulation of ‘platelet-like’ thrombi in the pulmonary vessels. The blood films of animals injected with active serum showed erythrocytes ghosts, but no hemagglutination or distinctive microangiopathic changes. The fatal consequence of serum injections could not be prevented by the administration of cortisone, histamine and serotonin antagonists, anticoagulants, or by <i>β</i>-adrenergic blockade. The injections of homologous erythrocytes lysed by human serum, but not of sonicated red cell, produced histopathologic lesions suggestive of disseminated intravascular coagulation (DIC) or thrombotic thrombocytopenic purpura (TTP) in the lungs. It is suggested that the interaction of complement and the coagulation system might induce the development of syndromes characterized by DIC or TTP, or thrombotic phenomena in other conditions.