Pathogenesis of Hemorrhage in Artificially Induced Fever

Abstract

Every therapeutic agent of value has its potential dangers and hyperpyrexia is no exception to this general rule. Two of the most constant pathologic findings following induced fever in experimental animals and in human subjects are hemorrhage and acute parenchymatous degeneration of the liver. Hartman 1 has pointed out the similarity of these pathologic changes to those encountered following prolonged mild asphyxia, and has demonstrated that anoxia is a common accompaniment of artificially induced fever.

The mechanism underlying the hemorrhage following artificially induced fever has never been entirely satisfactorily explained. In the present study selected cellular and humoral factors important in the complex phenomenon of blood coagulation have been determined under experimental conditions in rabbits and during fever therapy in human patients. Total platelet counts have been correlated with qualitative and quantitative studies of the megakaryocytes in serial marrow punctures; quantitative prothrombin and fibrinogen determinations have been followed by histopathologic studies of the liver. Fever was induced in the experimental animals with the radiotherm and in human subjects with the Kettering hypertherm.

Marked differences in the susceptibility of these several coagulation factors to fever were noted from individual to individual. During and following artificially induced fever in rabbits there was a decrease in total platelets in all instances, the lowest determinations being one-fourth to one-third of the pre-fever control values. More or less extensive megakaryocytic damage was apparent during the period of low platelet values and a prompt and rapid regeneration of new megakaryocytes always preceded the return of the circulating platelets to normal levels. A quantitative decrease in prothrombin and fibrinogen occurred in those animals in which liver damage was later found, and where no hepatic damage could be demonstrated no disturbance in prothrombin had been recorded.