Effect of Heparin upon Various Forms of the Thrombohemorrhagic Phenomenon

I N EARLIER communications we have described a thromhohemorrhagic phenomenon (THP) which can readily be elicited in rats by the intravenous injection of various metal combinations, reticuloendothelial blocking agents and certain agar preparations, especially if these are given in conjunction with catecholamines (epinephrine, norepinephrine) or severe systemic stressors. This syndrome is characterized by multiple hemorrhages and microthromboses located mainly in the kidneys, duodenum, heart and lung. In addition, very severe and sometimes necrotizing thrombohemorrhagic lesions are observed at the site of catecholamine injection. In its morphologic manifestations, the THP resembles the generalized and local forms of the Sh vartzmanSanarelli phenomenon; however, unlike the latter, the THP does not depend upon the properly spaced administration of a “preparatory” and a “provocative” treatment, one of which at least must be a bacterial endotoxin.’4 It had been observed, furthermore, that if an anaphylactoid inflammation is produced in rats by dextran, dextrin, egg white or other similarly acting mastcell dischargers, the concurrent intravenous administration of agar induces a type of anaphylactoid purpura. Here, the thrombohemorrhagic lesions affect particularly the anaphylactoid shock organs-namely the snout, paws and sometimes the root of the tail.5 Cyproheptadine (an antiserotonin and antihistaminic agent), which prevents the ordinary anaphylactoid inflammation, also blocks the production of this thrombohemorrhagic variant. At the same time, however, it aggravates the accompanying thrombohemorrhagic lesions in internal organs and the mortality rate.6 In view of the prominence of fibrin thrombi among the lesions characteristic of the THP, the question arose whether this syndrome could be prevented by heparin. It will be recalled that both the classical Shwartzman-Sanarelli phenomenon in the rabbit7’8 and several apparently related diseases of man-e.g.. the thrombohemorrhagic phenomena of septic abortion#{176} and purpura fulminans10-are favorably influenced by heparinization.