Treatment of paroxysmal nocturnal hemoglobinuria with ACTH.

pAROXYSMAL NOCTURNAL HEMOGLOBINURIA is a rare hemolytic disease characterized by intravascular hemolysis and excretion of hemoglobin in the urine during sleep. Crosby,’ in an extensive review of the literature, found reports of 123 cases of this condition and gave credit to StrUbing for first recognizing it as an entity in 1882. It was not until another description was published by Marchiafava2 in 1928, however, that the disease became generally recognized. The real nature of the hemolytic process is still unknown. Van den Bergh, in 1911, discovered that the defect lay in the red cells and that their destruction was increased by exposure to carbonic acid. Subsequently, it was cotlfirmed that the plasma of these patients is normal and that a factor present in normal plasma is essential for the hemolytic action.3 The nocturnal occurrence of hemoglobinuria was explained on the theory that during sleep there is (lecreased pulmonary ventilation, consequent carbon dioxide retention, and thus a lowered hydrogen ion concentration of the body fluids which would be conducive to hemolysis. rfhe evidence, however, that such a change occurs is not strong. Recently it has been fairly defitlitely demonstrated4 that the hemolysis does not depend on an antigen-antibody reaction, and that tile degree of hemolysis parallels the accelerator-globulin activity (Ac-globulin of Seegers, Factor V of Owren, labile factor of Quick), suggesting that this globulin fraction may be the essential plasma hemolytic factor noted previously. The clinical and pathologic aspects of this disease have been well described ill previous reviews by Scott,5 Ross6 and Marks7 and need not be discussed here. This cotldition has been classed as an acquired hemolytic disease in the absence of any evidence that the red cell defect is hereditary or congenital. Because of the ineffectiveness of all forms of therapy used in the pasts and in view of recent reports of the beneficial effects of ACTH in acquired hemolytic anemias,9 to a patient in whom the diagnosis of paroxysmal nocturnal hemoglobinuria was established was recently treated with ACTH. It is the purpose of this communication to describe the results of this therapy.