Notes on the mechanism of paroxysmal hemoglobinuria.

Abstract

The assumption that the Landsteiner 1 phenomenon constitutes the actual mechanism in paroxysmal hemoglobinuria has been questioned on clinical grounds, and has led to several attempts to demonstrate some other factor promoting intravascular hemolysis in this disease. Hijmans, van den Bergh and Hijmans, 2 and Hannema and Rytma 3 have reported an activating effect on the hemolysin by CO₂. They found that, in the presence of CO₂, the hemolytic mechanism operates at room temperature. The effect was observed when the hemoglobinuric serum was set up with normal cells as well as with the patient's cells, and when the serum alone was exposed to CO₂ and afterwards mixed with the red cells and complement. The action of CO₂ therefore seemed to be on the hemolysin alone.

Two patients with this disease have recently been under observation. They are congenital syphilitics 5 and 8 years of age. One has frequent spontaneous attacks of hemoglobinuria even in temperatures above 16 degrees C. He has a low titer of hemolysin in his serum. The other has spontaneous attacks only after outdoor exposure on the coldest days of winter, or after immersion of an extremity in ice water. The hemolysin in his serum is present in a high titer. Hence in these patients the susceptibility to spontaneous attacks is inversely proportional to the titer of Landsteiner hemolysin in the serum, suggesting that some other factor in addition to the Landsteiner mechanism is operative. The presence of anti-complementary substances in the serum of the patient with a low hemolysin titer alnd high clinical susceptibility has been excluded. Repeated efforts to show with the blood of these patients that CO₂ acts in vitro as an activator of the Landsteiner hemolytic mechanism have been unsuocessf ul. The serum of each of these patients and mixtures of serum, cells and cornplernent have been exposed at room temperature to concentrations of CO₂ varying from 3.5 per cent to 80 per cent with no hemolysis, upon subsequent warming to 37.5 degrees C. Nor has the titer of the hemolysin been any higher when the usual chilling test was carried out in the presence of CO₂ in concentrations from 20 to 40 per cent.