Anemia is one of the most common clinical features in patients on long-term hemodialysis. Its etiology is usually multifactorial, but hemolysis is not an infrequent cause^1,3). The hemolysis may result from underdialysis, mechanical damage to red blood cells, abnormal erythrocyte metabolism⁴⁾, overheated dialysate⁵⁾ or the presence of contaminants in the dialysis bath. The contaminants, such as formaldehyde⁶⁾, copper⁷⁾, nitrate⁸⁾, zinc⁹⁾ and chloramine^10–13) in dialysate, have been reported to cause hemolytic anemia and methemoglobinemia.

There was an outbreak of hemolytic anemia in 34 patients on maintenance hemodialysis in Guro Hospital, Korea University Medical Center, during four months from December 1988 to March 1989. A series of studies were tried to identify and neutralize the offending substrates. We detected high levels of chloramine in the treated water. To elucidate the cause of the high chloramine level, we compared the ammonia nitrogen concentrations of our water source (A) with another (B). After we changed the source of the water supply, there were striking improvements in laboratory findings, as well as in the general condition of the patients. In this paper, we report the clinical and laboratory features of the outbreak, the identification of the offending agent, the implementation of control measures and the improved findings after switching the water source.

Chloramines, which are oxidant compounds made up of chlorine and ammonia and widely used as bactericidal agents in urban water supplies, have been found responsible for the epidemics of acute hemolytic anemia characterized by Heinz bodies in hemodialysis patients^10,11,13). Chloramines produce denaturation on hemoglobin (Heinz body), both by their direct oxidizing capacity and their ability to inhibit red cell reductive (hexose monophosphate shunt; HMPS) metabolism¹²⁾. The HMPS, through generation of reduced nicotinamide adenine dinucleotide phosphate (NADPH), protects the red cell from oxidant damage. When this pathway is defective, red cells become vulnerable to damage from oxidant compounds. Pure chlorine in water can not cause these changes, but chloramine at the level of 0.25 mg/L invariably leads to hemolysis¹²⁾.

From the beginning, chloramine-incuced hemolytic anemia was suggested by outbreak of hemolysis, methemoglobinemia and Heinz bodies on blood film in our patients. Diagnosis was made by high concentrations of chloramine in the treated water. Most of our patients showed positive Heinz body and ascorbate-cyanide test. Nitrates and copper can also induce hemolytic amemia^7,8), but concentrations of nitrates and copper in the treated water in our center were within the standards for hemodialysis.

Chloramines represent a hazard in many dialysis centers since the reverse osmosis method of water purification does not remove these compounds. These compounds can be removed from water by adequate carbon filtration, but the disadvantage of expense and the danger of bacterial growth hide behind this method. Boiling and vacuum treatment are all effective but unacceptable in practice¹²⁾. The control measures of chloramine-induced hemolysis in previous epidemics were by adding ascorbic acid to the bath (2g/120L of dialysate) in Minnesota¹²⁾ and by fitting all dialysis machines with individual carbon filters in Sydney¹¹⁾. We reinforced the water treatment system by changing the charcoal column, setting up the carbon filter at individual dialysis machines and adding ascorbic acid to the tank water, but the episodes of hemolysis were not reduced. The unresponsiveness to the above mentioned procedures in our epidemic may be related to the enormous amount of chloramine in water. In fact, our bedside carbon filters could not effectively remove the residual chlorine in water. Recently, Cohen et al experienced the same situation as ours in S. Africa¹³⁾. They also tried to neutralize the high chloramien in water with ascorbic acid and inserted charcoal filters ahead of the reverse osmosis system, but both methods were unsuccessful as in our case. They had to decrease chlorination of the municipal water to control the hemolysis.

Chloramines are preferred to chlorine in some western countries, as they have more stable chemical structure and do not evaporate as readily as chlorine. Chlorine is used as bactericidal agents in urban water supplies in Korea. However, residual chlorine can combine with ammonia in water, contaminated by raw sewage, and produce oxidant compounds, chloramine. Especially, in dry and winter seasons, the concentration of ammonia in water increases and the evaporation of residual chlorine decreases. Therefore, the hazard of chloramine increases in dry and winter seasons.

In conclusion, chloramine is one of the major contaminants causing dialysis-induced hemolytic anemia and regular determinations are necessary, especially during winter and dry seasons.