British Journal ofHaematology. zyxwvutsrqpon 1995, 91, 511-520 Correspondence HAEMOGLOBINURIA AND HAPTOGLOBIN IN G 6PD DEFICIENCY In the February issue, Ohga et zyxwvutsrqp a1 (1995) reported the experimental use of haptoglobin in the treatment of an episode of favism in a child with severe G6PD deficiency. We found the report interesting but several aspects perplexing. 1. The stated rationale for the use of haptoglobin was to prevent acute renal failure (ARF).We think this is misplaced and misleading for two reasons. (a) This complication is exceedingly rare in children. One of us (T.M.) has seen personally more than 1500 children with favism, and none of them has developed ARF. One reported case took place in a G6PD-deficient child who had viral hepatitis, and who responded to peritoneal dialysis (Gabbas et al, 1969). (b) In experimental animals intravenous infusion of large amounts of haemoglobin does not cause ARG (Maluf, 1995), unless the infusion is associated with dehydration (Lalich, 1947; Jaenike, 1966) and/or acidosis (Bing, 1944; Zager zyxwvut & Gamelin, 19S9). In humans, newborns who develop acute intravascular haemolysis do not develop ARF, despite the fact that haptoglobin does not reach measurable levels in plasma until the age of zyxwvutsr 3 months: patients with paroxysmal nocturnal haemoglobinuria who have (often massive) haemoglobinuria for long periods of time rarely develop renal failure. In summary, ARF triggered by acute intra- vascular haemolysis is extremely rare and is reversible unless some form of renal damage pre-existed. Its mechan- ism is not damage to the kidney by free plasma haemoglobin, but renal ischaemia consequent to hypovolaemic shock. 2. The claim that haptoglobin administration was effective for relieving bilirubinaemia and haemoglobinuria is unsupported, since of course we do not know how long either would have lasted if haptoglobin had not been administered. It is not unusual for haemoglobinuria in favism to resolve in <48 h, as it did in this case. It is not clear how haptoglobin would relieve bilirubinaemia, since the haemoglobin-haptoglobin complex is catabolized by liver cells and therefore bilirubin production is actually expected to increase. Moreover, the mathematics of the experiment reported zyxwvutsrqp is intriguing. If the child weighed about 12 kg (the median value for his age), his estimated blood volume was about 900 ml. A drop in haemoglobin from 8.4 to 5.8 g/dl means that (8.4 - 5.8) x 9 = 23.4g of Hb must be accounted for. Even if only half of the haemolysis was intravascular. this means about 11.7 g of Hb. The haptoglo- bin infused (2000 units) will bind zyxwvutsrq 2 g of Hb, i.e. less than one-fifth. It does not seem likely that this may have altered significantly the clinical course of the patient. We suspect that the patient recovered quickly because of the blood transfusion, although, in view of the relatively modest fall in Hb and the high reticulocytosis, he might have recovered even without that. 3. Since this patient had a class I G6PD variant (i.e. a type associated with chronic non-spherocytic haemolytic anae- mia), the episode reported would be best designated as ‘acute exacerbation of chronic haemolysis’. If it was indeed triggered by ingestion of fava beans it can be also called concisely ‘favism’: but it is important to realize that it is very different from the thousands of cases of favism that occur in patients without pre-existing haemolysis. 4. One of us is quoted as reporting favism to be ‘rare’ with G6PD deficiency of the A- type. The point of our paper (Galiano et al, 1990) was that, contrary to previous claims, it does occur with this variant: subject to exposure, it is probably not rare at all. Where subjects with this variant eat fava beans, for instance in Spain (Vives-Corrons et al. 1990) and in Algeria (Nafa et al, 1994), G6PD A- is one of the G6PD variants commonly associated with favism. In conclusion, contrary to the authors’ statement, their observations do not indicate the potential usefulness of human haptoglobin products in treating AHA in G6PD deficiency. We believe it is unwarranted to recommend this agent for the treatment of favism. Department of Human Genetics, Memorial Sloan Kettering Cancer Center, New York, NY 10022, U.S.A. L IJ CI o L u z z Arr zyx T o Department of Naematology, Ai-uL MEHTA Royal Free Hospital, London NW3 2QG, U.K. Department of Paediatrics, University of Sassari, Sassari, Italy TULLIO MELONI REFERENCES Bing, R.J. (1944) The effect of hemoglobin and related pigments on renal functions of the normal and acidotic dog. Bulletin oJthe Johns Hopkins Hospital. 73, 161-176. Gabbas, F., Contu. L. & Mosca. A. (1969) Su di un caso di epatite virale complicato da grave anemia emolitica. emoglobinuria e blocco renale in un bambino con difetto di G6PD. Annuli ltaliuni zy di Pediatria, 22, 125-132. Galiano, S., Gaetani, G.F.. Barabino, A., Cottafava, F., Zeitlin, H., Town, M. & Luzzatto, L. (1990) Favism in the African type of glucose-6-phosphate dehydrogenase deficiency (A-). British Medical Journal, 300, 236. Jaenike, J.R. (1966) The renal lesion associated with hemoglobin- emia. I. Its production and functional evolution in the rat. Journal ofExperimentn1 Medicine, 123. 523-535. Lalich, J.J. (1947) The influence of injections of homologous hemoglobin on the kidneys of normal and dehydrated animals. Journal of Experimental Medicine, 86, 153-157. zyx 0 1995 Blackwell Science Ltd 511