• Bhalla Ashish


Development of haemolysis in any febrile patient is a cause of concern for a physician. However with careful history and examination the underlying cause can be detected. The wide spread empirical use of anti-malarial drugs and NSAIDs in febrile patients can result in haemolysis in susceptible population.G6PD deficiency leads to haemolysis in patients whenever they are exposed to oxidative stress in the form of drugs. There is a long list of drugs, which can cause this dreadful complication and serious problems for the patients. These drugs are to be avoided in G6PD deficient patients but it is difficult to anticipate this complication. Since it is difficult to predict which patient might develop this complication when drugs like NSAIDs and anti-malarial drugs are used in febrile patients, it is important to be careful while using these drugs in susceptible population.Key words: G6PD, anti-malarial drugs, haemolysis


Glader BE. “Glucose 6 phosphate Dehydrogenase deficiency and related disorders”. In Wintrobe’s Clinical Hematology. 10th ed. Lee GR, Forrster J, Luken SJ, et al (eds). Baltimore;Williams & Wilkins. Pp 1176-90.

Ruwande G, Khoo SC, Snow RW, Yates SN, Kwiatkowski D, Gupta S, Warn P, Allsopp CE, Gilbert SC, Peschu N, et al. Natural selection of hemi and heterozygotes of G6PD deficiency in Africa by resistance to severe malaria. Nature 1995; 376:246-51.

Wandell R, Bunn Franklyn H, “Haemolytic anemia and acute blood loss” chapter 109, page 659-671 in Harrison’s principles of internal medicine, (14th ed, vol 1) Faucci A S, Braunwald E, Isselbacher K J, Wilson J D, Martin J B, Kasper DL, Hauser S L, Longo D L.(eds) New York; McGraw Hill publication:1998

Salvemini F, Franze A, Iervolino A, Filosa S, Salzano S, Ursini MV. Enhanced Glutathion levels and oxidative resistance mediated by inhibited G6PD expression. J Biol Chem 1999;274:2750-54.

Kirkman HN, Hendrikson EM. Sex linked electrophoratic difference in G6PD. Am J Hum Genit 1963;5:241-3.

Beutler E. “Molecular biology of enzymes of erythrocyte metabolism”. In The Molecular basis of blood diseases. Stamatoyannopoulos G, Nienhus AW, Majerus PW, (eds). Philadalphia; WB Saunders:1993.

“Standardization of procedure for G6PD deficiency” Report of WHO scientific group. WHO technical report series. Sr. no 366. 1967.

Beutler E. “G6PD deficiency; clinical manifestations, genetics and treatment” Blood 1994;84(11):3613-23.

Tizianello A, Pannawulli I, Ajmar F, Salvidio E. Sites of destruction of RBCs in G6PD deficient. Scand J haematol 1968;5: 16-20.

Beutler E. “G6PD deficiency and other enzyme abnormalities” in Beutler E, Lichtmann M A, Coller B S, Kipps T J (eds). Williams haematology, 1995. New York;McGraw Hill publications:1995,p564.

Beutler E, Dern R, Alying A S. The hemolytic effect of Primaquine IV; The relationship of haemolysis to cell age. J Lab Clin Med 1954;44:439-42.

Piomelli S, Corash LM, Davenport PD, Miraglia J, Amorosi EL. In vivo liability of G6PD in GdA- and Gd Mediterranean deficiency. J Clin Invest 1968;47:940-5.

Yoshida A, Stamatoyonnapoulos G, motulsky AG. Negro variant of G6PD deficiency (A-) in man. Science 1967; 155:97-99.

Beutler E. Red cell metabolism. in A manual of biochemical methods, 3rd ed. New York;Grune & Strattan:1984.

Beutler E, Mitchell M. Special modifications of fluorescent screening method for G6PD deficiency. Blood 1968;32:816-20.

Brewer GJ. The methemoglobin reduction test for primaquine type sensitivity of erythrocytes. JAMA 1962; 180:386-89.

Gall JG. Studies of G6PD activity of individual erythrocytes. Am J Hum Gent 1965; 17:359-63.

James E F Reynolds (ed). Primaquine phosphate in ‘Antimalarials” in Martindales The extra pharmacopoeia (29th ed). London;The pharmaceutical press:1989. p 514

Khoo KK . The treatment of malaria in glucose-6-phosphate dehydrogenase deficient patients in Sabah. Ann Trop Med Parasitol 1981;75(6):591-5.

Chan TK, Todd D, Tso SC. Drug induced haemolysis in glucose 6 phosphate dehydrogenase deficiency. Br Med J 1976;2 (6046):1227-9.

Brewer GJ, Zaraforetis JD. The haemolytic effect of various regimens of primaquine in American negros with G6PD deficiency. Bull WHO 1967; 36:303-7.

Choudhry VP, Ghafary A, Zaher M, Qureshi MA, Fazel I, Ghani R. Drug-induced haemolysis and renal failure in children with glucose-6-phosphate dehydrogenase deficiency in Afghanistan. Ann Trop Paediatr 1990;10(4):335-8.

Choudhry VP, Madan N, Sood SK, Ghai OP. Chloroquine induced haemolysis and acute renal failure in subjects with G-6-PD deficiency. Trop Geogr Med 1978;30(3):331-5.

Bruneel F, Gachot B, Wolff M, Bedos JP, Regnier B, Danis M, et al. Blackwater fever. Presse Med 2002;31(28):1329-34.

Djibo A, Souna-Adamou A, Brah Bouzou S.Blackwater fever in adults with sickle cell anemia. Two fatal cases. Med Trop 2000;60(2):156-8.(French.