Methemoglobinemia
Keywords:
Methemoglobinemia, methylene blue, cytochrome-bAbstract
Methemoglobinemia refers to the existence of high blood concentrations of methemoglobin, resulting from the oxidation offerrous iron to ferric iron within the hemoglobin molecule. An extensive review of methemoglobinemia is done, initiaJJy focusing on physiological enzymatic mechanisms of oxidation/ reduction of hemoglobin, referring its efficacy in pathologic methemoglobinemia. Methe moglobinemia causes tissue hypoxia, being responsible for chocolate colour type of cyanosis, and other progressive symptoms, including abnormalities of respiratory and cardiac function as the concentration of methemoglobin grow up.
Etiology can be genetic or acquired. Acquired form is much more common, and there are a great number of oxidizing agents causing it, namely dn,gs. The most common genetic cause is deficiency of enzymatic system of cytochrome-b5 reductase, from which we know three differentgenetic variations with weak activity.
Laboratory confirmation of methemoglobinemia requires co-oxymetry, but clinicai diagnosis is essential.
Oxidizing agents besides causing methe moglobinemia can be responsible for some degree of hemolysis, mostly if there is concomitant deficiency of glucose-6-phosphate dehydrogenase, in which case it is better not to use methylene blue in the treatment of methemoglobinemia. ln high doses methylene blue is an oxidizing agent, causing induction of methemoglobin. If there is deficiency of the referred enzyme, the haemolytic action of methylene blue will happen with lower doses of the drug. Exchange transfusions are alternative therapy in serious cases. Recently N-acetylcysteine is being considered as alternative therapy to methylene blue.
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References
Darling R, Roughton S. Effects of methemoglobinemia on equilibrium between oxygen and hemoglobin. Am J Physiol 1942; 137: 56-62.
Mansouri A, Luri A. Concise review: Methemoglobinemia. Am J Hematol 1992; 42: 7-12.
Jaffé E. Hereditary methemoglobinemia associated with abnormalities in the metabolism of erythrocytes. Am J Med 1966; 41: 786-798.
Stryver L. Oxygen transporting proteins. ln Biochemistry 3rd ed. Ed. Freeman WH. New York. 1988: 143-171.
Curry S. Methemoglobinemia. Ann Emerg Med. 1982; 11: 214-221.
Wright R, Lewander W, Woolf A. Methemoglobinemia: etiology, pharmacology, and clinical management. Ann Emerg Med 1999; 34: 646-656.
Beutler E. Methemoglobinemia and other causes of cyanosis. ln William's Hematology 5,h ed. Ed. Beutler E, Lichtman MA. Coller RS, et al. McGraw-Hill, Inc 1995: 654-663.
Tauher A. Blanchard R. Congenital methemoglobinemia with cytochrome-b1 deficiency. N Engl J Med 1986; 315: 894.
Harvey J, Keitt A. Studies of the efficacy and potential hazards of methylene blue therapy in aniline-induced methemoglobinemia. Br J Haematol 1983; 54: 29-41.
Sanchez-Echaniz J, Benito-Fernández J, Miguel-Raso S. Consumo de vegetais e metahemoglobinémia infantil. Pediatrics (ed. Port.) 2001; 9: 249-253.
Jaffé E. Enzymogenic hereditary methemoglobinemia. A clinical biochemical classification. Blood Cells 1986: 12: 81-90.
Jaffé E, Hulquist D. Cytochrome-b, reductase deficiency and enzymopenic hereditary methemoglobinemia. ln The Metabolic and Molecular Basis of Inherited Disease 81h ed. Ed. Scriver C. Beaudet A, Sly WS. Valle D. New York. McGraw-Hill 2001: 4555- 4570.
Townes PL, Morrison M. lnvestigation of lhe defect in a variant of hereditary methemoglobinemia. Blood 1962; 19: 60-74.
Cohen R, Sachs J, Wicker D et al. Methemoglobinemia provoked by malarial chemoprophylaxis in Vietnam. N Engl J Med 1968: 279: 1127-1131.
Higasa K, Manabe JI, Yubisui T et al. Molecular basis of hereditary methemoglobinemia, types I and II. two novel mutations in the
NADH-cytochrome-b5 reductase gene. Brit J Hematol 1998: 103: 922-930.
Yawata Y, Ding L, Tanishim K et al. New variant of cytochrom b, reductase deficiency (b5kurashiki) in red cells, platelets, lymphocytes and cultured fibroblasts with congenital methemoglobinemia. mental and neurologic retardation and skeletal anomalies. Am J Hematol 1992; 40: 299.
Scott E. Congenital methemoglobinemia due to DPNH-diaphorase. ln Hereditary Disorders of Erythrocyte Metabolism. Ed. Beutler
E. Grune and Stratton. New York 1968: 102.
Methemoglobinemia and other Disorders usually accompanied by cyanosis. ln Wintrobe's Clinical Hematology 8o ed. Ed. Wintrobe M, Lee OR, Boggs DR, et ai. Lea and Febiger. Philadelphia 1981: 1011-1015.
Metz E, Balcerzak S, Sagon L. Mechanism of methylene blue stimulation of the hexase monophosphate shunt in the erythrocyte. J Clin lnvest 1976: 58: 797-802.
Beutler E, Baluda M. Methemoglobin reductase. Studies in the interaction between cell populations and of the role of methylene blue. Blood 1963; 22: 323-333.
Rosen P, Johnson C, McGehee, et ai. Failure of methylene blue treatment in toxic metemoglobinemia. Association with glucose-6-phosphate dehydrogenase deficiency. Ann Int Med 1971; 75: 83-86.
Nadler J, Green H, Rosenbaun A. Intravenous injection of methylene blue in man with reference to its toxic symptoms and effect on the electrocardiogrnm. Am J Med Sei 1934: 188: 15-21.
Golden P. Weinstein R. Treatment of high-risk. refractory acquired methemoglobinemia with automated red blood cell exchange. J Clin Apheresis 1998: 13: 28-31.
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