Page 728 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 43 Hemoglobin Variants Associated With Hemolytic Anemia, Altered Oxygen Affinity, and Methemoglobinemias 615

Diagnosis the dose can be repeated at 1 mg/kg after 30 minutes if necessary.
This treatment is usually effective. Methylene blue acts through the
Methemoglobinemia should be suspected in patients with unex- reduced form of nicotinamide adenine dinucleotide (NADPH)
plained cyanosis. It is obviously a medical emergency when any reductase system, which in turn requires G6PD activity. The method
patient has cyanosis and altered mental status; a PaO 2 more normal is therefore ineffective in patients who also have G6PD deficiency.
than expected on the basis of the O 2 saturation should trigger a These patients, or patients who are severely affected, may require
consideration of methemoglobinemia. The ingestion of nitrites as a exchange transfusion or hyperbaric oxygen therapy. Oral ascorbic acid
suicidal gesture, especially in people knowledgeable with respect to is not useful for emergency situations because it acts too slowly.
chemistry, medicine, or pharmacology, should be considered. Expo- Follow-up maintenance management, however, can be accomplished
sure to nitrate-containing therapeutic compounds, e.g., in the setting with either ascorbic acid or oral methylene blue.
of the intensive care unit, should also raise suspicion. Methemoglo- Mild cases of methemoglobin intoxication do not require treat-
binemia can be suspected from the brownish color of blood when it ment. The patient can be monitored for 1 to 3 days, during which
is drawn. Laboratory detection is simple; methemoglobin exhibits time methemoglobin levels gradually return to normal if the offend-
characteristic peaks of absorption at 630 and 502 nm, rendering it ing agent is eliminated. The most important follow-up therapy for
easily distinguishable from normal hemoglobin. Pulse oximetry, using patients with toxic methemoglobinemia involves a thorough search
a ratio of absorption at 660 nm and 940 nm, gives an inaccurate for the offending agent and its removal from the environment.
reading of 85% oxygen saturation for blood with 100% methemo-
globin. The inherited M hemoglobin mutants are frequently detect-
able by altered electrophoretic mobility, especially if ferricyanide SUGGESTED READINGS
treatment in vitro is used to convert all the hemoglobin solution to
methemoglobin. Bunn HF: Sickle hemoglobin and other hemoglobin mutants. In Stamatoy-
In the case of toxic methemoglobinemia, recognition of exposure annopoulos G, Nienhuis AW, Majerus PO, et al, editors: The molecular
to an appropriate agent provides the most important historical clue. basis of blood disease, ed 2, Philadelphia, 1993, WB Saunders.
Acute poisoning can represent a life-threatening emergency; therefore Bunn HF, Forget BG: Hemoglobin: Molecular, cellular and clinical aspects,
laboratory evaluation for methemoglobin should be requested for any Philadelphia, 1985, WB Saunders.
person displaying atypical cyanosis or cyanosis occurring along with Dickerson RE, Geis I: Hemoglobin: Structure, function, evolution, and pathol-
more normal than anticipated blood gas values. Methemoglobin due ogy, Menlo Park, CA, 1983, Benjamin-Cummings.
to deficiencies of the reductase system can be further evaluated in Ernst A, Zibrak J: Carbon monoxide poisoning. N Engl J Med 339:1603,
reference laboratories by direct analysis of these enzymes. 1998.
Fermi G, Perutz MF: Atlas of molecular structures in biology. Vol. 2: hemoglobin
and myoglobin, Oxford, 1981, Oxford University Press.
Management Ho C, editor: Hemoglobin and oxygen binding, New York, 1982, Elsevier
Biomedical.
Patients with M hemoglobins are usually asymptomatic and require Park CM, Nagel RL: Sulfhemoglobinemia: Clinical and molecular aspects.
no management. The secondary cyanosis can present a cosmetic N Engl J Med 310:1579, 1984.
problem. The cyanosis is not reversible because ascorbic acid and Perutz MF: Molecular anatomy, physiology, and pathology of hemoglobin.
methylene blue are usually ineffective. In Stamatoyannopoulos G, Nienhuis AW, Leder P, et al, editors: The
Patients with deficiency of the reductase system usually do not molecular basis of blood diseases, Philadelphia, 1987, WB Saunders, p 127.
require treatment. Cyanosis in these cases can be improved by treat- Smith RP, Olson MV: Drug-induced methemoglobinemia. Semin Hematol
ment with oral methylene blue, 100 to 300 mg/day, or 500 mg/day 10:253, 1973.
of oral ascorbic acid. Riboflavin (20 mg/day) has also been reported Wishner BC, Ward KB, Lattman EE, et al: Crystal structure of sickle-cell
to be effective and may be the preferred agent, because methylene deoxyhemoglobin at 5Å resolution. J Mol Biol 98:179, 1975.
blue produces discolored (blue) urine, and ascorbic acid can cause Wright RO, Lewander WJ, Woolf AD: Methemoglobinemia: Etiology,
sodium oxalate stones. pharmacology, and clinical management. Ann Emerg Med 34:646, 1999.
Emergency treatment of high levels of toxic methemoglobinemia Wynngaarden JB, Smith LH, Jr, Bennett JC, editors: Cecil textbook of medi-
begins with 1 to 2 mg/kg of intravenous methylene blue as a 1% cine, Philadelphia, 1992, WB Saunders.
solution in saline. It is usually infused rapidly (over 3 to 5 minutes);