Page 818 - Williams Hematology ( PDFDrive )

792 Part VI: The Erythrocyte Chapter 50: Methemoglobinemia and Other Dyshemoglobinemias 793

0.8 blue per kilogram body weight has produced acute hemolysis even in
patients with normal glucose-6-phosphate dehydrogenase levels. 89
The response to treatment is so rapid, with marked lowering or
normalization of methemoglobin levels within an hour or two, that no
other treatment is usually needed, but the patient should be observed
D
carefully because continued absorption of a toxic substance from the
0.6
gastrointestinal tract may cause recurrence of the methemoglobinemia.
In patients who are in shock, blood transfusion may be helpful. Cimeti-
dine, used as a selective inhibitor of N-hydroxylation, may decrease the
methemoglobinemia produced by dapsone in patients with dermatitis
Optical density 0.4 C herpetiformis. 90

Hereditary Methemoglobinemia
The course of hereditary methemoglobinemia is generally benign
B
(although not in type II cytochrome b5 reductase deficiency), but
patients with this disorder should be shielded from exposure to aniline
derivatives, nitrites, and other agents that may, even in normal persons,
0.2 induce methemoglobinemia.
A Hereditary methemoglobinemia resulting from cytochrome b5
reductase deficiency is readily treated by the administration of ascor-
bic acid, 300 to 600 mg orally daily divided into three or four doses.
Although intravenously administered methylene blue is very effective
in correcting this type of methemoglobinemia, it is not suitable for the
0 long-term therapy that needs to be given if the state is to be treated at
500 600 700 all. Riboflavin administration seems to benefit some patients but not
91
Wavelength (mm)
others. 92
The iron phenolate complex that exists in the hemoglobins M pre-
Figure 50–2. Absorption spectra at pH 7.0. A, Methemoglobin A; B,
methemoglobin M Boston ; C, methemoglobin M Saskatoon ; D, methemoglo- vents the reduction of ferric to ferrous iron. For this reason, the methe-
bin A fluoride complex. For purposes of comparison, all the optical moglobinemia does not respond to administration of ascorbic acid or
densities have been made equal to 0.61 at 500 nm. (Reproduced with of methylene blue. No effective treatment exists for the cyanosis that is
permission from Gerald PS, George P: Second spectroscopically abnormal present in patients with abnormal hemoglobins with reduced oxygen
methemoglobin associated with hereditary cyanosis. Science 1959 Feb affinity.
13;129(3346):393-394.)

TREATMENT AND COURSE SULFHEMOGLOBIN
Toxic Methemoglobinemia DEFINITION AND HISTORY
Acute toxic methemoglobinemia may represent a serious medical emer- Sulfhemoglobinemia refers to the presence in the blood of hemoglobin
gency. Because of the loss of oxygen-carrying capacity of the blood and derivatives that are defined by their characteristic absorption of light
the left shift in the oxygen dissociation curve that occurs when methe- at 620 nm, even in the presence of cyanide. Sulfhemoglobin derives its
moglobin is present in high concentrations, acute methemoglob- name from the fact that it can be produced in vitro from the action of
80
inemia may be life-threatening when the level of the pigment exceeds hydrogen sulfide on hemoglobin and that the feeding of dogs with ele-
93
one-third of the total circulating hemoglobin. Levels of methemoglobin mental sulfur has been associated with sulfhemoglobinemia. 94
exceeding 50 percent of the total pigment may be associated with vascu-
lar collapse, coma, and death, 81,82 but recovery was documented in one
patient with a level as high as 81.5 percent of the total pigment. 83 ETIOLOGY AND PATHOGENESIS
Methylene blue is an effective treatment for patients with methe- Sulfhemoglobin may contain one excess sulfur atom. The sulfur atom
84
moglobinemia because NADPH formed in the hexose monophosphate appears to be bound to a β-pyrrole carbon atom at the periphery of the
pathway can rapidly reduce this dye to leukomethylene blue in a reac- porphyrin ring. 95–97 Sulfhemoglobinemia has been associated with the
tion catalyzed by NADPH diaphorase (Chap. 47). Leukomethylene blue, ingestion of various drugs, particularly sulfonamides, phenacetin, ace-
in turn, nonenzymatically reduces methemoglobin to hemoglobin. An tanilid, and phenazopyridine. 65,98 It also occurs independently of drug
85
exception to the efficacy of this treatment exists in those patients who use, and has been thought to be related to chronic constipation or to
are glucose-6-phosphate dehydrogenase deficient (Chap. 47). In these purging. Some patients with sulfhemoglobinemia or a past history of
99
subjects, methylene blue would not only fail to give the desired effect this disorder appear to have increased levels of red blood cell reduced
on methemoglobin levels, but might compound the patient’s difficulty glutathione (GSH). The reason for this and its relationship to sulfhe-
100
by inducing an acute hemolytic episode or increasing the level of moglobinemia are not clearly understood, but it may be of significance
86
methemoglobin. 87 that some of the types of drugs that are associated with sulfhemoglob-
In patients with acute toxic methemoglobinemia who are symp- inemia cause an elevation of red cell GSH levels, probably by activating
tomatic or whose methemoglobin level is rising rapidly, the intravenous the enzyme glutathione synthase or by increasing intracellular gluta-
101
administration of 1 or 2 mg methylene blue per kilogram body weight mate levels. 102
over a period of 5 minutes is the preferred treatment because of its Evidence for the occurrence of hereditary sulfhemoglobinemia is
very rapid action. Use of excessive amounts of methylene blue should not convincing, and it is likely that the single family reported rep-
88
103
be avoided; the administration of repeated doses of 2 mg methylene resents a hemoglobin M hemoglobinopathy.

Kaushansky_chapter 50_p0789-0800.indd 793 9/17/15 2:38 PM