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March 1994, Vol 148, No. 3 >
Article | March 1994

Methylene Blue–Induced Heinz Body Hemolytic Anemia FREE

Marion R. Sills, MD; William H. Zinkham, MD
Arch Pediatr Adolesc Med. 1994;148(3):306-310. doi:10.1001/archpedi.1994.02170030076017.
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Objective:  To describe the manifestations of methylene blue toxicity, with a review of the literature.

Design:  A descriptive analysis of physical findings and significant laboratory tests in patients with methylene blue toxicity.

Setting:  A pediatric referral center.

Patients:  Two infants, one a neonate with trisomy 21 exposed to methylene blue as an intraoperative diagnostic marker and the other a neonate treated with methylene blue for type II glutaric acidemia.

Interventions:  Laboratory tests to define the occurrence of methylene blue toxicity, phototherapy for hyperbilirubinemia, and transfusions for anemia.

Measurements and Results:  Within hours after exposure to methylene blue, the infants voided green-blue urine, followed by hyperbilirubinemia, recurrent anemia requiring transfusions, and red blood cell dysmorphology, including the appearance of blister cells and Heinz bodies visible in both Wright's- and supravital-stained peripheral blood smears. After the initiation of phototherapy, both infants exhibited cutaneous bullae followed by desquamation.

Conclusion:  Significant neonatal morbidity may occur following postpartum administration of methylene blue. Toxic manifestations include hyperbilirubinemia, Heinz body hemolytic anemia, and possibly desquamation of the skin. In our infants toxicity was secondary to an overdose of methylene blue, as is true for most of the previously reported cases. Methods for defining the mechanism of dye-related hemolysis and simple screening tests for elucidating the unique sensitivity of certain individuals to dye toxicity are suggested.(Arch Pediatr Adolesc Med. 1994;148:306-310)

REFERENCES

1 +
Faucet RL, Miller JC.  Methemoglobinemia occurring in infants fed milk diluted with well water of high nitrate content . J Pediatr . 1946;;29:585-592.
2 +
Girardi G, Viaz L, Fritas E, Otero M, Larrain A, Pope CE.  Diagnosis of gastroesophageal reflux in infants and children by methylene-blue test . Lancet . 1978;; 1:1236-1237.
3 +
Scanlon JW.  Rapid maneuvers to determine location of endotracheal tube in new born infants . J Pediatr . 1973;;82:1091-1092.
4 +
Kirsch IR, Cohen HJ.  Heinz body hemolytic anemia from the use of methylene blue in neonates . J Pediatrics . 1980;;96:276-278.
5 +
Atlay RD, Sutherst JR.  Premature rupture of the fetal membranes confirmed by intra-amniotic injection of dye . Am J Obstet Gynecol . 1970;;108:993-994.
6 +
Cowett RM, Hakanson DO, Kocon RW, Oh W.  Untoward neonatal effect of intra-amniotic administration of methylene blue . Obstet Gynecol . 1976;;48( (suppl 1) ): 74s-75s.
7 +
Crooks J.  Hemolytic jaundice in a neonate after intra-amniotic injection of methylene blue . Arch Dis Child . 1982;;57:872-873.
8 +
McEnerney JK, McEnerney LN.  Unfavorable neonatal outcome after intra-amniotic injection of methylene blue . Obstet Gynecol . 1983;;61( (suppl 3) ):35s-37s.
9 +
Plunkett GD.  Neonatal complications . Obstet Gynecol . 1973;;41:476-477.
10 +
Serota FT, Bernbaum JC, Schwartz E.  The methylene blue baby . Lancet . 1979;; 2:1142-1143.
11 +
Vincer MJ, Allen AC, Evans JR, Nwaesei C, Stinson DA.  Methylene-blue-induced hemolytic anemia in a neonate . Can Med Assoc J . 1987;;136:503-504.
12 +
Spahr RC, Salsburey DJ, Krissberg A, Prin W.  Intra-amniotic injection of methylene blue leading to methemoglobinemia in one of twins . Int J Gynaecol Obstet . 1980;;17:477-478.
13 +
Goluboff N, Wheaton R.  Methylene blue induced cyanosis and acute hemolytic anemia complicating the treatment of methemoglobinemia . J Pediatr . 1961;; 58:86-89.
14 +
Oski FA, Growney PM.  A simple micromethod for the detection of erythrocyte glucose-6-phosphate dehydrogenase deficiency . J Pediatr . 1965;;66:90-93.
15 +
Standardization of Procedures for the Study of Glucose-6-Phosphate Dehydrogenase . Geneva, Switzerland: World Health Organization; 1967;:2-53. WHO Technical Report Series No. 366.
16 +
Sass MD, Caruso CJ, Farhangi M.  TPNH-methemoglobin reductase deficiency: a new red cell enzyme defect . J Lab Clin Med . 1967;:70:760.
17 +
Bunn HF, Forget BG. Hemoglobin: Molecular, Genetic and Clinical Aspects . Philadelphia, Pa: WB Saunders Co; 1986;:582.
18 +
Nathan DG, Oski FA. Hematology of Infancy and Childhood . 4th ed. Philadelphia, Pa: WB Saunders Co; 1993;:26.
19 +
Greenberg MS.  Heinz body hemolytic anemia: 'bite cells'—a clue to diagnosis . Arch Intern Med . 1976;;136:153.
20 +
Frick PG, Hitzig WH, Betke K.  Hemoglobin Zurich, I: a new hemoglobin anomaly associated with acute hemolytic episodes with inclusion bodies after sulfonamide therapy . Blood . 1962;;20:261-271.
21 +
Virshup DM, Zinkham WH, Sirota RL, Caughey WS.  Unique sensitivity of Hb Zurich to oxidative injury by phenazopyridine: reversal of the effects by elevating carboxyhemoglobin levels in vivo and in vitro . Am J Hematol . 1983;;14:315-324.
22 +
Santus R, Kohen C, Kohen E, et al.  Permeation of lysosomal membranes in the course of photosensitization with methylene blue and hematoporopyrin: study by cellular microspectrofluorometry . Photochem Photobiol . 1983;;38:71-77.
23 +
Ruhlen JL.  Tissue necrosis: cutaneous and subcutaneous damage following extravasation of methylene blue . J Kansas Med Soc . 1982;;83:236, 260.
24 +
Perry PM, Meinhard E.  Necrotic subcutaneous abscesses following injections of methylene blue . Br J Clin Pract . 1974;;28:289-291.
25 +
Sharr MM, Weller RO, Brice JG.  Spinal cord necrosis after intrathecal injection of methylene blue . J Neurol Neurosurg Psychiatry . 1978;;41:384-386.

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

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References

1 +
Faucet RL, Miller JC.  Methemoglobinemia occurring in infants fed milk diluted with well water of high nitrate content . J Pediatr . 1946;;29:585-592.
2 +
Girardi G, Viaz L, Fritas E, Otero M, Larrain A, Pope CE.  Diagnosis of gastroesophageal reflux in infants and children by methylene-blue test . Lancet . 1978;; 1:1236-1237.
3 +
Scanlon JW.  Rapid maneuvers to determine location of endotracheal tube in new born infants . J Pediatr . 1973;;82:1091-1092.
4 +
Kirsch IR, Cohen HJ.  Heinz body hemolytic anemia from the use of methylene blue in neonates . J Pediatrics . 1980;;96:276-278.
5 +
Atlay RD, Sutherst JR.  Premature rupture of the fetal membranes confirmed by intra-amniotic injection of dye . Am J Obstet Gynecol . 1970;;108:993-994.
6 +
Cowett RM, Hakanson DO, Kocon RW, Oh W.  Untoward neonatal effect of intra-amniotic administration of methylene blue . Obstet Gynecol . 1976;;48( (suppl 1) ): 74s-75s.
7 +
Crooks J.  Hemolytic jaundice in a neonate after intra-amniotic injection of methylene blue . Arch Dis Child . 1982;;57:872-873.
8 +
McEnerney JK, McEnerney LN.  Unfavorable neonatal outcome after intra-amniotic injection of methylene blue . Obstet Gynecol . 1983;;61( (suppl 3) ):35s-37s.
9 +
Plunkett GD.  Neonatal complications . Obstet Gynecol . 1973;;41:476-477.
10 +
Serota FT, Bernbaum JC, Schwartz E.  The methylene blue baby . Lancet . 1979;; 2:1142-1143.
11 +
Vincer MJ, Allen AC, Evans JR, Nwaesei C, Stinson DA.  Methylene-blue-induced hemolytic anemia in a neonate . Can Med Assoc J . 1987;;136:503-504.
12 +
Spahr RC, Salsburey DJ, Krissberg A, Prin W.  Intra-amniotic injection of methylene blue leading to methemoglobinemia in one of twins . Int J Gynaecol Obstet . 1980;;17:477-478.
13 +
Goluboff N, Wheaton R.  Methylene blue induced cyanosis and acute hemolytic anemia complicating the treatment of methemoglobinemia . J Pediatr . 1961;; 58:86-89.
14 +
Oski FA, Growney PM.  A simple micromethod for the detection of erythrocyte glucose-6-phosphate dehydrogenase deficiency . J Pediatr . 1965;;66:90-93.
15 +
Standardization of Procedures for the Study of Glucose-6-Phosphate Dehydrogenase . Geneva, Switzerland: World Health Organization; 1967;:2-53. WHO Technical Report Series No. 366.
16 +
Sass MD, Caruso CJ, Farhangi M.  TPNH-methemoglobin reductase deficiency: a new red cell enzyme defect . J Lab Clin Med . 1967;:70:760.
17 +
Bunn HF, Forget BG. Hemoglobin: Molecular, Genetic and Clinical Aspects . Philadelphia, Pa: WB Saunders Co; 1986;:582.
18 +
Nathan DG, Oski FA. Hematology of Infancy and Childhood . 4th ed. Philadelphia, Pa: WB Saunders Co; 1993;:26.
19 +
Greenberg MS.  Heinz body hemolytic anemia: 'bite cells'—a clue to diagnosis . Arch Intern Med . 1976;;136:153.
20 +
Frick PG, Hitzig WH, Betke K.  Hemoglobin Zurich, I: a new hemoglobin anomaly associated with acute hemolytic episodes with inclusion bodies after sulfonamide therapy . Blood . 1962;;20:261-271.
21 +
Virshup DM, Zinkham WH, Sirota RL, Caughey WS.  Unique sensitivity of Hb Zurich to oxidative injury by phenazopyridine: reversal of the effects by elevating carboxyhemoglobin levels in vivo and in vitro . Am J Hematol . 1983;;14:315-324.
22 +
Santus R, Kohen C, Kohen E, et al.  Permeation of lysosomal membranes in the course of photosensitization with methylene blue and hematoporopyrin: study by cellular microspectrofluorometry . Photochem Photobiol . 1983;;38:71-77.
23 +
Ruhlen JL.  Tissue necrosis: cutaneous and subcutaneous damage following extravasation of methylene blue . J Kansas Med Soc . 1982;;83:236, 260.
24 +
Perry PM, Meinhard E.  Necrotic subcutaneous abscesses following injections of methylene blue . Br J Clin Pract . 1974;;28:289-291.
25 +
Sharr MM, Weller RO, Brice JG.  Spinal cord necrosis after intrathecal injection of methylene blue . J Neurol Neurosurg Psychiatry . 1978;;41:384-386.

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