dehydrogenase (G6PD) deficiency is a well-known, X-linked genetic disorder that
most commonly affects up to 25% of primarily male patients from Africa, Asia,
and the Mediterranean.1-2 The most common clinical manifestation is
jaundice due to hemolysis of red blood cells (RBC).1 A number of
different factors can trigger these patients to develop hemolytic anemia, which
most commonly includes medications, fava beans, and/or an infection.1 When
placed under some type of stressor, RBCs must maintain the level of
nicotinamide adenine dinucleotide phosphate (NADPH) in order to allow
glutathione to protect the RBC from undergoing damage in the presence of
oxidative metabolites. It is the presence of a functionally active G6PD
enzyme that allows the RBC to maintain adequate amounts of NADPH and thus
allows glutathione to act as protector against oxidative stressors.
As it relates to the
oxidative stressors mentioned above, medications and other chemicals are
commonly associated with the development of this in type of hemolytic anemia
and are summarized below.3-9
- Chloroquine (Aralen)* - Antimalarial Agent
- Dapsone* - Antimycobacterial Agent
- Fava Beans* - Natural Supplement
- Flutamide (Eulexin) - Anti-androgen (Non-steroidal Oral Agent)
- Methylthioninium chloride (Methylene Blue) - Antidote
- Nitrofurantoin (Macorbid)* - Antibiotic
- Pegloticase (Krystexxa) - Recombinate Urate-Oxidase Enzyme
- Phenazopyridine (Pyridium) - Analgesic (Urinary Tract)
- Primaquine Phosphate* - Antimalarial Agent
- Rasburicase (Elitek)* - Recombinate Urate-Oxidase Enzyme
- Trimethoprim/Sulfamethoxazole (Bactrim; Bactrin DS; Septra)* - Inhibitor of Dihydrofolate Reductase/Dihydropteroate Synthetase
- Red blood cells (RBC) on histologic examination reveal "bite cells" or Heinz bodies due to oxidative damage to RBC membranes.
- * = Medications most common or classically associated with hemolysis if used in G6PD deficient patients.
For those taking or preparing for board or
specialty exams, those medications or substances that are stared (*) are the most
common to know. If a patient should develop acute, new onset jaundice, a
complete blood cell count (CBC) with differential, reticulocyte count, a
peripheral smear looking for the presence of "bite cells" or Heinz
bodies, indirect bilirubin, and measurement of G6PD enzyme are helpful in
establishing a diagnosis. If it is determined that a patient has
hemolytic anemia from the use of any of these medications, the medication
should be stopped, the patient should rest or even be put on bed rest for a few
days, and if necessary add supplemental oxygen if the pulse ox is < 90%
and/or if other comorbidities exist that might be exacerbated by a period of
- Beutler E. Glucose-6-phosphate dehydrogenase deficiency. N Engl J Med 1991;324:169-74.
- Nkhoma ET, Poole C, Vannappagari V, et al. The global prevalence
of glucose-6-phosphate dehydrogenase deficiency: a systematic review and
meta-analysis. Blood Cells Mol Dis 2009;42:267-78.
- Grossman S, Budinsky R, Jollow D. Dapsone-induced hemolytic
anemia: role of glucose-6-phosphate dehydrogenase in the hemolytic
response of rat erythrocytes to N-hydroxydapsone. J Pharmacol Exp Ther
- Fanello CI, Karema C, Avellino P et al. High risk of severe
anaemia after chlorproguanil-dapsone+artesunate antimalarial treatment
in patients with G6PD (A-) deficiency. PLoS One 2008;3:e4031.
- Schuurman M, van Waardenburg D, Da Costa J et al. Severe
hemolysis and methemoglobinemia following fava beans ingestion in
glucose-6-phosphate dehydrogenase deficiency: case report and literature
review. Eur J Pediatr 2009;168:779-82.
- Tishler M, Abramov A. Phenazopyridine-induced hemolytic anemia
in a patient with G6PD deficiency. Acta Haematol 1983;70:208-9.
- Browning LA, Kruse JA. Hemolysis and methemoglobinemia secondary
to rasburicase administration. Ann Pharmacother 2005;39:1932-5.
- Youngster I, Arcavi L, Schechmaster R et al. Medications and
glucose-6-phosphate dehydrogenase deficiency: an evidence based review.
Drug Saf 2010;33:713-726.
- Chisholm-Burns MA, Patanwala AE, Spivey CA. Aseptic meningitis,
hemolytic anemia, hepatitis, and orthostatic hypotension in a patient
treated with trimethoprim-sulfamethoxazole. Am J Health Syst Pharm