Glucose-6-Phosphate Dehydrogenase Deficiency

Suspect G6PD-related hemolysis when acute anemia or jaundice follows an intercurrent infection, an oxidative medication, fava-bean ingestion, henna exposure, or another acute oxidative stressor. G6PD deficiency causes nonimmune hemolytic anemia because impaired red-cell antioxidant capacity increases susceptibility to oxidative injury. BMJ+3BMJGlucose-6-phosphate dehydrogenase deficiency - Symptoms, diagnosis and treatment | BMJ Best Practice USNatureGlucose-6-phosphate dehydrogenase deficiency in the Han Chinese population: molecular characterization and genotype–phenotype association throughout an activity distribution | Scientific ReportsWolters KluwerGlucose-6-phosphate dehydrogenase deficiency with... : Indian Journal of Pathology and Microbiologycdn clinicaltrialsEvaluation of a diagnostic to identify G6PD deficiency in ...

Immediately stop a suspected oxidant exposure and identify and treat the precipitating infection or acute illness. Obtain a CBC with hemoglobin, reticulocyte count, bilirubin fractions, lactate dehydrogenase, haptoglobin, creatinine, urinalysis, and peripheral smear review to establish hemolysis severity and detect complications such as hemoglobinuria or kidney injury. G6PD-associated episodes may be clinically significant enough to produce severe hyperbilirubinemia and renal failure. BMJ+1BMJGlucose-6-phosphate dehydrogenase deficiency - Symptoms, diagnosis and treatment | BMJ Best Practice USPubMedGlucose-6-phosphate dehydrogenase deficiency - PMC

Use direct antiglobulin testing when the presentation could represent immune hemolysis rather than an oxidant episode. Persistent anemia after trigger removal, marked splenomegaly, multilineage cytopenias, or an atypical smear should redirect the evaluation toward concurrent hemolytic, marrow, hepatic, infectious, or inherited red-cell disease rather than attributing all anemia to G6PD deficiency. Coexisting disorders can independently contribute to anemia and cytopenias. Wolters KluwerWolters KluwerGlucose-6-phosphate dehydrogenase deficiency with... : Indian Journal of Pathology and Microbiology

Confirm suspected disease with a blood-based G6PD enzyme activity assay and peripheral-smear review. In routine practice, the diagnosis is made from blood testing that includes smear examination and a specific enzyme assay. BMJBMJGlucose-6-phosphate dehydrogenase deficiency - Symptoms, diagnosis and treatment | BMJ Best Practice US

Interpret enzyme activity in the clinical context. During or shortly after hemolysis, selective destruction of the most deficient erythrocytes can leave younger circulating cells with relatively higher activity, producing a falsely reassuring phenotypic result. If clinical suspicion remains high after a normal acute-phase test, repeat enzyme activity testing after hematologic recovery. ASHASHGlucose-6-phosphate dehydrogenase deficiency | Blood | American Society of Hematology

Do not use a limited genotyping panel as the sole exclusion test when the clinical question is functional deficiency, particularly in heterozygous females. X-inactivation creates a wide range of normal-to-deficient erythrocyte proportions, so genotype does not reliably predict the degree of enzyme deficiency in heterozygotes; phenotypic testing is therefore more informative for functional risk in this group. ASHASHGlucose-6-phosphate dehydrogenase deficiency | Blood | American Society of Hematology

Laboratory cutoffs are assay-, age-, and population-dependent. Published newborn screening programs have used a fluorescent spot test followed by quantitative enzyme testing for reduced activity, but a threshold from one laboratory should not be transferred to another laboratory's assay. NatureNatureNewborn screening of glucose-6-phosphate dehydrogenase deficiency in Guangxi, China: determination of optimal cutoff value to identify heterozygous female neonates | Scientific Reports

After confirmed deficiency, place G6PD deficiency and any implicated drug reaction prominently in the medication record, counsel the patient to avoid oxidative triggers, and provide a written exposure plan. Most individuals remain asymptomatic unless exposed to infection, fava beans, or oxidative medications; prevention therefore centers on anticipatory avoidance rather than chronic treatment. BMJ+1BMJGlucose-6-phosphate dehydrogenase deficiency - Symptoms, diagnosis and treatment | BMJ Best Practice USNatureGlucose-6-phosphate dehydrogenase deficiency in the Han Chinese population: molecular characterization and genotype–phenotype association throughout an activity distribution | Scientific Reports

For malaria radical cure or prophylaxis decisions, do not prescribe tafenoquine unless G6PD testing has documented acceptable status. FDA labeling states that all patients must be tested before tafenoquine initiation and lists G6PD deficiency or unknown G6PD status as contraindications because of hemolytic-anemia risk. fdafdaTable of Pharmacogenomic Biomarkers in Drug Labeling

Primaquine also carries a clinically important hemolysis risk in G6PD deficiency. Severe G6PD deficiency is a contraindication; when primaquine is considered in mild to moderate deficiency, FDA-linked labeling requires individualized risk-benefit assessment, baseline hemoglobin and hematocrit, and close hematologic monitoring including assessment at day 3 and day 8. fdafdaTable of Pharmacogenomic Biomarkers in Drug Labeling

Avoid rasburicase in known G6PD deficiency. The drug is contraindicated because hemolytic anemia and methemoglobinemia can occur; a patient with unknown status who is likely to require rasburicase should undergo G6PD assessment before exposure when clinical circumstances permit. PubMedPubMedRasburicase-induced haemolysis and methemoglobinemia

In a neonate with significant indirect hyperbilirubinemia, include G6PD deficiency in the etiologic evaluation, particularly when ancestry, family history, an affected sibling, or an unexplained bilirubin trajectory raises suspicion. G6PD deficiency is associated with neonatal jaundice, bilirubin encephalopathy, and severe hyperbilirubinemia that can cause kernicterus if not recognized. Nature+3NatureGlucose-6-phosphate dehydrogenase deficiency and neonatal indirect hyperbilirubinemia: a retrospective cohort study among 40,305 consecutively born babies | Journal of PerinatologyNatureGlucose-6-phosphate dehydrogenase deficiency in the Han Chinese population: molecular characterization and genotype–phenotype association throughout an activity distribution | Scientific ReportsScienceDirectGlucose-6-Phosphate Dehydrogenase Deficiency and Borderline Deficiency: Association with Neonatal Hyperbilirubinemia - ScienceDirectcdn clinicaltrialsEvaluation of a diagnostic to identify G6PD deficiency in ...

Do not dismiss G6PD deficiency because hemoglobin, reticulocyte count, or other routine hematologic indices do not show striking hemolysis. In G6PD-deficient neonates with severe hyperbilirubinemia, standard hematologic indices may correlate poorly with hemolysis, even though hemolysis contributes substantially to pathophysiology. NatureNatureGlucose-6-phosphate dehydrogenase deficiency and neonatal indirect hyperbilirubinemia: a retrospective cohort study among 40,305 consecutively born babies | Journal of Perinatology

Obtain quantitative G6PD testing when the result will alter bilirubin surveillance, exposure counseling, or family risk assessment. Newborn screening may identify infants with reduced activity, but confirmatory quantitative enzyme testing and, when used, mutation analysis are needed to characterize the result. Nature+1NatureGlucose-6-phosphate dehydrogenase deficiency and neonatal indirect hyperbilirubinemia: a retrospective cohort study among 40,305 consecutively born babies | Journal of PerinatologyNatureNewborn screening of glucose-6-phosphate dehydrogenase deficiency in Guangxi, China: determination of optimal cutoff value to identify heterozygous female neonates | Scientific Reports

For patients with confirmed deficiency and no ongoing hemolysis, focus follow-up on exposure avoidance, medication reconciliation before new prescriptions, and recognition of recurrent hemolysis. Most affected individuals are asymptomatic for most or all of life, with episodes triggered by oxidative stress rather than a continuously active disease process. BMJ+1BMJGlucose-6-phosphate dehydrogenase deficiency - Symptoms, diagnosis and treatment | BMJ Best Practice USNatureGlucose-6-phosphate dehydrogenase deficiency in the Han Chinese population: molecular characterization and genotype–phenotype association throughout an activity distribution | Scientific Reports

Refer to hematology when enzyme results remain discordant with a convincing clinical phenotype, when recurrent hemolysis occurs without a clear exposure, when chronic hemolysis is suspected, or when a specialized phenotypic/genotypic interpretation is needed in a heterozygous female. Genotype-phenotype discordance is especially relevant in females because X-inactivation makes genotype an unreliable predictor of red-cell functional deficiency. ASHASHGlucose-6-phosphate dehydrogenase deficiency | Blood | American Society of Hematology

For a patient who may require an 8-aminoquinoline antimalarial, coordinate testing and treatment planning before travel or malaria therapy rather than addressing G6PD status after exposure. The safety requirements for tafenoquine and the monitoring requirements for selected primaquine use make pre-treatment planning clinically consequential. fda+1fdaTable of Pharmacogenomic Biomarkers in Drug LabelingNEJMTafenoquine versus Primaquine to Prevent Relapse ...