What is the management and treatment of Glucose-6-phosphate dehydrogenase (G6PD) deficiency?

From the Guidelines

The management of G6PD deficiency primarily involves preventing hemolytic crises by avoiding triggers, and patients with this deficiency should avoid certain medications and foods, as outlined below. The goal is to prevent oxidative damage to red blood cells, which lack sufficient G6PD enzyme to protect against oxidative stress, leading to cell membrane damage and premature destruction of erythrocytes.

Key Points to Consider

• Patients should avoid certain medications including antimalarials (primaquine, chloroquine), antibiotics (sulfonamides, nitrofurantoin, ciprofloxacin), analgesics (aspirin in high doses), and other drugs like rasburicase and methylene blue, as these can trigger hemolytic crises 1.
• Fava beans and certain legumes should be eliminated from the diet, as they can also trigger hemolytic episodes.
• During acute hemolytic episodes, treatment is supportive, focusing on maintaining adequate hydration, monitoring hemoglobin levels, and providing blood transfusions if anemia becomes severe (typically when hemoglobin drops below 7-8 g/dL) 1.
• In cases of severe hemolysis with acute kidney injury, hemodialysis may be necessary.
• Splenectomy is rarely indicated.
• Neonatal jaundice due to G6PD deficiency may require phototherapy or exchange transfusion.
• Patient education is crucial, including providing a list of medications to avoid and teaching recognition of early symptoms of hemolysis such as dark urine, fatigue, and jaundice.

Screening and Diagnosis

Screening for G6PD deficiency is recommended upon entry into care or before starting therapy with an oxidant drug in patients with a predisposing racial or ethnic background, as stated in the guidelines 1.

Treatment of Methemoglobinemia

In patients with G6PD deficiency, methylene blue should be avoided due to the risk of inducing hemolysis and worsening methemoglobinemia, and alternate treatments such as ascorbic acid or exchange transfusion should be considered 1.

From the FDA Drug Label

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a condition that affects the enzyme G6PD, which helps protect red blood cells from damage. The management and treatment of G6PD deficiency involves avoiding certain medications, such as primaquine, that can trigger hemolytic anemia in individuals with the deficiency. Key considerations:

• G6PD testing should be performed before using primaquine.
• Primaquine should not be prescribed for patients with severe G6PD deficiency.
• In cases of mild to moderate G6PD deficiency, a decision to prescribe primaquine must be based on an assessment of the risks and benefits.
• Baseline hematocrit and hemoglobin must be checked before treatment, and close hematological monitoring is required.
• Adequate medical support to manage hemolytic risk should be available. 2

From the Research

Glucose-6-phosphate Dehydrogenase (G6PD) Deficiency

• G6PD is a housekeeping gene expressed in all cells, and its main physiologic role is to provide NADPH as part of the pentose phosphate pathway 3.
• The enzyme is indispensable to maintenance of the cytosolic pool of NADPH and thus the cellular redox balance 4.
• G6PD deficiency is one of the commonest inherited enzyme abnormalities in humans, arising through one of many possible mutations, most of which reduce the stability of the enzyme and its level as red cells age 3.

Management and Treatment of G6PD Deficiency

• G6PD-deficient persons are mostly asymptomatic, but they can develop severe jaundice during the neonatal period and acute hemolytic anemia when they ingest fava beans or when they are exposed to certain infections or drugs 3.
• Acute hemolytic anemia can be managed effectively provided it is promptly diagnosed, with reliable diagnostic procedures available, including point-of-care tests 5.
• Avoidance of triggers such as fava beans, certain drugs (e.g., primaquine, rasburicase), and infections is crucial in preventing hemolytic crises 5.

Role of G6PD in Cellular Physiology

• G6PD is essential for cell survival, as it is a major source of NADPH required by many essential cellular systems, including antioxidant pathways, nitric oxide synthase, NADPH oxidase, and cytochrome p450 system 6.
• G6PD is highly regulated by many signals that affect transcription, post-translation, intracellular location, and interactions with other proteins 6.
• Pathophysiologic roles for G6PD have been identified in disease processes such as diabetes, aldosterone-induced endothelial dysfunction, cancer, and others 6.

Geographic Distribution and Malaria Endemicity

• G6PD deficiency correlates remarkably with past/present malaria endemicity, and it is a unique example of an X-linked human polymorphism balanced through protection of heterozygotes from malaria mortality 5.
• G6PD deficiency has been positively selected by malaria, and recent knowledge seems to show that it also confers an advantage against the development of cancer, reduces the risk of coronary diseases, and has a beneficial effect in terms of longevity 7.