Why Methylene Blue Is Unsafe for G6PD Deficiency

Methylene blue is contraindicated in G6PD deficiency because it requires NADPH for its therapeutic action of reducing methemoglobin to functional haemoglobin.

In G6PD-deficient individuals, NADPH production is impaired, resulting in insufficient glutathione levels necessary to combat oxidative stress.

When administered, methylene blue can trigger severe intravascular hemolysis by exacerbating oxidative damage to red blood cells, which are already vulnerable due to compromised antioxidant pathways. This interaction can worsen methemoglobinemia and potentially cause acute hemolytic crisis, requiring immediate medical intervention.

Alternative treatments, such as ascorbic acid supplementation and hyperbaric oxygen therapy, offer safer therapeutic options for managing these critical conditions.

Key Takeaways

• G6PD deficiency reduces NADPH production, which methylene blue requires to function effectively in reducing methemoglobin to functional haemoglobin.
• Administration of methylene blue triggers intravascular hemolysis in G6PD-deficient patients, worsening oxidative stress and red blood cell destruction.
• The medication can exacerbate oxidative damage in red blood cells due to the compromised NADPH pathways in individuals with G6PD deficiency.
• Methylene blue’s reliance on NADPH-dependent processes can paradoxically increase methemoglobin formation, further impairing oxygen transport.
• The drug’s interaction with deficient G6PD enzyme pathways can lead to acute hemolytic crisis requiring emergency medical intervention.

Understanding G6PD Deficiency

G6PD deficiency is a hereditary genetic disorder that impairs the function of glucose-6-phosphate dehydrogenase, an essential enzyme in red blood cells. This X-linked genetic condition mainly affects males and demonstrates the highest prevalence in African populations, where it can affect up to 20% of individuals. The G6PD genetics involve specific mutations that alter either the structure or quantity of the enzyme, resulting in compromised red blood cell function. Red blood cells in affected individuals typically survive only 60 to 90 days before breaking down.

While most affected individuals remain asymptomatic under normal conditions, exposure to specific hemolytic triggers can precipitate acute episodes of illness. These episodes typically manifest through a constellation of symptoms including pallor, jaundice, dark urine, fatigue, and weakness. The severity of symptoms correlates directly with the extent of red blood cell destruction, potentially leading to hemolytic anaemia, characterised by a rapid heart rate and breathing difficulties.

The condition requires particular vigilance regarding potential triggers, which encompass various medications, infections, and certain foods—especially fava beans. This specific food sensitivity, known as favism, can induce severe hemolytic reactions upon consumption or even exposure to pollen. The management of G6PD deficiency centres primarily on trigger avoidance rather than active treatment.

Diagnostic confirmation requires specialised blood testing, enabling healthcare providers to guide patients in identifying triggers and developing avoidance strategies. For newborns, early recognition is vital as they may present with jaundice, necessitating prompt medical attention. Understanding these fundamental aspects of G6PD deficiency is essential for implementing effective preventive measures and ensuring ideal patient care.

The Role of NADPH

NADPH production in red blood cells critically depends on glucose-6-phosphate dehydrogenase (G6PD), which catalyses the rate-limiting step in the pentose phosphate pathway. This essential coenzyme maintains cellular redox balance by regenerating reduced glutathione, which protects against oxidative damage and keeps haemoglobin in its functional ferrous state. The enzyme typically functions as paired identical monomers that can form tetramers under specific pH conditions.

In G6PD deficiency, the compromised NADPH production pathway severely limits the therapeutic efficacy of methylene blue, as the conversion to its active form, leucomethylene blue, requires adequate NADPH levels.

NADPH Production Pathway Explained

Within the complex metabolic network of human cells, the pentose phosphate pathway (PPP) serves as the primary mechanism for generating NADPH. This crucial reducing agent protects cells against oxidative stress. The pathway initiates when glucose-6-phosphate dehydrogenase (G6PD) catalyses the conversion of glucose-6-phosphate to 6-phosphogluconate, yielding the first molecule of NADPH through electron transfer from NADP+. Similar to web applications that display error messages repeatedly, cellular pathways can experience recurring disruptions that impact their normal function.

This critical process of NADPH synthesis continues in the oxidative phase as 6-phosphogluconate undergoes further modification, producing an additional NADPH molecule. The efficiency of this glucose metabolism pathway is tightly regulated through multiple mechanisms, including feedback control by the NADPH/NADP+ ratio and post-translational modifications.

Significantly, SIRT2-mediated deacetylation of G6PD at lysine 403 enhances enzymatic activity, while HIF1 regulates G6PD at the transcriptional level. These regulatory mechanisms ensure the production of appropriate NADPH to maintain cellular redox balance. When this pathway is compromised, particularly in G6PD deficiency, cells become vulnerable to oxidative stress, resulting in severe clinical manifestations, such as hemolytic anaemia and tissue hypoxia.

Oxidative Balance During Treatment

During treatment of methemoglobinemia, the vital interplay between methylene blue therapy and NADPH availability becomes particularly significant in patients with G6PD deficiency. The therapeutic efficacy of methylene blue relies heavily on sufficient NADPH levels to facilitate methemoglobin reduction. However, G6PD deficiency compromises cellular defence mechanisms by limiting NADPH production, creating a paradoxical situation in treatment. X-linked inheritance patterns mean males are typically more severely affected by G6PD deficiency and face greater risks from methylene blue therapy.

When methylene blue is administered to G6PD-deficient patients, the already compromised oxidative pathways are subjected to additional stress. The limited availability of NADPH not only impairs the therapeutic action but also increases the risk of intravascular hemolysis. This occurs because G6PD deficiency restricts the cell’s ability to maintain redox balance through glutathione recycling, a process essential for protecting against oxidative damage.

The impaired oxidative defence system necessitates alternative therapeutic approaches. Ascorbic acid supplementation and oxygen therapy emerge as safer alternatives, bypassing the NADPH-dependent pathways. Understanding these molecular interactions is essential for healthcare providers to make informed decisions that protect G6PD-deficient patients from potentially harmful oxidative stress while effectively treating methemoglobinemia.

How Methylene Blue Works

Methylene blue operates through multiple biochemical pathways to achieve its therapeutic effects. The primary mechanism involves the reduction of oxidised haemoglobin (Fe3+) to its functional form (Fe2+) through an NADPH-dependent process. During this conversion, methylene blue transforms into leukomethylene blue, which serves as the active agent in reducing methemoglobin back to functional haemoglobin. The compound’s distinctive properties also cause a characteristic bluish-green discolouration of urine in patients receiving treatment.

The compound’s therapeutic versatility extends beyond haemoglobin reduction, demonstrating significant effects on vascular tone and the treatment of parasitic infections. Through the inhibition of endothelial and inducible nitric oxide synthase, as well as the suppression of guanylate cyclase, methylene blue modulates vascular function by reducing nitric oxide release and promoting vasoconstriction.

• Facilitates NADPH-dependent conversion of oxidised haemoglobin to its functional state
• Inhibits both eNOS and iNOS pathways to regulate vascular tone
• Enhances antimalarial efficacy by inhibiting P. falciparum glutathione reductase
• Prevents neurotoxicity in ifosfamide therapy through metabolite regulation
• Functions as a redox mediator in biological systems

In malaria treatment, methylene blue demonstrates particular efficacy by inhibiting Plasmodium falciparum glutathione reductase, thereby enhancing the effectiveness of traditional antimalarial medications. Additionally, in cases of ifosfamide-induced encephalopathy, methylene blue prevents neurotoxicity by inhibiting the formation of harmful metabolites, specifically by blocking the conversion of chloroethylamine to chloroacetaldehyde. This diverse mechanistic profile makes methylene blue a valuable therapeutic agent across multiple clinical applications.

Oxidative Stress and Cell Damage

Understanding oxidative stress is central to explaining why methylene blue poses risks in G6PD deficiency. In this condition, cells lack sufficient NADPH production, which is essential for maintaining reduced glutathione levels. This deficiency creates a fundamental cellular vulnerability to oxidative damage, as reduced glutathione normally converts the harmful hydrogen peroxide into water, thereby protecting cellular structures from oxidation.

The mechanism of oxidative stress in G6PD deficiency particularly affects red blood cells, which are inherently susceptible due to their oxygen-carrying function and inability to synthesise new proteins. When exposed to oxidative agents, these cells undergo degradation of proteins and lipids, resulting in structural compromise and ultimately leading to cell destruction through hemolysis. This process can precipitate acute hemolytic anaemia, a serious medical condition requiring immediate intervention. More than 300 variants of G6PD have been identified, contributing to varying levels of enzyme activity and susceptibility to oxidative stress.

The oxidative damage cascade becomes especially problematic when methylene blue is administered, as its therapeutic action depends on the availability of NADPH. In G6PD-deficient individuals, this creates a paradoxical situation where the intended treatment actually exacerbates cellular stress. The formation of methemoglobin, which cannot effectively bind oxygen, further compounds the problem by contributing to tissue hypoxia.

Various triggers can initiate or worsen oxidative stress in G6PD deficiency, including certain medications, infections, and dietary factors. The cumulative effect of these stressors, particularly when combined with methylene blue administration, can overwhelm the already compromised antioxidant defences of affected cells, potentially resulting in severe hemolytic episodes that increase patient morbidity and mortality risks.

Recognising Symptoms of Hemolysis

Clinicians must recognise the diverse manifestations of hemolysis in G6PD-deficient patients exposed to methylene blue, as early detection can prevent severe complications. Symptom recognition begins with the observation of characteristic physical signs, including pallor of the mucous membranes, jaundice affecting the skin and sclera, and the presence of dark-coloured urine, indicating hemoglobinuria. These hemolysis indicators may be accompanied by systemic manifestations such as fever, profound weakness, and fatigue. The risk of hemolytic episodes significantly increases when patients are exposed to oxidant medications or substances.

Critical physical and haematological findings that warrant immediate clinical attention include:

• Tachycardia and cardiac murmurs suggest compensatory circulatory responses
• Splenomegaly is indicative of increased red blood cell destruction
• Reticulocytosis reflects the bone marrow’s compensatory response
• Presence of characteristic peripheral blood smear abnormalities
• Development of methemoglobinemia with associated tissue hypoxia

The severity of hemolysis correlates with the extent of red blood cell destruction, ranging from mild cases with transient symptoms to severe presentations requiring urgent intervention. When hemolysis affects less than 25% of red blood cell mass, patients may experience temporary jaundice and dark urine. However, profound hemolysis can precipitate acute kidney injury due to hemoglobinuria, accompanied by back pain, confusion, and respiratory distress. Healthcare providers must maintain vigilance for signs of tissue hypoxia and deteriorating organ function, as severe hemolytic episodes in G6PD-deficient individuals carry significant morbidity and mortality risks if not promptly addressed.

Screening Before Treatment

Given the potentially severe consequences of methylene blue-induced hemolysis in G6PD-deficient patients, proper screening protocols before treatment initiation are an essential preventive strategy. While routine screening is not standard practice in the United States, it becomes particularly vital for high-risk populations, such as those with prevalence rates exceeding 3-5 per cent in males. Individuals of Mediterranean, African, or Asian descent warrant particular attention due to higher prevalence rates in these populations. The disease affects approximately 400 million people worldwide, making it the most common enzymatic disorder in humans.

Several screening techniques are available for detecting G6PD deficiency. Quantitative spectrophotometric analysis serves as the gold standard for definitive diagnosis, while the rapid fluorescent spot test offers a practical screening alternative. PCR testing enables the detection of specific mutations, proving valuable for population screening and family studies. However, diagnostic challenges arise in female heterozygotes due to X-chromosome mosaicism and in cases of acute hemolysis where older erythrocytes have already been destroyed.

The evidence supporting screening before methylene blue administration is compelling, with documented cases of severe hemolysis, particularly in premature neonates. While certain medications like hydroxychloroquine may not necessitate routine G6PD screening, methylene blue presents a clear risk that warrants preventive testing. A strategic approach to screening should focus on high-risk populations and clinical scenarios involving significant oxidative stress. When G6PD deficiency is identified, healthcare providers must pursue safe alternative treatments to ensure ideal patient care while preventing potentially severe adverse reactions.

Safe Treatment Alternatives

While methylene blue is contraindicated in G6PD deficiency, alternative treatments such as vitamin C supplementation may provide safer therapeutic options for managing methemoglobinemia. Blood transfusion remains a primary intervention for severe cases of hemolysis, offering immediate support for patients experiencing acute symptoms. Hyperbaric oxygen therapy presents a potential treatment modality, particularly in cases where rapid oxygen delivery is essential for patient stabilisation. Patients must carefully avoid sulfa-containing drugs to prevent triggering dangerous hemolytic reactions.

Vitamin C as an Alternative

Although vitamin C has been considered as an alternative treatment option for certain conditions, its use in patients with G6PD deficiency requires careful consideration due to potential risks of hemolysis. High-dose vitamin C, particularly when administered intravenously, can generate oxidative stress through the production of hydrogen peroxide and superoxide, potentially triggering hemolytic episodes in individuals with G6PD deficiency. Vitamin C exists in both reduced and oxidised forms, which affects its potential impact on cellular processes. The risk of hemolysis typically manifests 24-72 hours post-administration.

While high doses are contraindicated, physiologic doses of vitamin C may be safely utilised in specific therapeutic contexts, such as treating methemoglobinemia. Clinical guidelines emphasise several essential considerations:

• Mandatory G6PD deficiency screening before initiating high-dose vitamin C therapy
• Avoidance of rapid vitamin C infusions to prevent dangerous serum concentration spikes
• Close monitoring of patients for signs of hemolysis, particularly within the first 72 hours
• Recognition that older red blood cells are more susceptible to vitamin C-induced damage
• Implementation of reduced dosing protocols when vitamin C administration is essential

Healthcare providers must carefully weigh the benefits against potential risks when considering vitamin C therapy in patients with G6PD deficiency, prioritising patient safety through appropriate screening and monitoring protocols.

Blood Transfusion Treatment Options

Blood transfusions serve as an essential therapeutic intervention for patients with G6PD deficiency experiencing severe hemolytic episodes. When implementing blood transfusion options, healthcare providers must guarantee that donor red blood cells possess regular G6PD activity to prevent further complications and enhance treatment outcomes. The use of G6PD-deficient donor units can lead to diminished transfusion efficacy and increased hemolysis.

Patient monitoring during and after transfusion is vital, particularly for signs of alloimmunisation and adverse reactions. For newborns presenting with severe jaundice, exchange transfusion may be necessary, while less severe cases might benefit from alternative approaches such as phototherapy. The management strategy should be tailored to the individual patient’s needs, considering factors such as the severity of hemolysis and underlying triggers.

While blood transfusions effectively manage acute crises, they do not cure the underlying G6PD deficiency. Healthcare providers must remain vigilant regarding potential complications, especially during infections or exposure to oxidative stressors. Regular assessment of haemoglobin levels, reticulocyte counts, and other relevant parameters ensures the optimal therapeutic response and patient safety throughout the transfusion process.

Hyperbaric Oxygen Therapy Benefits

For patients with G6PD deficiency who cannot safely receive methylene blue treatment, hyperbaric oxygen therapy (HBOT) emerges as a crucial therapeutic alternative by effectively managing methemoglobinemia through direct oxygen dissolution in the blood plasma.

The HBOT mechanisms operate independently of NADPH pathways, making it particularly valuable for individuals with G6PD deficiency. Through increased atmospheric pressure and pure oxygen delivery, HBOT enhances tissue oxygenation by dissolving oxygen directly into the plasma, circumventing the compromised haemoglobin-dependent oxygen transport system.

Key therapeutic benefits of HBOT for methemoglobinemia include:

• Immediate elevation of dissolved oxygen in plasma, ensuring adequate tissue oxygenation
• Direct reversal of hypoxic conditions without requiring functional haemoglobin
• Enhanced oxygen diffusion gradients that facilitate cellular respiration
• Reduction of inflammatory responses and oxidative stress
• Support of crucial organ function through improved oxygen delivery

This treatment modality proves especially effective in acute cases where rapid intervention is necessary. The physiological benefits extend beyond immediate oxygenation, as HBOT also promotes long-term tissue healing through enhanced angiogenesis and vasculogenesis, offering extensive support for affected patients.

Managing Hemolytic Crisis

The management of hemolytic crisis in G6PD-deficient patients requires a systematic approach combining diagnostic testing, immediate intervention, and careful monitoring. When hemolytic triggers initiate a crisis, healthcare providers must implement rapid diagnostic measures, including complete blood count, reticulocyte count, and peripheral blood smear analysis. Crisis management focuses on identifying and removing the precipitating factor while providing essential supportive care.

Laboratory evaluation plays a crucial role in assessing crisis severity and informing treatment decisions. Decreased haptoglobin levels, elevated bilirubin, and the presence of Heinz bodies on blood smear indicate active hemolysis. In severe cases where haemoglobin levels drop considerably, blood transfusions may become necessary to stabilise the patient. Oxygen supplementation supports tissue perfusion during acute episodes of hypoxia.

Vital to long-term management is the prevention of future crises through careful medication selection and avoidance of triggers. Specific drugs, including methylene blue and rasburicase, are contraindicated due to their potential to precipitate severe hemolytic reactions when treating concurrent conditions such as methemoglobinemia; alternative therapeutic approaches must be considered, such as hyperbaric oxygen therapy.

Ongoing monitoring of blood counts and liver function helps detect early signs of hemolysis and guides chronic management strategies. Healthcare providers must educate patients about the importance of rigorous avoidance and maintaining adequate folate and iron stores to support erythropoiesis. Family history assessment helps identify individuals at risk, enabling proactive management and crisis prevention through appropriate precautions and monitoring protocols.

Risks During Viral Infections

Viral infections pose significant challenges for individuals with G6PD deficiency due to their heightened vulnerability to oxidative stress. During viral infections, particularly those caused by SARS-CoV-2, patients experience an increased oxidative burden, which can precipitate intravascular hemolysis and tissue hypoxia. The impaired redox balance characteristic of G6PD deficiency compromises the body’s ability to manage this additional oxidative stress, potentially leading to severe complications.

The relationship between viral infections and G6PD deficiency presents several critical clinical considerations:

• Viral-induced oxidative stress can trigger acute hemolytic episodes, requiring immediate medical intervention
• NADPH deficiency impairs the reduction of methemoglobin, exacerbating tissue hypoxia during infection
• Secondary complications may develop, including methemoglobinemia, which cannot be treated with standard methylene blue therapy.
• Diagnostic challenges arise from discrepancies in SpO2 and PaO2 readings, complicating treatment decisions.s
• Conventional treatments may be contraindicated, necessitating alternative therapeutic approaches.

The management of patients with IIRL infections and G6PD deficiency requires careful consideration of treatment options and potential complications. Healthcare providers must maintain heightened vigilance for signs of hemolysis and methemoglobinemia while avoiding oxidative agents that could worsen the patient’s condition. The use of supportive care measures, including oxygen therapy and ascorbic acid administration, may be necessary to effectively manage complications. This highlights the importance of early G6PD deficiency testing in populations at risk and underscores the need for specialised treatment protocols during viral infections.

Prevention and Monitoring Strategies

Effective prevention and monitoring strategies represent cornerstone elements in managing G6PD deficiency and avoiding potentially life-threatening complications. A thorough monitoring protocol includes regular blood tests, genetic screening, and vigilant medication reviews. Patient education plays a crucial role in preventing hemolytic episodes by ensuring understanding of trigger substances and early warning signs.

Implementation of preventive measures requires a coordinated approach through collaborative care involving multiple healthcare professionals. Geneticists, pharmacists, and clinicians must maintain open communication channels to guarantee safe medication administration. Regular monitoring should include peripheral blood smears to detect early signs of hemolysis, particularly during periods of increased risk such as infections.

Prevention strategies extend beyond medication management to include dietary modifications and lifestyle adjustments. Healthcare teams must emphasise the importance of avoiding trigger substances, maintaining adequate hydration, and seeking prompt medical attention for infections. Alternative treatment protocols should be established for conditions typically treated with contraindicated medications, such as using Vitamin C instead of methylene blue for methemoglobinemia.

Future Treatment Developments

Current research into G6PD deficiency treatment focuses on emerging therapies that target alternative antioxidant pathways and oxidative stress mechanisms independent of NADPH-dependent processes. Gene therapy approaches show promise in addressing the underlying genetic defect, while studies of genotype-phenotype correlations may lead to more personalised treatment strategies. Novel screening methods, combined with genetic testing capabilities, are enhancing early detection and preventive care options for affected populations.

Emerging Alternative Treatment Options

As medical research continues to advance, innovative approaches to treating G6PD deficiency are emerging beyond traditional methylene blue therapy. These therapeutic innovations focus on preventive care, supportive treatments, and patient education to manage the condition effectively while avoiding potentially harmful interventions.

Key alternative treatment strategies include:

• Ascorbic acid supplementation as a safer alternative to methylene blue for treating methemoglobinemia
• Thorough oxygen therapy protocols to address tissue hypoxia during hemolytic episodes
• Targeted folic acid supplementation regimens to support red blood cell production
• Phototherapy and exchange transfusions for managing severe cases, particularly in newborns
• Customised preventive care plans focusing on trigger avoidance and prompt infection management

Recent research developments have expanded our understanding of oxidative stress mechanisms in G6PD deficiency, leading to more refined treatment approaches. Studies investigating the relationship between viral infections, including SARS-CoV-2, and hemolysis are providing valuable insights for treatment optimisation. This evolving knowledge base enables healthcare providers to implement more effective and personalised treatment strategies while ensuring patient safety through the careful avoidance of contraindicated substances and medications.

Research Into Gene Therapy

Recent advances in gene therapy research have opened promising avenues for treating G6PD deficiency through genetic modification techniques. Current gene therapy advancements focus on developing effective vectors for delivering functional G6PD genes to erythroid progenitor cells, while simultaneously addressing challenges of vector toxicity and immune responses. Researchers are particularly interested in targeted gene delivery methods using viral vectors and CRISPR/Cas9 technology to correct G6PD mutations.

Preclinical trials in animal models are evaluating both the safety and efficacy of these approaches, with a special focus on achieving controlled gene expression and preventing gene silencing. Scientists are exploring combination therapies that integrate gene therapy with other treatment modalities, including epigenetic interventions and stem cell therapies, to enhance therapeutic outcomes.

As research progresses toward human clinical trials, key considerations include regulatory compliance, long-term efficacy assessment, and ensuring treatment accessibility. The development of personalised approaches based on individual genetic profiles represents a significant advancement in the field. These ongoing investigations may ultimately provide viable treatment options for severe cases of G6PD deficiency, potentially transforming the standard of care for affected individuals.

Novel Screening Methods

Significant advancements in point-of-care (POC) testing have revolutionised deficiency screening methods, with quantitative assays, such as the CareStart TM Biosensor and STANDARD G6PD kits, demonstrating sensitivities of 72-100% and specificities of 92-100%. These novel diagnostics address vital diagnostic challenges, particularly in females with intermediate enzyme activity levels who are often misclassified by traditional qualitative tests.

The global applicability of these screening methods has been validated across diverse geographic contexts, from Asia to the Americas, with impressive predictive values. Positive predictive values range from 35% to 72%, while negative predictive values reach up to 100%, enabling more accurate diagnosis and treatment planning.

Key features of modern G6PD screening advances:

• Quantitative measurement capabilities that overcome gender-specific diagnostic limitations
• Enhanced accuracy in detecting intermediate enzyme activity levels
• Validated performance across multiple geographic regions
• Improved diagnostic precision for antimalarial drug administration
• Integration potential with existing healthcare infrastructure in resource-limited settings

These screening innovations represent significant progress in managing G6PD deficiency, particularly in malaria-endemic regions, where accurate diagnosis is crucial for implementing safe treatment protocols.

Frequently Asked Questions

Can Methylene Blue Be Used Topically in G6PD-Deficient Patients?

Topical application of methylene blue is not recommended for G6PD-deficient patients due to potential skin absorption and systemic effects, which could trigger hemolysis despite the external application method.

How Long Does Methylene Blue Stay in the Body After Administration?

Methylene blue metabolism results in a primary half-life of 5-6 hours, with drug elimination occurring through urine for up to 24 hours, though tissue retention can extend its presence considerably longer.

Are There Genetic Tests to Predict Methylene Blue Sensitivity?

Like a genetic compass guiding treatment decisions, PCR and DNA sequencing tests can identify G6PD gene variants, enabling healthcare providers to predict individual genetic predisposition to methylene blue sensitivity.

Do all G6PD-deficient patients react the Same to Methylene Blue?

Individual responses to methylene blue vary among G6PD-deficient patients due to variations in enzyme activity, the severity of the deficiency, genetic variants, and other physiological factors that influence oxidative stress sensitivity.

Can Methylene Blue Cause Permanent Damage to Organs Besides Blood Cells?

Like a cascading domino effect, methylene blue toxicity can inflict permanent damage to the kidneys, liver, and heart through severe oxidative stress and subsequent organ dysfunction beyond its impact on blood cells.

Conclusion

Methylene blue poses profound peril for patients with G6PD deficiency due to its potent oxidative properties. The compound’s interaction with compromised NADPH pathways triggers severe hemolytic responses, potentially precipitating life-threatening crises.

Critical clinical vigilance, molecular monitoring, and meticulous medication management remain paramount in preventing adverse outcomes. Advancing alternative therapeutic approaches and enhanced diagnostic protocols will fortify future treatment strategies for this significant enzymatic disorder.