Nonspherocytic Hemolytic Anemia Due to G6PD Deficiency

Nonspherocytic hemolytic anemia due to G6PD deficiency is a lifelong, inherited blood condition in which red blood cells (RBCs) break down too soon. The problem is not a “spherocyte” shape change (as in hereditary spherocytosis), but a shortage of an enzyme called glucose-6-phosphate dehydrogenase (G6PD). G6PD normally makes NADPH, which protects RBCs from “oxidative stress.” Without enough G6PD, common stresses like certain medicines, infections, or foods can damage hemoglobin, form Heinz bodies, and lead to “bite cells,” causing anemia and jaundice. The chronic, rare form with ongoing hemolysis is called “Class I” or “CNSHA” (chronic nonspherocytic hemolytic anemia). PMC+3ASH Publications+3NCBI+3

G6PD deficiency is an inherited condition where red blood cells (RBCs) do not make enough of the enzyme glucose-6-phosphate dehydrogenase (G6PD). This enzyme helps the cell make NADPH, which protects hemoglobin and the cell membrane from “oxidative” damage. Without enough G6PD, red cells are fragile; when a person gets an infection, eats fava beans, or takes certain medicines, the cells break apart (hemolyze) faster than the body can replace them, causing anemia and jaundice. Some people have rare, severe “chronic nonspherocytic hemolytic anemia” (CNSHA) variants, where hemolysis happens even without triggers. G6PD is on the X-chromosome, so the condition mainly affects males, while females can be carriers or sometimes affected. MedlinePlus+2NCBI+2

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Other names

Doctors and articles may use several names for the same condition. You might see: “G6PD deficiency, Class I”; “chronic nonspherocytic hemolytic anemia (CNSHA) due to G6PD deficiency”; “X-linked nonspherocytic hemolytic anemia (G6PD)”; or “G6PD deficiency—CNSHA variant.” All refer to severe G6PD variants that cause chronic hemolysis even without obvious triggers. PMC+2PMC+2

Red cells need G6PD to run the pentose phosphate pathway, which makes NADPH. NADPH keeps glutathione in a reduced form that neutralizes oxidants. If G6PD is low, oxidants build up and damage hemoglobin. Hemoglobin then clumps (Heinz bodies). The spleen removes those clumps, “biting” part of the RBC membrane and creating bite or blister cells. Damaged RBCs break early, causing anemia, jaundice, and dark urine. Merck Manuals+3NCBI+3NCBI+3

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Types and classifications

There are many G6PD gene variants worldwide. Clinically, the World Health Organization groups them by how much enzyme activity remains. Class I variants have very low activity and cause chronic nonspherocytic hemolytic anemia (CNSHA)—the topic of this guide. Class II–III variants have intermittent hemolysis, usually only after a trigger. (The WHO classification has been updated, but Class I is specifically retained for the chronic form.) WHO+1

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Causes

Note: Because this is a genetic condition, “cause” usually means what precipitates hemolysis. Class I disease may hemolyze chronically, but these common triggers can worsen it.

1. Infections (viral or bacterial). Any infection can raise oxidative stress inside red cells. That stress can tip a person with G6PD deficiency into sharper hemolysis, so people often first present during an illness. MedlinePlus

2. Fava beans (favism). Fava beans contain vicine and convicine, which become strong oxidants (divicine, isouramil). In G6PD deficiency, this can cause rapid hemolysis and jaundice. NCBI+2The Blood Project+2

3. Primaquine (antimalarial). Primaquine can cause life-threatening hemolysis in G6PD deficiency; testing for G6PD activity is required before prescribing. CDC+1

4. Tafenoquine (antimalarial). Like primaquine, tafenoquine is oxidant-producing and unsafe without prior G6PD testing. CDC

5. Dapsone. This antibiotic/anti-inflammatory drug can oxidize hemoglobin and trigger Heinz-body hemolysis in G6PD-deficient patients. PMC

6. Nitrofurantoin. Used for UTIs, nitrofurantoin is an oxidative stressor and can precipitate hemolysis in susceptible individuals. (Clinician references warn about use in G6PD deficiency.) Medscape

7. Sulfonamides (e.g., sulfamethoxazole). Sulfa antibiotics are classic oxidant drugs that may cause hemolysis in G6PD deficiency. Medscape

8. Methylene blue. Often used in methemoglobinemia, methylene blue itself is an oxidant and can worsen hemolysis in G6PD deficiency. NCBI

9. Rasburicase. This uric-acid–lowering enzyme makes hydrogen peroxide as a by-product; it is contraindicated in G6PD deficiency because it can cause severe hemolysis. FDA Access Data+1

10. Naphthalene (mothballs). Naphthalene exposure—by ingestion or fumes—can cause oxidative hemolysis and even methemoglobinemia, especially in G6PD-deficient children. CDC+2PMC+2

11. Henna (lawsone). Topical or ingested henna has been repeatedly linked to severe hemolysis in G6PD-deficient infants and children due to its oxidant dye component. PubMed+1

12. High-dose aspirin and some NSAIDs. Salicylates at higher doses can be oxidant stressors and have been associated with hemolysis in susceptible people. (Clinicians weigh risks and alternatives.) Medscape

13. Quinolone antibiotics (some agents). Certain quinolones may increase oxidative stress; caution is advised in G6PD deficiency. Medscape

14. Phenazopyridine. This urinary analgesic is an oxidant drug and can precipitate hemolysis in G6PD deficiency. NCBI

15. Nitrates/nitrites/aniline derivatives. These chemicals can oxidize hemoglobin; G6PD-deficient individuals are more susceptible to hemolysis after exposure. ATSDR

16. Severe metabolic stress (e.g., acidosis). Physiologic stress increases oxidant load and can accelerate hemolysis in people with low G6PD activity. NCBI

17. Certain antimalarial regimens beyond primaquine/tafenoquine. Regimens that include strong oxidants should be reviewed carefully; guidelines emphasize screening before radical cure. CDC Stacks

18. Naphthoquinone dyes and related compounds. Structurally related dyes (like lawsone in henna) can be potent oxidants and have repeatedly caused hemolysis in case reports. Semantic Scholar

19. Antineoplastic/oncology contexts (e.g., rasburicase in tumor lysis). The oncology setting sometimes exposes patients to potent oxidants; rasburicase is the clearest example and is contraindicated. FDA Access Data

20. Chronic oxidative exposures (e.g., mothball-stored clothing). Repeated low-level naphthalene exposure from mothballs can also precipitate hemolysis, especially in infants and small children. PMC

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Common symptoms

1. Pallor (pale skin or inner eyelids). Fewer healthy RBCs means less hemoglobin, so skin and conjunctiva can look pale. MedlinePlus

2. Jaundice (yellow skin/eyes). When RBCs break, bilirubin rises, turning skin and sclera yellow. MedlinePlus

3. Dark or tea-colored urine. Hemoglobin and bilirubin breakdown products can darken urine during hemolysis. MedlinePlus

4. Fatigue and low energy. With fewer RBCs, oxygen delivery drops, so people feel tired and weak. MedlinePlus

5. Shortness of breath with activity. The heart and lungs work harder to deliver oxygen when anemia is significant. MedlinePlus

6. Fast heartbeat (palpitations). The body compensates for anemia by increasing heart rate (sinus tachycardia). NCBI

7. Headache or dizziness. Less oxygen to tissues can cause light-headedness or headaches, especially during acute episodes. MedlinePlus

8. Scleral icterus (yellow eyes). This is jaundice visible in the whites of the eyes, common in hemolysis. MedlinePlus

9. Abdominal discomfort in the spleen area. The spleen may enlarge as it clears damaged RBCs, causing a sense of fullness or mild pain. MedlinePlus

10. Back pain during a crisis. Rapid hemolysis can cause flank or back discomfort as pigments are filtered by the kidneys. MedlinePlus

11. Neonatal jaundice (newborns). G6PD deficiency is a risk factor for significant newborn jaundice and bilirubin neurotoxicity, requiring careful monitoring. AAFP+1

12. Poor exercise tolerance. Anemia limits oxygen delivery during exertion, so endurance drops. MedlinePlus

13. Cold hands/feet. Reduced oxygen and perfusion in anemia can make extremities feel cool. MedlinePlus

14. Nausea or loss of appetite during crises. Acute illness and hemolysis often come with general “sick” feelings and reduced appetite. MedlinePlus

15. Yellowing of the skin appearing or worsening after a trigger (drug/food). A classic pattern is feeling well until exposure, then sudden jaundice and dark urine. MedlinePlus

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Diagnostic tests

A) Physical examination (simple bedside checks)

1. Conjunctival and palmar pallor check. Looking at the inner eyelids and palms helps screen for anemia when lab testing is not immediately available. MedlinePlus

2. Scleral icterus and skin jaundice check. Visible yellowing guides urgency for bilirubin testing, especially in newborns with G6PD deficiency risk. AAFP

3. Pulse and heart rate assessment. Tachycardia suggests the body is compensating for anemia and helps grade severity. NCBI

4. Abdominal palpation for spleen size. Splenomegaly can develop as the spleen removes damaged RBCs in hemolytic states. MedlinePlus

5. Hydration and capillary refill. Dehydration can worsen jaundice and hemolysis; simple refill testing supports clinical judgment. AAFP

B) “Manual” or bedside tests (quick, low-tech or point-of-care)

6. Urine inspection/dipstick for blood/urobilinogen. Dark urine and positive heme without many RBCs suggests hemoglobinuria from hemolysis. MedlinePlus

7. Bedside hemoglobin (e.g., HemoCue). A quick finger-stick estimate helps decide on urgency and need for transfusion evaluation. MedlinePlus

8. Visual jaundice assessment tools in newborns. Regular checks trigger confirmatory bilirubin measurements per AAP guidance. Indian Pediatrics

9. Orthostatic vitals. Falling blood pressure or rising pulse on standing can reflect symptomatic anemia. NCBI

10. Bedside reticulocyte estimation (if available). A high retic count suggests the marrow is responding to hemolysis. NCBI

C) Laboratory & pathological tests (core diagnostics)

11. Complete blood count (CBC) with reticulocyte count. CBC shows anemia; reticulocytes are usually high in hemolysis as the marrow tries to keep up. NCBI

12. Peripheral blood smear. In G6PD hemolysis you may see “bite” and “blister” cells; Heinz bodies are visible with a supravital stain. Merck Manuals+1

13. Bilirubin panel (total/direct) and liver tests. Indirect (unconjugated) bilirubin rises in hemolysis; AST/ALT and alkaline phosphatase help rule out hepatobiliary disease. MedlinePlus

14. LDH and haptoglobin. LDH goes up and haptoglobin goes down in intravascular hemolysis, supporting the diagnosis. NCBI

15. Direct antiglobulin (Coombs) test. A negative Coombs favors non-immune causes like G6PD deficiency over autoimmune hemolysis. NCBI

16. G6PD screening test (fluorescent spot test). A widely used qualitative screen; if low/absent fluorescence, deficiency is likely. (Best done when patient is not in acute crisis.) WHO Apps+1

17. Quantitative G6PD enzyme assay. Confirms the diagnosis and grades deficiency; timing matters because young reticulocytes can mask deficiency right after a crisis. BSH

18. Molecular (DNA) testing for G6PD variants. Genetic testing can identify the specific variant, which is helpful for counseling and epidemiology. MedlinePlus

19. Heinz body preparation (supravital stain). Demonstrates denatured hemoglobin clumps, supporting oxidant injury as a mechanism. NCBI

20. Urinalysis for hemoglobin/urobilinogen and urine microscopy. Helps distinguish hemoglobinuria from hematuria and monitor kidney impact during severe hemolysis. MedlinePlus

D) Electro-diagnostic / device-based monitoring (to grade severity or complications)

21. Pulse oximetry. Tracks oxygen saturation and pulse; helpful during acute hemolysis and in infants with jaundice to watch for illness. (Interpret with caution in anemia.) NCBI+1

22. Electrocardiogram (ECG). May show sinus tachycardia during significant anemia; helps assess strain and rule out other causes of symptoms. jebmh.com

23. Transcutaneous bilirubin (TcB) in newborns. A noninvasive device to screen bilirubin and decide when to do a serum level, emphasized in modern newborn guidelines. Indian Pediatrics

E) Imaging (to look for downstream effects of chronic hemolysis)

24. Abdominal ultrasound—gallbladder and bile ducts. Chronic hemolysis can promote pigment gallstones; ultrasound is first-line to detect stones or sludge. PMC

25. Ultrasound during childhood for stone screening when indicated. Studies in chronic hemolytic anemias (and some reports specific to G6PD deficiency) show higher rates of cholelithiasis. Lippincott Journals+1

26. MRCP/ERCP (selected cases). If jaundice or pain suggests common bile duct stones, advanced imaging or ERCP can define and treat obstruction. ScienceDirect

Non-pharmacological treatments (therapies & others)

(Each item: brief description, purpose, and mechanism of benefit.)

1. Strict avoidance of known high-risk drugs
   Purpose: prevent drug-triggered hemolysis. Mechanism: avoiding agents that generate oxidants in RBCs (notably rasburicase/pegloticase; primaquine/tafenoquine) prevents Heinz-body formation and cell destruction. Use trusted lists (e.g., CPIC risk categories; CDC/FDA labels). files.cpicpgx.org+2CDC+2

2. Avoid fava beans (favism) and similar oxidative foods/chemicals (e.g., naphthalene/mothballs)
   Purpose: prevent classic food/chemical triggers. Mechanism: these contain oxidant compounds (e.g., vicine/convicine in fava) that deplete glutathione and injure hemoglobin in G6PD-deficient RBCs. MedlinePlus+1

3. Prompt infection control (seek care early, treat source)
   Purpose: infections commonly precipitate hemolysis. Mechanism: infections increase reactive oxygen species; controlling infection reduces oxidative stress on RBCs. MedlinePlus

4. Hydration during attacks
   Purpose: maintain kidney perfusion and reduce risk from hemoglobinuria. Mechanism: fluids dilute and flush free hemoglobin and support renal function while hemolysis settles. (Supportive care emphasized in reviews.) NCBI

5. Medical alert identification
   Purpose: inform clinicians quickly in emergencies. Mechanism: prevents inadvertent exposure to contraindicated medications and guides safe therapy choices. (Guideline counseling recommendation.) files.cpicpgx.org

6. Neonatal jaundice pathways with AAP 2022
   Purpose: prevent bilirubin-induced neurologic dysfunction in G6PD-positive newborns. Mechanism: earlier bilirubin checks, standardized intensive phototherapy, and escalation protocols lower exchange-transfusion needs. American Academy of Pediatrics+2Pediatrics +2

7. Phototherapy for neonatal hyperbilirubinemia
   Purpose: reduce bilirubin levels safely. Mechanism: light converts bilirubin to excretable isomers, lowering neurotoxicity risk in at-risk infants (including G6PD deficiency). AAFP

8. Exchange transfusion in severe neonatal cases (procedure)
   Purpose: rapidly remove bilirubin and sensitized/fragile RBCs when phototherapy fails. Mechanism: replaces circulating blood, cutting bilirubin and hemolysis load. (AAP algorithms). AAFP

9. Genetic counseling (family education, X-linked inheritance)
   Purpose: help families understand risks, carrier status, and testing. Mechanism: clarifies X-linked transmission and guides future pregnancy/newborn planning. MedlinePlus

10. Workplace/household chemical safety
    Purpose: avoid oxidative chemicals (e.g., naphthalene). Mechanism: reduces cumulative oxidative exposure that might trigger hemolysis. PMC

11. Vaccinations (routine schedule)
    Purpose: fewer infections → fewer hemolytic triggers. Mechanism: preventing infectious illnesses reduces oxidative stress episodes. MedlinePlus

12. Breastfeeding guidance when mothers require primaquine/tafenoquine
    Purpose: protect infants from indirect exposure. Mechanism: per CDC/AAP, these drugs are contraindicated in G6PD deficiency; testing and alternatives are considered to avoid infant risk. CDC

13. Educated self-monitoring during illness
    Purpose: recognize early signs—fatigue, pallor, dark urine, jaundice. Mechanism: earlier presentation allows faster supportive care and prevention of complications. NCBI

14. Retesting G6PD after crisis if initial result normal
    Purpose: avoid missed diagnosis. Mechanism: reticulocytosis can mask deficiency; confirm after recovery for accurate labeling and lifelong trigger avoidance. AAFP

15. Use of quantitative (not only qualitative) G6PD testing when decisions depend on it
    Purpose: avoid false reassurance in heterozygous females/intermediate activity. Mechanism: quantitative assays detect partial deficiency more reliably. PMC

16. Perinatal/newborn screening in high-prevalence regions
    Purpose: earlier identification prevents severe neonatal jaundice. Mechanism: screening identifies infants needing closer bilirubin monitoring. Nature

17. Nutrition emphasizing folate-rich foods
    Purpose: support RBC production in chronic hemolysis (CNSHA). Mechanism: folate is required for erythropoiesis; deficiency worsens anemia. (Folate supplementation is standard in hemolytic disorders.) AAFP

18. Avoid unnecessary oxidant supplements at high dose (e.g., mega-dose vitamin C) without medical advice
    Purpose: prevent potential oxidative stress. Mechanism: some agents at high doses can act as pro-oxidants; CPIC reviewed common myths and actual risks. files.cpicpgx.org

19. Travel planning for malaria regions (choose prophylaxis that does NOT require G6PD testing)
    Purpose: safe malaria prevention without hemolysis risk. Mechanism: use agents like atovaquone-proguanil, doxycycline, mefloquine, or chloroquine when appropriate; avoid primaquine/tafenoquine unless quantitatively G6PD-normal. CDC

20. Written “safe-care” plan shared with clinicians
    Purpose: keep a personalized list of medicines to avoid, safe alternatives, and emergency steps. Mechanism: aligns care across settings; CPIC encourages drug-specific risk awareness. files.cpicpgx.org

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Drug treatments

Important note: there is no curative drug that fixes the G6PD enzyme. Treatment is supportive and trigger-avoidant. I’m listing medicines commonly and appropriately used around hemolytic episodes or related situations, with what they’re for and key safety notes. Where possible, I cite CPIC, CDC, AAP, or major references.

1. Folic acid (folate) – vitamin; 1 mg orally daily in chronic hemolysis
   Purpose: support bone marrow to make new red cells. Mechanism: folate is required for DNA synthesis in erythropoiesis; ongoing hemolysis depletes folate stores. Side effects: very well tolerated. AAFP

2. Acetaminophen (paracetamol) – analgesic/antipyretic; standard dosing
   Purpose: treat fever/pain from infections without raising hemolysis risk. Mechanism: antipyretic without meaningful oxidant effect at normal doses. Side effects: liver toxicity at overdose. files.cpicpgx.org

3. Amoxicillin (± clavulanate) – beta-lactam antibiotic; usual dosing
   Purpose: treat bacterial infections that can trigger hemolysis. Mechanism: clears infection, reducing oxidative stress. Safety: beta-lactams are not linked to G6PD-specific hemolysis. files.cpicpgx.org

4. Azithromycin – macrolide; usual dosing
   Purpose: respiratory or other susceptible infections. Mechanism: reduces infection-related triggers. Safety: not a known G6PD hemolytic risk in CPIC framework. files.cpicpgx.org

5. Ceftriaxone – third-generation cephalosporin; standard dosing
   Purpose: moderate–severe infections needing parenteral therapy. Mechanism: rapid bactericidal action. Safety: no specific G6PD hemolysis signal. files.cpicpgx.org

6. Doxycycline – tetracycline-class; usual dosing
   Purpose: alternative for respiratory/tick-borne infections; also a malaria prophylaxis option. Mechanism: antibacterial; prevents infection-triggered oxidative stress. Safety: does not require G6PD testing. CDC

7. Artemether–lumefantrine – antimalarial; per regimen
   Purpose: treat malaria without 8-aminoquinolines. Mechanism: kills malaria parasites; avoids oxidant hemolysis risk seen with primaquine/tafenoquine. Side effects: GI upset; no G6PD warning. CDC

8. Atovaquone–proguanil – antimalarial; prophylaxis/treatment per CDC
   Purpose: malaria prophylaxis/treatment where recommended, without G6PD testing. Mechanism: antiparasitic action without 8-aminoquinoline-type hemolysis. CDC

9. Chloroquine – antimalarial (for sensitive regions)
   Purpose: treatment/prophylaxis in areas with chloroquine-sensitive malaria. Mechanism: antiplasmodial activity. Safety: does not share the G6PD-specific hemolysis profile of primaquine/tafenoquine. CDC

10. Mefloquine – antimalarial; prophylaxis per CDC
    Purpose: prophylaxis in certain regions. Mechanism: antiplasmodial. Safety: no G6PD-testing requirement; neuropsychiatric cautions unrelated to G6PD. CDC

11. Packed red blood cell transfusion – (not a drug, but core therapy)
    Purpose: quickly corrects severe or symptomatic anemia. Mechanism: immediately raises hemoglobin and oxygen-carrying capacity while hemolysis subsides. Risks: transfusion reactions, iron overload with frequent use. AAFP

12. Sodium bicarbonate (IV) when significant hemoglobinuria + AKI risk
    Purpose: kidney protection in massive intravascular hemolysis (selected cases). Mechanism: urine alkalinization may reduce heme-mediated tubular injury; supportive measure only. NCBI

13. Antipyretic/analgesic alternatives (ibuprofen) – usual dosing
    Purpose: fever/pain control. Mechanism: COX inhibition; not a G6PD-specific oxidant trigger at standard doses per CPIC evidence synthesis. files.cpicpgx.org

14. Broad-spectrum antibiotics (as indicated by culture/local guidance)
    Purpose: sepsis or severe infection management. Mechanism: source control reduces oxidative stress driving hemolysis. Example classes: piperacillin-tazobactam, carbapenems (no specific G6PD warning). files.cpicpgx.org

15. Folate-repleting multivitamin (medical-grade)
    Purpose: support erythropoiesis alongside dedicated folic acid when diet is poor. Mechanism: corrects co-deficiencies that exacerbate anemia. AAFP

16. Avoid/Do-NOT-use examples (for clarity): rasburicase, pegloticase, primaquine, tafenoquine
    These are contraindicated or high-risk and are listed here to emphasize avoidance. If malaria radical cure is essential, quantitative G6PD testing and alternative plans are required. files.cpicpgx.org+1

Why not 20 drugs? Because for G6PD-related hemolysis, evidence-based care is mostly supportive plus avoiding triggers—there isn’t a long list of disease-specific drugs. The items above reflect what high-quality guidelines and reviews actually recommend in practice. NCBI

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Dietary molecular supplements

1. Folic acid – 1 mg daily in chronic hemolysis; supports RBC production and prevents megaloblastic changes. AAFP

2. Vitamin B12 – replace if deficient; deficiency worsens anemia and macrocytosis; check levels before supplementing. NCBI

3. Iron – only if proven iron-deficient (ferritin, iron studies); unnecessary iron won’t help hemolysis. NCBI

4. Balanced multivitamin (physician-guided) – fills general dietary gaps that could impact marrow output; not a treatment for hemolysis itself. NCBI

5. Riboflavin (B2) – cofactor in redox pathways; consider only if deficient; evidence for routine use in G6PD deficiency is limited. NCBI

6. Vitamin D – general health; no direct anti-hemolysis evidence; use if deficient per standard care. NCBI

7. Vitamin E – antioxidant; small studies in other hemolytic states exist but routine use in G6PD deficiency is not established; discuss with a clinician. PMC

8. Protein-adequate diet – provides amino acids for hemoglobin and RBC membrane proteins; supports recovery from anemia. NCBI

9. Folate-rich foods – legumes (not fava), dark leafy greens, fortified grains—dietary support alongside supplements in chronic hemolysis. AAFP

10. Hydration (not a supplement, but essential) – keeps urine dilute during hemolysis to protect kidneys. NCBI

Caution: Avoid “mega-dose antioxidant” supplements without medical advice. CPIC’s review highlights that many drug/supplement warnings in G6PD are based on weak evidence; stick to proven triggers and individualized care. files.cpicpgx.org

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Immunity-booster, regenerative, or stem-cell drugs

There are no approved immunity-boosting, regenerative, or stem-cell drugs that treat G6PD deficiency or reverse the enzyme defect. Management is supportive and trigger-avoidant; research on gene or enzyme replacement strategies remains experimental. Claims to the contrary are not supported by clinical guidelines. PMC

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Surgeries/procedures

1. Phototherapy (procedure) – first-line for neonatal jaundice at AAP-defined thresholds; lowers bilirubin and prevents kernicterus. AAFP

2. Exchange transfusion (procedure) – for severe neonatal hyperbilirubinemia when phototherapy fails; rapidly reduces bilirubin and removes fragile RBCs. AAFP

3. Packed RBC transfusion (procedure) – for severe/symptomatic anemia in children or adults during acute hemolysis. AAFP

4. Laparoscopic cholecystectomy (surgery) – indicated if recurrent pigment gallstones arise from long-standing hemolysis (more relevant in rare chronic variants). NCBI

5. Splenectomy (surgery; rarely used) – generally not recommended in G6PD deficiency; occasionally considered in exceptional chronic, severe CNSHA cases—evidence for benefit is limited. AAFP

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Prevention

1. Know your G6PD status (quantitative test). PMC

2. Avoid high-risk drugs: rasburicase/pegloticase, primaquine/tafenoquine. files.cpicpgx.org+1

3. Avoid fava beans and mothballs (naphthalene). MedlinePlus+1

4. Treat infections promptly; seek care early. MedlinePlus

5. Keep an updated medication card/medical alert ID. files.cpicpgx.org

6. For travel to malaria areas, pick prophylaxis that doesn’t require G6PD testing (e.g., atovaquone-proguanil), and avoid primaquine/tafenoquine unless confirmed G6PD-normal. CDC

7. Ensure neonatal bilirubin monitoring if baby or family is at risk. AAFP

8. Maintain folate-adequate nutrition (or supplement if chronic hemolysis). AAFP

9. Share your status with all healthcare providers and pharmacists. files.cpicpgx.org

10. Retest G6PD if a crisis test was normal but suspicion remains. AAFP

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When to see a doctor

• Immediately if you notice dark/cola-colored urine, sudden yellowing of eyes/skin, severe fatigue, shortness of breath, or rapid heartbeat—these can signal active hemolysis. NCBI

• Promptly if you have fever or infection symptoms, especially if you have a known trigger exposure. MedlinePlus

• Right away for newborns with rising jaundice or poor feeding—follow AAP bilirubin pathways. AAFP

• Before travel to malaria regions, to select safe prophylaxis. CDC

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What to eat—and what to avoid

1. Eat a balanced diet with folate-rich foods: leafy greens, beans (not fava), citrus, fortified grains. AAFP

2. Avoid fava beans (all forms), the classic food trigger. MedlinePlus

3. Stay well hydrated, especially during illness. NCBI

4. Normal amounts of common foods are fine; focus on variety and iron-rich foods only if iron-deficient. NCBI

5. Do not use “mega-dose” antioxidant supplements without medical advice. files.cpicpgx.org

6. For infants with G6PD deficiency, breastfeeding is encouraged; if a nursing parent requires high-risk drugs (e.g., primaquine), discuss testing/alternatives first. CDC

7. Moderate tea/coffee is fine; no evidence of G6PD-specific harm. files.cpicpgx.org

8. Seafoods and spices are generally acceptable; avoid unverified “detox” products. files.cpicpgx.org

9. Maintain adequate protein intake to aid red cell production. NCBI

10. If you follow vegetarian/vegan diets, plan folate/B12/iron intake carefully with your clinician. NCBI

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FAQs

1) Is there a cure for G6PD deficiency?
No. Management focuses on trigger avoidance, treating infections, and supportive care during episodes; rare chronic variants may need ongoing folate and occasional transfusions. NCBI

2) What makes the hemolysis “nonspherocytic”?
The red cells break from oxidative damage rather than antibodies; smears show Heinz bodies and “bite/blister cells,” not spherocytes or a positive Coombs test. Medscape

3) Why can my G6PD test be normal during a crisis?
Young reticulocytes have higher enzyme activity; retest weeks later for an accurate result. AAFP

4) Which medicines are the biggest problems?
Rasburicase/pegloticase and the antimalarials primaquine/tafenoquine are the clearest, guideline-recognized risks; avoid unless carefully managed after quantitative testing. files.cpicpgx.org+1

5) Are common antibiotics safe?
Many are fine (e.g., amoxicillin, ceftriaxone, azithromycin). Always check with your clinician; CPIC classifies drug risks based on evidence, and many “avoid lists” online are outdated. files.cpicpgx.org

6) Can ibuprofen or acetaminophen trigger hemolysis?
Used at normal doses, these are not linked to G6PD-specific hemolysis in guideline reviews; acetaminophen is often preferred for fever. files.cpicpgx.org

7) What about aspirin?
Low-dose aspirin is generally low-risk per CPIC analysis, though some labels urge caution. Discuss your specific case (e.g., cardiovascular indications) with your doctor. files.cpicpgx.org

8) Do I need special malaria pills?
Yes—avoid primaquine/tafenoquine unless proven G6PD-normal. Use other CDC-recommended agents that don’t require G6PD testing. CDC

9) Why do fava beans cause attacks?
They contain oxidants that overwhelm G6PD-deficient cells, forming Heinz bodies and leading to hemolysis. MedlinePlus

10) What should newborn care look like if G6PD runs in the family?
Screen if available; monitor bilirubin more closely; use phototherapy per AAP thresholds; escalate promptly if levels rise. AAFP

11) Can women be affected?
Yes—heterozygous females can have intermediate enzyme levels due to X-inactivation and can hemolyze with triggers; quantitative testing is best. files.cpicpgx.org

12) Is splenectomy a solution?
Generally no; it’s rarely considered and usually not helpful in typical G6PD deficiency. AAFP

13) Does folate really help?
For chronic hemolysis, yes—folate supports marrow production of new RBCs; many patients are prescribed 1 mg/day. AAFP

14) What lab clues point to a G6PD crisis?
Falling hemoglobin, high indirect bilirubin, high LDH, low haptoglobin, reticulocytosis, and “bite/Heinz body” cells on smear. Medscape

15) Where can I find reliable medication risk guidance?
Use the CPIC G6PD guideline (risk-ranked medications), plus CDC/FDA labels for antimalarials and other drugs. Avoid random internet lists. files.cpicpgx.org+1

Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical  history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.

The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members

Last Updated: September 17, 2025.

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