FBC – Case F Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency

1. FBC – Case FGlucose-6-Phosphate Dehydrogenase (G6PD) Deficiency Tuan Tran Thi Trang Tu Nguyen

2. Patient History

3. Discussion Issues • Variations of G6PD • Clinical features of G6PD • Management of G6PD • Potential adverse effects of patients medication (Bactrim and Aspirin) on his FMC • Other classes of medicines contraindicated in G6PD deficiency

4. What is G6PD Deficiency? • G6PD deficiency is the most common human enzyme deficiency • Also known as Favism – since G6PD deficient patients are also allergic to fava beans • A genetic condition – inherited in an X-linked recessive gene • Most G6PD deficient patients have abnormality in the structure of the G6PD enzyme (Scriver et al., 1995)

5. Variations of G6PD • G6PD genes is highly polymorphic • Over 300 variants resulting from a single-point mutationa are known to exist in different populations of the world • Several variants have significantly reduced activity and result in a condition called G6PD deficiency

6. Clinical Features of G6PD • G6PD is 3 times the size of haemoglobin • Major carrier of oxygen • A deficiency results in lack of oxygen transport throughout the body causing; • haemolytic anaemia • neonatal jaundice • abdominal and/or back pain • dizziness • Headache • dyspnoea (irregular breathing) • palpitations (Cecil 1992)

7. Clinical Features of G6PD • Most of the symptoms of G6PD deficiency are general symptoms often associated with other disease states • The two major pathologies associated with G6PD deficiency are; • haemolytic anaemia • neonatal jaundice (Cecil 1992)

8. Haemolytic Anaemia • Induced in patients by; • Oxidative drugs • Result in the denaturation or unfolding of the hemoglobin molecule • Leads to the inability of the red blood cell to effectively transport oxygen throughout the body (Yoshida & Beutler, 1986) • Death occurs if the hemolytic episode is not properly treated

9. Haemolytic Anaemia • Induced in patients by; • Fava beans (Favism) • The only food product to be implicated in inducing an anemic response in G6PD deficient individuals (Scriver et al. 1995) • Inhaling the pollen of the fava bean plant can also induce an effect • The abundant compounds vicine and isouramil, abundant in fava beans are suspected to be the causative agents of the hemolytic response (Beutler 1994).

10. Haemolytic Anaemia • Induced in patients by; • Infections • Besides favism, infection is probably the most common cause of hemolysis in G6PD deficiency patients • Caused by oxidative metabolites produced by numerous bacterial, viral, and rickettsial infections • Important infections that can precipitate a hemolytic episode are viral hepatitis, pneumonia and typhoid fever (Cecil 1992).

11. Neonatal Jaundice • Induced in patients by; • Infections • Besides favism, infection is probably the most common cause of hemolysis in G6PD deficiency patients • Caused by oxidative metabolites produced by numerous bacterial, viral, and rickettsial infections • Important infections that can precipitate a hemolytic episode are viral hepatitis, pneumonia and typhoid fever (Cecil 1992).

12. Management of G6PD • Ensure body tissues are provided with enough oxygen by the red blood cells • Avoid trigger factors • Oxidative medications • Fava beans • Maintain good health to prevent attracting bacterial or viral infections • Infants with prolonged neonatal jaundice are placed under special lights, called bili-lights, which alleviate the jaundice

13. Management of G6PD • Anaemic episodes are treated with nasal oxygen and are placed on bed rest, which may give symptomatic relief • Anemic patients are sometimes treated with human haptoglobin products (Ohga et al. 1995), and/or blood transfusions (Cecil 1992) • In acute hemolytic anemia, patients are administered with folic acid

14. New Development • Engineered fava beans • Eliminate the causative agents of hemolytic response from the fava beans • Fava beans are an important part of the diet in the Middle East, where the frequency of G6PD deficiency and favism is high

15. Patient with G6PD + medication • Bactrim should not be given to patients with G6PD because megaloblastic anaemia can occur • Patient with G6PD deficiency are at increased risk of developing haemolytic anaemia when given oxidant drugs e.g. aspirin, anti-malarial…etc

16. Bactrim… • Folic acid is important in the synthesis of nucleic acid i.e. required by rapidly dividing cells • Bactrim (trimethoprim & sulfamethoxazole) may prevents the convertion of folic acid in diet to the active form • Therefore, folic acid deficiency can lead to megaloblastic anaemia

17. Megaloblastic anaemia • Megaloblastic anaemia presents with abnormal form of cells that are precursors of RBC • i.e. cells are large & nucleis fail to mature in normal way

18. Megaloblastic anaemia continued… Adverse effect on laboratory findings: • Increase cytoplasmic mass & maturation  megaloblast • Macro-ovalocytic RBCs enter circulation • Ineffective erythropoiesis  reticulocytopenia • Hyperbilirubinemia & hyperuricemia • Leukopenia/thrombocytopenia may occur

19. G6PD protects RBC from natural oxygen chemicals that may build up in people with fever or taking certain medications Therefore if this patient takes aspirin  unable to protect his RBC against the buildup of oxygen chemicals  blood cells are destroyed leading to haemolytic anaemia Aspirin…

20. Haemolytic anaemia • Haemolytic anaemia = RBC are detroyed faster than the bone marrow can produce them • Abnormally shaped red cells presence in the blood

21. Haemolytic anaemia continued… Adverse effect on laboratory findings: • Early stage = presence of Heinz bodies • Smear shows = anisocytosis & poikilocytosis • Reticulocytopenia & neutropenia • Thrombocytopenia & platelets are bizarre in shape & size • Shorten survival of the defective RBCs • Elevated LDH = shows sig. ineffective haemopoiesis &  haemolysis • End stage = haemoglobinuria & acute renal failure

22. Infections • Patient suffering from overwhelming infections (likely this patient) can also experience  in leucocytes (i.e. WBC) • Because leucocytes are host defense against invading microorganisms

23. Conclusion… • Bactrim  • Megaloblastic anaemia • Thrombocytopenia • G6PD + Aspirin  • Haemolytic anaemia • Thombocytopenia • Infections  • Haemolysis •  leucocytes

24. Effect on patient’s FBC

25. Other classes of drugs contraindicated in patients with G6PD deficiency • Many compounds reported to induce haemolysis in G6PD deficient individuals…however some unjustifiably labelled as haemolysis precipitants! • aspirin: in a review found that low dose 400mg aspirin in G6PD deficient pxs caused haemolytic episodes in 2 out of 40 cases….but open to much debate

26. Medications with proven haemolytic potential • Currently available medications with proven haemolytic potential are relatively few in numbers. Known examples are: • primaquine • chloroquin • quinine

27. Other drugs with haemolytic potential…. • Sulfonamides/sulfones • sulfamethoxazole • dapsone -> causes haemolytic anaemia when daily dose is greater than 200mg • Cytotoxic/antibacterials • chloramphenicol • cotrimoxazol

28. Other drugs with haemolytic potential…. • Miscellaneous • vit K derivatives • hydralazine • probenecid • vit C (ascorbic acid): is an antioxidant and present in many foodstuff and food supplements. The problem arises when G6PD deficient persons take high doses

29. Prescribing drugs for patients with G6PD defiency • 3 points to keep in mind • 1) G6PD deficiency is genetically heterogeneous, susceptibility to the haemolytic risk varies, thus a drug found to be safe in some G6PD deficient individuals may not be equally safe in others. • 2)Manufacturers do not routinely test drugs for their effects in G6PD deficient individuals. • 3) The risk and severity of haemolysis is almost always dose related.