Transcript (G6PD) Deficiency

FBC – Case F
Glucose-6-Phosphate
Dehydrogenase (G6PD)
Deficiency
Tuan Tran
Thi Trang
Tu Nguyen
Patient History
Patient
Mr GS
Age
40
Prescription
Bactrim
Aspirin
Chest infection
Diagnosed
illness
Other medical
condition
G6PD
deficiency
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
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)
Variations of G6PD
G6PD genes is highly polymorphic
Over 300 variants resulting from a singlepoint 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
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;
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


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
haemolytic anaemia
neonatal jaundice
abdominal and/or back pain
dizziness
Headache
dyspnoea (irregular breathing)
palpitations

(Cecil 1992)
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)
Haemolytic Anaemia
Induced in patients by;
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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
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).
Haemolytic Anaemia
Induced in patients by;

Infections
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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).
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).
Management of G6PD
Ensure body tissues are provided with
enough oxygen by the red blood cells
Avoid trigger factors
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
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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
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
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
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
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
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
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
Aspirin…
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
Haemolytic anaemia
Haemolytic anaemia
= RBC are detroyed
faster than the bone
marrow can produce
them
Abnormally shaped
red cells presence in
the blood
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
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
Conclusion…
Bactrim 
Megaloblastic anaemia
 Thrombocytopenia

G6PD + Aspirin 
Haemolytic anaemia
 Thombocytopenia

Infections 
Haemolysis
  leucocytes

Effect on patient’s FBC
RBC
WBC
Hb
Hct




MCV
MCH
MCHC
RDW
Platelets


N


Haemolytic anaemia from aspirin
Infections
Oxygen transport capability
Haematocrit (vol. of RBC expressed
as a fraction of total blood vol.)
Average volume of single red cell
Average weight of Hb in red cell
Average conc of Hb in 100mL red cell
Reticulocytes  from haemolysis
Thrombocytopenia
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
Medications with proven
haemolytic potential
Currently available medications with proven
haemolytic potential are relatively few in
numbers. Known examples are:
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primaquine
chloroquin
quinine
Other drugs with haemolytic
potential….
Sulfonamides/sulfones
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sulfamethoxazole
dapsone -> causes haemolytic anaemia when
daily dose is greater than 200mg
Cytotoxic/antibacterials
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chloramphenicol
cotrimoxazol
Other drugs with haemolytic
potential….
Miscellaneous
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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
Prescribing drugs for patients
with G6PD defiency
3 points to keep in mind
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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.