Kunwardeep Sohal, R3
HEINZ BODY ANEMIA
HEMOLYTIC ANEMIAS
2 ways to destroy RBC: issues within the RBC
and/or its membrane (intracorpuscular defects)
vs extracorpuscular
 Examples of the former: sickle cell anemia,
thalassemia, glucose-6-phosphate
dehydrogenase (G6PD) deficiency, hereditary
spherocytosis

LAB FINDINGS
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True of all hemolytic anemias
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Increased concentration of serum indirect bilirubin,
lactate dehydrogenase, and decreased haptoglobin
Differentiate the 2?: For intravascular HA,
increased concentration of free hemoglobin in the
plasma, presence of free hemoglobin in the urine
(hemoglobinuria), presence of hemosiderin in the
urine (hemosiderinuria), which is a more chronic
event
DRUG-INDUCED OXIDATIVE HEMOLYSIS
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Acquired G6PD deficiency in essence
Red blood cells contain relatively high concentrations of
reduced glutathione (GSH), a sulfhydryl-containing
tripeptide that functions as an intracellular reducing
agent
Under normal circumstances, oxidant accumulation
does not occur, since these compounds are rapidly
inactivated by GSH in conjunction with glutathione
peroxidase
GSHGSSG (oxidized), GSH levels are restored by
glutathione reductase (this reaction requires the NADPH
generated by G6PD)
CONTD
What else is NADPH required for? Major
physiologically important pathway for reducing
methemoglobin back to hemoglobin is the
NADH-dependent reaction catalyzed by
cytochrome b5 reductase (b5R)oxidative
stress leads to buildup of methemoglobin and
oxygen carrying capacity drops
 The oxygen dissociation curve is "left-shifted"
and oxygen delivery to the tissues is impaired

HEINZ BODIES
Methemoglobin is not directly harmful to RBCs
 But if oxidative assault is large enough,
methemoglobin is converted to hemichromes,
which are hemoglobin intermediates that are
variably denatured
 Continued oxidation results in irreversible
hemichrome oxidation, precipitation, and
eventually the formation of Heinz bodies

WHATS BITING THE RBCS?
Oxidative denaturation of hemoglobin also leads to
its crossbonding
 Hemoglobin is no longer free to flow in the cytosol,
producing bite or hemiblister cells in the peripheral
smear that reflect puddling of hemoglobin on one
side and an empty veil of membrane on the other
 An alternative mechanism for these bite cells is
the removal of membrane-attached Heinz bodies
via the monocyte-macrophage system in the
spleen

SMEAR (L: BITE CELLS, R: PRECIPITATES)
Blister
cell
CAUSATIVE AGENTS

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As a result, patients with G6PD deficiency are susceptible to
oxidative hemolysis by a number of drugs, however, those
with nml amounts of G6PD are still open to this event if
quantity is high enough
Common ones we see: Dapsone, Nitrofurantoin,
Phenazopyridine, Primaquine, Sulfamethoxazole, Ribavirin
Pyridium (bladder analgesic): The recommended maximum
duration of therapy is two days. However, it is not uncommon
to see patients who have been given a prescription for one to
four weeks. In some patients, the hemolysis is sufficiently
severe to induce acute renal failure, presumably due to
hemoglobinuria
CLINICAL PRESENTATION
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Signs of anemia (vitals, physical exam)
CBCs: irregularly shaped cells, since these
undeformable cells are unable to undergo elastic recoil
after fighting their way through the sinus wall of the
spleen
Blood Gas: presence of clinical "cyanosis" in the face of
a normal arterial PO2 (PaO2) as obtained by arterial
blood gases
Methemoglobinemia has been variously described as
dark-red, chocolate, or brownish to blue in color
Pulse oximetry is inaccurate in monitoring oxygen
saturation in the presence of methemoglobinemia
TREATMENT
Avoid the causative agent
 Methemoglobin levels in excess of 30 percent of
hemoglobin can be dangerous and values above
50 percent fatal
 Blood transfusion or exchange transfusion may be
helpful in patients who are in shock, and dialysis
may be necessary for those with renal failure
 Methylene blue IV provides an artificial electron
acceptor for the reduction of methemoglobin to
hemoglobin (can’t use in G6PD, ascorbic acid
used instead)

G6PD DIAGNOSIS
Important to check levels after event has
occurred (several weeks)
 Immediately after a hemolytic episode, G6PD
levels in pts with A- (one of the variants) may be
normal, since the mature cells have been lysed,
and only younger cells with normal G6PD
levels, are present (A- retic faster while taking
drug)

SOURCES
www.uptodate.com, “Extrinsic nonautoimmune
hemolytic anemia due to drugs”
 Dr Ma’s brain
 “Diagnostic Approach to Hemoglobinopathies”
Kutlar F. Hemoglobin. 2007;31(2):243-50
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