This document discusses hemolytic anemias, which can be caused by issues within red blood cells (intracorpuscular defects) like sickle cell anemia or by factors outside of red blood cells. Laboratory findings that are common to all hemolytic anemias include increased bilirubin, lactate dehydrogenase, and decreased haptoglobin. For intravascular hemolytic anemia, there is also increased plasma free hemoglobin, hemoglobinuria, and hemosiderinuria. Drug-induced oxidative hemolysis can occur through acquisition of glutathione-6-phosphate dehydrogenase deficiency, preventing the reduction of oxidants and methemoglobin in red blood cells. Treatment involves avoiding causative agents, blood transfusion for severe cases,

1. 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

2. Lab findings
 True of all hemolytic anemias
 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

3. DRUG-INDUCED OXIDATIVE
HEMOLYSIS
 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)

4. 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

5. 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)