Lec 4 Hemolytic Anemia Flashcards
What is normal mech of RBC destruction?
normal RBCs liver for 4 months; disposal carried out by spleen “extravascularly”
What 3 things is hemoglobin degraded into?
- amino acids from globin
- Fe
- biliverdin
What happens to biliverdin?
reduced to bilirubin and released in blood where carried to liver as unconjugated bilirubin
in liver conjugated and excreted through bile
What happens to free hemoglobin released from splenic hemolysis?
bound to haptoglobin carrier protein
taken up in liver and degraded by hepatic phagocytes
What clinical features should you expect to see in patients with extravascular hemolysis regardless of etiology?
- jaundice [from unconjugated bili if liver function normal]
- splenomegaly from work hypertrophy
- increased RBC production [high EPO]
- increased reticulocyte count + possibly nucleated RBCs
- erythroid hyperplasia
- high LDH from hemolysis
- decreased haptoglobin b/c its being cleared wtih hemoglobin
What kind of bilirubin will you see if extravascular hemolysis and liver disease?
both conjugated and unconjugated
What is a complication of higher load of excreted bilirubin?
bilirubin/pigment gallstones
What should you see in peripheral blood smear of patient with extravascular hemolysis?
- polychromasia [larger bluer looking RBCs = reticulocytes]
- nucleated RBCs
What does presence of spherocytes indicate?
autoimmune hemolysis; hereditary spherocytosis
What does presence of schistocytes indicate?
microangiompathic hemolysis due to DIC, thrombotic thrombocytopenic purpura [TTP],
traumatic hemolysis –> prosthetic heart valve
What does presence of target cells indicate?
HbC disease asplenia sickle cell thalassemia liver disease
What does presence of acanthocytes indicate?
acanthocytes = spiny spur cels
liver disease
spur cell anemia
abetalipoproteinemia
What are some clinical consequences of intravascular hemolysis?
- hemoglobinemia
- hemoglobinuria
- hemosiderinuria
- increased LDH
- increased retic
- jaundice
What is warm agglutination autoimmune anemia? What type of hemolysis?
warm = IgG mediated; seen in SLE, CLL, methyl-dopa
extravascular hemolysis
What is cold agglutination autoimmune anemia? What type of hemolysis?
cold = IgM; acute anemia triggered by cold; seen in CLL, mycoplasma pneumonia, mono
intravascular hemolysis
Do you see splenomegaly in intravascular hemolysis?
nope b/c the spleen isn’t doing the work
What does the Coombs test tell you?
presence of IgM or IgG antibody on surface of RBC
What is direct coombs test?
anti-Ig antibody aded to patients blood
if RBCs agglutinate –> tells you RBCs are coated wtih Ig
What is indirect coombs test?
normal RBC added to patient’s serum –> add anti-Ig antibodies
if serum has anti-RBC surface Ig it will bind the RBCs; then when you add the anti-Ig it will aggglutinate
What do you see on peripheral smear with warm immune hemolytic anemia?
- spherocyte
- polychromasia [reticulocytes]
- nucleated RBCs
What do you see on CBC in autoimmune anemia?
high reticulocyte count
MCV normal or high due to elevated retic count
What type of autoimmune anemia associated with EBV?
IgM = cold autoimmune hemolytic anemia
What kind of autoimmune anemia do you get when ABO incompatible blood is transfused?
intravascular hemolysis = IgM mediated = Cold
What kind of autoimmune anemia do you get when Rh/minor antigen incompatible blood is transfused?
extravascular = IgG mediated
not as severe at from ABO incompatible
What is hereditary spherocytosis?
defect in RBC cell membrane cytoskeletal proteins –> membrane may be lost in some areas; lose biconcave shape
What is the most common inherited RBC membrane disorder?
hereditary spherocytosis
How is hereditary spherocytosis transmitted?
autosomal dominant
What labs can you use to test for hereditary spherocytosis?
- positive osmotic fragility = less ability to increase cell volume
What do you see on peripheral smear in hereditary spherocytosis?
spherocytes
What is treatment for hereditary spherocytosis?
splenectomy = removes site of hemolysis
What is spur cell anemia?
changes in RBC shape b/c membrane enlarged w/out change in cell volume due to increased cholesterol in RBC membrane
caused by liver disease
What do you see on smear in spur cell anemia?
spur cells [acanthocytes]
target cells
What do you see in paroxysmal nocturnal hemoglobinuria?
loss of CD55 / CD59 –> complement mediated lysis of RBCs = intravascular hemolysis
What is pathogenesis of G6PD deficiency?
G6OD helps produce NADPH for RBC –> used for reduction of glutathione which is used for reduction of hydrogen peroxide –> increased susceptibility to oxidant stress
How is G6P dehydrogenase deficiency inherited?
x linked recessive
Why do you see heinz bodies in G6PD deficiency?
heinz bodies = precipitants of hemoglobin that have been damaged by oxidants
What kind of hemolysis do you see in G6PD deficiency?
intravascular hemolysis from oxidant damage to RBC cell membrane
extravascular hemolysis
What are some classic causes of oxidant stress leading to hemolytic anemia in patients with G6PD deficiency?
- infection
- alcohol
- sulfa drugs
- antimalarials
- fava beans
What do you see on smear with G6PD deficiency?
RBCs with Heinze bodies and bite cells
Why might G6PD level may be paradoxically normal during an acute hemolytic episode?
b/c there are higher levels of G6PD enzyme in reticulocytes; during episode –> have increased reticulocyte production
What is the pathogenesis of microangiopathic anemia?
traumatic fragmentation of RBCs as they pass through obstructed blood vessels
What do you see on peripheral smear in patient wtih microangiopathic anemia?
fragmented RBCs = schistocytes
What are two conditions classically associated wtih microangiopathic hemolysis?
- disseminated intravascular coagulation [DIC]
- thrombotic thrombocytopenic purpura [TTP]
