Anemia Due to Decreased RBC Survival: Hemolytic Anemias Flashcards
What are the general features of Hemolytic Anemias?
- increased rate RBC destruction
- Shortened RBC lifespan
- Increased erythropoietin secretion
- bone marrow erythroid hyperplasia
- peripheral blood reticulocytosis
- accumulation of RBC breakdown products (vary based on intravascular or extravascular)
What type of hemolysis is always pathologic?
intravascular
Describe the pathogenesis of intravascular hemolysis
Red blood cells lyse within the blood vessels
Free hemoglobin is released - then binds to haptogloblin
haptoglobin is cleared by the reticuloendothelial cells
if all haptoglobin is used up, then you will have free heme that will head toward the kidneys or will become oxidized to methemoglobin
in the kidneys you will see hemoglobinuria & hemasidenuria
What are the clinical findings associated with extra-vascular anemia?
anemia
jaundice
splenomegaly
normal / mildly decreased plasma haptoglobin
What are the clinical & lab findings associated with intra-vascular hemolysis?
anemia
jaundice
hemoglobinemia
hemoglobinuria
hemosiderinuria
decreased / absent plasma haptoglobin
What are the common causes of extravascular hemolytic anemia?
cytoskeletal abnormalities
enzyme deficiencies
globin chain abnormalities
antibody-mediated
What are the common causes of intravascular hemolytic anemia?
mechanical injury
complement fixation
intracellular parasites
exogenous toxins
What is seen in the bone marrow in hemolytic anemia?
erythroid hyperplasia - erythroid islands
- when the bone marrow is capable of responding
What finding is shown in the provided image?
erythroid island
What findings in the peripheral blood are consistent with hemolytic anemia?
polychromasia & reticulocytosis
What findings in bone marrow / other organs are consistent with hemolytic anemia?
hemosiderosis
extramedullary hematopoiesis
pigment gallstones
If you suspect hemolytic anemia, what test should you order?
- serum total bilirubin
- serum indirect (unconjugated) bilirubin
- lactate dehydrogenase
- plasma haptoglobin
- urine hemoglobin
- plasma hemoglobin
- serum / plasma methemoglobin
If spherocytes are seen in a patient suspected to have hemolytic anemia – what are the possible causes?
hereditary membrane abnormalities
autoimmune
delayed hemolytic transfusion reaction
If schistocytes are seen in a patient suspected to have hemolytic anemia – what are the possible causes?
DIC
TTP / HUS
vasculitis
valve disorders
If sickle cells are seen in a patient suspected to have hemolytic anemia – what are the possible causes?
sickling disorders
If target cells are seen in a patient suspected to have hemolytic anemia – what are the possible causes?
hemoglobinopathies
liver disease
post-splenectomy
Why do we see an overlap of areas in the world with the highest concentration of alpha & beta-thalassemia with malaria?
thalassemia offers a protective avantage in malarial infections
What causes thalassemia?
quantitative deficiency in the alpha (alpha-thalassemia) or beta (beta-thalassemia) chain in hemoglobin
The alpha chain for hemoglobin is encoded for by what chromosome?
chromosome 16
The beta chain for hemoglobin is encoded for by what chromosome?
chromosome 11
What are the pathologic consequences associated with thalassemia?
chronic hemolytic anemia
toxic effects of excess globin chains → insoluble inclusions causing membrane damage & decreased survival of RBC precursors
iron overload
expansion of hematopoietic compartment
What are the risks & benefits associated with treating beta-thalassemia major with blood transfusion?
treat symptoms
adds to systemic iron overload
The provided image is suggestive of what condition?
beta-thalassemia major
marked expansion of the hematopoiesis in severe thalassemia causes new bone formation in the outer table of the skull, causing perpendicular radiations
What is the general difference in symptoms between beta-thalassemia major & minor?
major: severe & requires frequent blood transfusions (probably shortened lifespan)
minor: asymptomatic or mild
What are the 4 different genotype possibilities of alpha-thalassemia & how are their clinical presentations different?
What are the clinical features seen in beta-thalassemia?
severe anemia
HbF or HbA2 is elevated
shortened lifespan, unless transfused
untreated children- growth retardation & death
hepatosplenomegaly, lymphadenopathy, bony abnormalities
iron overload
What feature of the provided peripheral blood smear are characteristic of beta-thalassemia?
- severe microcytic hypochromic anemia
- marked anisocytosis & poikilocytosis
- many nucleated RBC (black arrow)
- polychromasia (red arrow)
What features would you expect to seen in a peripheral blood smear in a patient with beta-thalassemia minor?
morphology may be normal or microcytic hypochromic
basophilic stippling & target cells may be seen
degree of anemia is variable
usually asymptomatic
How do we diagnose hemoglobin abnormalities?
high-performance liquid chromatography
different hemoglobins elute at different times & concentrations are read automatically
Fill out the provided table
What is the mutation associated with sickle cell anemia?
single point mutation in beta-globin gene
Valine for Glutamate substitution position 6 beta chain
What is the pathogenesis of sickle cell anemia?
sickling with hypoxia or dehydration
if resolve in a timely manner, cells will go back to the correct shape– if not, they become irreversible sickled
Why is HbS so prevalant?
because heterozygosity confers protection against malaria
What features would you expect to see in a peripheral blood smear of a patient with sickle cell disease?
normochromic normocytic anemia
sickle cells during crises
target cells (dehydration)
anisoporikilocytosis
polychromasia/reticulocytosis
What are the clinical symptoms that are common in persons with sickle cell diseas?
splenic infarction (b/c sludge in blood)
skin ulcers
bone infarcts
osteomyelitis
streptococcus pneumonia infections (esp if asplenic)
What is the abnormality associated with hereditary spherocytosis? Describe the pathogenesis associated with this disease.
cytoskeletal abnormality
normal when first produced, but as the RBC ages, it is notable to make more cytoskeletal proteins, so the cytoskeleton will degenerate
make blebs, lose part of their membrane & become spherocytic (much less deformable & destroyed in the spleen)
What is the abnormality associated with hereditary spherocytosis? Describe the pathogenesis associated with this disease.
cytoskeletal abnormality
normal when first produced, but as the RBC ages, it is notable to make more cytoskeletal proteins, so the cytoskeleton will degenerate
make blebs, lose part of their membrane & become spherocytic (much less deformable & destroyed in the spleen)
What features would you expect to see in a peripheral blood smear of a patient with hereditary spherocytosis?
cytoskeletal defects
spherocytes, loss of membrane
How do you diagnose hereditary spherocytosis?
osmotic fragility test
&
flow cytometry
What is the function of G6PD?
protect red cells from oxidative damage
catalyzes the first step in the pentose phosphate pathway & reduces NADP to NADPH - keeps glutathione in the reduced state- protects cell form oxidation damage
What can happen to patients with a G6PD deficiency?
when red blood cells experience oxidative stress (certain medications/food/infections)
transient intravascular hemolysis
form Heinz bodies that attach to RBC membranes that are plucked out from the spleen -creating “bite cells”
What are the genetics of G6PD deficiency?
X-linked (many variants)
What are the genetics of G6PD deficiency?
X-linked (many variants)
What features would you expect to see in a peripheral blood smear of a patient with G6PD deficiency?
anemia ONLY after exposure to oxidizing agents
bite cells (center)
Heinz bodies (insert)
When should you test for G6PD deficiency and how do you do it?
Do NOT test at time of hemolytic episode – wait until after they have cleared it
Rapid: Fluorescent Spot Test
Quantitative: Spectrophotometry
What are the 3 groups of antibodies that are involved in immune hemolytic anemia?
autoantibodies
alloantibodies
drug-related
Immune hemolytic anemia can be cause by autoantibodies due to what cause?
infections
lymphoproliferative disorders
autoimmune disorders
Immune hemolytic anemia can be cause by alloantibodies due to what cause?
transfusion-related
hemolytic disease of fetus & newbord
Drug-related immune hemolytic anemia can be due to what causes?
drug adsorption to RBC membrane
autoantibody induction
neoantigen formation
What features would you expect to see in a peripheral blood smear of a patient with warm autoimmune hemolytic anemia?
- spherocytes/microspherocytes
- polychromasia (larger blue erythrocytes)
- nucleated red blood cells (in severe cases)
What process is being depicted in the provided image of a peripheral blood smear?
cold agglutination (IgM)
exception in old people- Donath Landsteiner hemolytic anemia (IgG)
What is the hemolytic anemia due to acquired intrinsic RBC defect?
paroxysmal nocturnal hemoglobinuria
What is the mutation that leads to acquired hemolytic anemia? Describe this pathogenesis.
Acquired stem cell defect: GPI deficiency - anchors proteins to the surface of RBC
lose anchor CD59 & CD55, which regulate complement in the blood stream → leads to inappropriate coagulation cascade
chronic intravascular hemolytic anemia
What are the clinical features of PNH?
chronic intravascular hemolytic anemia
impaired bone marrow function
susceptibility to thrombosis
varying degrees of hemolysis at different times of day
What feature of PNH is depicted in the provided slide?
hemosiderin deposition in the renal tubules
What is the test of choice to diagnose PNH?
Flow Cytometry
