Hemolytic Anemias Flashcards
What is hemolysis?
premature destruction of circulating red cells
What is hemolytic anemia?
hemolysis when the bone marrow cannot compensate
What is compensated hemolytic anemia?
when body has increased the red cell production (reticulocytosis) in the bone marrow
What are the 5 general categories of hemolytic diseases?
membrane defects metabolic defects hemoglobin defects mechanical destruction immune destruction
Where does extravascular hemolysis occur?
typically in the spleen (reticuloendothelial system), but also sometimes in liver and bone marrow
What gets released when a red cell lyses?
lots of things - but LDH and hemoglobin
What binds to the free hemolglobin to carry to the liver?
haptoglobin
So what labs do you see with intravascular hemolysis?
haptoglobin goes down
LDH goes up
products of hemoglobin breakdown go up
What effects in the urine can be seen from hemolysis?
when severe, hemoglobinuria (alpha-beta dimers in the urine) and hemosiderinuria (RTCs take up and metabolize the dimers to form hemosiderin granules in the urine - not good for the kidney)
What percent of red cells are destroyed extravascularly every day?
11%
WHat cells degrades these RBCs in the spleen?
macrophages
Do you see a decrease in haptoglobin in pathologic extravascular hemolysis?
yes, because some free Hgb will spill into the circulation
What is the heme broken down to?
bilirubin, so you get an increase in unconjugated bili
What will happen due to that increased unconjugated bilirubin?
gallstones
biliary obstruction
increased fecal and urinary urobilinogen
What will you see in the bone marrow due to hemolytic anemia?
erythroid hyperplacia, thinning of cortical bones/bony deformities
Hemolytic anemia will usually be ___chromic and ____cytic
normochromic
normocytic
What will RBC morphology look like in hemolytic anemia?
Poikilocytosis (red cell shape changes)
plus extra reticulocytes
What is the term for elevated levels of circulating nucleated red cells?
erythroblastemia
What happens in a chronic hemolytic anemia-aplastic crisis?
erythroid aplasia iwth severe exacerbation of anemia
usually from parvovirus B19 erythroid maturation arrest
Again, what do you need to correct the reticulocyte count for?
the degree of anemmia
How long can it take for a reticulocyte response to occur after hemolysis becomes severe enough to cause anemia?
up to 72 hrs
WHat produces haptoglobin?
the liver
Why might a haptoglobin be normal even if someone is hemolyzing?
haptoglobin is also an acute phase reactant
Low haptoglobin can also be seen in what other conditions?
advanced liver disease recent massive transfusion genetic variant megaloblastic anemias hematoma breakdown
WHy is LDH such a nonspecific test?
it increases due to ANY type of tissue damage
Which LDH isoenzyme is most useful for hemolysis?
LDH1
Why does the unconjugated biliruin increase if the liver is just fine in hemolysis?
because the unconjugated bili is so high the liver can’t keep up
What are some other causes of indirect bili elevation?
crigler najjar, gilbert’s breast milk jaundice
What lab can confirm there’s free hgn in the plasma?
easy - a plasma free hgb level
What kind of other anemia does Dr. D get all hot and bothered about mistaking for hemolytic anemia
megaloblastic anemia (bc the big precursors get broken down in the bone marrow)
What lab tests can differentiate between hemolytic anemia and megaloblastic anemia?
reticulocyte count (should be low in megaloblastic and high in hemolytic)
and blood smear for morphology (look very different)
What are the main hereditary RBC membrane defects?
defects in spectrin of ankyrine = hereditary spherocytosis
What are some presentations of hereditary spherocytosis?
highly variable from nearly asymptomatic to death in utero
clinical clues are anemia, jaundice, splenomegaly, biliary obstruction, gallstones and aplastic crisis due to pB19
What lab clues will tip you off to hereditary spherocytosis?
high retic
high indirect bili
high LDH
spherocytes on blood smear
What is the confirmatory test for herditary spherocytosis?
flow cytometry to look for the altered spectrin
used to do osmotic fragility test, but not anymore
What is the important metabolic congenital cause of hemolysis?
glucose 6 phosphate dehydrogenase deficiency
you need G6PD to charge the NADPH to reduce glutathione in order to reduce the ROS in the RBCs from oxygen carriage
In G6PD deficiency you end up getting crystalized oxidized hemoglobin collecting in the RBCs, called what?
Heinz bodies, which then get destroyed in the spleen
What are some drugs associated with hemolysis in G6PD deficiency?
antimalarials sulfonamides nitrofurantoin sulfones dimercaprol napthalene methylene blue TNT fava beans (not a drug)
WHat will be seen on blood smear for G6PD deficiency?
Heinz bodies (need a special heinz body prep) (and their byproducts): Bite cells Helmet cells Veil cells
What are some congenital causes of mechanical hemolyssi?
AVMs
heart valve defect
Congenital immune hemolysis is usually caused by what antibodies?
mom’s IgG (since that’s what Goes across the pkacenta)
WHat are some clinical presentations of acquired hemolytic anemia?
fever abdominal pain back/limb pain CV symptoms (dyspnea, angina, tachy) jaundice dark urine maybe even shock and renal failure
Overal, what labs should you test for an acquired hemolytic anemia?
CBC type and screen blood smear eval reticulocyt count LDH Bili Heptoglobin Direct antiglobulin test coags
then consider urine hemosiderine, plasma free hgb, radioactive isotope labeled RBC scan
What is an example of an acquired clonal neoplastic membrane defect? Super rare.
paroxysmal nocturnal hemoglobinuria
What acquired membrane defect do patients get with extensive thermal burns?
spectrin will denature!
What are some examples of acquired mechanical hemolysis?
malignant HTN prosthetic heart valves DIC TTP/HUS Autoimmune vasculitis March hemoglobinuria
What do you see on a blood smear in mechanical hemolysis?
schistocytes
What are the two types of autoimmune hemolytic anemia?
Warm agglutinins
cold agglutinins
What are the usual causes for warm AIHA?
mostly idiopathic, but also drugs and lymphoma
What is the typical presentation for warm AIHA?
jaundice and splenomegaly, usually abrupt onset
What are the usual causes for cold AIHA?
mostly idiopathic, but also lymphoma and infections (mycoplasma, EBV, CMV)
How does the presentation for cold AIHA differ from warm?
cold is usually insidious and usually no jaundice or splenomegaly
Wram AIHA is Ig__
IgG
What is the classic laboratory clue to warm AIHA?
positive “Screen” on the type and screen
or blood bank struggling to cross match
Cold AIHA is Ig__
IgM
What is the classic lab clue for cold AIHA?
CBC difficult bc red cells stick together from the cold agglutinin and Hgbx3-Hct is more than +2
What test will detect immunoglobulins absorbed to the red cells?
direct antiglobulin test
If the DAT is positive, how do you know what the antibody on the surface of the RBC is directed again?
use the red cell eluate test
you wash the antibody off the red cell and then test it against lab red cells that have known antigoens (so do an indirect AT on the eluate)
What are the situations where you’ll see an alloimmune hemolytic anemia?
from blood transfusion
during or after pregnancy
hematopoietic stem cell transplant
What are two antibiotics that will nonspecifically bind to RBC membrane and then we make an antibody against the combo?
penicillin and cephalosporins
can lead to a drug-induced immune mediated hemolytic anemia
(particularly common in people with CF!!)
they’ll get a positive DAT but negative RBC eluate test bc the RBCs in the IAT part of the eluate test will not have the antibiotic bound to them