Hem: Hemolytic Anemias

Front 1

What are hemolytic anemias?

Back 1

Blood disorders characterized by decreased RBC lifespan (normal = 120 days.)

Front 2

Are patients with hemolytic anemia always anemic?

Back 2

No. It depends on the amount of marrow compensation.

Front 3

What are the clinical features of hemolytic anemia?

Back 3

Jaundice,
scleral icterus,
pigmented gallstones,
ankle ulcers,
splenomegaly,
aplastic crises (parovirus B19),
increased requirement for folate.

Front 4

How does parovirus cause an aplastic crisis?

Back 4

It lyses precursor cells in the marrow, causing a transient period of aplastic crisis.

Front 5

What are the functions of the spleen?

Back 5

1. repository for white cells and platelets,
2. contains macrophages that phagocytose bacteria and damaged red cells, and
3. contains red cells responsible for generating atntibodies.

Front 6

What does a peripheral blood smear show after splenectomy?

Back 6

Howell-Jolly bodies,
schistocytes, acanthocytes, and nucleated red cells.

Front 7

How are hemolytic anemias classified?

Back 7

1. sites of red cell destruction,
2. aquired or congenital,
3. mechanism of red cell damage.

Front 8

What are the two sites of red cell destruction in hemolytic anemia?

Back 8

1. Extravascular (macrophages in spleen, liver, and marrow remove damaged/coated RBCs), or
2. Intravascular (red cells rupture within the vasculature, releasing free Hg)

Front 9

What is evidence for increased red cell production in the blood smear?

Back 9

Elevated reticulocyte count, polychromasia, elevated MCV and RDW.

Front 10

What is evidence for increased red cell production in the bone marrow?

Back 10

Erythroid hyperplasia (increase in number of red cell precursors.)

Front 11

What is evidence for increased red cell destruction?

Back 11

Elevated LDH and
elevated unconjugated bilirubin.

Front 12

What are the biochemical consequences of intravascular hemolysis?

Back 12

1. low levels of serum haptoglobin,
2. hemoglobinemia,
3. hemoglobinuria, and
4. hemosiderinuria.

Front 13

What is seen on the blood smear after intravascular hemolysis?

Back 13

1. schistocytes (a subset of which are "helmet cells,")
2. spherocytes, and
3. bite cells or blister cells.

Front 14

What are the two categories of congenital hemolytic anemias?

Back 14

1. Hereditary spherocytosis and
2. Hereditary elliptocytosis.

Front 15

What causes hereditary spherocytosis?

Back 15

Defects in spectin and ankyrin of the membrane skeleton cause hemolysis.
Membrane blebbing and loss of surface area causes spherocytosis and extravascular hemolysis.

Front 16

How is hereditary spherocytosis passed down genetically?

Back 16

It is an autosomal dominant trait.

Front 17

What diagnoses hereditary spherocytosis?

Back 17

Increased osmotic fragility

Front 18

What is the treatment for hereditary spherocytosis?

Back 18

Folate, and
splenectomy (but be careful of OPSS - overhwelming post-splenectomy sepsis.)

Front 19

What is the rate-limiting step in the pentose phosphate shunt pathway?

Back 19

G6PD

Front 20

What happens in the pentose phosphate shunt pathway?

Back 20

Glucose is converted to NADPH, which detoxifies metabolites from oxidative stress and getting rid of methemoglobin (oxidized Hg.)

Front 21

What do you see on the stain with G6PD deficiency?

Back 21

Heinz bodies, bite cells, blister cells.

Front 22

What are the two types (and demographics) of G6PD deficiency?

Back 22

Type A (most prevalent)
and Type B (20% of health Africans)

Front 23

How is G6PD deficiency passed down genetically?

Back 23

The deficiency is X-linked.

Front 24

What are the clinical features of G6PD deficiency?

Back 24

Hemolysis is triggered by drugs or infections, and
anemia is maximal after 7-10 days of drug exposure.

Front 25

Why would G6PD levels in patients with A- may be normal after a hemolytic episode?

Back 25

Mature cells have been lysed and only younger cells with normal G6PD levels are present.

Front 26

What drugs cause hemolysis in G6PD deficiency?

Back 26

Sulfa drugs,
dapsone,
quinine,
chloroquine,
and vitamin K.

Front 27

What are two types of auto-immune hemolysis?

Back 27

1. IgG-coated RBCs interact with Fc receptors on macrophages, leading to spherocytosis (extravascular hemolysis), or
2. C3-coated RBCs interact with C3 receptors on macrophages (extravascular hemolysis), OR complement cascade (intravascular hemolysis.)

Front 28

What's the difference between warm and cold antibodies in auto-immute hemolytic anemias?

Back 28

Warm antibodies react best at 37 degrees and do not agglutinate red cells.
Cold antibodies react best at less than 32 degrees and do cause agglutination.

Front 29

What is the difference between a direct and indirect Coomb's test for auto-immune hemolytic anemia?

Back 29

Direct Coomb's (DAT) test for IgG or C3 that is directly on the red cells.
Indirect Coomb's (antibody screen) tests for IgG in the serum which react with generic normal red cells.

Front 30

What happens in warm antibody hemolytic anemia (AIHA)?

Back 30

IgG antibodies are formed against RBCs and coat them, and the RBCs are engulfed by macrophages.

Front 31

What do you see in the blood smear for someone with warm antibody hemolytic anemia?

Back 31

Spherocytes.

Front 32

What is Evan's syndrome?

Back 32

AIHA associated with immune platelet destruction (ITP.)

Front 33

What tests are positive in warm-antibody hemolytic anemia?

Back 33

Direct and indirect Coomb's test will be positive for IgG.

Front 34

How do you treat someone with warm-antibody hemolytic anemia?

Back 34

Immunosuppression (corticosteroids, followed by splenectomy, folloewd by stronger immunosuppressive agents.)

Front 35

What three mechanisms cause drug-induced immune hemolysis?

Back 35

1. Innocent bystander (drug-antibody immune complexes deposit on surface of red cell,)
2. Hapten (drug binds to red cell surface and antibody forms against it), or
3. True Autoimmune (drug induces antibody formation against RBCs)

Front 36

What happens in cold agglutinin diesease?

Back 36

IgM-coated RBCs agglutinate and clump in the microvasculature, leading to cyanosis and ischemia.

Front 37

What lab test will be positive for cold agglutinin disease?

Back 37

Direct Coomb's test (NEG DAT bc no IgG.)
The test is positive for C3 because IgM causes complement to fix to the cell surface.

Front 38

What two types of hemolysis can be seen in cold agglutinin disease?

Back 38

1. Intravascular hemolysis: complement-coated red cells can be lysed directly within the vessel.
2. Complement-coated red cells can be engulfed by complement receptors on macrophages.

Front 39

What conditions is cold agglutinin disease associated with?

Back 39

Mycoplasma pneumoniae, EBV (mononucleosis,) and lymphoproliferative disease.

Front 40

What is the treatment for cold agglutinin disease?

Back 40

Keep patients warm!
Steroids/spenectomy usually ineffective.