Bhl Week 1: Hemolytic Anemias I

Front 1

In general, how does hemolytic anemia occur?

Back 1

Bone marrow is unable to compensate for the amount of premature destruction of RBCs.

Front 2

What is compensated hemolysis?

Back 2

Normal hemoglobin is maintained despite premature RBC destruction
(Bone marrow can compensate for relatively low levels of hemolysis)

Front 3

List 3 signs of increased RBC production.

Back 3

1.* Increased reticulocyte count
2. Polychromasia (nucleated RBCs on smear)
3. Erythroid hyperplasia in marrow)

Front 4

List 3 signs of increased RBC destruction.

Back 4

1. Increased LDH,
2. Increased unconjugated bilirubin
3. Decreased haptoglobin

Front 5

What are some diagnostic clues for compensated hemolysis?

Back 5

(Might be difficult to diagnose since hemoglobin will be normal)

Look for:
1. Elevated LDH
2. Elevated unconjugated bilirubin
3. Gallstones

Front 6

Why should you not rely on a reticulocyte count to diagnose hemolysis?

Back 6

Hemolysis occurs prior to reticulocyte response-- takes about 4 - 7 days for marrow to mount a response.

Front 7

How are intrinsic hemolytic anemias obtained?

What is the one exception?

Back 7

Nearly always INHERITED

*Paroxysmal nocturnal hemoglobinuria (PNH) is an exception. It is an acquired genetic abnormaility affecting hematopoietic stem cells including RBC precursors.

Front 8

How are extrinsic hemolytic anemias obtained?

Back 8

Nearly always ACQUIRED

Front 9

List 3 abnormalities that lead to inherited hemolytic anemias.

Back 9

1. Hemoglobinopathy
2. Membrane abnormality
3. Enzyme deficiency

Front 10

List 6 factors that can lead to an acquired form of hemolytic anemia.

Back 10

1. Immune
2. Drugs or medications
3. Oxidative stress
4. Mechanical or thermal injury
5. Infectious
6. Increased complement susceptibility (PNH)

Front 11

In general, what causes extravascular hemolytic anemias?

Back 11

Phagocytosis of RBCs by macrophages in the spleen (and/or liver)

Front 12

Severe cases of intravascular hemolytic anemias are associated with which life-threatening conditions?

Back 12

1. Shock
2. DIC
3. Renal failure

Front 13

Which is more common-- intravascular or extravascular hemolytic anemias?

Back 13

Extravascular

Front 14

What type of hemolytic anemia is more likely to be life-threatening-- intravascular or extravascular?

Back 14

Intravascular

Front 15

What usually causes immediate immune hemolytic transfusion reactions?

Back 15

Usually due to a person with Group O blood given an unit of Group A blood

Front 16

What is cold agglutin disease and what type of hemolytic anemia does it cause?

Back 16

Immune disease caused by IgM antibody against RBC antigens. The antibodies bind at cooler temperatures and then cause the RBCs to aggregate.

*Generally caused by Mycoplasma pneumonia

*Results in intravascular hemolytic anemia

Front 17

What is paroxysmal cold hemoglobinuria (PCH)?

What type of hemolytic anemia does it cause?

Back 17

Immune disease caused by IgG antibodies (Donath-Landsteiner) that fix complement at cold temperatures and then dissociate from the RBC surface. The complement cascade goes to completion after the RBC returns to warmer central circulation

*Intravascular hemolytic anemia

Front 18

What causes Hemolytic Uremic Syndrome?

Back 18

Caused by bacteria which produce Shiga toxin. Results in mechanical intravascular fragmentation of RBCs

Front 19

List 4 markers of intravascular hemolysis.

Back 19

1. Hemoglobinemia (red plasma)
2. Hemoglobinuria (red or dark brown urine)
3. Hemosiderinuria
4. Decreased haptoglobin

Front 20

Will hemosiderinuria be seen during an acute or chronic phase of hemolytic anemia?

Back 20

Chronic
(Formation of hemosiderin in renal tubular cells, and then shedding the cells into the urine takes time).

Front 21

Will a test for urine hemosiderin be positive or negative in extravascular hemolysis?

Back 21

NEGATIVE
(no free Hb in the circulation to spill into the urine. Iron from phagocytized RBCs is recycled back to the bone marrow or stored within macrophages).

Front 22

Are most cases of immune hemolysis intravascular or extravascular?

Back 22

Extravascular

Front 23

Is drug-related hemolysis usually intravascular or extravascular?

Back 23

Can be both

Front 24

List 4 basic tests for determining the cause of hemolyic anemia.

Back 24

1. Reticulocyte count
2. Chemistry panel (LDH, bilirubin, haptoglobin)
3. Examination of peripheral blood smear
4. Direct antiglobin (Coombs') test

Front 25

List 3 exotic tests you might have to resort to when determining the cause of hemolytic anemia.

Back 25

1. Hemoglobin electrophoresis (Hemoglobinopathies)
2. Osmotic fragility (Hereditary spherocytosis)
3. Enzyme assays (RBC enzyme deficiencies)

*Usually done for evaluation of presumed INHERITED hemolytic anemias

Front 26

Which positive test result is the prime indicator of an immune hemolysis?

Back 26

Postive Direct antiglobulin (Coombs') test --> DAT

This test looks for immunoglobulin and/or complement components on the RBC surface

Front 27

Cases with spherocytes on the blood smear but a negative DAT would most likely be diagnosed as..?

Back 27

Hereditary spherocytosis

Front 28

List 2 complications of chronic hemolysis.

Back 28

1. Bilirubin gallstones
2. Aplastic crisis-- RBC production is shut off

Front 29

What is the most common structural hemoglobinopathy in the world?

Back 29

Hemoglobin S
(Sickle Hb)

Front 30

What mutation results in sickle hemoglobin?

Back 30

Valine for glutamic acid at 6th position of B-globin chain

Front 31

What is the advantage of sickle cell trait (heterozygous Hb S)?

Back 31

Protects against falciparum malaria

Front 32

What is the fundamental pathophysiologic problem in sickle cell diseases?

Back 32

Irreverisbly sickled cells plug up small vessels, causing ischemia in tissues

*Deoxygenated Hb S polymerizes into rigid, rod-like structures, which distort and damage RBCs. Eventually cells become irreversibly sickled.

Front 33

What is the difference between sickle cell anemia and sickle cell diseases?

Back 33

Sickle cell anemia --> Homozygous Hb S (HbSS)

Sickle cell disease --> Hb S with significant clinical complications; can be Hb SS or Hb SC, Hb SB-Thal.

Front 34

What are the most common compound heterozygous states of sickle cell diseases?

Back 34

1. Sickle-Hemoglobin C (Hb SC)
2. Sickle/B-Thalassemia (Hb SB-Thal)

Front 35

In a patient who has undergone a splenectomy, what types of infections are they predisposed to?

Back 35

Infections with organisms where opsonization is very important (encapsulated organisms like Strep pneumoniae and Hemophilus species)

Front 36

List 4 clinical syndromes associated with sickling diseases.

Back 36

1. Acute vasoocclusive (painful) crises
2. Sequestration crisis
3. Acute hemolytic crisis
4. Acute aplastic crisis

Front 37

Which virus can result in an acute aplastic crisis in patients with sickling diseases?

Back 37

Parvovirus B19

Front 38

What are acute vasooclussive crises characterized by?

Back 38

Pain in the abdomen, back, and extremities

Front 39

What's the difference between a sequestration crises and a hemolytic crises?

Back 39

In a sequestration crisis, the blood is trapped in sinusoids in the spleen, but the cells are not being phagocytized by splenic macrophages)

Front 40

What is the primary cause of death of those with sickle cell diseases?

Back 40

Infections

Front 41

Why are patients with sickle cell diseases predisposed to infections?

Back 41

Hyposplenism
(splenic infarction, autosplenectomy)

Front 42

After Hb S, what is the second most common hemoglobinopathy in the U.S?

Back 42

Hemoglobin C

Front 43

How does the clinical presentation of Hb SC compare to Hb SS?

Back 43

Hb SC is often, but not always, clinically less severe than Hb SS.

*Clinical manifestations are similar to SS.

Front 44

People with Hb SC are especially predisposed to which condition?

Back 44

Proliferative retinopathy

*Patients require careful opthalmologic examination and follow-up

Front 45

What crystal-shape forms in Hb CC disease?

Back 45

Rectangular crystals

Front 46

What is the 2nd most common structural hemoglobinopathy worldwide? (different than 2nd most common in U.S.)

Back 46

Hemoglobin E

Front 47

What is the most common RBC enzyme defect?

Back 47

Glucose-6-phosphate dehydrogenase

Front 48

Which enzyme is the most common deficiency of glycolysis?

Back 48

Pyruvate kinase

Front 49

What sort of inheritance pattern is G6PD deficiency?

Back 49

X-linked

Front 50

On the cellular level, what is the pathological outcome of a G6PD deficiency?

Back 50

1. Inability to maintain glutathione in reduced state--> unable to detoxify H2O2
2. Increased sensitivity to oxidant stress

Front 51

What are Heinz bodies?

Back 51

Aggregates of denatured hemoglobin
(Attach to and damage the RBC membrane)

Front 52

Does hemolysis occur in the majority of cases of G6PD deficiencies?

Back 52

No.
Hemolysis usually doesn't occur unless stressed (infections, drugs, etc)

Front 53

G6PD deficiencies of what descent are generally the most severe?

Back 53

Mediterranean descent

Front 54

Why are reticulocytes protected in the common African variant of G6PD deficiency?

Back 54

G6PD enzyme activity declines with the age of the RBC.
In the African variant, the enzyme activity is normal, but it has a shorter half life. Therefore reticulocytes are not damaged, but RBCs are.

Front 55

What is the most common cause of hemolysis in patients with G6PD deficiency?

Back 55

Infections

Front 56

What diagnosis should be a consideration in any acute, non-immune hemolysis?

Back 56

G6PD deficiency

Front 57

How do you diagnose a G6PD deficiency?

Back 57

1. Blood smear ("blister and bite" cells)
2. G6PD enzyme assays

Front 58

Which variant of G6PD deficiency is more susceptible to hemolysis with exposure to fava beans?

Back 58

Mediterranean variant

Front 59

Which variant of G6PD deficiency results in damage to reticulocytes?

Back 59

Mediterranean variant

Front 60

Does the Mediterranean variant of G6PD deficiency usually cause baseline hemolysis?

Back 60

No.

Front 61

Why might a false negative test for G6PD deficiency occur during or immediately after an episode?

Back 61

Severely affected cells are lysed, leaving younger, more protected cells with normal G6PD enzyme activity.

Front 62

What is the most common RBC membrane defect associated with hemolysis?

Back 62

Hereditary spherocytosis

Front 63

Within RBCs, which protein forms the skeleton of the RBC and which protein anchors the lipid bilayer to the spectrin cytoskeleton?

Back 63

Spectrin --> forms skeleton of RBC
Ankyrin --> anchors lipid bilayer to spectrin cytoskeleton

Front 64

Which RBC membrane defect involves defective VERTICAL attachment?

Back 64

Hereditary spherocytosis
(defective attachment of lipid bilayer to spectrin cytoskeleton)

Front 65

Which RBC membrane defect involves defective HORIZONTAL stability of spectrin cytoskeleton?

Back 65

Hereditary elliptocytosis

Front 66

What is the inheritance pattern of Hereditary Spherocytosis?

Back 66

Autosomal dominant

Front 67

What is the molecular defect that results in Hereditary Spherocytosis?

Back 67

Defect in ankyrin protein
(lipid bilayer not attached properly to spectrin cytoskeleton)

Front 68

What is the most common congenital hemolytic anemia in people of northern European descent?

Back 68

Hereditary spherocytosis

Front 69

Where is the primary site of RBC destruction in Hereditary Spherocytosis?

Back 69

Spleen

(Also participates in membrane loss and spherocytic transformation)

Front 70

What do spherocytes look like?

Back 70

Small, dark, solid -- no central pallor

Front 71

Are cases of autosomal dominant Hereditary Spherocytosis generally mild or severe?

What about autosomal recessive cases?

Back 71

Autosomal dominant --> Usually mild
(may be asymptomatic, with normal hemoglobin)

Autosomal recessive --> Often more severe

Front 72

Can new mutations result in Hereditary Spherocytosis?

Back 72

YES
(patients may have no family history)

Front 73

What treatment is important for patients with Hereditary spherocytosis during the neonatal period?

Back 73

Treatment for hyperbilirubinemia
(may require exchange transfusions)

Front 74

What treatments might be necessary for patients with severe Hereditary Spherocytosis?

Back 74

1. RBC transfusions
2. Cholecystectomy (for gallstones)
3. Splenectomy

Front 75

Hereditary Elliptocytosis is usually due to a defect in which protein?

Back 75

Spectrin

Front 76

Hereditary elliptocytosis is most common in which ethnic group?

Back 76

African Americans

Front 77

What is the inheritance pattern of Hereditary Elliptocytosis?

Back 77

Autosomal dominant

Front 78

Is Hereditary elliptocytosis generally a mild or severe disease?

Back 78

Mild
(most cases are asymptomatic, with little or no anemia or hemolysis in baseline state)

Front 79

What is the diagnostic test for Hereditary elliptocytosis?

Back 79

Look at a blood smear.

Front 80

Hereditary Pyropoikilocytosis is most common in which ethnic group?

Back 80

African Americans

Front 81

What is the inheritance pattern of Hereditary Pyropoikilocytosis?

Back 81

Autosomal recessive