Hemolytic Anemias

Question 1

What is the disorder characterized by decreased red cell lifespan?

Answer 1

hemolytic anemia

Question 2

What is the lifespan of normal RBCs?

Answer 2

120 days (4 months)

Question 3

Jaundice, pigmented gallstones, ankle ulcers, splenomegaly, and aplastic crises associated with Parvovirus B19, increased folate requirement are clinical presentations of

Answer 3

Hemolysis

Question 4

Yellowing of sclera is known as

Answer 4

scleral icterus

Question 5

more generalized yellow discoloration of tissues is known as

Answer 5

jaundice

Question 6

jaundice is caused by ____ which is a byproduct of hemoglobin breakdown

Answer 6

bilirubin

Question 7

What can be found on peripheral blood smear of RBCs post splenectomy as an indication that the spleen has grown back?

Answer 7

Howell-jolly bodies (small round blue DNA remnants)

Question 8

What organism can cause aplastic crisis in patients with hemolytic anemias by halting erythropoiesis for a week?

Answer 8

Parvovirus B19 (non-encapsulated DNA virus)

Question 9

3 classifications of hemolytic anemia

Answer 9

sites of RBC destruction
acquired v. congenital
mechanism of red cell damage

Question 10

Differentiate between extravascular v. intravascular hemolysis

Answer 10

• Extravascular has macrophages in spleen, liver, and marrow remove damaged RBCs.
• Intravascular has RBCs rupture “within” vasculature, releasing free Hb into circulation

Question 11

What are the evidences for increased RBC production?

Answer 11

1. Elevated reticulocyte count (in blood)
2. Erythroid Hyperplasia (in bone marrow)
3. Skeletal deformities (frontal bossing in bones)

Question 12

What are outcomes/consequences of hemolysis?

Answer 12

1. Elevated LDH (lactate dehydrogenase; released after any cell lysis)
2. Elevated Unconjugated Bilirubin
3. Reduced serum haptoglobin

Question 13

What is glycosylated hemoglobin that is used as a measure of glucose control?

Answer 13

Hb A1C

Question 14

In patients with hemolysis, Hb A1C can be

Answer 14

falsely low (because hemoglobin doesn’t last long enough to get glycosylated)

Question 15

Most common defect leading to anemia

Answer 15

hereditary spherocytosis (autosomal dominant)

Question 16

What pinches off in hereditary spherocytosis? What is the defect causing this?

Answer 16

• Lipid microvesicles (in the spleen) pinch off

- Defect in ankyrin (RBC membrane cytoskeleton) leads to loss of SA and more spherocytic shape

Question 17

How is hereditary spherocytosis diagnosed?

Answer 17

• Decreased Eosin-5’ Maleimide Flow cytometry staining

- Increased Osmotic fragility

Question 18

2 treatment options for hereditary spherocytosis

Answer 18

1. folate supplementation

2. splenectomy

Question 19

What test can be beneficial to spherocytosis?

Answer 19

MCHC (can be elevated)

Question 20

What is rate-limiting enzyme in pentose-phosphate shunt?

Answer 20

G6PD

Question 21

A defect in G6PD results in low levels of _____ and reduced _____ which protect hemoglobin from oxidative damage.

Answer 21

NADPH; glutathione

Question 22

In the absence of G6PD, hemoglobin is converted to methemoglobin and eventually precipitate as

Answer 22

Heinz Bodies

Question 23

Heinz Bodies are pinched off by ____ and become _____

Answer 23

spleen; bite cell (or blister cell)

Question 24

Genetic transmission of G6PD deficiency

Answer 24

X-linked

Question 25

anti-malarials, sulfa drugs, dapsone, Vitamin K, fava beans, Naphtha (mothballs) are agents to avoid in

Answer 25

G6PD deficiency

Question 26

In patients with G6PD deficiency, hemolysis is trigger by

Answer 26

drugs or infections

Question 27

How can AA patients with G6PD deficiency may have normal G6PD levels?

Answer 27

Mature cells have been lysed and only younger cells (reticulocytes) with normal G6PD levels are left.

Question 28

What are lab findings of G6PD deficiency?

Answer 28

1. Bite and Blister cells | 2. Low G6PD Levels

Question 29

What are examples of acquired hemolytic anemias?

Answer 29

AIHA (warm & cold); PNH

Question 30

hallmark of autoimmune hemolytic anemia

Answer 30

Positive Coomb's Test

Question 31

Describe characteristics of warm antibodies.

Answer 31

React best at 37C (body temp.), IgGs are the antibodies, do not agglutinate RBCs

Question 32

Describe characteristics of cold antibodies.

Answer 32

React best <32C (extremities), IgMs are the antibodies, cause RBC agglutination

Question 33

What does the Direct Coomb's test look for?

Answer 33

Tests for IgG or C3 that are bound DIRECTLY on the RBCs

Question 34

What does Coomb's reagent consist of?

Answer 34

antibodies to human IgG and C3

Question 35

True or False: Agglutination in the "test tube" is NOT the same as cold antibodies agglutination disease

Answer 35

True

Question 36

Smear finding in warm-antibody hemolytic anemias

Answer 36

spherocytes

Question 37

AIHA can be induced by

Answer 37

drugs

Question 38

AIHA is what type of hypersensitivity?

Answer 38

Type II

Question 39

Splenomegaly, jaundice, and anemia are clinical presentations of

Answer 39

warm-antibody AIHA

Question 40

Anemia of warm-antibody AIHA can be VERY symptomatic depending on

Answer 40

rate of fall in hemoglobin

Question 41

Positive coomb's test, spherocytes , elevated MCHC are lab findings of

Answer 41

warm-antibody AIHA

Question 42

What is the mainstay of therapy for warm -antibody AIHA?

Answer 42

immunosuppressant drugs - 1st line: corticosteroids - 2nd: Rituximab - 3rd: splenectomy

Question 43

What is the main mechanism of warm-antibody AIHA?

Answer 43

IgG or/and C3 bind to RBCs and they are removed by macrophages (have Fc and C3b receptors)

Question 44

What is the main mechanism of cold-agglutinin AIHA?

Answer 44

IgM bind to RBCs in the cooler extremities and then fix complement. Complement-coated RBCs are lysed within the vessel (intravascular hemolysis) or by macrophages (extravascular hemolysis).

Question 45

How can IgM lead to RBC agglutination?

Answer 45

because IgM is pentameric

Question 46

After forming cold agglutinins, what can happen if they cannot pass through microvasculature?

Answer 46

Distal Occlusion (cyanosis and ischemia in extremities)

Question 47

What can be seen on smear of cold agglutinin disease?

Answer 47

RBC agglutination

Question 48

What infections and disease are associated with cold agglutinin disease?

Answer 48

mycoplasma and mononucleosis lymphoproliferative disease

Question 49

Positive coomb's test for C3 but not IgG, RBC agglutination are the lab findings of

Answer 49

cold-antibodies (cold-agglutinin) AIHA

Question 50

Treatment of cold agglutinin disease

Answer 50

keep patient warm (immunosuppressants are INEFFECTIVE)

Question 51

Hallmark of microangiopathic hemolytic anemia

Answer 51

presence of schistocytes on peripheral smear

Question 52

TTP/HUS and DIC are the causes of

Answer 52

microangiopathic hemolytic anemia

Question 53

What is an acquired clonal disorder of hematopoietic stem cells?

Answer 53

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Question 54

What is the cause of PNH?

Answer 54

A defect in PIG-A gene that makes GPI proteins that anchor other protein on the cell surface.

Question 55

What are the two GPI proteins that can lead to PNH due to PIG-A defect making them?

Answer 55

CD55 (DAF) CD59 * their normal function is to inhibit complement; defect leads to complement mediated RBC destruction (hemolysis)

Question 56

PNH-derived hemolysis usually occurs

Answer 56

at night when the pH falls

Question 57

The smooth msucle relaxation symptoms (esophageal spasm, erectile dysfunction, pulmonary hypertension) can occur from intravascular hemolysis of PNH due to

Answer 57

low nitric oxide levels

Question 58

What is the treatment for PNH?

Answer 58

Eculizumab *targets C5 and blocks terminal complement activation

Question 59

What is the risk of using Eculizumab?

Answer 59

Increased susceptibility to Neisseria infection.