Normocytic Anemia - Intravascular Hemolysis

Question 1

What molecules protect RBCs from complement?

Answer 1

• DAF - Decay accelerating factor
• MIRL
  Both anchored to RBC via GpI

Question 2

What causes Paroxysmal nocturnal hemoglobinuria?

Answer 2

Acquired defect in myeloid stem cells

• GpI is not produced - meaning DAF and MIRL are not able to attach
• Renders cells vulnerable to complement

Question 3

Why does PNH occur at night?

Answer 3

• Mild respiratory acidosis develops with shallow breathing during sleep and activates complement

Question 4

What cells are lysed in PNH?

Answer 4

RBCs WBCs and platelets are lysed

Question 5

What tests are used to diagnose PNH?

Answer 5

• Sucrose test (as screening)

- Confirmatory test is acidified serum test or flow cytometry to detect lack of CD55 (DAF)

Question 6

What do patients with PNH die from?

Answer 6

• Thrombosis (in hepatic, portal or cerebral veins)

- Destroyed platelets release cytoplasmic contents into circulation inducing thrombosis

Question 7

What is a complication of PNH?

Answer 7

• Iron deficiency anemia (losing hemoglobin/iron in urine)

- AML (10% of patients)

Question 8

How is G6PD deficiency inherited?

Answer 8

X-linked recessive

Question 9

What are G6PD deficienct patients RBCs vulnerable to?

Answer 9

Oxidative stress

Question 10

What happens to G6P in G6DP deficiency?

Answer 10

Reduced half-life

Question 11

What is the difference between the African and Meditereanean variant of G6PD deficiency?

Answer 11

• Med - Markedly reduced half-life (cells die are killed more quickly)
• African - Mildly reduced

Question 12

How long is the half-life of G6PD in normal people

Answer 12

same as RBCs

Question 13

What (drugs) can cause oxidative stress?

Answer 13

• Primaquine
• Sulfa drugs
• Dapsone
• Fava beans

Also infections

Question 14

What does oxidative stress result in?

Answer 14

Heinz bodies

Question 15

What are Heinz bodies removed by?

Answer 15

Splenic macrophages - resulting in Bite cells

Question 16

What kind of hemolysis is G6PD deficiency predominantley?

Answer 16

Intravascular

Question 17

What does G6PD deficiency present with?

Answer 17

• Hemoglobinuria + back pain (hours after exposure to oxidative stress)
• Trigger for oxidative stress needed

Question 18

How is G6PD deficiency screened?

Answer 18

Heinz preparation

- Enzyme studies confirm deficiency (can only do after acute hemolytic episode)

Question 19

What is immune hemolytic anemia?

Answer 19

Antibody-mediated (IgG or IgM) destruction of RBCs

Question 20

IgG-mediated immune hemolytic anemia usually involves what kind of hemolysis?

Answer 20

Extravascular hemolysis

Question 21

IgG-mediated immune hemolytic anemia has what type of cells?

Answer 21

Spherocytes

- Due to membrane of antibody-coated RBCs being consumed by splenic macrophages

Question 22

What other conditions are associated with IgG-mediated immune hemolytic anemia?

Answer 22

SLE CLL

- Also certain drugs (e.g penicillin or methodopa)

Question 23

How can IgG-mediated immune hemolytic anemia be treated?

Answer 23

• Cessation of the offending drug
• Steroids
• IVIG - eats these instead of RBCs
• Splenectomy

Question 24

What kind of hemolysis is involved in IgM-mediated immune hemolytic anemia?

Answer 24

Intravascular

Question 25

What temperatures are associated with IgM and then IgG mediated immune hemolytic anemias?

Answer 25

• Cold in IgM - cold agglutination

- Warm in IgG

Question 26

What does the direct coombs test confirm?

Answer 26

Presence of antibody-coated RBCs

• Anti-IgG added to the patients RBCs
• Agglutination occurs if RBCs are already coated with IgG antibody
• Most important test for IHA

Question 27

What does nthe indirect coombs test confirm?

Answer 27

Anti-IgG antibodis in serum

- Agglutination occurs if serum antibodies are present

Question 28

Microangiopathic hemolytic anemia has what type of cells?

Answer 28

Schistocytes

Question 29

What are the different kinds of microangiopathic hemolytic anemias?

Answer 29

• TTP (platelet thrombi - do not have ADAMS13)

Question 30

What can cause schistocytes?

Answer 30

• Microthrombi (e.g TTP-HUS, DIC, HELLP)
• Prosthetic heart valves
• Aortic stenosis

Question 31

What can Malaria cause?

Answer 31

A normocytic hemolytic anemia

• Cyclical fever
• Mostly intravascualr but spleen also destroys some infected cells -> splenomegaly

Question 32

What organism causes Malaria?

Answer 32

Plasmodium falciparum - daily fever

Plasmodium vivax and ovale - fever every other day

Question 33

What mosquito carries plasmodium?

Answer 33

Anopheles mosquito (female)

Question 34

What anemias may cause a low corrected reticulocyte count?

Answer 34

• Microcytic and macrocytic
• Renal failure
• Damage to bone marrow precursor cells

Question 35

What does parvovirus B19 infection result in?

Answer 35

• Infects progenitor red cells
• Temporarily halts erythropoeisis
• Leads to significant anemia in the setting of preexisting marrow stress
• Treatment is supportive

Question 36

What is aplastic anemia?

Answer 36

• Damage to hematopoietic stem cell

- Results in pancytopenia w low reticulocyte count

Question 37

What can cause aplastic anemia?

Answer 37

• Drugs/chemicals
• Viral infections
• Autoimmune damage

Question 38

What would biopsy show in aplastic anemia?

Answer 38

Empty bone marrow - surrounded by fat

Question 39

How may aplastic anemia be treated?

Answer 39

• Cessation of causitive drug
• Transfusions
• Marrow stimulating factors (EPO, GM-CSF, G-CSF)
• Immunosuppression
• BMT (bone marrow transplant) (last resort)

Question 40

What is myelophthisic process?

Answer 40

• Pathologic process that replaces bone marrow

- Hematopoiesis is impaired resulting in pancytopenia