Lecture 4: Normocytic Anemias

Question 1

Normocytic anemias: DDx (6)

Answer 1

(1) Acute blood loss
(2) Primary bone marrow disorders
(3) Anemia of chronic disease/ inflammation (AOCD)
(4) Splenomegaly
(5) Hemolytic anemia with low or normal retic count
(6) Endocrine disorders

Question 2

Anemia of Inflammation: Definition

Answer 2

Mild or moderate anemia that is persistent for greater than 1 to 2 months in patients with the associated conditions

• Infection
• Malignancy
• Endocrine disorders
• Immune disorders (SLE, RA)
• Others: HIV, DM, heart failure

Question 3

Pathophysiology of Anemia of inflammation (4)

Answer 3

(1) Epo production is inhibited, so inappropriately low levels
(2) increased levels of inflammatory cytokines
(3) alterations in iron metabolism
(4) suppression of erythropoiesis

Question 4

Anemia of inflammation: lab values

Answer 4

• Serum Fe: low to normal
• TIBC: Low to low-normal
• % iron sat: low
• ferritin: normal to high
• MCV: low to normal
• RDW: normal to high

Question 5

T/F Iron replacement is necessary for anemia of inflammation.

Answer 5

FALSE; erythrocyte-stimulating agent can be given associated with hypertension and thrombosis

Question 6

What is the pathogenesis of Aplastic Anemia?

Answer 6

Bone marrow failure

Question 7

What is pancytopenia? What is it associated with?

Answer 7

hematopoietic stem cell injury associated with aplastic anemia

Question 8

Aplastic Anemia: Causes (6)

Answer 8

• Idiopathic ( >50%): autoimmune, T-cell mediated
• Drugs (Chloramphenicol, sulfanomides, chemotherapy, etc.)
• Industrial and agricultural chemicals (benzene), radiation
• Congenital (FA)
• Infection (EBV, hepatitis, HIV, etc)
• Pregnancy

Question 9

Aplastic Anemia: DDx (4)

Answer 9

- Other bone marrow failure syndromes
     ~ Myelodysplasia
     ~ Leukemias
     ~ Metastatic disease to the bone marrow 
- Splenomegaly/portal HTN
- Severe B12 or Iron deficiency
- Autoimmune disorder

Question 10

Clinical features of Aplastic Anemia

Answer 10

• Bleeding and ecchymoses (thrombocytopenia)
• Frequent infections, usually bacterial (neutropenia)
• Fatigue, pallor, decreased exercise tolerance, CV compromise (anemia)

Question 11

What is not seen with Aplastic Anemia?

Answer 11

Splenomegaly/Hepatomegaly

Question 12

Aplastic Anemia:Lab Findings (Peripheral blood and bone marrow)

Answer 12

- Peripheral blood:
     ~Pancytopenia
     ~variable, may be very severe
- Bone marrow
     ~ Hypocellular marrow
     ~ Cytogenetics are normal

Question 13

What condition does the normal cytogenetics finding in Aplastic anemia distinguish against?

Answer 13

Myelodisplastic syndrome; cytogenetics would be abnormal

Question 14

Aplastic Anemia- Management (4)

Answer 14

(1) Prompt hematology referral if suspected
(2) Immunosuppressive therapy
- ATG, cyclosporine, corticosteroids
(3) Supportive care
- Recognition and tx of infections
- RBC and platelet transfusions if symptomatic
(4) Allogenetic bone marrow transplantation

Question 15

What percentage of people survive Aplastic Anemia with immunotherapy?

Answer 15

75%

Question 16

What is likely the cause of death in Aplastic Anemia?

Answer 16

Bleeding and infection

Question 17

What percentage of people survive with Aplastic Anemia beyond one year with supportive therapy only? With bone marrow transplantation?

Answer 17

30-35%; 80-90%

Question 18

What virus causes Aplastic Crisis? What does this virus do? How do you treat it?

Answer 18

Parovirus; arrests erythropoiesis; blood transfusion

Question 19

When is Aplastic Crisis especially life threatening?

Answer 19

In patients with sickle cell anemia or hereditary spherocytosis that are heavily dependent on erythopoiesis due to the reduced lifespan of the red cells

Question 20

What is Hemolytic Anemia?

Answer 20

Accelerated rate of red cell destruction beyond the ability of the bone marrow to fully compensate

Question 21

What are the two main causes of hemolysis?

Answer 21

Intrinsic RBC defects (inherited)
Extrinsic causes (acquired)

Question 22

What is hemolysis?

Answer 22

Premature or accelerated destruction of RBCs (<100 days)

• elevated retic count
• may be well compensated by increased red cell production by the bone marrow

Question 23

What happens to RBC with age? (3)

Answer 23

(1) Decreased membrane lipid component
(2) Spherocytic shape
(3) Less pliability and deformability

Question 24

What are the hereditary hemolytic disorders (intrinsic)? (4)

Answer 24

(1) RBC enzyme defects (metabolic)
(2) RBC membrane defects
(3) Hemoglobinopathies
(4) Thalassemias

Question 25

What are the acquired hemolytic disorders (extrindic)? (6)

Answer 25

(1) Immune hemolytic anemias
(2) Splenomegaly
(3) Microangiopathic hemolytic anemia
(4) PNH
(5) Direct toxic effect (malaria, clostridial infections)
(6) Spur cell anemia

Question 26

In what other way can hemolytic disorders be classified? What do each entail?

Answer 26

According to anatomic site of RBC destruction
- Extravascular:
~ RBC destruction by macrophages in the liver
and spleen (more common)
~ Splenomegaly
- Intravascular
~ RBC destruction occuring primarily in the blood
vessels
~ Release of contents in the plasma
~ Hemoglobinuria, hemoglobinemia
- Overlap

Question 27

Hemolytic Anemia: Clinical Presentation (8)

Answer 27

(1) Anemia
(2) Hypotension, syncope
(3) Pallor
(4) Jaundice, scleral icterus
(5) Gallstones secondary to increased bilirubin (chronic)
(6) Splenomegaly
(7) Hemoglobinuria
(8) Ulcers (sickle cell)

Question 28

What additional studies would you get for hemolytic anemia? (3)

Answer 28

(1) Hemoglobin electrophoresis
(2) G6PD assays
(3) Bone marrow aspirate/biopsy

Question 29

What is the most common cause of hereditary hemolytic anemia in Caucasians. What is it a deficiency of?

Answer 29

Hereditary Spherocytosis; membrane proteins

Question 30

Hereditary Spherocytosis facts (4)

Answer 30

(1) Often the hemolysis is well compensated
(2) Very diverse clinical presentation
(3) History of gallstones is common
(4) Splenectomy is often effective