Hypoproliferative Anemia

Question 1

What are some different ways someone could have iron deficiency anemia (IDA)?

Answer 1

Iron depletion in diet

Lost in chronic blood loss or malabsorption leading to decreased iron stores and incorporation into hemoglobin

Question 2

How does IDA present on PB smear?

Answer 2

Microcytic, hypochromic anemia with pronounced anisopoikilocytosis

Question 3

What is particularly important with a diagnosis of IDA in someone >50 yo?

Answer 3

GI carcinoma until proven otherwise

Question 4

How does anemia of chronic disease occur?

Answer 4

Increased hepcidin levels from inflammatory markers

Blocks the transfer of iron from marrow macrophages to sideroblasts

Question 5

How does anemia of chronic disease present on PB smear?

Answer 5

Normocytic, normochromic (80%)
Microcytic (20%)

Increased serum ferritin
Decreased TIBC

Question 6

What is the most common anemia of hospitalized patients?

Answer 6

Anemia of chronic disease

Seen in inflammatory, infectious and neoplastic conditions

Question 7

What is the treatment for anemia of chronic disease?

Answer 7

Treat the underlying disorder

EPO/iron therapy

Question 8

What is anemia of renal failure? How does it appear on PB smear?

Answer 8

Decreased EPO secondary to kidney disease –> decrease erythropoiesis

Normocytic, normochromic

Question 9

What two deficiencies can lead to megaloblastic anemia/

Answer 9

Folate or vitamin B12 deficiency

Question 10

How do folate or vitamin B12 deficiency lead to anemia?

Answer 10

Impair DNA synthesis (specifically thymidine) which produces nuclear to cytoplasmic asynchrony in erythroid and granulocytic maturation

Question 11

How does Megaloblastic anemia appear on PB smear?

Answer 11

Macrocytic
Macroovalocytes
Hypersegmented neutrophils
Nuclear to cytoplasmic asynchrony in marrow

Question 12

How can you differentiate if megaloblastic anemia is caused by folate or vit B12?

Answer 12

Neurologic deficits in vitamin B12

Question 13

What is aplastic anemia?

Answer 13

Suppression of BM pluripotent stem cells likely by autoreactive T cells

Normocytic, normochromic

Pancytopenia

Question 14

What are some things that can cause aplastic anemia?

Answer 14

Exposure to toxins, drugs, infectious agents

Question 15

What is myelophthisic anemia?

Answer 15

Cytopenias related to marrow infiltration by a carcinoma or storage disorder

Question 16

What do you see on PB smear in myelophthisic anemia?

Answer 16

Tear drop cells 
Leukoerythroblastic reaction (immature cells in PB)

Question 17

What causes anemia of liver disease?

Answer 17

unknown

Seen with chronic hepatitis and cirrhosis

Question 18

Why does anemia of liver disease look like on PB smear?

Answer 18

Macrocytic

Question 19

What causes pure red cell aplasia?

Answer 19

Unknown but thought to be autoimmune destruction of erythroid precursors in the marrow

Question 20

What are some things associated with pure red cell aplasia?

Answer 20

Thymic hyperplasia, thymoma, large granular lymphocytic leukemia, autoimmune disease

Question 21

What are some things that may cause a megaloblastic anemia?

Answer 21

Dihydrofolate reductase deficiency (methotrexate)
Thymidylate synthetase deficiency (5-FU)
Folate deficiency
Vitamin B12 deficiency

Question 22

Explain how we take in vitamin B12.

Answer 22

Bound to protein in food
Released in stomach by HCl & pepsin
Binds mainly to R-protein
In duodenum, R protein degraded, releasing B12 which then binds IF
Complex of B12:IF binds receptor and absorbed in terminal ileum

Question 23

What are some things that may cause impaired absorption of B12?

Answer 23

IF deficiency, Ileal resection, pancreatic insufficiency
Decreased intake
Increased requirement
Tapeworm (diphyllobothrium lathum)

Question 24

What are some clinical manifestations of vit B12 deficiency?

Answer 24

Megaloblastic anemia/Pernicious anemia
Subacute combined degeneration–dorsal and lateral tract demyelination, parasthesias, spastic paraparesis, sensory ataxia

Question 25

What is pernicious anemia?

Answer 25

Deficiency of B12 secondary to IF abnormalities

Question 26

What would the lab findings look like in pernicious anemia?

Answer 26

Low vit B12 levels Low retics Auto-antibody to IF or parietal cells (if pernicious anemia) Elevated methylmalonic acid (substrate that needs B12)

Question 27

What are some causes of folate deficiency?

Answer 27

``` Decreased intake (alcoholism, poverty) Increased requirements (growth, pregnancy, states of high cell turnover, hemolytic anemias, leukemias) Defective absorption (jejunal resection/malabsorption) Folic acid antagonists ```

Question 28

What are some clinical presentations of folate deficiency?

Answer 28

Megaloblastic anemia | Neural tube defects (spina bifida occulta)

Question 29

What shouldn't you treat vit B12 deficiency with folate?

Answer 29

Anemia will reverse, neurological manifestations will not

Question 30

Differentials for microcytic, hypochromic anemia

Answer 30

IDA Thalassemia Anemia of chronic disease

Question 31

What are some of the different uses of iron in the body?

Answer 31

Component of heme (80%) Component of myoglobin, cytochromes, catalases (20%) Storage

Question 32

What are some causes of IDA?

Answer 32

Dietary lack (milk-fed infants) Impaired absorption (duodenum) Increased requiredment Chronic blood loss (GI sources, menstrual)

Question 33

What are some ways iron is absorbed and transported?

Answer 33

Heme iron --> heme iron transporter Non-heme iron --> reduced by duodenal cytochrome c (vit D, DMT-1) Mucosal ferritin Ferroportin transporter --> regulated by Hepcidin Hephaestin --> oxidized to 3+, binds transferring to cells

Question 34

What is TIBC essentially equivalent to?

Answer 34

Transferrin