Bl Week 1 Pbl Objective 3

Front 1

What are the common etiologies of microcytic anemias?

Back 1

TAILS
1. T - Thalassemia
2. A - Anemia of chronic disease
3. I - Iron-deficiency anemia
4. L - Lead-poisoning
5. S - sideroblasitc anemia

Front 2

What compound is it important to measure to distinguish between the various etiologies of microcytic anemia?

Back 2

Iron

Front 3

How is iron status biochemically assessed?

Back 3

1. serum iron
2. TIBC
3. Transferrin saturation
4. serum ferritin
5. free erythrocyte protoporphyrin

Front 4

What biochemical marker is most reliable when establishing iron-deficiency anemia?

Back 4

decreased ferritin

Front 5

What is the clinical presentation of iron-deficiency anemia?

Back 5

-fatigue
-dysphagia (due to esophageal web)
-brittle nails with koilonychia
-glossitis
-angular stomatitis
-pica

Front 6

What is the other major Ddx when considering iron-deficiency anemia?

Back 6

anemia of chronic disease

Front 7

What changes in the serum might you see with iron-deficiency anemia?

Back 7

-decreased ferritin
-thrombocytosis (unknown as to why)

Front 8

What changes would you see in the peripheral blood smear in iron deficiency anemia?

Back 8

-microcytosis (represented in lab by decreased MCV)
-hypochromia (represented in lab by decreased MCH)
-elliptocytes (pencil/cigar cells)

Front 9

What changes would you seen in the bone marrow with iron-deficiency anemia?

Back 9

-Fe stain (Prussian blue) shows decreased Fe in macrophages
-decreased normal sideroblasts
-intermediate (polychromatic erythroblast)and (late) erythroblasts show micronormoblastic differentiation

Front 10

What are the pathologic causes of iron-deficiency anemia based on the three pathologic explanations of anemia?

Back 10

1. decreased production of Hb due to lack of iron due to:
a) poor intake
b)poor absorption
c) hemorrhage (where loss is greater than intake - ie. chronic occult GI bleed)
d) intravascular hemorrhage

Front 11

Both intravascular and extravascular hemolysis lead to iron-deficiency anemia. True or False?

Back 11

False. Only intravascular hemolysis leads to iron-deficiency because iron cannot be recycled if it is lost outside of the RES.

Front 12

What is the pathophysiology of anemia of chronic disease?

Back 12

- a mild hemolytic component
- Epo levels are normal or slightly elevated, but inappropriate for degree of anemia (should be much higher!)
- Fe cannot be accessed from m0's and hepatocytes

Front 13

Anemia of chronic disease is a diagnosis of exclusion. True or False?

Back 13

True.

Front 14

What biochemical parameter iw most useful in distinguishing ACD from iron-deficiency anemia (highest on Ddx)?

Back 14

serum ferritin!

-very, very decreased in IDA
-normal or even elevated in ACD

Front 15

Anemia of chronic disease may be either microcytic or normocytic. True or False?

Back 15

True. Is most commonly normocytic, but may also present as microcytic.

Front 16

What other biochemical parameters (other than serum ferritin) may be altered in anemia of chronic disease?

Back 16

-TIBC: normal or decreased
-serum iron: normal or decreased
-transferrin (normal or decreased)

Front 17

ACD is rarely hypochromic. True or false?

Back 17

True. Usually only hypochromic if anemia is marked (ie. <90 g/L Hb)

Front 18

What changes would you observe in the bone marrow in ACD?

Back 18

-normal or decreased iron stores
-decreased "normal" sideroblasts

Front 19

Mnemonic for remembering the clinical presentation, hematologic changes and treatment for lead poisoning:

Back 19

LEAD
L-Lead lines on gingivae and epiphyses of long bones on x-ray
E- Encephalopathy; erythrocyte basophilic stippling
A- Anemia (microcytic); abdominal colic
D- Drops: wrist and foot drops; Dimercaprol and EDTA as 1st line tx

Front 20

What is sideroblastic anemia?

Back 20

-deficiencies in porphyrin biosynthetic pathway leading to decreased heme synthesis and increase in cellular Fe uptake
-characterized by presence of abnormal erythroid precursors in bone marrow

Front 21

What forms of sideroblasts (abnormal erythroid precursors) would you see in sideroblastic anemia?

Back 21

1. "normal" sideroblasts
2. ring sideroblasts

Front 22

What characterizes "normal" sideroblasts?

Back 22

-aggregates of ferritin diffusely spread through RBC cytoplasm
-small
-found in normal individuals

Front 23

What characterizes "ring" sideroblasts?

Back 23

-Fe deposited in mitochondria forms ring around nucleus
-large
-abnormal finding

Front 24

Sideroblastic anemia is only hereditary. True or false?

Back 24

False.

Can be acquired:
1. primary form - as preleukemia
2. secondary form - toxins, drugs, chemotherapy, collagen vascular disease

Front 25

What changes would you notice in the serum with sideroblastic anemia?

Back 25

IRON OVERLOAD:
-increased serum iron
-increased serum ferritin
-normal TIBC

Front 26

What changes would you notice in the peripheral blood?

Back 26

-hypo and normochromic cells

Front 27

What changes would you observe in the bone marrow?

Back 27

- increased iron stores arranged in a ring around the nucleus
- dx when 15% or more of erythroblasts look like this

Front 28

What is the most common gene mutation involved in hereditary sideroblastic anemia?

Back 28

- mutations in ALA-S gene (aminolevulinic acid synthase)
-RBC version of this gene is encoded on X chromosome

Front 29

What does ALA-S do?

Back 29

The rate-limiting enzyme in porphyrin and heme biosynthesis.
Catalyses glycine and succinyl-CoA into D-Aminolevulinic acid.
In humans, transcription of ALA synthase is tightly controlled by the presence of Fe2+-binding elements, to prevent accumulation of porphyrin intermediates in the absence of iron.

Front 30

What peripheral blood changes would be noted in beta-thalassemia minor?

Back 30

-microcytosis +/- hypochromia
-TARGET cells and increased poikilocytosis (fish/teardrop cells)
-basophilic stippling is usually present

Front 31

What other laboratory test would allow you to differentiate thalassemia from other causes of microcytic anemia?

Back 31

-PAGE:
-Hb A2 is increased
-HbF is increased

Front 32

What other anomalies would you notice in the peripheral smear of a post-splenectomy thalassemia patient?

Back 32

-Howell Jolly bodies [basophilic nuclear remnants (clusters of DNA) in circulating erythrocytes; common finding in pt's sans spleen]
-erythroblasts
-thrombocytosis

Front 33

How can you categorize macrocytic anemia?

Back 33

megaloblastic and non-megaloblastic

Front 34

What are common causes of megaloblastic anemia?

Back 34

-Vitamin b12 deficiency
-folate deficiency

Front 35

What are common causes of non-megaloblastic macrocytic anemia?

Back 35

-liver failure
-hypothyroidism
-MDS/aplastic anemia

Front 36

Pernicious anemia is an immuned-mediated type of anemia. True or False?

Back 36

True. Auto-Ab's are produced against gastric parietal cells leading to achlorhydia and no IF secreation. Without IF, Vit B12 cannot be absorbed leading to anemia.

Front 37

What is essential to include in Review of Systems if you suspect a megaloblastic anemia due to B12/folate deficiency?

Back 37

-targeted neurologic questions and neurologic exam
-look for:
confusion, delirium, dementia, paresthesias, decreased propioception, etcc.

Front 38

What changes would you notice in the serum in megaloblastic anemia?

Back 38

-anemia is often severe +/- neutropenia +/- thrombocytopenia (ie. pancytopenia)
-low retic count relative to degree of anemia
-look at B12/ folate levels

Front 39

What characteristic changes would be noted in the peripheral blood smear in megaloblastic anemia?

Back 39

-ovalocytes
- hypersegmented PMN's

Front 40

Which nutrient deficiency producing megaloblastic anemia is more common, folate or B12?

Back 40

Folate!
folate stores are depleted in only 3-6 months, whereas depletion of B12 takes 2-3 years.

Front 41

What conditions would produce a normocytic anemia?

Back 41

-hemolysis
-hemorrhage
-ACD
-bone marrow suppression

Front 42

How can you best categorize hemolytic anemias?

Back 42

1. intrinsic RBC defects (mostly hereditary)
a) problems with membrane
b) problems with enzymes
c) problems with Hb
2. Extrinsic RBC defects (mostly acquired)
a) immune attack (allo; auto; methyldopa)
b) non-immune (RBC fragmentation; infx; chemical/physical)

Front 43

What is the clinical presentation of hemolytic anemia?

Back 43

- jaundice
- cholelithiasis (bile pigment stones)
- spleno/hepatomegaly
- skeletal abnormalities (from extra-medullary hematopoiesis)
- Fe overload with extravascular hemolysis (Fe recycling can occur)
- Fe deficiency with intravascular hemolysis (no recycling)

Front 44

What changes in the serum would you expect to see as a result of hemolysis?

Back 44

-increased inconjugated bilirubin
-(urine - increased urine bilinogen)
-increased LDH

Front 45

What is the value of the Coomb's test (DAT) in diagnosing the etiology of hemolytic anemia?

Back 45

- Will be positive in immunohemolytic anemia as detects Ab's on surface of RBC

Front 46

When would you use an indirect Coomb's test?

Back 46

- cross-matching serum b/w donors and recipients
- searching for blood group Ab's in pregnant women

Front 47

What are the more common types of hereditary hemolytic anemia?

Back 47

1. Hereditary spherocytosis
2. Hereditary elliptocytosis
3. G6PD deficiency

Front 48

In which forms of anemia is an increased reticulocyte count expected?

Back 48

1. Anemia due to loss of RBC's
2. Anemia due to increased destruction of RBC's