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Flashcards in Pathology of Anemia 2 Deck (33):
1

What are thalassemias?

group of genetic disorders characterized by the lack or decreased synthesis of either alpha or beta globin chains of hemoglobin a
a thalassemia-alpha globin chain synthesis is reduced
b thalassemia-b globin chain synthesis is absent (b0) or deficient (b+)

2

Alpha thalassemia?

deletions
two genes on chromosome 16
4 degrees
silent:
-a/aa
alpha thalassemia trait:
--/aa(asian) , -a/-a (black)
HbH disease:
--/-a
Hydrops fetalis:
--/--

3

B-thalassemias

mutations
one gene on chromosome 11

4

How does B-thalassemia lead to anemia? hemolytic anemia?

Anemia:
reduced synthesis of B-globin leading to inadequate HgbA formation

Hemolytic:
relatively excess alpha globulins
-form insoluble aggregates which damage cell membranes-reduce cell membrane plasticity and allow RBCs to be susceptible to phagocytosis

5

Thalassemia major vs minor?

major: severe disease, reliance on transfusions
minor: asymptomatic, mild or absent anemia, some RBC abnormalities

6

What is B thalassemias major?

-marrow space is expanded causing skeletal deformities

-hepatosplenomegaly from extramedullary hematopoiesis causes abdominal distention

-multiple transfusions necessary, leading to excessive deposition of iron (death may result from cardiac failure)

7

What is B-thalassemia minor?

-minor microcytic hypochromic anemia (must be distinguished from an iron deficiency)
-hemoglobin electrophoresis and iron studies are used to make diagnosis
-HgbA(a2b2)-reduced
-HgbA2 (a2g2)-increased

Mediterranean patients

8

What do you see on a blood smear of a patient with B-thalassemia?

target cells
-decrease in hemoglobin in cytoplasm(basketball)-bleb in the membrane in the center

9

What is paroxysmal nocturnal hemoglobinuria?

the only acquired defect in the red cell membrane

1. stem cell disorder that results from a mutation in the phosphatidylinositol glycan A gene (PIGA)
2. deficiency of GPI anchor
3. lack of expression of GPI linked proteins
such as
-CD55 (DAF)
-CD59(MIRL)
-C8 binding protein
-->involved in inactivating the complement pathway

10

What are classical findings in PNH?

1. patient has classic intravascular hemolysis
2. paroxysmal and nocturnal in only 25% of cases
3. infections and venous thrombosis
4. occasional evolution to aplastic anemia or acute leukemia

11

Some intrinsic abnormalities of RBC caused hemolysis, such as hereditary spherocytosis, G6PD deficiency, sick cell anemia, thalassemia, and PNH, what are some extrinsic abnormalities that can lead to hemolysis of the RBC?

1. antibody mediated
2. mechanical trauma
3. infections
4. chemical injury

12

What are some examples of mechanical trauma that cause hemolysis?

1. prosthetic cardiac valves
2. narrowing of small vessels and fibrin deposition (microangiopathic hemolytic anemia)
-TTP, HUS, DIC
-->presence of schistocytes in peripheral blood

13

What causes iron deficiency anemia?

1. malabsorption of iron
-low dietary intake not often the cause of deficiency in the us
2. may not meet demand during pregnancy or infancy
3. most common cause of iron deficiency is western world is blood loss!

14

What is the order of depletion in iron deficiency anemia?

1. stored iron first depleted
-serum ferritin declines, bone marrow iron depleted
2. circulation iron then decreases
-measured serum iron low
3. increased total iron binding capacity (TIBC)
4. hemoglobin eventually decreases
5. RBCs become small with reduced hemoglobin concentration

15

What are signs of iron deficiency anemia?

1. nails may develop ridges and become spoon shaped
2. tongue may become smooth
3. intestinal malabsorption may develop
4. esophageal webs may appear (rare today)

16

What does iron deficiency anemia look like on a blood smear?

central pallor is almost entire cell

17

What leads to megaloblastic anemias?

Disturbances of proliferation and maturation of erythroblasts due to defective DNA synthesis

Two Principle types
1. B12 deficiency
2. folate deficiency

18

megaloblasts

enlarged red cell precursors

19

macrocytes

enlarged red blood cells

20

What is the ratio of cytoplasm to nuclei like in megaloblastic anemias?

nuclei are immature and cytoplasm is fully mature: nuclear cytoplasmic asynchrony

21

What leads to vitamin b12 megaloblastic anemia?

1. inadequate diet-takes a long time
2. increased requirements
3. impaired absorption

22

What leads vitamin B12 impaired absorption?

1.IF deficiency
2. pancreatitis
3. gastrectomy
4. ileal resection, regional enteritis
5. parasites (fish tapeworm)

23

What is pernicious anemia?

B12 deficiency secondary to atrophic gastritis with failure of production of intrinsic factor

24

How does B12 affect THF and DNA synthesis?

transfer of methyl group to B12 so THF can do its DNA job without B12 impaired DNA synthesis

25

How does B12 affect homocysteine and methionine?

B12 transfers methyl group to homocysteine to make methionine without B12 homocysteine builds up

26

How does B12 affect succinyl Coenzyme A?

For methylmalonyl coA to make succinyl coA there needs to be B12
-without it there is an increase in methylmalonate and that is associated with CNS symptoms

27

What are clinical findings of a b12 deficiency?

1. alimentary tract: atrophic glossitis, chronic gastritis

2. blood and bone marrow: megaloblastic anemia, leukopenia with hypersegmented granulocytes, mild to moderate thrombocytopenia

3. CNS findings: involvement of posterolateral spinal tracts, leading to sensory and motor abnormalities
-subacute combined degeneration-->spastic paraparesis, sensory ataxia, lower limb paresthesias

28

How does someone get a folate deficiency?

-inadequate intake or impaired absorption
-reserves are modest-still does not appear for months unless demand increased

29

Is there CNS abnormalities in folate deficiency? Can you reverse the problems seen in folate deficiency, what about B12 deficiency?

no

30

Can you reverse the problems seen in folate deficiency, what about B12 deficiency?

yes but there is no reversal of CNS abnormalities with B12 deficiency

31

What is anemia of chronic disease?

associated with:
1. chronic infections
2. chronic immune disorders
3. malignancies

-caused by high levels of plasma **hepcidin that blocks the transfer of iron from macrophages to erythroid precursors

like iron deficiency but
high ferritin
decreased total iron binding capacity
increased bone marrow iron stores

32

What is aplastic anemia?

failure or suppression of stem cells leads to hypocellular marrow

Peripheral blood findings:
-anemia
-granulocytopenia
-thrombocytopenia

*PANCYTOPENIA

Frequently idiopathic but may result from:
1. whole body irradiation
2. myelotoxic drugs/chemicals
3. viral infections

Bone marrow is typically hypocellular with increased fat and small foci of lymphocytes and plasma cells

Clinically:
symptoms may develop insidiously and reflect effects of anemia, neutropenia, and thrombocytopenia
-must be distinguished from other syndromes causing pancytopenia
-prognosis unpredictable

33

What is aplastic anemia likely secondary to?

1. defect or deficiency of hematopoietic stem cells
2. defect in bone marrow stroma
3. suppression of marrow stem cells by T cell mediated immune mechanisms