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Flashcards in Intro Anemia Deck (57):
1

What is anemia? (i.e. what leads to the final physiologic consequence)

  1. Decreased circulating red cell mass ⇒ 
  2. Decreased hemoglobin concentration of blood ⇒ 
  3. Decreased O2-carrying capacity of blood ⇒ 
  4. Decreased O2 delivery to tissues (final physiologic consequence)

2

What are the physiologic compensatory mechanisms for anemia?

  • Increased red cell production
  • Increased 2,3-DPG
  • Shunting of blood from non-vital to vital areas
  • Increased cardiac output
  • Increased pulmonary function

3

What are signs/symptoms of anemia? What mechanisms lead to these?

  • Weakness, malaise, easy fatigability ⇒ Tissue hypoxia
  • Marrow expansion with potential bony abnormalities ⇒ Increased red cell production
  • Pallor ⇒ Shunting of blood from non-vital to vital areas
  • Tachycardia; cardiac ischemia in severe cases ⇒ Increased cardiac output
  • Dyspnea on exertion ⇒ Increased pulmonary function

4

What kind of disease is anemia?

Anemia is NOT a disease

  • it is a symptom of other diseases and must be explained!

5

What is the functional classification of anemia?

  • Blood Loss
  • Decreased Production
  • Accelerated Destruction

6

What are the morphologic categories of anemia?

  • microcytic
    • normochromic
    • hypochromic
  • normochromocytic/normocytic
  • macrocytic

7

What causes microcytic anemias?

  1. Normochromic
    • Iron deficiency--early
    • Thalassemia trait
    • (Anemia of chronic disease)*
      • Most commonly normochromic/normocytic
    • Some hemoglobinopathies (e.g., hemoglobin E)
  2. Hypochromic
    • Iron deficiency
    • Thalassemia trait
    • Sideroblastic anemia
    • Anemia of chronic disease*
      • Most commonly normochromic/normocytic

8

What causes normochromic/normocytic anemias?

  1. Anemia of chronic disease
  2. Anemia of renal failure
  3. Marrow infiltration
  4. Aplastic anemia
  5. Blood loss**
    • normocytic or macrocytic, depending on degree of blood loss
  6. Hemolysis**
    • normocytic or macrocytic, depending on degree of blood loss

9

What causes macrocytic anemias?

  1. B12 and folate deficiency
  2. Liver disease
  3. Myelodysplastic syndromes
  4. Blood loss**
    • normocytic or macrocytic, depending on degree of blood loss

  5. Hemolysis**
    • normocytic or macrocytic, depending on degree of blood loss

  6. Some drugs

10

Investigation of anemia:

  • Clinical history
  • Physical exam
  • Complete blood count (CBC)
  • Reticulocyte count
  • Examination of peripheral blood smear
  • Specific diagnostic tests (guided by above)

11

What can be assessed on a peripheral blood smear?

  • Red cell shapes (poikilocytosis)
  • Red cell size variability (anisocytosis)
  • Average red cell size (microcytosis, macrocytosis)
  • Hemoglobinization (hypochromia, normochromia)
  • Polychromasia (reticulocytes)
  • Red cell inclusions
  • Red cell arrangement
  • White cell and platelet morphology

12

What CBC parameters are used to evaluate anemia?

this is a really long card, sorry :/

  1. Hemoglobin concentration (Hb; g/dL or g/L)
    • Most important parameter for assessment of O2-carrying capacity of blood
  2. Hematocrit (Hct; %)
    • Packed cell volume (percentage of blood volume comprised by RBCs)
    • Usually 3 times hemoglobin--does not add independent information in vast majority of cases
  3. Red blood cell count (RBC; # x 109/L)
    • Direct measure of # of RBCs per unit volume
    • Generally correlates well with Hb and hematocrit, adds little independent information
  4. Mean cellular (corpuscular) volume (MCV; fL)
    • Very useful in the differential diagnosis of anemia (e.g., microcytic, normocytic, and macrocytic anemias)
  5. Mean corpuscular hemoglobin (MCH; pg)
    • Calculated as Hb/RBC
    • Measure of average amount of hemoglobin per RBC
    • High correlation with MCV
  6. Mean corpuscular hemoglobin concentration (MCHC; g/dL)
    • Measure of “chromicity” of RBCs
    • Calculated as Hb/(MCVxRBC)
    • Decreased in hypochromic anemias
    • Increased in a few “hyperchromic” states (e.g., hereditary spherocytosis, hemoglobin CC disease)
  7. Red cell distribution width (RDW)
    • Measure of variability of red cell volume
    • Coefficient of variation of red cell volumes = svolume/MCV)
    • Useful for the separation of anisocytotic anemias (e.g., Fe deficiency) from non-anisocytotic anemias (e.g., anemia of chronic disease)

13

What is the differential diagnosis for a microcytic anemia?

  1. Iron deficiency
  2. Thalassemia
  3. Anemia of chronic disease
  4. Other (rare)

14

Macrocytic Anemia: Differential Diagnosis

  • Megaloblastic:
  • Non-megaloblastic:

  • Megaloblastic:
    • B12 and folate deficiency
    • Some drugs
    • Myelodysplastic syndromes
  • Non-megaloblastic:
    • Reticulocytosis
    • Liver disease
    • Hypothyroidism
    • Some drugs

15

What measures ''chromicity" of RBCs?

Mean corpuscular hemoglobin concentration (MCHC)

16

What CBC parameter would be used to differentiate between Fe deficiency anemia (anisocytosis) vs. anemia of chronic disease (non-anisocytosis)?

Red cell distribution width (RDW)

17

What CBC parameter is used to differentiate between microcytic, normocytic and macrocytic anemias?

Mean cellular (corpuscular) volume (MCV)

18

Type of cell and associations?

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Spherocytes

  • Round
  • Smaller Diameter
  • More densely staining
  • Lack of central pallor
  • Associations:
    • hereditary spherocytosis
    • autoimmune hemolytic anemia

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19

Type of cell and associations?

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Bite cells

  • Oxidant hemolysis (G6PD deficiency)

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20

Type of cell and associations?

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Target cells

  • liver dz
  • splenectomy
  • hemoglobinopathies

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21

Type of cell and associations?

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Elliptocytes (ovalocytes)

  • hereditary elliptocytosis
  • megaloblastic anemia
  • iron deficiency
  • myelofibrosis

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22

Type of cell and associations?

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Schistocytes (fragments)

  • TTP
  • DIC
  • HUS
  • malignant hypertension

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23

Type of cell and associations?

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Teardrop cells

  • megaloblastic anemia
  • myelofibrosis
  • extramedullary hematopoiesis

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24

Type of cell and associations?

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Sickled cells

  • Sickle cell disease

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25

Describe this peripheral blood smear:

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Macrocytosis

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26

Describe this peripheral blood smear:

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Microcytosis

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27

Describe this peripheral blood smear:

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Normochromic

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28

Describe this peripheral blood smear:

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Hypochromic

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29

Describe this peripheral smear: 

What type of cell is this?

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Polychromasia = Reticulocytes

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30

What is this?

What are the associations?

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Howell-Jolly Bodies (nuclear fragments)

  • splenectomy
  • megaloblastic anemia

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31

What is this?

What are the associations?

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Pappenheimer bodies (iron granules)

  • splenectomy
  • iron overload

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32

What is this?

What are the associations?

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Basophilic stippling (coarse) 

  • Thalassemias
  • MDS
  • Lead poisoning

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33

What is this? 

What are the associations?

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Hemoglobin C crystals

  • Hb CC disease
  • Hb SC disease

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34

What is this pattern? Causes?

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Rouleaux

  • Decreased repulsive forces between RBCs
  • Examples: Increased serum proteins (Ig, fibrinogen)

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35

What is this pattern?

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Agglutination

  • IgM RBC antibodies (cold agglutinins)

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36

What can cause anemia?

  • Blood Loss
  • Decreased Production
  • Accelerated Destruction

37

What are the changes seen in acute blood loss?

  • Initially no anemia by CBC parameters despite decrease in blood volume
  • Anemia develops as tissue fluid enters vascular space to restore blood volume
    • producing dilution of cellular elements
  • Reticulocyte count increases after 2-3 days
    • peaks after 7-10 days

38

What are the changes seen in chronic blood loss?

  • No anemia initially because marrow is able to compensate
  • Slight reticulocytosis
  • Eventual development of iron deficiency ⇒ iron deficiency anemia

39

RBC Production:

  • Sites of Production
  • Regulation of RBC Production

  • Sites of RBC production
    • Embryo ⇒ Yolk sac
    • Fetus (3 months gestation until birth) ⇒ Liver
    • Shortly after birth through adult life ⇒ Bone Marrow
  • Regulation of RBC production
    • Decreased oxygen deliveryproduction of erythropoietin by kidney
    • Erythropoietin ⇒ proliferation and differentiation of committed progenitor cells

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40

Normoblastic Maturation

  • What is their function?
  • How many reticulocytes are produced from 1 pronormoblast?
  • What is the normal reticulocytes:normoblasts?

  • Normoblasts (nucleated RBC precursors) obtain iron from plasma transferrin for hemoglobin synthesis
  • Up to 16 reticulocytes produced from each pronormoblast 
  • Roughly equal numbers of reticulocytes and normoblasts in marrow

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41

  • What are reticulocytes?
  • How do they appear morphologically?
  • How long are they normally in the marrow?

  • Earliest anucleate erythroid form
    • Larger than mature RBCs
  • Contain residual RNA which gives cytoplasm a blue tinge on routinely stained blood smears (polychromasia)
  • Stay in marrow for 1 to 2 days synthesizing hemoglobin before being released into circulation

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42

  • How long are reticulocytes normally in the peripheral blood?
  • What is the normal % of reticulocytes in the peripheral blood?

  • Normally circulate for approximately one day before losing residual ribosomes, mitochondria, and other organelles to becoming mature erythrocytes
  • Normally 1% of peripheral erythrocytes

43

  • What is the reitculocyte count?
  • Why do we use this?
  • How can anemias be classified based on the reticulocyte count?

  • Can be detected using RNA stains to obtain a “reticulocyte count”
    • Expressed as % of total RBCs
  • Used as measure of marrow RBC production
  • Cleaves anemias broadly:
    • decreased red cell production
    • adequate marrow response to blood loss 
    • increased RBC destruction

44

  • What are the potential drawbacks of the reticulocyte count?
  • How is this overcome?

  • Problem: Reticulocyte % varies depending on total RBC count
  • Solution: Corrected reticulocyte percentage
    • Retic% x (patient HCT/45)
  • Better Solution: Absolute reticulocyte count

45

What can cause decreased RBC production?

  • Ineffective erythropoieis
  • Decreased RBC precursors (marrow failure)
  • Anemia of chronic disease (anemia of inflammation)

46

  • Define ineffective erythropoeisis:
  • Give examples of ineffective erythropoeisis

  • Definition: Decreased red cell production despite increased RBC precursors in marrow
    • Characterized by defects in maturation
  • Examples:
    • Iron deficiency (cytoplasmic maturation defect)
    • Megaloblastic anemia (nuclear maturation defect)
    • Myelodysplastic disorders

47

Ineffective Erythropoiesis:

General Features

  • Prominent morphologic abnormalities of erythrocytes due to disordered maturation
  • Dysmaturation of erythroid precursors in marrow
  • Decreased reticulocyte count despite increased erythroid mass in marrow

48

What can cause decreased RBC precursors?

  • Proliferation defect
  • Characterized by an absolute decrease in the marrow mass of erythroid precursors:
    • Decreased erythroid progenitors available for RBC production

or

  • Decreased proliferative capacity of numerically adequate erythroid progenitors
     

49

Decreased RBC precursors:

General features

  • Usually normochromic/normocytic
  • Usually little anisopoikilocytosis (compared to maturation defects/ineffective erythropoiesis)
  • Decreased reticulocyte counts

50

Decreased RBC precursors:

  • What is casued by stem cell defects with adequate erythropoietin?

  • Red cell aplasia (pure) vs. pan-aplasia (aplastic anemia)
  • Congenital
    • Diamond-Blackfan syndrome (pure red cell aplasia)
    • Fanconi’s anemia (pan-aplasia)
    • Others
  • Acquired
    • Idiopathic
    • Drugs and toxins
    • Autoimmune
    • Infections
    • Paraneoplastic

51

Other causes of decreased RBC precursors:

  • Marrow replacement
  • Decreased erythropoeitin

  • Marrow replacement
    • Leukemias/lymphomas
    • Metastatic carcinoma
    • Fibrosis
    • Storage disease
  • Decreased erythropoietin
    • Anemia of renal failure

52

What is the RBC structure?

  • Biconcave disc
    • 7.5-8.7 m in diameter
    • Average volume of 90 fl
  • Special membrane structure which provides durability, flexibility, and tensile strength
    • Can swell to a volume of 150 fl
    • Can get through a 2.8 m diameter capillary
    • Springs back to original shape after distortion

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53

Accelerated RBC destruction (hemolysis):

  • How does this affect the bone marrow?
  • When will anemia develop?
  • What will cause anemia not to develop?

  • Red cells normally circulate for ~120 days
  • Increased destruction results in increased marrow production
    • 8 times normal in ideal circumstances
      • Enough iron
      • Enough folate
      • Otherwise good health
  • When rate of destruction exceeds bone marrow’s ability to compensate, anemia develops
    • New steady state at lower hemoglobin level
  • Can have hemolysis without anemia if bone marrow is able to compensate

54

How is hemolysis classified?

  • Intravascular
  • Extravascular
  • Combination

55

Extravascular Hemolysis

  • What is it?
  • Describe the final common pathway:

  • Predominates in most forms of hemolytic anemia
  • Final common pathway: Decreased RBC deformability
    • Rigid, non-deformable cells have trouble traversing narrow slits between splenic cords and sinusoids
    • Cells are damaged further with prolonged exposure to splenic cordal environment
    • Damaged cells phagocytized by cordal macrophages

56

Fate of Hemoglobin

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57

Hemolysis:

General Features

  • Reticulocytosis
  • Increased indirect bili from heme metabolism
  • Increased LDH released from destroyed RBCs
  • Decreased haptoglobin
  • Morphologic abnormalities of red cells characteristic of specific disorders
  • Splenomegaly in chronic cases
  • Bony abnormalities in severe chronic hemolytic anemias