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1

What is the definition of anemia?

-Operationally defined as reduction in one or more of the major RBC measurements:
---Hemoglobin concentration, hematocrit, or RBC count
---All of these are concentration measures
-Anemia is a CONCENTRATION ISSU - ration of plasma to RBCs

2

With ___ _____ you won't be anemic.

acute bleeding

3

There are two questions with anemia:

1. Is it caused by production problems?
2. Is it caused by survival/destruction problems?

4

What is the key test for anemia?

Reticulocyte count!!
-Reticulocytes are early precursors of RBCs. The majority of RBCs are in the bone marrow but some are in the blood/periphery

5

What are the two main approaches (not mutually exclusive) for looking at anemia?

1. Biologic or kinetic approach
2. Morphology

6

How do you make a reticulocyte count useful?

The reticulocyte count must be adjusted for the patient's hematocrit (erythrocyte volume function). When hematocrit is lower, reticulocytes are released earlier from the marrow - so one can adjust for this phenomenon.

7

What does reticulocyte count tell us (kinetic approach)?

-Increased reticulocytes (greater than 2-3% or 100,000 mm^3 total) are seen in blood loss and hemolytic processes, although up to 25% of hemolytic anemia will present with a normal reticulocyte count due to immune destruction of red cell precursors.
-Reticulocyte counts are most helpful if extremely low (

8

What does reticulocyte count tell us (kinetic approach)?

-Increased reticulocytes (greater than 2-3% or 100,000 mm^3 total) are seen in blood loss and hemolytic processes, although up to 25% of hemolytic anemia will present with a normal reticulocyte count due to immune destruction of red cell precursors.
-Reticulocyte counts are most helpful if extremely low (

9

What is normal hemoglobin in men and women?

Men - 13-16
Women - 11.5-14

10

What is normocytic normochromic anemia?

-Reticulocyte count - Index

11

What is micro or macrocytic anemia?

-Reticulocyte count - Index

12

What is hemolysis/hemorrage anemia?

-Reticulocyte count - Index >/= 2.5
-Hemolysis/hemorrhage: blood loss, intravascular hemolysis, metabolic defect, membrane abnormality, hemoglobinopathy, immune destruction, fragmentation hemolysis

13

What does a normal reticulocyte count indicate?
What does a high reticulocyte count indicate?

Normal - production problem
High - problem with destruction (cross out blood loss - especially acute)

14

Whites the morphological approach of investigating anemia?

Big vs. little (measurement)

15

How do you determine RBC size?

MCV

16

What is normal MCV?

80-100

17

What causes MCV of 80-100 (normocytic)?

-Anemia of chronic disease
-Mixed deficiencies
-Renal failure

18

What causes MCV > 100 (macrocytic - over production)?

-B12, Folic acid deficiency (B12 and folic acid go together like ham & eggs!)
-Drugs that impair DNA synthesis (AZT, chemotherapy, alcohol, azathioprine)

19

What causes MCV

-Iron deficiency
-Thalassemia trait
-Anemai of chronic disease (30-40%)
-Sideroblastic anemias

20

What does CBC tell you?

Complete blood count
-Tells you your white blood cell count - differential (WBC)
-Hemoglobin
-Platelets
-Indices - various measures of red cell size: MCV - mean corpuscular volume, MCHC

21

What is the etiology of Macrocytic Anemia?

B12/Folate Deficiency
-Anemia: Vitamin B12 and folate are needed for DNA synthesis deoxyuridate to thymidylate, including RBC precursors
-Deficiency: B12 - dietary intake (rare), decreased gastric secretion of intrinsic factor, Folate - poor dietary intake +/- EtOH, malabsorption, increased demand (pregnancy, hemolytic anemias)

22

How to diagnose macrocytic anemia?

-Smear: Macrocytic (High MCV) RBCs, +/- hypersegmented neutrophils, +/- modest neutropenia (low count neutrophils), but . . .
---B12
-Low serum B12, elevated serum methylmalonic acid levels
-Anti-IF Abs, Schilling test (?), PA accounts for 75%
---Folate
-Serum folate level-- can normalize with a single good meal

23

What causes MCV

-Iron deficiency
-Thalassemia trait
-Anemia of chronic disease (30-40%)
-Sideroblastic anemias

24

What causes MCV

-Iron deficiency
-Thalassemia trait
-Anemia of chronic disease (30-40%)
-Sideroblastic anemias

25

How to treat B12/Folate Deficiency?

B12 deficiency: B12 1 mg/month IM

26

What can cobalamin/Vitamin B12 deficiency cause?

Neurological problems
-Subacute combined degeneration of the dorsal and lateral spinal columns

27

When do you have increased iron requirements?

-Blood loss
-GI disorder (esophageal varices, hemorrhoids)
-Extensive and prolonged menstruation
-Chronic blood donations
-Rapid growth in body size between 2 and 36 months of age
-Pregnancy and lactation

28

When do you have an inadequate iron supply?

-Poor nutritional intake in children
-Malabsorption
-Gastric bypass surgery for ulcers or obesity
-Achlorhydria from gastritis or drug therapy
-Severe malabsorption (for example, celiac disease [nontropical sprue])

29

How to test for iron deficiency?

-Decreased hemoglobin
-Microcytic MCV
-Decreased serum iron
-Increased or normal TIBC (total iron binding capacity)
-Decreased iron saturation
---Serum Fe/TIBC

30

What are Thalassemias?

-Genetic defects in hemoglobin synthesis!
---Dec. synthesis of one of the 2 globin chains (alph or beta)
---Imbalance of globin chain synthesis leads to depression of hemoglobin production and precipitation of excess globin (toxic)
---

31

What are Thalassemias?

-Genetic defects in hemoglobin synthesis!
---Dec. synthesis of one of the 2 globin chains (alph or beta)
---Imbalance of globin chain synthesis leads to depression of hemoglobin production and precipitation of excess globin (toxic)
---"ineffective erythropoiesis"
---Ranges in severity from asymptomatic to incompatible with life (hydrous fetalis)
---Found in people of African, Asian, and Mediterranean heritage

32

How do you diagnose Thalassemias?

-Smear: microcytic/hypochromic, misshapen RBCs
-Beta-thal will have an abnormal Hgb electrophoresis (Inc. HbA2, Inc. HbF)
-The more severe alpha-thal syndromes can have HbH inclusions in RBCs
-Fe stores are usually elevated

33

How do you treat Thalassemias?

Mild: None
Severe: RBC transfusions + Fe chelation, Stem cell transplants

34

What is anemia of chronic disease?

-Normocytic (normal red cell size)
-You NEED a chronic disease (usually inflammatory or infectious)

35

What is the pathogenesis of anemia of chronic disease?

-Cytokines are produced (IFN-gamma, IL-1beta, TNF-alpha,etc.) and cause:
---Decreased EPO production
---Suppression of erythroid progenitors
---Blockade of reticuloendothelial iron release

36

What does anemia of chronic disease look like (lab panel)?

-Microcytic or normocytic anemia
-Decreased serum iron
-Decreased serum TIBC (total iron binding capacity)
-Normal Fe/TIBC percentage
-Normal or increased ferritin (stores and releases iron in a controlled fashion)

37

What is ferratin?

Measures your total body iron stores!
-If you're iron deficient, this number will be decreased
-If you have anemia of chronic disease - your fourteen number will be normal

38

What are sideroblastic anemias?

-Sideroblasts are produced instead of healthy red blood cells
-Heterogenous grouping of anemias defined by presence of ringed sideroblasts in the BM

39

What are the etiologies of sideroblastic anemias?

-Hereditary (rare), type of porphyria
-Myelodysplasia
-EtOH
-Drugs (INH, Chloramphenicol)

40

Auto-immune conditions can cause. . .

hemoglobin and platelets to decrease

41

What should you do after an MCV test if its normal?

Bone marrow biopsy to diagnose
-If MCV normal, you need to determine, is there a chronic disease?

42

What should you do if you find anemia?

-If MCV is high, could be B12, folate or hemolytic anemia (if you have tons of reticulocytes -> but we always do retriculocyte count first)

43

What are the general principles of anemia?

-It's a sign, not a sieges
-Anemias are a dynamic process
-It's never normal to be anemic
-The diagnosis of iron deficiency anemia mandates further work-up