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4-3-03
Bob Richard
faculty.washington.edu/rrichard
connect to Talks for handout
Anemias so far...
Jan Abkowitz - MDS
Definition:
Anemia is operationally defined as a reduction in
one or more of the major RBC measurements:
hemoglobin concentration, hematocrit, or RBC
count
Keep in mind these are all concentration
measures
Anemia?
Production?
Survival/Destruction?
Anemia: Etiologies
Production defects:
Nutritional deficiencies - Vitamin B12, folate or iron deficiency.
Inflammation/chronic disease.
Primary marrow disorders- pure red cell aplasia,myelodysplasia.
Anemia: Etiologies
Blood Loss:
Iatrogenic bleeding, such as from repeated
venipuncture in patients undergoing a medical
evaluation, blood losses associated with repeated
hemodialysis procedures, or excessive blood
donations
Factitious bleeding, secondary to surreptitious
blood drawing by the patient.
Bleeding during or after surgical procedures may
be difficult to quantitate, and is often
underestimated.
Bleeding into the upper thigh and/or retroperitoneal
areas can often be significant, but not clinically
obvious.
Morphological Approach
(big versus little)
First, measure the size of the RBCs:
41%
Hemoglobin
13.3 g/dL
Erythrocyte count
3.13million/m
Leukocyte count
11,500/mL
68%
Lymphocytes
24%
Monocytes
7%
Eosinophils
1%
Basophils
0%
131 fL
30.8 g/dL
42.5 pg
Underproduction (1)
(morphological approach)
MCV>115
B12, Folate
Drugs that impair
DNA synthesis (AZT,
chemo., azathioprine)
MDS
Underproduction (2)
Normocytic
Anemia of chronic
disease
Mixed deficiencies
Renal failure
Microcytic
Iron deficiency
Thal. trait
Anemia of chronic
disease (30-40%)
sideroblastic anemias
Prevalence (%) of iron deficiency and irondeficiency anemia, United States, third
National Health and Nutrition Examination
Survey, 1988199.
Sex and age (years)
deficiency anemia
Iron deficiency
Iron-
Both sexes
12
35
<1
611
<1
3*
Nonpregnant females
1215
1619
11*
2049
11
2*
3*
5*
Iron Compartments in a 70 kg
person
Compartment
Hemoglobin Fe
2000
67
1000
27
Myoglobin Fe
130
3.5
Labile pool
80
2.2
Other tissue Fe
0.2
Transport Fe
0.08
No benefit
Investigational
Absolute iron deficiency is defined as ferritin <200 g/L with or without iron
saturation <20%, or relative iron deficiency (ferritin <400 g/L in dialysis patients
receiving erythropoietin therapy or the presence of >10% hypochromic
erythrocytes, reticulocytes, or both.
ACD
Iron-def. anemia
Plasma Fe
Reduced (normal)
Reduced
Plasma transferrin
Reduced (normal)
Increased
Transferrin sat.
Reduced (normal)
Reduced
Plasma ferritin
Increased (normal)*
Reduced
Plasma TfR
Normal
Increased
TfR/log ferritin
Low (<1)
High (>4)
Papadaki HA, Kritikos HD, Valatas V, Boumpas DT, and Eliopoulos GD, Anemia of
chronic disease in rheumatoid arthritis is associated with increased apoptosis of bone
marrow erythroid cells: improvement following anti-tumor necrosis factor-alpha antibody
therapy. Blood 2002
a. Low Fe inflam.
b. Nl Fe stores inflam.
c. Fe def anemia
Utility of supraphysiologic
doses of erythropoietin in the
setting of inflammatory block.
Rheumatoid arthritis
Fe-deficiency
Conclusions of meta-analysis
Epoeitin reduces the odds of transfusion for
cancer patients undergoing therapy.
The number of patients needed to treat to
prevent one transfusion is 4.4 (5.2 - 2.6)
Strongest evidence for QOL improvement is
in patients with <10 g/dL baseline hgb
concentration (Littlewood et al.,
JCO;19:2865-74, 2001) but...
May
Vitamin B12
methyltetrahydrofolate
(cobalamin)
L-methylmalonyl
CoA mutase
Methylmalonyl CoA
Homocysteine-methionine
methyltransferase
methionine
B12/Folate Deficiency
Etiology:
Anemia-- Vitamin B12 and folate are needed
for DNA synthesis deoxyuridate to
thymidylate , including RBC precursors
Deficiency
B12 - Dietary intake, acid-pepsin in the
stomach, pancreatic proteases, gastric
secretion of intrinsic factor, an ileum with Cbl-IF
receptors (fish tapeworm)
Folate-- Poor dietary intake EtOH,
malabsorption, increased demand (pregnancy,
hemolytic anemias), inhibitors of DHFR
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
Serum methylmalonic
acid and serum
homocysteine
$125
$30
Antibodies to IF and
Parietal cells
$78.50 x 2
Schilling test
$300
$18
Sideroblastic Anemias
Heterogenous grouping of anemias defined by
presence of ringed sideroblasts in the BM
Etiologies:
Hereditary (rare), type of porphyria
Myelodysplasia
EtOH
Drugs (INH, Chloramphenicol)
Tx:
Trial of pyridoxine for hereditary or INH induced
SA
Hemolytic Anemias
Hemolytic anemias are either acquired or congenital. The laboratory
signs of hemolytic anemias include:
1. Increased LDH (LDH1) - sensitive but not specific.
2. Increased indirect bilirubin - sensitive but not specific*.
3. Increased reticulocyte count - specific but not sensitive
4. Decreased haptoglobin - specific but not sensitive.
5. Urine hemosiderin - specific but not sensitive.
*The indirect bilirubin is proportional to the hematocrit, so with a
hematocrit of 45% the upper limit of normal is 1.00 mg/dl and with a
hematocrit of 22.5% the upper limit of normal for the indirect bilirubin is
0.5mg/dl. Since tests for hemolysis suffer from a lack of sensitivity and
specificity, one needs a high index of suspicion for this type of anemia.
General Principles
Thalassemias
Genetic defect in hemoglobin synthesis
synthesis of one of the 2 globin chains ( or )
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
(hydrops fetalis)
Found in people of African, Asian, and Mediterranean heritage
Thalassemias (2)
Dx:
Smear: microcytic/hypochromic, misshapen RBCs
-thal will have an abnormal Hgb electrophoresis (HbA2,
HbF)
The more severe -thal syndromes can have HbH inclusions
in RBCs
Fe stores are usually elevated
Tx:
Mild: None
Severe: RBC transfusions + Fe chelation, Stem cell
transplants