Anemia: Basic Approach

History and physical

Reticulocyte count
Blood smear
 Reticulocyte count
Needs to be corrected for hct
Absolute: % retic x rbc count
Corrected: retic% x (hct/45)
Retic index: correct retic/f
 Reticulocyte count
Corrected for hematocrit
(Pt/40)*retic
>2%: blood loss or hemolysis
0.5-2 marrow not responding
<0.5: marrow broken
Absolute retic count
 When to Do a Bone Marrow?
Circulating immature cells
Pancytopenia
Very low reticulocyte count (<0.01%)
Nucleated red cells
Evidence of marrow infiltration
Staging of malignancies
Unexplained anemias
 Iron Absorption
Food iron ferric (Fe+++) form
Stomach acid convert ferrous
(Fe++) form
Absorbed jejunum
Mobilferrin transport through cell
 Iron Absorption
Fe Fe

Fe

Fe Fe
Fe Fe
Fe Fe

Fe
Fe Tf
Fe
Fe
Fe
Fe Fe
Fe

Fe
 RBC

Developing Res
RBC Storage

Transferrin

Losses Po Intake
 2 Key Proteins
Transferrin:
Transports up to 2 Fe molecules
through blood
Ferritin:
Long-term storage of Fe
 Iron Stores

Other Proteins (14%)

Transferrin (0.4%)

Storage (24%)

Hemoglobin (62%)
 Fe and IRE
Cellular iron controls production of
transferrin receptor and ferritin
High Fe:
High ferritin and low transferrin receptor
Low Fe:
Low ferritin and high transferrin receptor
Groups That Develop Fe
Deficiency
Infants 20-50%
Kids 5%
Adolescents 5%
Menstruating women 20%
Pregnancy 50%
 Other Effects of Fe Deficiency
Pica
Exercise intolerance
Iron supplementation improved performance
in deficient but not anemia athletes
Central nervous system effects
Improved test scores with iron
supplementation
Prevalence of Iron Deficiency

Women 25-30%
Men 1%
Elderly 30%
Pregnant women 60%
 Etiology of Iron Deficiency
Kids: use for tissue growth
Women: menstruation
Others: blood loss
In patient with ferritin < 50 serous
pathology seen in over half (cancer in
10%)
 Differential Diagnosis
of Microcytosis
Anything that impairs hemoglobin
production
Iron: iron deficiency and anemia of
chronic disease
Globin: thalassemia
Heme: sideroblastic anemias
 Microcytosis
Iron Protoporphyrin
Sideroblastic
Iron Deficiency
ACD Heme + Globin
Thalassemia
Hemoglobin
 ACD: definition
??
Classic: anemia seen with cancer,
infection or severe inflammation
However, physiology of ACD seen
with many illness and in patients who
are otherwise healthy
 ACD: Definition
Anemia characterized by:
Iron sequestration
Relative lack of EPO response
Not due to any other cause
 ACD: diseases
Much broader range of diagnosis than
traditional infection, inflammation, or cancer
70% seen with severe CHF
COPD
Diabetes
No other disease
ACD is a common response to stress
 ACD: Laboratory Findings
Hct can be as low as 20%
Often microcytic but > 70fl
Very low serum irons
Low serum TIBC
High ferritin (>100 ng/dl)
 What Causes ACD?
Shortened RBC half-life
Inflammatory cytokines
Lack of EPO
Iron sequestration
 Shortened RBC Half-life
RBC survival studies suggested
increase RBC destruction
?Importance
 Inflammatory Cytokines
Cytokines such as IL-1 and TNF suppress
erythropoiesis
Infusions of inflammatory cytokines lead to
anemia
Suppression of red cell procurers
Suppression of EPO production
Anti-TNF antibodies correct anemia
 Lack Of EPO
Consistent finding is lack of appropriate
EPO response to anemia
EPO levels are only slightly raised
despite severe anemia
Can be aggravated by medicines and
other conditions
1000

100

10

1
15 20 25 30 35 40
 Iron Sequestration
Decreased iron absorption
Low serum irons
Low serum TIBC
Very high ferritins
Lack of iron in rbc precursors
 Iron Sequestration: Why?
Free iron is toxic to tissues
Microorganism need iron and can avidity
absorb it
In ACD serum iron drops to 10-15m
Microorganism need 10-6m
Increased infections seen with excess
iron
 Why ACD?
Decrease in iron
Decrease activity level
Decrease rbc due to increase
viscosity from acute phase reactants
 ACD: Therapy
Treat primary cause
EPO
40,000 units/wk
Improves QOL
Need iron!
Functional iron deficiency
PO iron
IV iron replacement for ESRD
 Diagnosis of
Iron Deficiency Anemia
MCV
Serum iron
TIBC
Iron saturation
Ferritin
Bone marrow tests
 Testing for Iron Deficiency
Classic tests only helpful in few patients
Tests affected by concurrent illness and age
Fe: VARIES WILDLY
MCV: lacks sensitivity and specificity
RDW: totally and completely worthless
Saturation: low in both ACD and iron deficiency
 MCV
Decreased due to lack of rbc iron
Can be decreased in anemia of chronic
disease
MCV < 70 seen only in iron deficiency and
thalassemia
Can be normal in iron deficiency
 RDW
Absolutely worthless test!
Of absolutely no predictive value for
Fe deficiency, anemia of chronic
disease, thalassemia, etc
Should never be use!!!!!!!
 Serum Iron
Decreased in any stressful situation
Marked variation in levels
 Total Iron Binding Capacity
Surrogate for transferrin
Increased in iron deficiency
Decreased in inflammation
Specific (diagnostic) but not
sensitive
 Iron Saturation
Iron/TIBC
<16% seen in both iron deficiency
and anemia of chronic disease
Does not add to information provided
by TIBC
 Serum Ferritin
Serum ferritin proportional to iron
stores
Needs iron to be produced
Acute phase reactant only in
presence of iron
Most accurate non-invasive test of
iron stores
 Ferritin
Needs iron to be synthesized
Rises with age
Value needs to be interpreted for age and
situation
 Iron Deficiency
Serum ferritin is best non-invasive test of
iron status
> 100 ng/dl rules out iron deficiency
Lower limit changes with age and condition
Patient over 65 with ferritin < 50 all iron
deficient
Iron deficiency predictor of colon cancer
 Bone Marrow
Direct measure of iron stores
Gold standard
Invasive and expensive
 Trial of Oral Iron
Effected by inflammation and
compliance
Useful in young women
 Summary

RDW, FEP, serum iron, saturation:

worthless
TIBC: specific but not sensitive
Ferritin: best non-invasive test
Bone marrow: gold standard
 Tests of Iron Deficiency
Test IDA ACDboth
sFe D D D
MCVD/N D/N D/N
TIBC I D D/N
Sat D D D
Ferr D I D
sTfr I D I
History of Iron Replacement
Nails driven in apples
Blaud pills 1832
325 mg ferrous sulfate
1890s role of iron disputed
No effect with 60 mg ferrous sulfate
 Therapy
Iron supplements
GI upset
Compliance
Take with vitamin C
Start with 1/day
Diet
Increase heme sources
Decrease fiber and tea
Intravenous iron
 Response to Oral Iron

Increased retic 7-10 days

Increased hct 2-3 weeks
Normalized 2 months
 Failure to Respond to Iron
Blood loss
Wrong diagnosis
Other heme disease
Noncompliance
Defective absorption
Concurrent B12 or folate deficiency
 Lack of Absorption
Iron absorption poorly understood
Reasons for poor absorption
Lack of stomach acid
Lack of stomach
? Genetic defects
 When to Use IV Iron
Unable to tolerate oral iron
Unable to be replaced with oral iron
Risk of anaphylaxis 1% with older preparation
Iron sorbitol and iron sucrose now used and
are much safer
 Cost
Form Iron Content Cost ($/G) Side Effects
Pills 66mg/tab 1 GI upset
Steak 1mg/oz 350 weight gain,
IV iron 50mg/ml 450 anaphylaxis
 Remember!
Iron deficiency in adults is
due to iron loss until proven
otherwise!!!
 Iron Deficiency: GI Evaluation
Most patients with identifiable source of GI
blood loss
Very high number with tumors
Most common cause of missed cancer
diagnosis
Who not to evaluate?
Lesions Identified in Patients With Iron
Deficiency

Esophageal: 12%
Stomach: 25%
Cancer: 3%
Ulcer: 6%
Large intestine: 22%
Cancer: 9%
Nothing: 35%