1

Anemia
Laura Zitella, MS, RN, ACNP-BC, AOCN
Nurse Practitioner
Stanford University Medical Center
Laura Zitella has no financial
disclosures to disclose for this
presentation.

Objectives
Discuss the impact of inflammation in the
setting of iron-deficiency anemia, including
interpreting relevant lab test results and
targeting iron replacement appropriately.

Discuss the pathophysiology of hemolysis and
delineate relevant interventions for its
management.
Normal Erythropoiesis
Normal RBC production: 200 billion RBC/d
Rate of RBC loss = rate of production
1% of RBCs are lost per day and must be
replaced
If there is additional RBC loss, the bone
marrow must increase production of RBC
An elevated reticulocyte count indicates
increased RBC production

Regulation of Erythropoiesis
Hodges, V. M., Rainey, S., Lappin, T. R., & Maxwell, A. P. (2007). Pathophysiology of anemia and erythrocytosis. Critical Reviews
in Oncology/Hematology, 64(2), 139-158.
Hepcidin
Transferrin
Kinetic Classification of Anemia
Decreased RBC production (Hypoproliferative anemia)
Nutritional deficiencies (iron, B12, folate)
Bone marrow disorders (myelodysplasia, tumor infiltration)
Bone marrow suppression (drugs, chemotherapy, radiation)
Anemia of inflammation
Decreased bone marrow response to EPO
Low levels of hormones
Erythropoietin (EPO) deficiency (chronic kidney disease)
Thyroid hormone (hypothyroidism)
Androgens (hypogonadism)
Increased RBC destruction
Hemolysis
Inherited (hereditary spherocytosis, sickle cell disease, thalessemia major)
Acquired (Autoimmune hemolytic anemia, TTP-HUS, malaria)
Blood loss
2
Differential Diagnosis of Anemia
Microcytic anemia
Iron deficiency
Thalassemia
Lead toxicity
Sideroblastic anemia
Anemia of inflammation (late,
uncommon)

Macrocytic anemia
Folate or Vitamin B12 deficiency
Medications (AZT, hydrea,
imatinib, sunitinib, methotrexate,
6MP, capecitabine, cladribine,
cytarabine)
Alcohol abuse
Liver disease
Hypothyroidism
Certain bone marrow disorders
(MDS, leukemia, pure red cell
aplasia)
Increased reticulocytes
(hemolytic anemia)

NORMOCYTIC ANEMIA
Anemia of inflammation
Anemia due to systemic
disease (CKD, malignancy,
endocrine dysfunction)
Acute blood loss
Iron deficiency anemia (early)
Anemia
Deficiency in the oxygen-carrying capacity of the
blood
Normal Hb Values:
Males: 14-18 g/dL
Females: 12-16 g/dL
Hematocrit is approximately 3 x the hemoglobin
WHO criteria for anemia:
Males: Hb <13 g/dL
Females: Hb <12 g/dL
Prevalence of Anemia in the Elderly
Pang, W. &Schrier, S. (2012). Anemia in the elderly. Current Opinion in Hematology. 19(3):133-140.
AIanemia of inflammation; CKDchronic kidney disease; Hem Malighematologic
malignancy; IDAiron-deficiency anemia; Susp MDSsuspicious for myelodysplastic
syndrome; Thalthalassemia; UAEunexplained anemia of the elderly.
Initial Approach to Anemia
Anemia is not normal; it is one of the major signs of
disease and requires thorough evaluation to
determine the cause.
The evaluation should assess:

Is the patient bleeding?
Is there evidence of hemolysis?
Is there suppression of RBC production?
Is there a nutrient deficiency (iron, folate, B12)?
History
Medical history
Is there a condition known to cause anemia?
Family history
Thalessemia more common in Mediterranean, Middle
eastern, sub-Saharan African, Southeast Asian
Medications/Drugs
Alcohol, aspirin, NSAIDS, herbal supplements
Nutritional history
Onset
Acute or chronic
Acute anemia is likely to be acquired rather than inherited
Central Nervous System
Fatigue
Headaches
Dizziness, vertigo
Depression
Retinal damage
Impaired cognitive function

Cardiorespiratory System
Exertional dyspnea
Tachycardia, palpitations
Angina, heart failure
Cardiac hypertrophy
Pulmonary edema
Increased pulse pressure,
systolic ejection murmur
Gastrointestinal System
Anorexia
Nausea
Malabsorption
Irregular bowel
movements
Genital Tract
Menstrual problems
Loss of libido
Vascular and Renal Systems
Proteinuria
Fluid retention
Edema, swollen legs
Signs and Symptoms of Anemia
Ludwig, H., &Strasser, K. (2001). Symptomatology of
anemia. Seminars in Oncology, 28, Supplement 8(0), 7-14.
Patient reported symptoms varies
significantly based on the rapidity of the
change in Hb, medical co-morbidities
and the cause of the anemia
Skin and Mucosal membranes
Pallor of skin, mucous
membranes, and conjunctivae
Cold skin
Brittle/broken /ridged nails


3
Initial Laboratory Evaluation
Parameter Function
Hemoglobin (Hb) Concentration of Hb (oxygen-carrying
pigment)
Hematocrit (Hct) Percentage of RBCs in whole blood
Mean corpuscular volume (MCV) Indicates size of RBC
Normal: 80-100 fl
Reticulocyte count Indicates bone marrow RBC activity
Normal: 0.5%-2.5%
Reticulocyte Index (RI) RI=reticulocyte % x Pt Hb/Normal Hb x 0.5
Normal RI: 1-2%
High (RI >2): hemolytic anemia, acute blood
loss
Low (RI< 1): hypoproliferative anemia
Diagnostic Evaluation of Anemia Based on
MCV and Reticulocyte Index
Hb < 12 g/dL ( Female) and Hb < 13 g/dL (Male)
Hypoproliferative
Normocytic
Anemia
MCV > 100
fl
MCV 80-
100 fl
MCV < 80 fl
Reticulocyte Index < 2
Hypoproliferative
Macrocytic
Anemia
Reticulocyte Index >
2
Hypoproliferative
Microcytic
Anemia

Acute Blood
Loss
Hemolysis

Differential Diagnosis of
Hypoproliferative Anemia
Iron deficiency
Anemia of inflammation
Bone marrow disorders (myelodysplasia, tumor
infiltration)
Bone marrow suppression (drugs, chemotherapy,
radiation)
Low levels of hormones
Erythropoietin (EPO) deficiency (chronic kidney
disease)
Thyroid hormone (hypothyroidism)
Androgens (hypogonadism)

Key Iron Indices
Munoz, M., Villar, I., & Garcia-Erce, J. A. (2009). An update on iron physiology. World Journal of Gastroenterology, 15(37), 4617-
4626. Up-to-date, 2012.
Parameter Function Laboratory
Values
Serum iron Measure of iron in blood 60-150 ng/mL
Ferritin Iron storage protein 40-200 ng/mL
Transferrin Iron binding protein 300-360 mg/dL
Transferrin saturation (TSAT) Percentage of iron-binding sites
on transferrin occupied by iron
20-50%
Soluble transferrin receptor
(sTfR)
Transferrin receptor present on
surface of RBC precursors in
bone marrow ;expression is
increased in response to iron
deficiency anemia
0.76-1.76 mg/L
sTfR/log ferritin Ratio of sTfR to serum ferritin < 1
Anemia of inflammation versus
Iron Deficiency Anemia
AI Iron Deficiency ACD and Iron
Deficiency
Serum iron Low Low Low
Transferrin Low - normal High Normal
Transferrin
saturation
Low Low Low
Ferritin Normal high Low Low - normal
Soluble
transferrin
receptor
Normal High Normal - High
Ratio of soluble
transferrin
receptor to
log ferritin
< 1 (Low) > 2 (High) > 2 (High)
Diagnosis of AI and IDA
Munoz, M., Villar, I., & Garcia-Erce, J. A. (2009). An update on iron physiology. World Journal of Gastroenterology, 15(37), 4617-4626
Hb < 12 g/dL ( Female) and Hb < 13 g/dL (Male)
AI
+
IDA
Ferritin
< 30 ng/mL
Ferritin
30-100 ng/mL
Ferritin
> 100 ng/dL
sTfR/log Ft > 2 sTfR/log Ft < 1
Transferrin Saturation < 20%
Iron
Deficiency
Anemia (IDA)
Anemia of
Inflammation
(AI)
4
Anemia of Inflammation
(Anemia of Chronic Disease)
Infection
Viral, bacterial, TB, parasitic, fungal
Autoimmune disease
Rheumatoid arthritis, systemic lupus erythematosus, polymyositis,
inflammatory bowel disease (ulcerative colitis, Crohns disease), sarcoidosis,
vasculitis
Malignancy
Severe trauma
Heart failure
Diabetes mellitus
Acute or chronic immune activation
Renal failure
Thyroid disease

Anemia of Inflammation
Inflammatory cytokines (TNF-a, IFN, IL-1, IL-6) cause:
Abnormal iron metabolism due to increased hepcidin
Iron is trapped in macrophages
Results in low serum ferritin, making iron unavailable
for Hb synthesis
Inability to increase RBC production in response to
anemia
Suppression of erythroid progenitors
Blunted marrow response to EPO
Suppression of EPO production
EPO production does not rise appropriately in
response to the degree of anemia

Adamson, J. W. (2008). The anemia of
inflammation/malignancy: Mechanisms and
management. ASH Education Program
Book, 2008, 159-165.
Abnormal Iron Metabolism in
Anemia of Inflammation
X
Hepcidin blocks
release of iron
from stores and
absorption of iron
from duodenum
X
X Hepcidin
Plasma
Goodnough, L. T., Nemeth, E., & Ganz, T. (2010). Detection, evaluation, and management of iron-restricted erythropoiesis. Blood,
116(23), 4754-4761; Hentze, M. W., Muckenthaler, M. U., & Andrews, N. C. (2004). Balancing acts: molecular control of mammalian iron
metabolism. Cell, 117(3), 285-297
Treatment of
Anemia of Inflammation
Treatment Anemia of
Inflammation

Anemia of Inflammation
with True Iron Deficiency
Treatment of underlying
disease
Yes Yes
Transfusion Yes Yes
Iron supplementation No Yes
Erythropoietin stimulating
agents
Yes * Yes, if no response to iron
therapy*
Weiss, G., & Goodnough, L. T. (2005). Anemia of chronic disease. NewEngland Journal of Medicine, 352(10), 1011-1023.
*ESAs indicated only for patients being treated with chemotherapy in the noncurative setting or
patients with chronic kidney disease
RBC Transfusion
Each unit contains ~ 200 mL RBCs
Hb rises ~ 1 g/dL with each unit RBC
Each unit contains 1 mg/mL iron (~200 mg iron)
RBC transfusion is indicated for
Hb 7-9 g/dL
Symptoms
Only treatment that immediately corrects
anemia
Schrijvers, D. (2011). Management of anemia in cancer patients: Transfusions. The Oncologist, 16(suppl 3), 12-18.
Symptoms of Anemia requiring
Intervention
Sustained tachycardia
Tachypnea
Chest pain
Hypotension
Shortness of breath
Lightheadedness
Dizziness
Syncope
Severe fatigue (preventing ADLs)
5
Risks of RBC Transfusion
RBC Transfusion Estimated Frequency
Risk Factors Per Actual Unit
Hepatitis B 1/1,100,00
Hepatitis C 1/4,400, 000
HIV 1/5,500,000
Bacterial infection 1/38, 500
Acute hemolytic reaction 1/10, 000 1/50,000
Delayed hemolytic reaction 1/1500
Transfusion-related acute lung injury 1/2,500,000
Febrile, nonhemolytic transfusion reaction 1/100 33/1000
Allergic reaction 1/1001/300
Red blood cell alloimmunization 2/100 -8/100
Anaphylactic transfusion reaction 1/20, 000 1/47, 000
Transfusion-associated GVHD 1/1,000 1/100
Schrijvers, D. (2011). Management of anemia in cancer patients: Transfusions. The Oncologist, 16(suppl 3), 12-18.
Diagnosis of AI and IDA
Munoz, M., Villar, I., & Garcia-Erce, J. A. (2009). An update on iron physiology. World Journal of Gastroenterology, 15(37), 4617-4626
Hb < 12 g/dL ( Female) and Hb < 13 g/dL (Male)
AI
+
IDA
Ferritin
< 30 ng/mL
Ferritin
30-100 ng/mL
Ferritin
> 100 ng/dL
sTfR/log Ft > 2 sTfR/log Ft < 1
Transferrin Saturation < 20%
Iron
Deficiency
Anemia (IDA)
Anemia of
Inflammation
(AI)
Iron Deficiency Anemia
In severe cases may observe:
Atrophic glossitis
Angular chelitis
Koilonychia


Iron Deficiency Anemia
Diagnosis
Gold standard: iron stains of bone marrow aspirate sample
(rarely performed since invasive)
Iron indices

Pang, W., & Schrier, S. (2012). Anemia in
the elderly. Current Opinion in Hematology,
19(3), 133-140
Excess Iron Loss
Blood loss
Gastrointestinal tract
Menses
Malignancy
Blood donation
Pregnancy and lactation

Inadequate Iron Supply
Insufficient dietary iron
(less common in Western
countries)
Impaired iron absorption
Gastric surgery
Intestinal malabsorption
Celiac disease
Iron Deficiency:
Absolute or Functional
Functional Iron deficiency

Assess for presence of
inflammation
Serum concentrations
of C -reactive protein
(CRP) <0.5 mg/dL
Ferritin is an acute
phase reactant and
may be elevated due
to systemic disease or
inflammation
Absolute iron deficiency

Transferrin saturation < 15%
Ferritin < 30 ng/mL
Transferrin saturation < 20%
Ferritin < 100 ng/mL
sTfR ratio > 2 indicates iron
deficiency
Calculation of Iron Deficit
Assumptions:
Blood volume = 65mL/kg
3.3 mg iron per g Hb

Calculate blood volume (dL)
65 mL/kg x body weight (kg)/ 100(mL/dL) =blood volume in dL
Iron deficit (mg) = {[Target Hb (g/dL) patient Hb (g/dL)] x blood
volume (dL) x 3.3 mg Fe/g Hb} + iron stores (~ 600 mg in women
and 1000 mg in men)

Example: 60 kg woman with Hb 8 g/dL
{[12-8 g/dL] x 39 dL x 3.3 mg Fe/g Hb} + 600 mg = 1115 mg iron
6
Oral Iron Supplementation
Dose: Elemental iron 150-200 mg/d = Ferrous sulfate 325 mg PO TID
Iron is absorbed best on an empty stomach
Ascorbic acid (Vitamin C) increases absorption and toxicity
Iron absorption inhibited by: coffee, tea, milk, cereals, dietary fiber, carbonated
beverages, dietary supplements with Ca, Zn, Mg, Cu, antacids, H2 blockers, and PPIs
Ferrous salts are absorbed better than ferric salts; non-enteric better absorbed than
enteric
Prescription iron (iron polysaccharide complex; carbonyl iron) generally better
tolerated than iron salts
Alleyne, M., Horne, M. K., & Miller, J. L. (2008). Individualized treatment for iron-deficiency anemia in adults. The American Journal
of Medicine, 121(11), 943-948.
Oral iron preparations Dose (mg) Elemental iron (mg)
Ferrous sulfate 325 mg tid 65
Ferrous gluconate 300 mg tid 36
Ferrous fumarate 100 mg tid 33
Iron polysaccharide complex 150 mg bid 150
Carbonyl iron 50 mg tid 50
Oral Iron Supplementation
Start Ferrous sulfate 325 mg PO daily and titrate up to
325 mg PO TID
Teach patient to take iron on empty stomach with
Vitamin C 250 mg PO to maximize absorption
Assess for tolerance
After one month, re-assess Hb and serum ferritin
Initial response within 7-14 days
Appropriate response after 1 month: 2 g/dL
Correction of anemia may require 2-3 months
6 months of therapy beyond correction of anemia
needed to replete stores, assuming no further loss of
blood/iron
Alleyne, M., Horne, M. K., & Miller, J. L.
(2008). Individualized treatment for iron-
deficiency anemia in adults. The American
Journal of Medicine, 121(11), 943-948.
IV Iron Products and Dose
Shander, A., Spence, R. K., &Auerbach, M.
(2010). CONFERENCE REPORT: Can
intravenous iron therapy meet the unmet
needs created by the new restrictions on
erythropoietic stimulating agents?
Transfusion, 50(3), 719-732.
Iron sucrose
(Venofer
)

Ferric
gluconate
(Ferrlecit
)

Iron dextran
(InFeD
)

Ferumoxytol
(Feraheme
)


IV Push
100 mg over 2-5
min
200 mg over 2-5
min
125 mg over
10 min
100 mg over 2-5
min
510 mg over 17 sec
Repeat dose 3-8 days
later
IV
Infusion
(0.9%
NaCl)
100 mg/100 mL
over 15 min
300 mg/250 mL
over 1.5hr
400 mg/250 mL
over 2.5hr
125 mg/100
mL over 1 hr
Not FDA-approved
(up to 1000 mg
infused at 6
mg/min)
Not FDA-approved
Iron dextran
(InFeD
)

Ferric gluconate
(Ferrlecit
)

Iron sucrose
(Venofer
)

Ferumoxytol
(Feraheme
)

Test Dose Yes
0.5 mL IV over 30
seconds
MD/APP discretion MD/APP discretion No
Pre-
medication
Acetaminophen and
diphenhydramine
No No No
Precautions High risk for
anaphylaxis
Observe patient for
at least one hour
after test dose for
anaphylaxis

Low risk for anaphylaxis Low risk for
anaphylaxis

Low risk for
anaphylaxis
Observe patient for
at least 30 minutes
after administration
for hypersensitivity
Duration Repeat once daily or
weekly for total dose
1000 mg

Repeat once daily or
weekly for 8 doses for
total dose 1000 mg

Repeat once daily or
weekly for total
dose 1000 mg

Repeat Hb and iron
studies at least one
month after dose
IV Iron Products
Arthralgia-Myalgia Syndrome
Common side effect of all IV iron products
Characterized by:
Fever
Muscle cramping
Generalized pain
Prevention:
Methylprednisolone 125 mg IV
Shander, A., Spence, R. K., &Auerbach, M.
(2010). CONFERENCE REPORT: Can
intravenous iron therapy meet the unmet
needs created by the new restrictions on
erythropoietic stimulating agents?
Transfusion, 50(3), 719-732.
Hemolysis
Destruction of RBC due to:
Inherited hemoglobinopathies or enzyme disorders
Medications
Incompatible blood transfusions
Autoimmune hemolytic anemia (AIHA)
Hypersplenism
Microangiopathic hemolytic anemia
Thrombotic thrombocytopenic purpura (TTP)
Hemolytic uremic syndrome (HUS)
Disseminated intravascular coagulation (DIC)
Vasculitis
Malignant hypertension
Metastatic neoplasm with vascular invasion
Valvular heart disease/mechanical valve
Preeclampsia/HELLP syndrome of pregnancy

Williams Hematology, 8th ed. 2010
7
Types of Hemolysis
Intravascular
IgM coats RBCs
RBCs destroyed by
complement
Occurs in blood vessels
Labs: Increased indirect
bili, LDH, retic count;
decreased /absent
haptoglobin
Acute process
Extravascular
IgG coats RBCs
RBCs destroyed by
macrophages
Occurs in spleen, less in
liver
Labs: Increased indirect
bili, LDH, retic count;
decreased haptoglobin
Usually slow, gradual
process
Williams Hematology, 8th ed. 2010
Intravascular Hemolysis
Mechanical damage
Microangiopathic
hemolytic anemia
Shearing due to
malfunctioning
mechanical heart valves
Thermal damage (burns)
Infection (malaria or
babesiosis)
Transfusion reaction (ABO
incompatibility

Extravascular Hemolysis
Extravascular (reticuloendothelial
system)
Hereditary
Hemoglobinopathies (sickle cell
anemia)
Enzyme abnormalities (G6PD
deficiency)
RBC membrane defects (hereditary
spherocytosis)

Acquired
Immune mediated
Autoimmune hemolytic anemia
Non-immune mediated
Spur cell hemolytic anemia
Paroxysmal nocturnal
hemoglobinuria (PNH)

Signs and Symptoms of Hemolysis
Rapid onset of pallor and anemia
Jaundice with increased indirect bilirubin concentration
History of pigmented (bilirubin) gallstones
Splenomegaly
Presence of circulating spherocytes or shistocytes or helmet
cells (fragmented RBC)
Increased serum lactate dehydrogenase (LDH) concentration
(released from lysed RBC)
Reduced or absent level of serum haptoglobin (free Hb
released from RBC lysis binds to haptoglobin)
Positive direct antiglobulin test (Coombs test) in
autoimmune hemolytic anemia
Increased reticulocyte count or index, indicating the bone
marrow is increasing RBC production to correct the anemia
Diagnostic Evaluation of Hemolytic
Anemia
Intravascular Extravascular
Peripheral smear schistocytes /helmet
cells
spherocytes
Haptoglobin decreased/absent mildly decreased
Urine hemosiderin ++ ( 7d after
hemolysis)
negative
Urine hemoglobin ++ negative
Direct Antiglobulin
Test (DAT)
usually negative ++++
LDH increased increased
Direct and Indirect Antiglobulin Tests
8
Glucose 6-Phospate Dehydrogenase
Deficiency
Common cause of non-immune hemolytic anemia
X-linked enzyme deficiency (heterozygous females are usually not clinically
affected, but have a variable level of enzyme activity)
Affects 200-400 million people worldwide
Highest incidence in African-Americans, Mediterraneans, South Africans and
Kurdish Jews
G6PD -reduces NADP/oxidizes glucose-6-phosphate
Detoxifies free radicals and peroxides
If oxidants accumulate in RBC, leads to cell death
Most common form results in severe hemolysis with medications
(primaquine, sulfa, dapsone), fava beans and some infections
Diagnosis:
enzyme activity testing
False negative test common in the setting of acute hemolysis, re-test at 2-3
months
Glucose-6-Phosphate Dehydrogenase
Deficiency: Treatment
In response to the anemia, erythropoiesis
increases
Increased reticulocytes within five days
Acute hemolytic process usually spontaneously
resolves in a week despite continued exposure to
drug
Treatment
Prevention
Avoid stressors (medications, fava beans)
Rarely warrants blood transfusion
Autoimmune Hemolysis
Etiology of
Autoimmune Hemolytic Anemia
Idiopathic
Medications
Lymphoproliferative disorders (~ 50%)
CLL
Lymphoma
Malignancy (e.g. ovarian cancer)
Autoimmune disease (esp. SLE)
Chronic inflammatory diseases
Infection
Williams Hematology, 8th ed. 2010
Warm Antibody AIHA
Most common (70%)
IgG antibodies bind to RBC
antigens at 37 C
As Ab-coated RBCs pass
through splenic circulation,
they are recognized and
destroyed by splenic
macrophages
Spherocytes seen on
peripheral smear
Cold Agglutinin AIHA
IgM antibodies bind to I-
antigens on RBC at temp
< 37 C
IgM coated RBCs triggers
complement which leads to
intravascular hemolysis
Peripheral smear shows
RBC clumping
(agglutination)
Complete responses rare;
usually chronic disorder
9
Treatment of AIHA
Type Steroids Splenectomy Rituximab Plasmapheresis
Warm Ab Yes Yes Yes Possibly
Cold
agglutinin*
No No Yes Yes
Williams Hematology, 8th ed. 2010
* Educating patient to keep extremities warm may provide symptomatic relief
Initial Treatment of Warm Antibody
Autoimmune Hemolytic Anemia
Prednisone (PSE)
1 mg/kg/day until Hb > 10 g/dL
Then decrease PSE to 20 to 30 mg/d and continue to taper PSE by 2.5-5
mg/d per month with careful monitoring of Hb and RI
After the steroids are tapered to 5 mg/d, continue for 3-4 more
months
Alternate-day regimen may reduce the side effects of steroids
All patients on steroid therapy should be treated with:
PCP prophylaxis
Bisphosphonates, vitamin D, and calcium
Monitor blood glucose and treat hyperglycemia
Supplementation with folic acid is recommended
If Hb < 10 g/dL after 3 weeks of steroids, consider second line
treatment
Lechner, K., & Jger, U. (2010). HowI treat
autoimmune hemolytic anemias in adults.
Blood, 116(11), 1831-1838.
Treatment of Steroid-Refractory AIHA
Splenectomy (Preferred)
Rituximab
375 mg/m
2
on days 1, 8, 15, 22 for 4 doses
Rituximab + steroids
Beyond second-line:
Azathioprine
MMF
Cyclosporine
Cyclophosphamide
Chlorambucil
Bortezomib (cold agglutinin)

Lechner, K., & Jger, U. (2010). HowI treat
autoimmune hemolytic anemias in adults.
Blood, 116(11), 1831-1838.
Conclusion
Anemia is a prevalent condition that is often sign
of an underlying disease
The two most useful tests in the initial evaluation
of anemia are the MCV and the reticulocyte index.
Anemia of inflammation may be exacerbated by
iron deficiency
Iron supplementation is effective to treat iron
deficiency anemia
Astute assessment of symptoms and identification
of the etiology of the anemia guides treatment
options
Differential Diagnosis of Anemia
Anemia
Due to:
MCV Ferritin

Iron

Transferrin Trans
Sat
Retic
Index
LDH Indirect
Bili
Hapto-
globin
Inflammation
N- N- N- N N N
BM
Infiltration
N N- N/A N N N
Iron
Deficiency
N N N
B12/Folate
Deficiency




N N N
Hemolysis
N N-
Blood Loss
N- N N N N
References
Adamson, J. W. (2008). The anemia of inflammation/malignancy: Mechanisms and management.
ASH Education Program Book, 2008, 159-165. doi: 10.1182/asheducation-2008.1.159
Alleyne, M., Horne, M. K., & Miller, J. L. (2008). Individualized treatment for iron-deficiency anemia
in adults. The American Journal of Medicine, 121(11), 943-948. doi: 10.1016/j.amjmed.2008.07.012
Ferrucci, L., & Balducci, L. (2008). Anemia of aging: The role of chronic inflammation and cancer.
Seminars in Hematology, 45(4), 242-249. doi: 10.1053/j.seminhematol.2008.06.001
Finberg, K. E. (2011). Unraveling mechanisms regulating systemic iron homeostasis. ASH Education
Program Book, 2011(1), 532-537. doi: 10.1182/asheducation-2011.1.532
Goodnough, L. T., Nemeth, E., & Ganz, T. (2010). Detection, evaluation, and management of iron-
restricted erythropoiesis. Blood, 116(23), 4754-4761. doi: 10.1182/blood-2010-05-286260
Hentze, M. W., Muckenthaler, M. U., & Andrews, N. C. (2004). Balancing acts: molecular control of
mammalian iron metabolism. Cell, 117(3), 285-297. doi: 10.1016/s0092-8674(04)00343-5
Hodges, V. M., Rainey, S., Lappin, T. R., & Maxwell, A. P. (2007). Pathophysiology of anemia and
erythrocytosis. Critical Reviews in Oncology/Hematology, 64(2), 139-158. doi:
10.1016/j.critrevonc.2007.06.006
Kaushansky, K., Lichtman, M.A., Beutler, E., Kipps, T.J., Seligsohn, U., Prchal, J.T. (Eds). (2010).
Williams Hematology, 8th ed. McGraw-Hill: New York
Lechner, K., & Jger, U. (2010). How I treat autoimmune hemolytic anemias in adults. Blood,
116(11), 1831-1838. doi: 10.1182/blood-2010-03-259325

10
References
Ludwig, H., & Strasser, K. (2001). Symptomatology of anemia. Seminars in
Oncology, 28, Supplement 8(0), 7-14. doi: 10.1016/s0093-7754(01)90206-4
Munoz, M., Villar, I., & Garcia-Erce, J. A. (2009). An update on iron physiology.
World Journal of Gastroenterology, 15(37), 4617-4626. Retrieved from
http://www.ncbi.nlm.nih.gov/pubmed/19787824
Pang, W., & Schrier, S. (2012). Anemia in the elderly. Current Opinion in
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