Approach to the Patient with

ANEMIA

Lisa Mohr, MD
Mike Tuggy, MD
 Objectives
Review basic science of the RBC
Define Anemia
Review key aspects of history, physical
and lab evaluation
Review a systematic approach to the
differential diagnosis
Case-based application of clinical
concepts
Erythropoesis-Brief Hematology
Review
Bone marrow
– Pluripotent stem cells
– Chemical regulation
Cytokines
Erythroid specific growth factor
Erythropoietin (EPO)
– Life span
Reticulocyte- 4 days
RBC –120 days
 RBC-The important players
Hemoglobin
– reversibly binds and transports 02 from lungs
to tissues
– 4 globin chains & iron
RBC-The important players (2)
Iron
– key element in the production of hemoglobin
– absorption is poor
Transferrin
– iron transporter
Ferritin
– iron binder, measure of iron stores, *also
acute phase reactant*
 Definitions
Anemia-values of hemoglobin, hematocrit
or RBC counts which are more than 2
standard deviations below the mean
– HGB<13.5 g/dL (men) <12 (women)
– HCT<41% (men) <36 (women)
 CASE
ML is a 64-year old male who has not had
any primary care for several years. When
he tried to give blood last week, he was
told that he was anemic. He presents to
your clinic for evaluation.
What would you do??
 Evaluation of the Patient
HISTORY
– Is the patient bleeding?
Actively? In past?
– Is there evidence for increased RBC
destruction?
– Is the bone marrow suppressed?
– Is the patient nutritionally deficient? Pica?
– PMH including medication review, toxin
exposure
 Evaluation of the Patient (2)
REVIW OF SYMPTOMS
Decreased oxygen delivery to tissues
– Exertional dyspnea
– Dyspnea at rest
– Fatigue
– Signs and symptoms of hyperdynamic state
Bounding pulses
Palpitations
– Life threatening: heart failure, angina, myocardial
infarction
Hypovolemia
– Fatiguablitiy, postural dizziness, lethargy,
hypotension, shock and death
 Evaluation of the Patient (3)
PHYSICAL EXAM
•Stable or Unstable?
-ABCs
-Vitals
•Pallor
•Jaundice
-hemolysis
•Lymphadenopathy
•Hepatosplenomegally
•Bony Pain
•Petechiae
•Rectal-? Occult blood
 Laboratory Evaluation
Initial Testing
– CBC w/ differential (includes RBC indices)
– Reticulocyte count
– Peripheral blood smear
 Laboratory Evaluation (2)
Bleeding
– Serial HCT or HGB
Iron Deficiency
– Iron Studies
Hemolysis
– Serum LDH, indirect bilirubin, haptoglobin, coombs,
coagulation studies
Bone Marrow Examination
Others-directed by clinical indication
– hemoglobin electrophoresis
– B12/folate levels
 Differential Diagnosis
Classification by Pathophysiology
– Blood Loss
– Decreased Production
– Increased Destruction
Classification by Morphology
– Normocytic
– Microcytic
– Macrocytic
 Blood Loss
Acute
– Traumatic
– Variety of sources
Melena, hematemesis, menometrorrhagia
Chronic
– Occult bleeding
Colonic polyp/carcinonma
 Decreased Production
Infectious
Neoplastic
Endocrine
Nutritional Deficiency
Anemia of Chronic Disease
 Decreased Production
INFECTIOUS
Bacterial
– Tuberculosis
– MAI
Viral
– HIV
– Parvovirus
 Decreased Production
NEOPLASTIC
Leukemia
Lymphoma/Myeloma
Myeloproliferative Syndromes
Myelodysplasia
 Decreased Production
ENDOCRINE
Thyroid Dysfunction
– Hypothyroidism
Erythropoietin Deficiency
– Renal Failure
 Decreased Production
NUTRITIONAL DEFICIENCY
Iron
B12
Folate
 Macrocytic Anemia
MCV > 100
Megaloblastic:Abnormaliti
es in nucleic acid
metabolism
– B12, Folate
Non-
megaloblastic:Abnormal
RBC maturation
– Myelodysplasia
ETOH, liver dz,
hypothryroidism,
chemotherapy/drugs
 Microcytic Anemia
MCV <80
Reduced iron
availability
Reduced heme
synthesis
Reduced globin
production
 Microcytic Anemia
REDUCED IRON AVAILABILTY
Iron Deficiency
– Deficient Diet/Absorption
– Increased Requirements
– Blood Loss
– Iron Sequestration
Anemia of Chronic Disease
– Low serum iron, low TIBC, normal serum ferritin
– MANY!!
Chronic infection, inflammation, cancer, liver disease
 Microcytic Anemia
REDUCED HEME SYNTHESIS
Lead poisoning
Acquired or
congenital
sideroblastic anemia
Characteristic smear
finding: Basophylic
stippling
 Microcytic Anemia
REDUCED GLOBIN PRODUCTION
Thalassemias
Smear Characteristics
– Hypochromia
– Microcytosis
– Target Cells
– Tear Drops
 Lab tests of iron deficiency of
increased severity
NORMAL Fe deficiency Fe deficiency Fe deficiency
Without anemia With mild anemia With severe
anemia

Serum Iron 60-150 60-150 <60 <40

Iron Binding 300-360 300-390 350-400 >410

Capacity
Saturation 20-50 30 <15 <10

Hemoglobin Normal Normal 9-12 6-7

Serum Ferritin 40-200 <20 <10 0-10

Differential Diagnosis-Revisited
Classification by Pathophysiology
– Blood Loss
– Decreased Production
– Increased Destruction
INCREASED DESTRUCTION
Immune Mediated
Non-immune Mediated
 Increased Destruction
IMMUNE MEDIATED
Cold Agglutinin
– Paroxysmal nocturnal hemoglobinuria
– Post mycoplasmal hemolytic anemia
Warm Agglutinin
– Drug induced
– Autoimmune hemolytic anemia
– Transfusion reaction
 Increased Destruction
NON-IMMUNE MEDIATED
Extra-corpuscular
– Macro-circulatory
Hypersplenism
Extracorporeal circulation
– Micro-circulatory
DIC
TTP
HUS
Intra-corpuscular
– RBC Wall (membrane or enzyme defects)
– Heme or globin abnormalities (HbS, C)
Back to M.L.-You appropriately
decide to obtain more history!
HPI: “I’ve been a little more tired than usual, but I’ve
been busy at work. I’m getting close to retirement.
Nothing else is unusual. I avoid doctors if I can”
PMH: Inguinal hernia repair 20 yrs ago
FH: F & MGF-heart attack(age 80), brother-alcoholism
SH: Married x44yr, smokes 1ppd, “a couple beers/night”
MEDS: daily multivitamin
ALLERGIES: none
ROS:+fatigue, +urine seems a little darker lately
 More on M.L.
P.E. findings
– T 98.4 HR 98 Resp 20 BP 112/70
– Gen: NAD, appears younger than stated age
– HEENT: skin and conjunctiva slightly pale
– NECK: no adenopathy or thyromegally
– Chest: CTAB
– CV: RRR, no murmur
– ABD: no HSM, soft, normoactive bowel sounds
– GU: normal male
– Rectal: no masses, prostate smooth/not enlarged,
guaiac negative stool
 M.L.’s Initial Labs
Only a CBC w/ diff was obtained:
– WBC: 8.2, HCT 32.2, MCV 79, Platelets 221,
differential - normal
 Initial Thoughts?
Blood loss?
– Age places him at risk for colon CA
Decreased Production?
– Alcohol use, Iron deficiency
Increased Destruction?
– “Darker urine” lately
 Further Work-up
CAGE questions
Peripheral Blood Smear
Reticulocyte count
Iron Studies
– Ferritin
– TIBC
– % Saturation
Urinalysis
FOBT or colonoscopy referal
 More Results
CAGE screen reveals no positive responses
Smear reveals microcytic, microchromic RBCs
Retic count is interpreted as “low”
Urinalysis negative for hemoglobin
FOBT: not completed by patient
Iron Studies
– Ferritin: 10
– TIBC: 350
– % Sat: 15
 What’s next?
Rule out Sources of Bleeding
– Counseling regarding colon CA and referral for
colonoscopy
Consider oral iron therapy
Dietary counseling (iron sources, limiting etoh,
etc)
Encourage follow-up for health care
maintenance
– Vaccinations (Tetnus/pneumovax)
– Other cancer screening
– Cholesterol Screen
 Diagnosis
Colonoscopy revealed
small suspicious lesion in
sigmoid colon, pathology
revealing
adenocarcinoma. –
Excised surgically, no
mets.
Routine labs, one year
later, reveal an HCT of
40%. He feels “better
than ever”!
 References
Schrier, Stanley.Approach to the patient with
anemia. Up to Date. 2004
Schrier, Stanley. Anemia of Chronic Disease. Up
to Date. 2004
Schrier, Stanley. Anemias due to decreased red
Cell Production. Up to Date 2004
Schrier, Stanley. Causes and diagnosis of
anemia due to iron deficiency. Up to Date. 2004
Tierney, et al. Anemias. Current Medical
Diagnosis and treatment. 2003. Pp469-489