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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

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

Nonmegaloblastic: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
Without anemia

Fe deficiency
With mild anemia

Fe deficiency
With severe
anemia

Serum Iron

60-150

60-150

<60

<40

Iron Binding
Capacity

300-360

300-390

350-400

>410

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: Ive been a little more tired than usual, but Ive
been busy at work. Im 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

Whats 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