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Differentiation of Anemia
KY STOLTZFUS, MD
ASSISTANT PROFESSOR, INTERNAL MEDICINE
UNIVERSITY OF KANSAS MEDICAL CENTER
JANUARY 23, 2013
Differentiating Anemia
 Anemia is a sign of a disease process or problem

But anemia has consequences if left untreated…

When you have a sign

Look further and investigate cause
Chronic affects of anemia
Anemia, physiological impairments, and clinical outcomes. Anemia has
been linked to a number of physiological impairments and clinical
outcomes in community-dwelling older populations.
RBCs
 Red Blood Cell
 Adults have approx. 20-30 trillion RBCs in circulation



Each having over 200 million molecules of hemoglobin
Each hemoglobin molecule has 4 heme molecules that carry
oxygen molecule
Flexible so can fit through tiny capillary spaces to offload
oxygen.
RBC production
RBCs
 Life cycle of RBC
 50,000 reticulocytes produced daily
 Reticulocyte circulates for about 1 day
 RBC survives approx. 110-120 days
Removed by reticuloendothelial system
 Iron recycled to make new RBCs


Under normal conditions about 1% of RBC’s removed daily
Anemia
 Anemia
Reduction in red blood cell mass
 NOT just a drop in Hgb lab value

 Definition
 World Health Organization
<13 g/dL males
 <12 g/dL females

Prevalence of anemia:
3.6 million
people in US
Differential Diagnosis of Anemia
 Signs/symptoms – how is anemia found?
 Depends on:
severity
 rate of onset
 etiology
 patient’s overall health & oxygen demand

Differential Diagnosis of Anemia
 Diagnosis
 Past medical history
 Family history
 Physical exam
 Lab
History
Patient’s age
 Ethnic background
 Females: Menstrual history (duration, frequency, flow,
pregnancy)
 Jaundice?
 GI problems – blood in stool
 Fatigue, hx of anemia, previous transfusions

History continued

Medications
Rx
 OTC
 Vitamins & supplements
 Dietary restrictions

Physical exam
 Physical exam
 Pallor
Conjunctiva
 Oral mucosa
 Nail beds
 Palmar creases


Orthostatic BP changes

Intravascular volume shifts
Physical findings
Differential Diagnosis
 Ways to classify anemia
 Etiology
 Reticulocyte response
 Lab value description

morphology of RBCs
Differential Diagnosis
 Classification of anemia
 Etiology
Blood loss
 Acute
 Chronic
 Deficient erythropoiesis (Nonproduction)
 Excessive RBC destruction
 Defects extrinsic to RBC
 Defects intrinsic to RBC

Differential Diagnosis
 Classification of anemia
 Lab value description of RBC
 MCV (Mean Corpuscular Volume)
Microcytic
 Normocytic
 Macrocytic

Differential Diagnosis
 Microcytic
 Iron deficiency
 Anemia of chronic disease
 Thalassemias
 Sideroblastic anemia
Differential Diagnosis
 Normocytic



Hemolytic (extrinsic)
 Alloimmune
 Autoimmune
 Nonimmune
 Hypersplenism
 Infections
 Physical trauma
Hemolytic (intrinsic)
 Enzyme deficiencies (G6PD)
 Hemoglobinopathies (sickle cell disease)
 Membrane defects (spherocytosis)
Nonhemolytic
 Acute blood loss
 Anemia of chronic disease
 Aplastic anemia
 Chronic renal insufficiency
Differential Diagnosis of Anemia
 Macrocytic
 Megaloblastic
Drug Related
 Folic acid deficiency


Nonmegaloblastic
Alcoholism
 Hypothyroidism
 Liver disease
 Myelodysplastic syndromes
 Reticulocytosis
 Spherocytosis

Anemia Algorithm
Establishment of
anemia based on
history, exam,
Hgb/Hct
Mean corpuscular volume
(MCV)
<80 fL
80 to 100 fL
Microcytic pathway
>100 fL
Normocytic pathway
Macrocytic pathway
Differential Diagnosis of Anemia
 CASE 1
JL – 42 y/o female c/o increasing fatigue, having to take nap
when getting home from work.
ROS – heavy menstrual flow Xs several years, no change in bowel
habits
PMH – no illnesses, hx anemia, transfusions
FH – no history of blood problems
Meds – Occasional NSAID for joint pain
Differential Diagnosis of Anemia
 Case 1 cont’d
Exam: BP 116/74, P 74, R 22
general – mild pallor, sclera & mucosal membranes pale.
CV, Resp – WNL
Abd/GI – no masses, stool heme neg.
GU – enlarged uterus with palpable masses
Differential Diagnosis of Anemia
 Case 1 cont’d
 RBC count
3.1x1012/L (3.9-5.2x1012/L)
 Hgb
7.8 g/dL (12-15.6 g/dL)
 Hct
23.1% (35-46%)
 MCV
73 fL (78-102 fL)
 MCH
20 pg/cell (27-33 pg/cell)
 Reticulocyte count 1.5% (0.5-2.3%)
Differential Diagnosis of Anemia
 Case 1 cont’d
 Iron
35 mcg/dL
(25-170 mcg/dL)
 Ferritin
12 ng/mL
(12-156 ng/mL)
 TIBC
550 mcg/dL (200-450 mcg/dL)
 % transferrin sat. 11%
(12-57%)
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Microcytic anemia
Differential Diagnosis of Anemia
 Microcytic anemia – Iron deficiency
 Most common cause of anemia
10-30% world population
 In US: 11% women, 4% men

Differential Diagnosis of Anemia
 Microcytic anemia – Iron Deficiency
 Average adult has 2-4 gm stored iron

Most located in RBCs
Usual loss of 1-2 mg/day replaced in diet
 Blood loss most common cause

Women lose additional 1mg daily compared to men
 Menses 15 mg/mo loss
 Pregnancy 900 mg loss


Deficiency results from excessive loss or poor intake
Differential Diagnosis of Anemia
 Microcytic anemia - Iron deficiency
 Serum Iron
 Serum ferritin
 Total iron binding capacity (TIBC)
 % transferrin saturation
Differential Diagnosis of Anemia
 Case 2
KR is 78 y/o female with history of HTN, DM, rheumatoid
arthritis and COPD. First office visit reveals no significant
abnormal exam findings. Her DM and HTN have been fairly
well controlled with insulin and ACE inhibitors.
Differential Diagnosis of Anemia
 Case 2 cont’d
RBC count 3.45x1012/L (3.9-5.2x1012/L)
Hgb
10.2 g/dL
(12-15.6 g/dL)
Hct
30.3% (35-46%)
MCV
76 fL
(78-102 fL)
Differential Diagnosis of Anemia
 Case 2 cont’d
Iron
85 mcg/dL
(25-170 mcg/dL)
Ferritin
260 ng/dL
(12-156 ng/dL)
TIBC
220 mcg/dL (200-450 mcg/dL)
% transferrin sat 60% (12-57%)
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Differential Diagnosis of Anemia
 Microcytic anemia – Anemia of Chronic Disease
 Occurs in patients with chronic diseases – cancer,
collagen vascular disease, chronic infections, DM,
CAD

Decreased RBC survival AND decreased production
Fe stores trapped in RE system – unavailable
 Decreased erythropoietin production
 Bone marrow less responsive to erythropoietin

Differential Diagnosis of Anemia
 Microcytic anemia – Anemia of Chronic Disease
 Can be difficult to differentiate from iron deficiency anemia
 MCV – low or normal
 Serum iron levels low or normal
 Ferritin levels high or normal
Target cells
Differential Diagnosis of Anemia
 Microcytic anemia - Thallasemias
 Low Hgb and elevated RBC count
 Inherited condition of abnormal alpha or beta Hgb chain
 Named for abnormal Hgb chain
 Spectum of mild to life threatening
 Thallassemia traits more common in individuals of African,
Mediterranean and South Asian descent
Microcytic Anemia
Iron
Deficiency
Anemia
Anemia of
Chronic
Disease
Thalassemia
Ferritin
Low
High
Normal or high
Iron
Low
High
Normal or high
TIBC
High
Low
Normal
% transferrin sat
Low
High
Normal
Common patient
findings
Infant, pregnant,
female, elderly
Chronic dz, CAD, DM,
malignancy
African,
Mediterranean,
South Asian heritage
Differential Diagnosis of Anemia
 Case 4
LR is 18 y/o female of Nigerian descent with multiple
hospitalizations in past for abdominal and chest pain.
Recurrence of sx’s 2 days. No hx abn or heavy menses.
PE: T-101.4, BP-157/82, R-32
Lungs – rales, decreased BS bilat.
Abd – diffusely tender, BS ok, enlgd spleen
GU - WNL
Differential Diagnosis of Anemia
 Case 4 cont’d
RBC count 4.0x1012/L
Hgb
9.8 g/dL
Hct
32%
MCV
84 fL
(3.9-5.2x1012/L)
(12-15.6 g/dL)
(35-46%)
(80-100 fL)
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Differential Diagnosis of Anemia
 Case 4 cont’d
Reticulocyte count
Peripheral smear
Bilirubin total
Bilirubin direct
Bilirubin indirect
3.7% (<2%)
sickled cells present
2.9 mg/dL
(<1.3 mg/dL)
0.2 mg/dL
(<0.4 mg/dL)
2.7 mg/dL (<0.7 mg/dL)
Differential Diagnosis of Anemia
 Normocytic anemia
 Hemolytic


Increased RBC destruction
 Inherited
 Acquired
Nonhemolytic

Decreased RBC production
Differential Diagnosis of Anemia
 Normocytic anemia
 Reticulocyte count
Hemolytic anemia – increased
 Nonhemolytic anemia - decreased

Differential Diagnosis of Anemia
 Normocytic anemia – Hemolytic anemia
 Rapid fall in Hgb
 Elevated reticulocyte count
 Abnormally shaped RBC’S
 Elevated LDH (lactate dehydrogenase)
 Elevated indirect bilirubin
 Low serum haptoglobin concentration
Differential Diagnosis of Anemia
 Normocytic anemia – Hemolytic anemia
 Inherited
Abnormal Hgb synthesis (sickle cell disease)
 Defects in enzyme function (G6PD)
 Defects in RBC membrane (spherocytosis)


Acquired

Traumatic destruction of RBC

DIC, TTP, HELLP, drugs, abnormal valves
Immune mediated
 Infection


Malaria
Differential Diagnosis of Anemia
 Normocytic anemia – Hemolytic anemia
 Coombs test (direct & indirect)


Distinguish between immune & nonimmune causes of
hemolysis (extrinsic)
Peripheral smear
Sickled cells – sickle cell disease
 ‘Bite’ cells – enzyme defects
 Spherocytes - spherocytosis

Differential Diagnosis of Anemia
 Normocytic anemia – Nonhemolytic anemia
 Alcoholism
 Thyroid disease
 Liver disease
 Bone marrow disorders
Differential Diagnosis of Anemia
 Case 5
BD 67 y/o male admitted to ER after assault.
Intoxicated, unable to provide PMH
PE: Ht-5’9, Wt-143#, T-98.2, BP-140/76, P-94, R20
Gen-intoxicated, skin-mild jaundice, pale
Differential Diagnosis of Anemia
 Case 5 cont’d
RBC count 4.0x1012/L
(4.4-5.8x1012/L)
Hgb
10.3 g/dL
(13-17 g/dL)
Hct
36%
(41-50%)
MCV
114 fL (80-100 fL)
Periph smear
Large, oval RBCs, multinucleated
WBCs
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Macrocytic anemia
Differential Diagnosis of Anemia
 Macrocytic anemia
 Megaloblastic
Large immature RBC precursors
 Maturation of nucleus & cytoplasm out of synch.


Nonmegaloblastic

Membrane abnormalities
Differential Diagnosis of Anemia
 Macrocytic anemia – Megaloblastic
 Deficiencies of Vit. B12 or Folic acid
 Medications (inhibit folate metabolism)
Alcohol
 Anticonvulsants
 Antiretroviral medications
 Oral contraceptives
 Sulfasalazine
 Trimethoprim

Differential Diagnosis of Anemia
 Macrocytic anemia – Nonmegaloblastic anemia
 Alcoholism
 Thyroid disorders
 Liver disease
 Bone marrow disorders
 Reticulocytosis
To Review…
 Classify based on history
Acute vs. chronic
 Severity
 Stability of the patient

 Etiology
Loss
 Lack of production
 Excessive destruction

Thank you!
Questions…