Transcript The peripheral blood of a patient with iron deficiency

Anemia – An Approach
James Czarnecki, D.O.
Internal Medicine Resident Lecture Series
Background
Definition
Strictly defined as a decrease in red blood
cell (RBC) mass.
 Usually discovered and quantified by
measurement of the RBC count,
hemoglobin concentration, and hematocrit.

Frequency

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

WHO chose 12.5 g/dL for both adult males and
females.
In the US, limits of 13.5 g/dL for men and 12.5
g/dL for women – these values are more realistic.
Using these values, approximately 4% of men and
8% of women have lower values.
A significantly greater prevalence is observed in
patient populations.
Mortality / Morbidity



Varies greatly depending on etiology.
Acute hemorrhage has variable mortality
depending on the site of bleeding (80% with aortic
rupture, 30-50% with bleeding esophageal varices,
approx. 1% with benign peptic ulcers).
The 2-year fatality rate for severe aplastic anemia
is 70% without bone marrow transplantation or a
response to immunosuppressive therapy.
Mortality / Morbidity



Many symptoms associated with anemia are not
caused by diminished RBC mass.
Patients with pernicious anemia are often
asymptomatic when they are detected incidentally
with an Hb of 6 g/dL.
Patients with iron deficiency anemia develop
symptoms at Hb of 10-11 g/dL because of
depletion of iron-containing protein other than Hb.
Mortality / Morbidity
Tolerance of anemia is proportional to the
anemia’s rate of development.
 Symptoms and mortality associated with
rapidly developing anemia are more
profound than in slowly developing anemia.

Race

Certain races and ethnic groups have an
increased prevalence of genetic factors
associated with certain anemias. For
example:
 Hemoglobinopathies
 Thalassemia
 G6-PD deficiency
Sex



Anemia is twice as prevalent in females than in
males. This difference is significantly greater
during the childbearing years due to pregnancies
and menses.
Approximately 65% of body iron is incorporated
into circulating Hb. Each gram of Hb contains
3.46 mg of iron.
Each healthy pregnancy depletes a mother of
approximately 500 mg of iron.
Sex
A male must absorb about 1 mg of iron to
maintain equilibrium, a premenopausal
female must absorb an average of 2 mg
daily.
 Females have a markedly lower incidence
of anemia from X-linked anemias such as
G6PD deficiency and sex-linked
sideroblastic anemia.

Age
Severe genetically acquired anemias (ie,
sickle cell disease, thalassemia, Fanconi
Syndrome) are more commonly found in
children because they do not survive to
adulthood.
 During the childbearing years, women are
more likely to become iron deficient.

Age

Neoplasia increased the prevalence with
each decade of life and can produce anemia
from
 bleeding
 from the replacement of bone marrow
with tumor
 from the development of anemia
associated with chronic disorders
Age

Use of aspirin, NSAIDs, and coumadin
increases with age and can produce
gastrointestinal bleeding.
Clinical Approach
History
Carefully obtain a history and perform a
physical examination in every patient with
anemia because the findings usually provide
important clues to the etiology of the
underlying disorder.
 Areas of inquiry found valuable are the
following.

History
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The duration can be established by obtaining a
history of previous blood examination
Obtain a careful family not only for anemia but
also for jaundice, cholelithiasis, splenectomy,
bleeding disorders, and abnormal Hbs.
Carefully document pregnancies, abortions, and
menstrual loss.
History

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Patients do not appreciate the significance of tarry
stools. Changes in bowel habits can be useful in
uncovering neoplasms of the colon.
Hemorrhoidal blood loss is difficult to quantify,
and it may be overlooked or overestimated from
one patient to another.
Seek a careful history of gastrointestinal
complaints that may suggest gastritis, peptic
ulcers, hiatal hernias, or diverticula.
History

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Abnormal urine color can occur in renal and
hepatic disease and in hemolytic anemia.
A thorough dietary history is important in a patient
who is anemic. It must include foods that the
patient both eats and avoids, as well as an estimate
of their quantity.
Nutritional deficiencies may be associated with
unusual symptoms that can be elicited by a history.
History
Obtain a history or presence of fever
because infections, neoplasms, and collagen
vascular disease can cause anemia.
 Cold intolerance can be an important
symptom of hypothyroidism or lupus
erythematosus.

History
Relation of dark urine to either physical
activity or time of day can be important in
march hemoglobinuria, or paroxysmal
nocturnal hemoglobinuria.
 Explore the presence or the absence of
symptoms suggesting an underlying disease,
such as cardiac, hepatic, and renal disease;
chronic infection, or malignancy.

Physical
Physical
Too often, the physical is rushed without
looking at the patient for an unusual habitus
or appearance of underdevelopment,
malnutrition, or chronic illness.
 Examine optic fundi carefully, but not at the
expense of the conjunctivaie and the
sclerae, which can show pallor, icterus,
petechia, or telangiectasia.

Physical
Perform systematic examination for
palpable enlargement of lymph nodes for
evidence of infection or neoplasia.
 Carefully search for both hepatomgaly and
splenomegaly. Their presence or absence is
important, as are the size, the tenderness,
the firmness, and the presence or absence of
nodules.

Physical
A rectal and pelvic examination cannot be
neglected because tumor or infection of
these organs can be the cause of anemia.
 The neurologic examination should include
tests of position sense and vibratory sense,
examination of the cranial nerves, and
testing for tendon reflexes.

Physical

The heart should not be ignored because
enlargement may provide evidence of the
duration and severity of an underlying
anemia, and murmurs may be the first
evidence of a bacterial endocarditis, which
could explain an etiology of an underlying
anemia.
Causes
Causes

Genetic
 Hemoglobinopathies
 Thalassemias
 Defects of the RBC cytoskeleton
 Rh null disease
 Hereditary xerocytosis
 Fanconi anemia
Causes
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Nutritional
 Iron deficiency
 Vitamin B-12 deficiency
 Folate deficiency
 Starvation and generalized malnutrition
Hemorrhage
Immunologic – Antibody-mediated abnormalities
Causes


Physical effects
 Trauma
 Burns
 Frostbite
 Prosthetic valves and surfaces
Drugs and chemicals
 Aplastic anemia
 Megaloblastic anemia
Causes

Chronic diseases and malignancies
 Renal disease
 Hepatic disease
 Chronic infections
 Neoplasia
 Collagen vascular diseases
Causes

Infections
 Virals – Hepatitis, infectious
mononucleosis, cytomegalovirus
 Bacterial – Clostridia, gram-negative
sepsis
 Protozoal – Malaria, leishmaniasis,
toxoplasmosis
Differentials
Differentials
Aplastic Anemia
 Cooley Anemia
 Hemolytic Anemia
 Iron Deficiency Anemia
 Low LDL Cholesterol
 Megaloblastic Anemia
 Pernicious Anemia

Differentials
Sickle Cell Anemia
 Spur Cell Anemia
 Thalassemia, Alpha
 Thalassemia, Beta

Work Up
Work Up
Detection of anemia involves the adoption
of arbitrary criteria. In the US:
 Anemia is suggested in male with Hb
levels less than 13.5 g/dL and in females
with Hb levels less than 12.5 g/dL.
 Once the existence of anemia is established,
investigate the pathogenesis.

Work Up

A rational approach is to begin by
examining the peripheral smear and
laboratory values obtained on the blood
count. If the anemia is either microcytic
(MCV < 84) or macrocytic (MCV > 96), the
investigative approach can be then limited.
Work Up

A rapid method of determining whether
cellular indices are normocytic and
normocromic is to multiply the RBC and
Hb by 3. The RBC multiplied by 3 should
equal the Hb, and the Hb multiplied by 3
should equal the Hct.
Work Up
In microcytic hypochromic anemia, seek a
source of bleeding.
 The appropriate lab tests are serum iron
level and TIBC and serum ferritin level.
 If the serum iron level is decreased and
TIBC is increase, a diagnosis of iron
deficiency can be made.

Work Up
When a normocytic, normochromic anemia
is encountered, classify the anemia into 3
possible etiologies (ie, blood loss,
hemolysis, or decreased production).
 In most anemias, one of these causes is the
dominant factor, however in some, more
than a single cause may play an important
role (ie, pernicious anemia).

Microcytic Hypochromic Anemia
(MCV < 83; MCHC < 31)
Serum Iron
TIBC
Bone Marrow Iron
Comment
Iron Deficiency
-
+
0
Responsive to iron
therapy
Chronic
inflammation
-
-
++
Unresponsive to iron
therapy
Thalassemia major
+
N
++++
Reticulocytosis and
indirect
bilirubinemia
Thalassemia minor
N
N
++++
Target Cells
Lead poisoning
N
N
++
Basophilic stippling
of RBCs
Sideroblastic
+
N
++++
Ring sideroblasts in
marrow
Hemoglobin
N
N
++
Hemoglobin
electrophoresis
Macrocytic Anemia (MCV > 95)

Megaloblastic bone marrow
 Deficiency of vitamin B-12
 Deficiency of folic acid
 Drugs affecting DNA synthesis
 Inherited disorders of DNA synthesis
Macrocytic Anemia (MCV > 95)

Nonmegaloblastic bone marrow
 Liver disease
 Hypothyroidism and hypopituitarism
 Accelerated erythropoiesis (reticulocytes)
 Hypoplastic and aplastic anemia
 Infiltrated bone marrow
Various Forms of RBCs
Macrocyte – Larger than normal
 Microcyte – Small than normal
 Hypochromic – less hemoglobin in cell
 Spherocyte – Loss of central pallor, stains
more densely, often microcytic.
 Target cell – hypochromic with central
“target” of hemoglobin (liver disease)

Various Forms of RBCs
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Leptocyte – Hypochromic cell with a normal
diameter and decreased MCV
Elliptocyte – Oval to cigar shaped (B-12, folate)
Schistocyte – Fragmented helmet-shaped RBC
Stomatocyte – Slitlike area of central pallor in
erythrocyte (liver disease, acute alcoholism)
Various Forms of RBCs
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Tear-shaped RBCs – Drop-shaped erythrocyte,
often microcytic.
Acanthocyte – Five to 10 spicules of various
lengths and at irregular intervals on the surface of
RBCs.
Echninocyte – Evenly distributed spicules on
surface of RBCs, usually 10-30 (uremia, peptic
ulcer, carcinoma)
Sickle Cell – Elongated cell with pointed ends.
Hemoglobin S and certain types of hemoglobin C.
Imaging Studies
Imaging Studies
Useful in the workup for anemia when a
neoplastic etiology is suggested.
 Permit discovery of the neoplasm or
centrally located adenopathy.
 Occasionally, they are useful in detecting or
confirming the existence of splenomegaly.

Procedures
Procedures
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Investigate gastrointestinal bleeding by endoscopy
and radiographic studies to identify the bleeding
site.
May leave the source of GI bleeding undetected if
the lesion is small.
Bone marrow aspirates and biopsy finding are
particularly useful in establishing the etiology of
anemia in patients with decreased production of
RBCs.
Treatment
Medical Care
Transfusion of packed RBCs should be
reserved for patients who are actively
bleeding and for patients with a severe and
symptomatic anemia
 Nutritional therapy is used to treat iron
deficiency, vitamin B12, and folic acid.
 Corticosteroids are useful in the treatment
of autoimmune hemolytic anemia.

Medical Care

Treatment of aplastic disorders includes
removal of the offending agent whenever it
can be identified, supportive therapy for the
anemia, and prompt treatment of infection.
Surgical Care
Surgical Care
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Surgery is useful to control bleeding in patients
who are anemic.
Most commonly, bleeding is from the GI tract, the
uterus, or the bladder.
Patients should be hemodynamically stable before
and during surgery.
Splenectomy has been advantageous in hereditary
spherocytosis and hereditary elliptocysosis.
Surgical Care

Bone marrow and stem cell transplantation
have been used in patients with:
 Leukemia
 Lymphoma
 Multiple myeloma
 Myelofibrosis
 Aplastic disease
Consultations
Consultations
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Surgical consultation is indicated to control
bleeding, for splenectomy when necessary, and for
biopsies to establish the presence of neoplasia
Consultation with gastroenterologists is frequently
sought to identify a bleeding site in the gut.
Urologic consultation may be needed to
investigate hematuria.
Diet
Diet
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Iron deficiency anemia is prevalent in geographic
locations where little meat is in the diet.
A strict vegetarian diet requires iron and vitamin
B-12 supplementation.
Folic acid deficiency occurs among people who
consume few leafy vegetables.
Coexistence of iron and folic acid deficiency is
common among Third World nations.
Activity
Activity

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The activity of patients with severe anemia should
be curtailed until the anemia is partially corrected.
Transfusion can often be avoided by ordering bed
rest.
March hemoglobinuria is a rare hemolytic disorder
usually observed in young males. Individuals
develop hemoglobinuria after marching or running
on hard surfaces. Can be treated by curtailing the
precipitating exercise.
Follow Up
Follow Up
Patients with chronic anemia can usually be
cared for on an outpatient basis.
 Follow-up care is necessary to ensure that
therapy is being continued and to assess the
efficacy of treatment.
 The most serious complications of severe
anemia arise from tissue hypoxia.

Follow Up
Shock, hypotension, or coronary and
pulmonary insufficiency can occur.
 This is more common in older individuals
with underlying pulmonary and
cardiovascular disease.
 Hemolytic transfusion reactions and
transmission of infectious disease are risks
of blood product transfusions.

Medical / Legal Pitfalls
Medical / Legal Pitfalls



Negligence in transfusion of either incompatible
blood or blood containing a potentially identifiable
infectious agent
Failure to recognize a hemolytic transfusion
reaction and to initiate prompt and appropriate
therapy
Delayed diagnosis, investigation, and treatment of
a neoplastic disorder because the etiology of an
anemia was not pursued in a timely manner
Medical / Legal Pitfalls
Failure to provide appropriate therapy and
to ensure that the patient has adequate
follow-up care
 Underestimating the potential severity of an
anemia.

Histopathology
Decreased Production of RBCs
Microcytic Anemia
Peripheral Smear
Peripheral Smear
Peripheral Smear
Bone Marrow Aspirate
Bone Marrow Aspirate
Competency Exam
Question #1
All of the following are matched correctly, except:
(A) Macrocyte – Larger than normal
(B) Microcyte – Smaller than normal
(C) Spherocyte – Loss of central pallor
(D) Schistocyte – Hypochromic cell with a normal
diameter
(E) Stomatocyte – Slitlike area of central pallor in
an erythrocyte.
Question #1
All of the following are matched correctly, except:
(A) Macrocyte – Larger than normal
(B) Microcyte – Smaller than normal
(C) Spherocyte – Loss of central pallor
(D) Schistocyte – Hypochromic cell with a normal
diameter
(E) Stomatocyte – Slitlike area of central pallor in
an erythrocyte.
Question #2
Which of the following deficiencies would
most likely lead to megaloblastic anemia?
A) vitamin E deficiency
B) vitamin B6 deficiency
C) iron deficiency
D) folic acid deficiency
E) Vitamin B12 deficiency
Question #2
Which of the following deficiencies would
most likely lead to megaloblastic anemia?
A) vitamin E deficiency
B) vitamin B6 deficiency
C) iron deficiency
D) folic acid deficiency
E) Vitamin B12 deficiency
Question #3
The peripheral blood of a patient with iron
deficiency anemia will most likely show
what picture?
a) microcytic, hypochromic red cells
b) microcytic, normochromic red cells
c) macrocytic, hypochromic red cells
d) normocytic, hypochromic red cells
e) normocytic, normochromic red cells
Question #3
The peripheral blood of a patient with iron
deficiency anemia will most likely show
what picture?
a) microcytic, hypochromic red cells
b) microcytic, normochromic red cells
c) macrocytic, hypochromic red cells
d) normocytic, hypochromic red cells
e) normocytic, normochromic red cells
End of Lecture
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