 CASE 21


 A healthy 52-year-old man presents to the doctor's office
complaining of increasing fatigue for the past 4 to 5 months. He
exercises every day, but lately he has noticed becoming short of

breath while jogging. He denies orthopnea, paroxysmal nocturnal
dyspnea (PND), or swelling in his ankles. The patient reports
occasional joint pain, for which he uses over-the-counter ibuprofen.
He denies bowel changes, melena, or bright red blood per rectum,
but he reports vague left-side abdominal pain for a few months off
and on, not related to food intake. The patient denies fever, chills,
nausea, or vomiting. He has lost a few pounds intentionally with
diet and exercise.
 On examination, he weighs 205 lb, and he is afebrile. There is slight
pallor of the conjunctiva, skin, and palms. No lymphadenopathy is
noted. Chest is clear to auscultation bilaterally. Examination of the
cardiovascular system reveals a regular rate and rhythm, with no
rub or gallop. There is a systolic ejection murmur. His. He has no
extremity edema, cyanosis, or clubbing. His peripheral pulses are
palpable and symmetric. abdomen is soft, nontender, and without
hepatosplenomegaly. Bowel sounds are present Hemoglobin level is
8.2 g/dL.
Summary:
 Healthy 52 year old man
 HPI
Several months PTA (4-5 months): increasing fatigue, dyspnea on exertion,
occasional joint pain and vague left-side abdominal pain for a few months off


and on that is not related to food intake
 Medications: ibuprofen
 ROS:
Respiratory: dyspnea on exertion
(-)orthopnea, paroxysmal nocturnal dyspnea (PND)Gastrointestinal: He denies
bowel changes, melena, or bright red blood per rectum
(-) Nausea and vomiting
(+)left-side abdominal pain
PE:
 HEENT: slight pallor of the conjunctiva
 Skin: slight pallor of the skin and palms, no cyanosis
 Cardiovascular: regular rate and rhythm, with no rub or gallop. (+)
systolic ejection murmur
 Lungs: Chest is clear to auscultation bilaterally
 Abdomen: is soft, nontender, and without hepatosplenomegaly.
Bowel sounds are present
 Extremities: has no extremity edema, peripheral pulses are palpable
and symmetric
 
 Objectives:
 Define anemia, its causes and types
 Understand the different diagnostic procedures to
diagnose anemia
 Identify treatment / medication management of
anemia; its indications, contraindications and
adverse effects

 What is the most likely diagnosis?
Iron-deficiency anemia as a result of chronic blood loss.

Next diagnostic step:


 First: Analyze the complete blood count (CBC), particularly
the mean corpuscular volume (MCV), to determine if the
anemia is microcytic, normocytic, or macrocytic; assess the
leukocyte count and platelet count.

 Second: Once iron-deficiency anemia is confirmed, a

thorough evaluation of the GI tract, including upper and
lower endoscopy, is needed.
 Cardinal Rule:

 The appearance of iron deficiency anemia in an adult
male or postmenopausal female means
gastrointestinal loss until proven otherwise.
 (Harrison’s Pinciple of Internal Medicine 20th
Edition)
 Diagnostic Approach to
anemia:

 Basic Hematological Lab Tests

 • Complete blood count (CBC) –

 Amount of hemoglobin – Number, size, and shape of
red blood cells (RBCs)
 Number of white blood cells (WBCs) and platelets –
 +/- automated WBC differential
 • Manual differential/manual peripheral smear
review: Abnormalities that fall outside of established
parameters result in manual review
Complete blood count (CBC)
Hemoglobin (g/dL) : Amount of oxygen carrying protein
Normal: M: 13.5 – 17.5 g/ dL
 F: 12 – 15.5 dL• Hematocrit (%)
: % of blood volume occupied by RBCs
Normal: M: 47 +/- 5%
F: 42 +/- 5%
RBC count (M/uL) # of RBCs :
M: 4.7 – 6.1 million cells / micro L
F: 4.2 – 5.4 million cells / micro L
 Serum Iron 50 -150 ug/ dL
 TIBC 300 – 360 ug / dL
 Transferin saturation: 25-50%

- Is obtained by the following formula:
- Serum iron x 100
TIBC
 Serum Ferritin :
-Adult Male : 100 ug/ L
-Adult Female: 30 ug/ L
Diagnostic of absent body iron store: <15 ug / L
MCV (fL) mean cell volume : volume of an average RBC
MCV = PCV (in percentage ) x 10
RBC
Normal: 78 – 96 fL

MCH (pg) mean cell hemoglobin: amount of hemoglobin that is
present in a RBC

MCH = Hb (g%) x 10
RBC
Normal: 27 – 33 pg (normochromic)
MCHC (g/dL) mean cell hemoglobin concentration : amount of
hemoglobin present in 100 ml of RBCs
MCHC = Hb (g%) x 100
PCV
Normal: 33-37 % (g/dL)
 MCHC denotes hemoglobin concentration in cells\
• RDW (%) red cell distribution width : The red blood cell
distribution width (RDW) is a calculated index that
quantitates the variation in the size of RBCs.


 RDW is a quantitative measure of anisocytosis that helps
to distinguish uncomplicated iron deficiencies from
uncomplicated thalassemia. An increased RDW
associated with microcytic anemia is suggestive of iron-
deficiency anemia, because the bone marrow produces
erythrocytes of various sizes. A normal RDW in the
presence of microcytic anemia may be more suggestive
of chronic disease, thalassemia, or even iron deficiency
associated with anemia of a chronic disease.
• WBC (K/uL) # of WBCs
• Platelet count (K/uL) # of platelets
 What is Anemia?

 DEFINITIONS

 ANEMIA:

 From Greek meaning “without blood”

 Decreased red blood cell (RBC) mass, leading to less oxygen-
carrying
capacity.
– Decreased hemoglobin, RBC count, and hematocrit
Hemoglobin levels less than 13 g/dL (13.5 – 17.5) in men and less
than 12 g/dL (12 – 15.5 )in women are generally used.
• Anemia is not a disease but a manifestation of disease
• Treatment depends on discovering underlying cause
 Anemia is most often diagnosed on a routine
laboratory test, and patients areoften asymptomatic.
More severe anemia may produce symptoms such as
fatigue, shortness of breath, dizziness, headache,

palpitations, and impaired concentration.

 Additionally, patients with chronic severe iron

deficiency may develop cravings fordirt, paint
(pica), or ice (pagophagia), and is also linked to
restless legs syndrome.

 Glossitis, cheilosis, or koilonychia may develop, and

in rare cases, dysphagia associated with a postcricoid
esophageal web (Plummer-Vinson syndrome) may
occur.
 
 When the anemia develops over a long period, the
typical symptoms of fatigue and shortness of breath
may not be evident. Many patients with iron
deficiency anemiamay be asymptomatic.

 The lack of symptoms reflects the very slow

development of iron deficiency and the ability of the
body to adapt to lower iron reserves and anemia.
 Evaluating anemia in the
lab:

Basic information
• Size of red blood cells: (small/ normal/ big)
• Abnormal cells on microscopic examination
• Status of leukocytes and platelets
• Reticulocyte count (ability of marrow to respond to
anemia)
• Evidence of destruction (elevated LDH, indirect
bilirubin)
 A practical approach to
anemia

Size of RBCs – MCV (Mean Cell Volume)
 Microcytic < 80 fl
 Normocytic 80-100 fl
 Macrocytic > 100 fl
 Table 1-2 Classification of anemia by MCV
Microcytic (low MCV) Lead poisoning Normocytic Macrocytic anemia (high MCV)
(normal MCV)

• Iron deficiency

• Acute blood loss • Folate deficiency
• Thalassemia • Hemolysis • Vitamin B12 deficiency
• Sideroblastic anemia • Anemia of chronic disease • Drug toxicity, eg, zidovudine
• Anemia of renal failure • Alcoholism/chronic liver disease
• Myelodysplastic syndromes
 IRON STUDIES:

Iron studies are very helpful to confirm a diagnosis of iron deficiency
anemia and to help in the differential diagnosis with other types of
anemia, such as anemia of chronic disease and sideroblastic anemia
 Ferritin is a marker of iron stores, but it also is an acute-phase
reactant, which is decreased in iron deficiency but increased with
chronic disease. The TIBC is an indirect measure of transferrin
saturation levels and is increased in iron deficiency.
 True iron deficiency: low serum iron level and normal or high
binding capacity, which will result in a low calculated saturation.
 In anemia of chronic disease: serum iron concentration is low, but
usually the TIBC is also reduced; therefore, percent transferrin
saturation typically is normal in anemia of chronic disease.
 Chronic disease : elevation in serum ferritin concentration.
Different anemias with characteristics and laboratory
Tests Iron Inflammation Thalassemia Sideroblastic

Smear
Deficiency

Microcytic/

Normal Microcytic/
Anemia

Variable
hypochromic microcytic/ hypochromic with
hypochromic targeting

Serum iron g/dL <30 <50 Normal to high Normal to high

TIBC g/dL >360 <300 Normal Normal

Percent <10 10-20 30-80 30-80

saturation

Ferritin g/L <15 30-200 50-300 50-300

Hemoglobin Normal Normal Abnormal Normal

electrophoresis
Differential diagnosis of
microcytic anemia

• Iron deficiency
• Thalassemias
• Anemia of Inflammation
• Myelodyplastic syndrome
 Thalassemia

 Serum iron: normal or increased
 Transferrin : normal
 RDW : normal
Anemia of Inflammation

 Iron : low
 TIBC: LOW
 Transferrin saturation: Low
 Ferritin: normal to high
 Iron deficiency anemia

• Iron facts – Body iron: 80% functional (Hgb,
myoglobin, cytochromes, etc.)
20% storage
– Absorption: primarily in the duodenum
– Transferrin: transports iron in blood
– Ferritin: storage form of iron
– Hemosiderin: derived from ferritin, long-term storage
of iron
 Iron deficiency anemia

• Common nutritional deficiency
• Bleeding is a leading cause of iron deficiency anemia
 Common causes of iron-deficiency anemia
Blood loss Malabsorption
Gastrointestinal blood loss
• Esophageal varices
• Peptic ulcer disease

• Gastrectomy
• Celiac disease
• Inflammatory bowel disease, eg, Crohn disease
• Gastritis, eg, NSAID induced Inadequate dietary intake/ increased physiologic
• Small-bowel polyp or carcinoma demands
• Colonic angiodysplasia • Infancy/adolescence
• Colon cancer • Pregnancy
• Inflammatory bowel disease, eg, ulcerative colitis • Vegetarian diet
• Hookworm infestation

Uterine blood loss

• Menstruation/menorrhagia
• Uterine fibroids

Other blood loss

• Chronic hemodialysis
• Surgical blood loss
• Repeated blood donation or phlebotomy
• Paroxysmal nocturnal hemoglobinuria
 Lab studies in iron
deficiency anemia

• Microcytic, hypochromic anemia – Decreased MCV,
MCH, & MCHC
• Iron studies
– Low serum iron
– High total iron binding capacity (TIBC, transferrin
concentration)
– Low % transferrin saturation
– Low ferritin – Decreased bone marrow storage iron
(hemosiderin)
 Treatment / Management
of Iron deficiency anemia:

 Although the treatment of iron deficiency is
straightforward, finding the underlying etiology is
paramount. (occult blood loss undetected with
chemical testing of stool specimens; for identification
of a source of bleeding that requires endoscopic
examinations or angiography; or for treatment of an
underlying major illness (eg, neoplasia, ulcerative
colitis).
Treatment / Management
of Iron deficiency
 anemia:
 Three major therapeutic approaches:

 Red cell Transfusion

 Oral iron therapy
 Parenteral iron therapy
 Red cell transfusion:

 Transfusion therapy is reserved for individuals who
have symptomsof anemia, cardiovascular instability,
and continued and excessiveblood loss from
whatever source and who require immediate
intervention.
 Oral iron therapy

 In the asymptomatic patient with established iron-
deficiency anemia, treatment with oral iron is
usually adequate. Multiple preparations are
available, ranging from simple iron salts to complex
iron compounds designed for sustained release
throughout the small intestine
 Oral iron therapy

 Typically, for iron replacement therapy, up to 200
mg of elemental iron per day is given, usually as
three or four iron tablets (each containing 50–65 mg
elemental iron) given over the course ofthe day.
Ideally, oral iron preparations should be taken on an
empty stomach, since food may inhibit iron
absorption.
 Some patients with gastric disease or prior gastric
surgery require special treatment with iron solutions,
because the retention capacity of the stomach may be
reduced.
 Oral iron therapy

 The goal of therapy in individuals with iron-
deficiency anemia is not only to repair the anemia,
but also to provide stores of at least 0.5–1 g of iron.

 Sustained treatment for a period of 6–12 months

after correction of the anemia will be necessary to
achieve this.
 Oral iron therapy

 Of the complications of oral iron therapy,
gastrointestinal distress is the most prominent and is
seen in 15–20% of patients.
 Abdominal pain, nausea, vomiting, or constipation
may lead to noncompliance.
 Although small doses of iron or iron preparations
with delayed release may help somewhat, the
gastrointestinal side effects are a major impediment
to the effective treatment of a number of patients.
 Response to Oral iron therapy

 Typically, the reticulocyte count should begin to
increase within 4–7 days after initiation of therapy
and peak at 1–1 ½ weeks
 Absence of response:

Maybe due to poor absorption, noncompliance or a
confounding diagnosis.

Useful test: Iron Tolerance test

 Iron Tolerance Test

 Two iron tablets are given to the patient on an empty
stomach, and the serum
iron is measured serially over the subsequent 2 h.
 Normal absorption will result in an increase in the
serum iron of at least 100 μg/dL.
 If iron deficiency persists despite adequate
treatment, it may be
necessary to switch to parenteral iron therapy.
PARENTERAL IRON THERAPY

 Intravenous iron can be given to patients who are
unable to tolerate oral iron; whose needs are
relatively acute; or who need iron on an ongoing
basis, usually due to persistent gastrointestinal blood
loss.
PARENTERAL IRON THERAPY

 High molecular weight DEXTRAN
 newer iron complexes are available:
 ferumoxytol (Feraheme), sodium ferric gluconate
(Ferrlecit), iron sucrose (Venofer), low molecular
weight iron dextran (InFed) and ferric
carboxymaltose (Injectafer), that have much lower
rates of adverse effects
PARENTERAL IRON THERAPY

 Parenteral iron is used in two ways:

 one is to administer the

total dose of iron required to correct the hemoglobin
deficit and provide the patient with at least 500 mg of
iron stores;
 the secondis to give repeated small doses of
parenteral iron over a protracted period.
PARENTERAL IRON THERAPY

 The amount of iron needed by an individual patient
is calculated by the following formula:

 Body weight (kg) × 2.3 × (15 – patient’s hemoglobin,

g/dL) + 500 or 1000 mg (for stores).
PARENTERAL IRON THERAPY

 Adverse reactions: ANAPHYLAXIS factors that have
correlated with an anaphylactic-like reaction include
a history of multiple allergies or a prior allergic
reaction to dextran (in the case of iron dextran).
 Generalized symptoms appearing several days after
the infusion of a large dose of iron caninclude
arthralgias, skin rash, and low-grade fever. These
may bedose-related, but they do not preclude the
further use of parenteraliron in the patient.
PARENTERAL IRON THERAPY

 If a large dose of iron dextran is to be given (>100
mg), the iron preparation should be diluted in 5%
dextrose in water or 0.9% NaClsolution. The iron
solution can then be infused over a 60- to 90-
minperiod (for larger doses) or at a rate convenient
for the attending nurse or physician.
PARENTERAL IRON THERAPY

 Early in the infusion of iron, if chest pain, wheezing,
a fall in blood pressure, or other systemic symptoms
occur, the infusion of iron should be stopped
immediately
 ClINICAL PEARLS

 ► Anemia is a clinical finding, not a diagnosis, and requires some
investigation to determine the underlying etiology.
 ► Iron-deficiency anemia in men or postmenopausal women is primarily a
result of gastrointestinal blood losses; therefore, finding iron-deficiency
anemia in this patient population warrants a thorough gastrointestinal
workup.
 ► Iron-deficiency anemia in women of reproductive age is most often
caused by menstrual blood loss.

 ► Fecal occult blood testing is negative in approximately 50% of patients
with gastrointestinal cancer. Therefore, a negative fecal occult blood test in
the presence of iron-deficiency anemia should not discourage you from
pursuing a thorough gastrointestinal workup.
 ► The mean corpuscular volume, red blood cell distribution width, and
reticulocyte index are important parameters in the evaluation of anemia.
 References:

 Harrisons Principles of Internal Medicine
20th Edition , Chapter 93 (Iron Deficiency Anemia)
 Lange Internal Medicine 5th Edition