CASE SCENARIO

A 66-year-old postmenopausal woman presents to her physician with complaints of fatigue,

dyspnea, dizziness and tachycardia. She says she craves chewing on ice cubes. Physical
examination reveals pallor of the mucous membranes of her mouth. The cells on a
peripheral blood film are microcytic and hypochromic. Relevant laboratory findings are as
follow:

 Haemoglobin: 10 g/dL
 Hematocrit: 30%
 Reticulocyte count: 0.2%
 MCV: 74 Fl
 Serum ferritin: 7µg/L

(First Aid Cases for the USMLE Step 1, 3rd Edition, 2017)

HISTORY PRESENTING ILLNESS

The case scenario above suggesting symptoms of anemia. Hence, in history

presenting illness, there are many points need to be asked to look for the cause of anemia.
First, I will ask about constitutional symptoms such as fatigue, weight loss, dizziness,
dyspnea and chest pain. For this patient, she has fatigue, dyspnea, dizziness and
tachycardia. History of pica also need to be asked as it points the diagnosis towards iron
deficiency anemia. As of this patient, she has symptom of pica as she always craves
chewing on ice cubes. The duration of these symptoms must be asked. I also will ask if she
or people around her noticed the changes of her skin color such as become more pale or
yellowish than usual to rule out hemolytic jaundice. I also will ask about any history of easy
bruising, gum bleeding, rash, recurrent fever to rule out other blood cell line involvement. If
more than two cell line involved, I will ask about any lymph node enlargement to rule out
leukemia.

I also will ask any occurrence of gastrointestinal bleeding such as melaena,

haematochezia and haematemesis and its risk factors such as dyspepsia, peptic ulcer
disease and prolonged use of NSAIDs. Any occurrence of vaginal bleeding also should be
asked to rule out source of bleeding. I also will ask any history of chronic disease as it can
cause anemia. Any abdominal pain, prior anemia or blood diseases such as thalassemia
should also be asked. Paradoxical weight loss with good intake may suggest celiac disease. I
also will ask symptoms of blood loss such as blood loss in stools, urine, from the vagina, or
through vomiting is a risk for iron deficiency.

Dietary habits also important. I will ask about a vegetarian diet, which may be
associated with lower serum ferritin levels & reduced non-heme iron absorption. Excessive
alcohol use also should be elicited as it is a common cause of macrocytosis (not usually with
anemia) in some settings. I will also ask when the last time patient take antihelminthic
medication because iron deficiency anemia could be caused by hookworm infestation. Ethnic
origin also important as Alpha- and ß-thalassemia traits are fairly common in patients of
African, Mediterranean, Middle Eastern, and Southeast Asian ancestry.

Family history of anemia is also should be ask as it can be a clue to inherited forms
of hemolytic anemia or thalassemia beta or alpha. History of blood donation also should be
asked as more than half of women who donate 3 or more units in 2 years can be expected
to be iron deficient.

SYSTEMIC REVIEW

Central nervous system:

I will ask about any reduce in sensation, headache, seizure, loss of consciousness, change in
behavior and change in visual.

Cardiovascular system:

Any palpitation, chest pain, dyspnea, orthopea but no no paroxysmal nocturnal dyspnea
and ankle edema

Respiratory system:

Any cough, sputum, tachypnea, wheezing

Gastrointestinal system:

Any vomiting, hematemesis, dyspepsia, abdominal pain, diarrhea, constipation, passing out
blood.

Genitourinary system:

Any hematuria, dysuria, frequency, urgency, polyuria, incontinence, loin and flank pain,
urethral discharge, nocturia
Endocrine system:

Any heat or cold intolerance, neck swelling

Musculoskeletal system:

Any muscle and joints pain, swelling, weakness, deformities

PAST MEDICAL HISTORY

I will ask about any other medical illness such as hypertension, diabetes mellitus,
dyslipidemia and chronic kidney disease.

PAST SURGICAL HISTORY

I will ask about any previous surgical procedure.

MEDICATION HISTORY

I will ask about medications she takes on daily basis and any use of traditional medication.

ALLERGY HISTORY

I will ask about any allergy to drugs and foods.

FAMILY HISTORY

I will ask about health condition of her parents if they are still alive, if they have passed
away I will ask about the cause of death. I also will ask the health condition of all her
siblings. Most importantly, I will ask about any history of blood diseases run in her family
such as thalassemia and any history of malignancy in her family.

SOCIAL HISTORY
I will ask about her marital status, her address and type of house she lives in, and who she
lives with. I also will ask about smoking and alcohol history. Financial status also will be
asked. It also important to know the distance of her house to nearest healthcare provider
and hospital as she may need to come for follow up or blood transfusion.

PHYSICAL EXAMINATION

Vital signs

I will measure her vital signs such as her blood pressure, pulse rate, respiratory rate,
temperature and oxygen saturation. Her body mass index will also be measured.

General examination

I will look to her position whether she is lying of sitting. I also will observe whether she is
alert conscious and in respiratory distress or not. I will also look into her surrounding,
whether there is branula inserted to her body. Then I will examine her peripheral which are:

 Face: any frontal bossing, prominent maxilla, conjunctiva pallor and jaundice
 Mouth: good/poor oral hygiene, any upper jaw protruberance, interdental
separation, central cyanosis, no angular stomatitis and leucoplakia
 Neck: any raised JVP, palpable cervical lymph nodes, any neck swelling
Hand: any palmar pallor, palmar erythema, clubbing, leuconychia, koilonychias,
capillary refill time and any tremor
 Ankle: any pitting edema

Abdomen examination

Inspection:

On inspection, the points that need to be observe are:

 Abdomen moves with respiration

 abdomen distended or flat
 flanks fullness
 Umbilicus is centrally located, inverted
 Any scar, deformity, visible pulsation, dilated veins and hernia orifices intactness

Palpation:
  On superficial palpation, I will feel for the abdomen consistency and tenderness. On
deep palpation, I will feel for any abdominal mass.
 Then I will palpate for liver on right hypochondria, it should move with respiration,
then I will look for any enlargement, tenderness, consistency, margin, and surface. If
there is liver enlargement, I will percuss upper and lower border of liver and
measure the liver enlargement from the right costal margin mid clavicular line.
 Then I will palpate for spleen. If it is not palpable I will try to percuss Traube’s
space.
 Then I will try to ballot both kidney.

Percussion:

I will percuss to look for any shifting dullness

Auscultation:

I will listen to bowel sound, any hepatic bruit and splenic rub

Systemic examination

1. Cardiovascular examination

Listen to normal heart sound, S1 followed by S2, and any murmur. Feel for apex beat,
normal will be at 5th intercostal space, mid clavicular line.

2. Respiratory examination

Look for chest wall whether it move equally with respiration, feel for trachea whether
centrally located or deviated, listen for air entry whether symmetrical at both sides and
vesicular breath sounds are heard all over the lung field and equal at both side. Look for
any added sound.

3. Neurological examination

Check for all sensory and motor functions and also all cranial nerves.
PROVISIONAL DIAGNOSIS

Iron deficiency anemia as she has anemic symptoms, pica, and pallor on examination. The
blood investigations also show low haemoglobin level, low reticulocytes count, low MCV, low
serum ferritin level and peripheral blood film shows microcytic hypochromic anemia. Hence,
it is most likely to be iron deficiency anemia.

DIFFERENTIAL DIAGNOSES

1. Thalassemia
This can be the differential diagnosis because she has symptoms and signs of
anemia and laboratory results shows hypochromic and microcytic anemia. However,
she also has pica which is the symptoms for iron deficiency anemia. The serum
ferritin level also very low which contradicts which thalassemia at which usually will
be high. She also has no family history of thalassemia in her family.

2. Anemia due to chronic disease

Due to her age, she might have other comorbidities which may cause anemia due to
chronic disease. However, anemia due to chronic disease will show normochromic
and normocytic anemia in peripheral blood film, unlike in this patient where she has
hypochromic and microcytic anemia.

3. Vitamin B12 deficiency macrocytic anemia

This can be the differential diagnosis as she has symptoms of anemia and low
haemoglobin level. However, vitamin B12 deficiency anemia will show megaloblastic
red blood cells in peripheral blood film, this contradicts this patient where she has
hypochromic and microcytic anemia.

4. Leukemia
This is can be one of the differential as she has symptoms of anemia, however other
cell lines deficiency symptoms also need to be elicited.
INVESTIGATIONS

1. Full blood count

To see low haemoglobin level, leukocytopenia, thrombocytopenia and low
reticulocyte count. Also to see red cell indices at which MCV, MCH and MCHC will be
low.

2. Peripheral blood film

It shows microcytic hypochromic anemia. Red blood cells vary in size and shape,
elongated and pencil cells. White blood cells are normal and platelets increase in
cases of blood loss.
3. Serum ferritin
It is most sensitive & specific test as It correlates with body iron storage. If the level
<12 µg/L indicated iron deficiency anemia.

4. Transferrin saturation
In iron deficiency anemia, it decreases to 10%

5. Serum iron
It will be decreased (normal 80-180 µgm%)

6. Total iron binding capacity

It will have increased (normal 300-400 µgm/dl) due to increase transferrin synthesis
and decrease saturation.

7. Bone marrow trephine biopsy

It will show micronormoblastic which the cells are smaller in size, decrease amount
of cytoplasm and ragged cell border. Also there will be decrease storage of iron due
to absence of stainable iron in bone marrow on Perl’s Prussian blue reaction which is
the diagnostic test for iron deficiency anemia.
 8. Oesophagogastroduodenoscopy (OGDS) and colonoscopy
To look for esophageal web because of the extreme lack of iron this patient is at risk
for Plummer-Vinson syndrome and to look for any source of bleeding in the digestive
tract

MANAGEMENT

1. Oral iron replacement: Ferrous sulphate 200 mg 3 times daily (195 mg of elemental iron
per day) is adequate and should be continued for 3–6 months to replete iron stores.
2. Educate patient to take iron rich diet such as red meat, poultry, fish, leafy greens and
legumes.
3. Admit patient for blood transfusion if her blood haemoglobin level drop to <7 g/dl or if
patient develops severe symptomatic anemia.
4. Treat underlying cause for iron deficiency anemia.

DISCUSSION

Anemia is one of the most common and prevalent diseases across the world. It may
effect at any life stage and any gender, race and ethnicity. It is common among women,
children, elderly and chronically ill patients, and those in the intensive care units of hospitals
(Kilip S, 2007). 50% of all anemia cases are iron-deficiency anemia. Nonetheless, there are
many different types of anemia each with different causes, morphology and etiology. In
general, anemia, is a condition resulting from a low red blood cell or hemoglobin quantity in
the blood, which therefore damages oxygen transportation via blood to tissues (McLean E,
2009).

When iron losses in blood loss and malabsorption or physiological requirements

exceed absorption, iron deficiency anemia occurs. The most common explanation in men
and postmenopausal women with anemia is gastrointestinal blood loss. This may result from
occult gastric or colorectal malignancy, gastritis, peptic ulceration, inflammatory bowel
disease, diverticulitis, polyps and angiodysplastic lesions. Worldwide, the most common
causes of gut blood loss are hookworm and schistosomiasis. Gastrointestinal blood loss may
be worsened by the long-term use of aspirin or non-steroidal anti-inflammatory drugs
(NSAIDs), which cause intestinal erosions and damage platelet function. In women of
productive age, menstrual blood loss, pregnancy and breastfeeding leads to iron deficiency
by reducing iron stores. In developed countries, 1/3 of premenopausal women have low iron
stores but only 3% display iron-deficient haematopoiesis. Very infrequently, chronic
haemoptysis or haematuria may cause iron deficiency.

A dietary assessment should be made in all patients to determine their iron intake.
Gastric acid is required to release iron from food and helps to keep iron in the soluble
ferrous state hence, achlorhydria in the elderly or that caused by drugs such as proton
pump inhibitors may lead to the lack of iron availability from the diet, as may previous
gastric surgery. Iron is absorbed actively in the upper small intestine and therefore can be
affected by coeliac disease. At periods of rapid growth, for example infancy and puberty,
iron requirements increase and may exceed absorption. In pregnancy, iron is diverted to the
fetus, the placenta and the increased maternal red cell mass, and then is lost with bleeding
at parturition.

To confirm iron deficiency anemia, plasma ferritin is a measure of iron stores in

tissues and is the finest single test to confirm iron deficiency which is very specific. A
subnormal level of plasma ferritin is due to iron deficiency. Ferritin levels can be raised in
liver disease and in the acute phase response, however, in these conditions a ferritin level of
up to 100 μg/L may still be compatible with low bone marrow iron stores.

Apart from that, plasma iron and total iron binding capacity (TIBC) are used to
measure of iron availability. A transferrin saturation (i.e. iron/TIBC × 100) of less than 16%
is consistent with iron deficiency but is less specific than a ferritin measurement.

All proliferating cells express membrane transferrin receptors to acquire iron; a small
amount of this receptor is shed into blood, where it can be detected in a free soluble form.
At times of poor iron stores, cells up-regulate transferrin receptor expression and the levels
of soluble plasma transferrin receptor increase.

This can now be measured by immunoassay and used to distinguish storage iron
depletion in the presence of an acute phase response or liver disease, when a raised level
indicates iron deficiency. In difficult cases, it may still be necessary to examine a bone
marrow aspirate for iron stores.

For investigation of the cause of iron deficiency anemia, this will depend upon the
age and sex of the patient, as well as the history and clinical findings. In men and in post-
menopausal women with a normal diet, the upper and lower gastrointestinal tract should be
investigated by endoscopy or radiological studies. Serum antiendomysial or anti-
transglutaminase antibodies and possibly a duodenal biopsy are indicated to detect coeliac
disease. In the tropics, stool and urine should be examined for parasites.

LITERATURE REVIEW

Regardless of patients with symptoms or asymptomatic, all patients with iron

deficiency anemia and most with iron deficiency without anemia should be treated
(Auerbach M, 2016). The reasoning is that there is risk for further organ damage or
ischemia and progression of anemia unless the underlying cause of the deficiency is
determined and adequate iron stores are replenished.

Some patients with iron deficiency anemia will be asymptomatic while others will
have symptoms that may include symptoms of anemia, which may include weakness,
headache, decreased exercise tolerance, fatigue, irritability, or depression. In children,
neurodevelopmental delay may occur. Patient with iron deficiency anemia also has pica and
pagophagia or ice craving, and beeturia which is reddish urine after eating beets. Restless
legs syndrome also may develop. Similar symptoms, especially fatigue and exercise
intolerance, can also be present in individuals who are iron deficient but not anemic.

The choice between oral and intravenous (IV) iron depends on a number of factors
including the insight of the anemia, costs and availability of different iron replacement
products, as well as the ability of the patient to tolerate oral iron preparations. Most patients
are treated with oral iron because it is generally effective, readily available, inexpensive, and
safe. However, up to 70 percent of patients for whom oral iron is prescribed (especially
ferrous sulfate) report gastrointestinal side effects (Tolkien Z, 2015).

There are a number of settings in which the use of IV iron may be preferable to oral
iron which are; 1) poor adherence or gastrointestinal side effects of oral iron, 2) prefer to
replete iron stores in one or two visits rather than over the course of several months, 3)
ongoing blood loss that exceeds the capacity of oral iron to meet needs (heavy uterine
bleeding, mucosal telangiectasias), 4) anatomic or physiologic condition that interferes with
oral iron absorption, and 5) coexisting inflammatory state that interferes with iron
homeostasis (Auerbach M, 2016).
 A number of IV iron formulations are available, including ferric carboxymaltose, ferric
gluconate, ferumoxytol, iron sucrose, iron isomaltoside and low molecular weight iron. All of
these products are equally effective in treating iron deficiency (Auerbach M, 2016).

REFERENCES

Auerbach M, Adamson JW. How we diagnose and treat iron deficiency anemia. Am J
Hematol 2016; 91:31.

Auerbach M, Deloughery T. Single-dose intravenous iron for iron deficiency: a new

paradigm. Hematology Am Soc Hematol Educ Program 2016; 2016:57.

Ralston, S. H., & Britton, R. (2018). Davidsons principles and practice of medicine.
Edinburgh: Elsevier.

Tolkien Z, Stecher L, Mander AP, et al. Ferrous sulfate supplementation causes significant
gastrointestinal side-effects in adults: a systematic review and meta-analysis. PLoS
One 2015; 10:e0117383.