topic conference 1 - anemias trans

8/14/2019 Topic Conference 1 - Anemias Trans

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Topic Conference 1: Anemias

OS 216: Hematology Dr. Edwin Trinidad

Exam 1

January 5, 2009 | Mon Page 1 of 7

MeMo3

Lecture Outline

I. Case Summary

II. Differential Diagnosis

III. Iron Deficiency Anemia

IV. Diagnostic Work-up

Case Summary

EM, a 30 year old female, married, housewife

was brought to the Emergency Room because she

fainted while attending church services. She gives a

history ofoccasional dizziness and exertional dyspnea

for the past 3 months. There were no other symptoms.

Family history is negative for anemia and bleeding

tendencies. Menstrual and obstetric history: Gravida 2

Para 2. Childrens ages are 3 and 1, all delivered

normally. She had an intrauterine device (IUD) inserted 2

months after her last delivery. Since then her menses

have become prolonged for 7 days (usual 3 days) but at

monthly interval. Her flow is described as profuse,

consuming 6 napkins/day, fully soaked with blood for

the first 4 days of menses.

Physical exam: PR = 80, BP = 110/70, RR = 20,

Temp = 37C. Pertinent findings include pale conjuctiva,

anicteric sclerae. She has a soft systolic murmur,

grade 1-2/6 in all valvular areas. No masses were

palpable. Hernail beds are pale.

*pertinent points in Hx and PE are in bold.

Differential Diagnosis

In our approach to establishing a diagnosis fromthe history and PE, first let us ask: Is the condition of EMacute or chronic?

Based on the history, EM already has a 3-monthstanding history of occasional dizziness and exertionaldyspnea alongside regular menorrhagia. Her PE reveals asoft systolic murmur. Both point to a chronic condition.

(Based on History) What chronic conditions

present with fainting, dizziness, and exertional dyspnea?(Taking into consideration the PE) Which of these

also present with pallor and a systolic murmur?

Differentials Rule in Rule out

Neurocardio

genic

syncope

Fainting (probably

due to crowded

environment), pale

conjunctiva, normal

PR, normal BP,

Three-month

history of

occasional

dizziness and

exertional dyspnea

suggests chronic

disease

Vertigo Faintness,

dizziness

No findings

pertaining to lesions

on visual,

somatosensory or

vestibular systems;

further evaluation

needed

Cardiac Fainting, dizziness, Normal PR, normal

problem exertional dyspnea,

grade 1-2/6 systolic

murmur, pale

cojunctiva, pale nailbeds

BP, needs further

testing

Anemia Fatigue Confirmatory

evaluation needed

Type of

Anemia

Hypoprolifer

ative?

Maturation

disorder?

Blood

loss/Hemolyt

ic?

History of regular

menorrhagia points

to chronic blood

loss

Further evaluation

needed

Anemia of

chronic

inflammation

/infection

Dizziness,

exertional dyspnea,

pale conjunctiva,

pale nail beds

No hx of chronic

disease, no signs of

acute infection,

laboratory

evaluation needed

to differentiate from

iron-deficiency

anemia

Thalassemia Dizziness,

exertional dyspnea,

pale conjunctiva,

pale nail beds (s/sx

of anemia)

Age of patient

(usually

thalassemia

diagnosed at an

early age), no

family history of

thalassemia, no

hepatosplenomegal

y,

Iron-

deficiency

anemia

Dizziness,

exertional dyspnea,

profuse menstrual

flow, pale

conjunctiva, pale

nail beds

Further evaluation

needed

Working Impression: Iron-Deficiency Anemia (IDA)

secondary to Chronic Blood Loss

Iron Deficiency Anemia

I. Definition

- a condition where there is a decrease in redblood cells and hemoglobin levels due to lack of iron.- occurs when iron stores have already been

used up due to inadequate intake, increased demand,impaired absorption or chronic blood loss.

II. PrevalenceIron deficiency is one of the most common

nutritional disorders globally. IDA accounts for 50% ofanemias and 841,000 deaths yearly worldwide. Seventyone percent of mortality can be found in Africa and parts ofAsia. North America accounts for only 1.4% of the total


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mortality and morbidity associated with IDA. It is commonin toddlers, adolescent girls and women of childbearingage.

The National Nutrition Survey (1998) conducted

by the Food and Nutrition Research Institute, Departmentof Science and Technology revealed that the followinggroups were anemic or suffering from IDA:

5-6 out of 10 infants aged 6 months to lessthan 1 year3 out of 10 children aged 1 to 5 years3 out of 10 young children aged 6 to 12years3 out of 10 teenagers aged 13 to 19 years2-3 out of 10 adults aged 20 to 593-4 out of 10 older persons aged 60 yearsand over5 out of 10 pregnant women4-5 out of 10 lactating women

III. Iron Absorption and Excretion

Iron is crucial for oxygen transport, energyproduction and cellular growth and proliferation. Humanbody contains around 3.5 g of iron, males having morestores than females. In the United States, the average ironintake in adult males is 15 mg/day with 6% absorption; forthe average female, the daily intake is 11 mg/day with12% absorption. Thus on the average, only 1-2mg ofdietary iron is absorbed per day, which is enough toreplace iron losses from epithelial desquamation. Inpregnancy during the last two trimesters, daily ironrequirements increase to 5-6 mg/day. Iron availability is

affected by the nature of the foodstuff, with heme iron (e.g.meat) being most readily absorbed.

Iron absorption takes place largely in the luminalcells of the proximal small intestines (duodenum andupper jejunum). Absorption is facilitated by the acidic pH ofthe stomach, which maintains iron in solution. Transportacross the membrane is accomplished by divalent metaltransporter 1 (DMT1). At the brush border of the luminalcell, ferrireductase converts ferric iron to ferrous iron,which is the form used by the body. After absorprtion, ironcan either be used by the body or stored.

Seventy-five percent of iron is used forhemoglobin production and erythropoiesis. Iron is

transported to the basolateral surface of luminal cells andare released into the bloodstream as transferrin.Transferrin is a bilobed glycoprotein with two iron-bindingsites. The iron-transferrin complex circulates in the plasmauntil it interacts with specific transferrin receptors on thesurface of marrow erythroid cells (Diferric transferrin hasthe highest affinity for the transferrin receptors). Once theiron-transferrin complex interacts with its receptor, it isinternalized via clarithrin-coated pits and transported to anacidic endosome, where the iron is released at the low pH.Within the erythroid cell, iron is used to form hemoglobin.Iron in excess of the amount needed for hemoglobinsynthesis binds to apoferritin, forming ferritin and is stored.The mechanism of iron exchange also takes place in othercells, especially liver parenchymal cells. (see Appendix 1)

Iron is stored in organs like the liver and heart in

the form of ferritin. Ferritin are molecules with a mineral

core containing thousands of iron atoms. The body

produces more ferritin in response to excess dietary

absorption of iron.

Iron is also recycled in the body. In a normal

individual, the average red cell life span is 120 days.

Senescent red cells undergo phagocytosis (through the

reticuloendothelial system) and the body recycles the

released iron.

There is no excretory pathway for iron. The only

mechanisms by which iron is lost from the body are blood

loss and the turnover of epidermal cells from the skin and

gut. The amount of dietary iron required to replace

ongoing losses averages about 1.0 mg among men and

1.4 mg among women of childbearing age, equivalent to

the amount absorbed in the diet. The following figure

summarizes the process or iron absorption, usage, and

storage.

Figure 1.

IV. Stages of Iron Deficiency

There are three stages of iron deficiency namely

negative iron balance, iron-deficient erythropoiesis and

iron-deficiency anemia.

Negative iron balance (iron depletion) results

when demands for iron exceed absorption of iron from the

diet. Blood loss, pregnancy, rapid growth spurts in

adolescents, or inadequate iron intake can result to

negative iron balance. The iron deficit is initially

compensated by mobilization of iron stores. During this

stage, these iron stores decrease. As long as there are

adequate stores, serum iron, total iron-binding capacity

(TIBC)---an indirect measure of circulating transferring---and red cell protoporphyrin (an intermediate in heme

synthesis) levels remain normal. Red cell morphology and

indices are normal during this stage. This stage is

generally asymptomatic and there is no overt effect on

erythropoiesis. It also escapes detection by hemoglobin

or hematocrit.

During iron-deficient erythropoiesis, iron stores

and serum iron decrease. TIBC and red cell

protoporphyrin levels gradually increase. Marrow iron


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stores are absent and serum ferritin levels are below 15

g/L. Hemoglobin synthesis is impaired when transferrin

saturation drops to 15-20%.

In iron-deficiency anemia, iron stores are

already inadequate to maintain hemoglobin production.

This stage is reflected by low hemoglobin and hematocrit

levels. Microcytic red cells and hypochromic reticulocytes

begin to appear. Transferrin saturation is now at 10-15%.

When there is moderate anemia (hemoglobin of 10-13

g/dL), the bone marrow remains hypoproliferative. With

severe anemia (hemoglobin of 7-8 g/dL), there is

prominent hypochromia and microcytosis. Target cells

and poikilocytes also appear on the blood smear. The

erythroid marrow also becomes more inefficient. Erythroid

hyperplasia of the marrow, instead of hypoproliferation,

occurs with prolonged IDA.

Figure 2. Comparison the 3 stages of irondeficiency

IV. Etiology and Pathogenesis of IDA

Iron deficiency anemia (IDA) is the most common

form of anemia. Iron is an essential component of

hemoglobin, the oxygen-carrying pigment in the blood.

Iron is usually obtained from ones diet and by recycling it

from old red blood cells. Blood cannot carry oxygen

effectively without iron and oxygen is needed for the

normal functioning of every cell in the body.

The causes of IDA are insufficient dietary intake

of iron, poor absorption of iron by the body, blood loss (like

from heavy menstrual bleeding) and need for iron exceeds

the reserves. Furthermore, in men and postmenopausal

women, anemia is usually caused by gastrointestinal

blood loss associated with ulcers, the use of aspirin or

nonsteroidal anti-inflammatory medications (NSAIDS), or

certain types of cancer (esophagus, stomach, colon).

Celiac diseasemay cause iron deficiency anemia.

Anemia develops slowly after the normal stores

of iron have been depleted in the body and in the bone

marrow. Women of child-bearing age, in general, have

smaller stores of iron than men and have increased lossthrough menstruation, placing them at higher risk for

anemia than men. Other high-risk groups include pregnant

or lactating women who have an increased requirement

for iron, infants, children, and adolescents in rapid growth

phases and those with a poor dietary intake of iron.

IDA during infancy

Iron deficiency anemia is a common

nutritional deficiency that affects children, especially

during the first two years of life (around 6-20 months).

There are several factors affecting the development of

IDA in infants, such as sex (more common in males),

rate of weight gain (faster gain associated with IDA),

term, iron stores of the mother, and episodes of intra-

and/or extrauterine bleeding.

After birth, there is decreased red blood cell

(RBC) formation (erythropoiesis) and iron from broken

down RBC is stored. However, when erythropoiesis

resumes (around 5.6-26 months according to some

studies), the stores are not enough, thus leading to a

state of iron deficiency. When iron stores are used up

(exacerbated in cases of decreased iron absorption

and blood loss), IDA (microcytic anemia) ensues.

Normal iron requirements are around 1 mg during

infancy, and factors that affect its absorption and

bioavailability in infants are important causes of iron

deficiency leading to IDA. Diet is one main factor.

Breastfeeding for 6 months usually provide the infant

with enough iron because breast milk contains more

iron and is more bioavailable than the iron found in

the alternative cows milk. Also, there is some

association between occult gastrointestinal bleeding

and cows milk. Introduction of different

complementary foods affect iron absorption differently

meat increase iron stores, while drinks such as tea

inhibit iron absorption.

IDA in infants generally results from either

decreased iron absorption or bleeding (blood loss).

Decreased iron absorption occurs in celiac disease,

wherein there is gluten intolerance. There are also

studies associating Helicobacter pylori infection with

reduced iron absorption because the bacteria

compete with the acquisition of iron from food. Blood

loss in infants can be due to a lot of conditions, such

as ulcers, polyps, Meckels diverticulum, inflammatory

diseases of the GIT and renal diseases (like

glomerulonephritis/Goodpastures syndrome).

Parasitic infections by nematodes like Ascaris,Trichuris and hookworm are also a source of chronic

blood loss.

IDA during pregnancy

Iron is an important nutrient duringpregnancy. Thus, it is imperative that pregnant women
http://www.nlm.nih.gov/medlineplus/ency/article/000560.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/000560.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/003645.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/003645.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/003133.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/003133.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/003133.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/003133.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/003228.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/003228.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/003228.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/000233.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/000233.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/003645.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/003133.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/003133.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/003228.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/000233.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/000560.htm


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ensure an adequate intake of iron in their diet. Iron isnecessary for the formation of maternal and fetalhemoglobin, the oxygen-carrying component of blood.Normally during pregnancy, erythroid hyperplasia of

the marrow occurs, and RBC mass increases.However, a disproportionate increase in plasmavolume results in hemodilution (hydremia ofpregnancy). Since a woman's blood volumeincreases by 25 to 50 percent during pregnancy, andthe baby is manufacturing blood cells too, more iron isneeded to make more hemoglobin for all thatadditional blood. The increased need for iron puts themother at risk for anemia. Furthermore, during the lasttrimester, the baby draws from the mother some ofthe iron reserves that it will need during the first fourto six months of life. Thus, it is really essential that themother has sufficient iron stores all throughout thepregnancy. The increased blood volume and ironstores will also help the mothers body adjust, to somedegree, to the blood loss that occurs during childbirth.

The causes of IDA during pregnancy may bepoor intake of iron, loss of blood from bleedinghemorrhoids or gastrointestinal bleeding. Maternaliron deficiency anemia is associated with anincreased incidence of anemia in the baby during thefirst year of life. Pregnant women with iron deficiencyanemia, particularly in the first and second trimesters,have an increased risk for premature delivery and fordelivering a low-birth weight infant.

IDA during lactation

Studies have shown that anemia is common

among lactating women. Ensuring adequate intake of

all hemopoietic nutrients during lactation is also

critical. The benefits of iron supplementation during

pregnancy to reduce the risk of anemia during

pregnancy and improve iron stores beyond 6 months

postpartum are well established. Although providing

supplements during lactation is not contraindicated,

the efficiency of absorption is much higher during

pregnancy. In contrast to iron, the requirements for

folate and vitamin B12 are increased during lactation.

The iron content of breastmilk is relativelyprotected and not influenced by maternal nutritional

status, but depletion of maternal stores can result

among poorly nourished women who are already

anemic prior to lactation. A randomized clinical trial of

pregnant women showed that iron supplementation

during the last trimester of pregnancy did not alter the

concentrations of iron, copper, selenium and zinc in

breast milk. In contrast, there is evidence that the

breast milk level of other hemopoietic nutrients such

as folic acid, vitamin A and vitamin B12 are affected

by maternal status.

* See Appendix 2 for Pathologic Correlation for EMsCase

V. Clinical Manifestations

Signs and symptoms of anemia depend on the

severity of the condition. People with mild anemia or

anemia that has come on very slowly may have no

symptoms at all. However, if the anemia is severe, the

symptoms increase and become more serious. Many of

the signs and symptoms of iron-deficiency anemia are true

for all kinds of anemia.

The main manifestations in EMs case were the

following: fainting, dizziness, exertional dyspnea, pale

conjunctiva, pale nail beds and a soft systolic murmur.

The major symptom of all types of anemia,

including iron-deficiency anemia, is fatigue (feeling tired).

Fatigue is caused by having too few red blood cells to

carry oxygen to the body. This lack of oxygen in the body

can cause people to feel weak or dizzy, have a headache,

or even pass out when changing position (for example,

standing up).

Since the heart must work harder to move the

reduced amount of oxygen, signs and symptoms may

include shortness of breath and chest pain. This can lead

to a fast or irregular heartbeat or a heart murmur.

In anemia, the red blood cells don't have enough

hemoglobin. Common signs of lack of hemoglobin include

pale skin, tongue, gums, and nail beds. Pallor of the skin

may be difficult to appreciate in dark skinned individuals,

therefore scleral or palmar pallor may be more reliable as

a finding.

Other Signs and Symptoms of Anemia

Other signs and symptoms of anemia can include:

Cold hands and feet as well as brittle nailsSwelling or soreness of the tongue and cracks in the sidesof the mouthAn enlarged spleenFrequent infectionsAdditional findings include blue sclera, koilonychias,

angular stomatitis, and functional gastrointestinal tract

abnormalities.

Signs and Symptoms of Iron-Deficiency Anemia

Symptoms of iron-deficiency anemia include

unusual cravings for nonfood items such as ice, dirt, paint,or starch. This craving for nonfood items is called pica.

Another symptom of iron-deficiency anemia is

developing restless legs syndrome (RLS). RLS is a

disorder that causes an uncomfortable feeling in the legs

that can only be relieved by movement. Sleep is difficult

for people with RLS.

Age of onset of anemia is an important clue, as

iron deficiency is uncommon before 4 to 6 months of age

in the absence of prematurity. In infants and young

children, signs and symptoms include a poor appetite,

being irritable, and a slower rate of growth anddevelopment.

Some of the signs and symptoms of iron-

deficiency anemia are related to its causes, such as blood

loss. Blood loss is most often seen with very heavy or long

lasting menstrual bleeding or vaginal bleeding in women

after menopause. Other signs of internal bleeding are

bright red blood in the stool or black, tarry-looking stools.

Diagnostic Work-Up


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I. CBC count

o To establish the presence of anemia

o May also indicate severity of anemia In chronic iron deficiency anemia, the cellular

indices show a microcytic and hypochromicerythropoiesis

both the mean corpuscular volume(MCV) and mean corpuscularhemoglobin concentration (MCHC)have values below the normal range(Normal ranges: MCV=83-97 fL;MCHC=32-36 g/dL

Platelet count is usually elevated(>450,000/L) while WBC count iswithin normal ranges (4500-11,000/L).

Note: If the CBC count is obtainedsucceeding blood loss, values reachabnormal levels only after most of theRBCs produced before bleeding aredestroyed at the end of their lifespan(120 days).

II. Peripheral Blood Smear

o The presence of microcytic and hypochromic

erythrocytes in the examination of a peripheral smearis indicative of chronic iron deficiency anemia.Microcytosis is apparent way before MCV valuesdecrease after an event causing iron deficiency.Platelet count is often elevated.

o No target cells (rules out thalassemia), anisocytosisand poikilocytosis not marked

o No intraerythrocytic crystals (rules out Hb C disorders)

III. Serum iron, total iron-binding capacity (TIBC), and

serum ferritin

o Serum iron

Reflects the amount of circulating iron bound to

transferring

Normal range: 50150 mcg/dL

Clinician must be aware of the diurnal variation

o Total Iron Binding Capacity (TIBC)

An indirect measure of the circulating

transferrin.

Normal range: 300360 mcg/dL

o Transferrin saturation

serum iron x 100 TIBC

Normal range: 2550%, Iron-deficiency state:


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Management

1. Removal of IUD

Profuse menstrual bleeding is one of the

possible side effects of IUDs, especiallyCopper IUDs

IUDs increase the risk of anemia

In this case, the patient is already

symptomatic, suggesting that theanemia could be severe

Other contraceptive methods may be

recommended

2. Red Blood Cell Transfusion

Patient is already symptomatic anemia

is probably severe Corrects the anemia acutely and

transfused RBCs provide a source ofiron for reutilization

Stabilizes patient while other options are

reviewed

3. Oral Iron Therapy

200-300 mg iron/day, in 3-4 iron tablets

each containing 50-65 mg elementaliron

Ideally, should be taken on empty

stomach (food may inhibit ironabsorption)

Must be sustained for 6-12 months

Goal: to correct anemia and provide

stores of at least 0.5-1.0 g of iron

Normal response to therapy: the

reticulocyte count should begin toincrease within 4-7 days after initiationof therapy and peak at 1 weeks

Inadequate response may be due to

poor absorption, noncompliance, or aconfounding diagnosis

To determine iron absorption, do an iron

tolerance testo 2 iron tables are given to the

patient on an empty stomacho

Serum iron is measuredserially over subsequent 2 hrso Serum iron should increase at

least 100 g/dL

If iron deficiency persists despite

adequate treatment, consider parenteraliron therapy

4. Parenteral Iron Therapy Usually given if no response to oral iron

therapy, if iron needs are relativelyacute, or if there is persistent need for

iron, usually due to persistent GI bloodloss

Possibility of anaphylaxis is a concern

Serious adverse reaction rate to iron

dextran is 0.7%

Newer iron complexes: sodium ferric

gluconate (Ferrlecit) and iron sucrose

(Venofer) much lower adversereaction rate

Amount of iron needed by individual:

Body weight (kg) x 2.3 x (15-patients hemoglobin,g/dL) + 500 or 1000 mg (for stores)

Appendix 1

Notes:

Appendix 2. Pathological Correlation of EMs Case


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For EMs case, the main cause of IDA is blood loss due to prolonged menstruation, a result of irritation to the

intrauterine lining from the inserted IUD. The following figure summarizes the pathogenesis of EMs condition.

Intrauterine device (IUD) inserted2 months after her last delivery

Intrauterine lining irritated

MenorrhagiaMenses prolonged for 7 days;(6 napkins/day) fully soaked decreased hematocrit; increased turbulence

w/ blood for first 4 days decreased blood viscosity

Iron deficiency Soft systolic murmur (due to unreplaced iron losses

from menstruation)

Decreased hemoglobin production

Decreased O2 transport by RBCs

Inadequate oxygen supply to tissues

Pallor, dizziness, dyspnea

Fainting

Appendix 3.

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