ANEMIA(GENERAL)

PART 1
Anemia 1 By
SISAY TAREKEGN,MD
OUTLINE OF THE PRESENTATION
◦Objective
◦Introduction
◦Definitions, Limitations & Special Conditions
◦Erythropoiesis & RBC Life Cycle
◦Consequences of Anemia
◦Clinical Features
◦Clinical Evaluation
◦Laboratory Evaluation
OBJECTIVE
◦At the completion of this session the student
should be able to:
◦Define anemia clinically with its limitation in special
population/settings
◦Understand erythropoiesis & RBC life cycle
◦Identify the clinical features with its consequences
◦Evaluate the anemic patient clinically
◦Know the basic laboratory evaluation of anemia
INTRODUCTION

◦Anemia is very common clinical sign which

is usually overlooked, especially in the
elderly.
◦Has serious implications in morbidity and
mortality
◦It is not a diagnosis by itself!
◦Various definitions & classifications
INTRODUCTION
◦Multi-factorial causations sometimes
◦Vigilant and systematic approach must be
followed in the clinical evaluation and
treatment of anemia.
◦Both the anemia and the underlying cause(s)
should be treated.
INTRODUCTION
◦The prevalence of specific anemia varies
depending on the gender, race, age,
geographic location, dietary habit, etc
◦Can be acquired or inherited
DEFINITIONS
◦Anemia can be defined precisely as the absolute
reduction in the number of circulating RBC or
reduction in RBC volume as determined by
measuring RBC volume or mass.
◦"direct" RCM measurement-
◦Adv.-Not Influenced by plasma volume
◦cumbersome and are becoming obsolete.
◦Alternative definitions are designed.
DEFINITIONS
◦ Anemia has been defined as a reduction in
one or more of the major red blood cell (RBC)
measurements:
◦hemoglobin concentration,
◦hematocrit, or
◦RBC count:

Are Influenced by plasma volume!!!!

 DEFINITIONS
◦Serum Hgb level or Hct less than the expected value
for age- and sex-matched normal persons
Definition of anemia( WHO)
◦Adult men-ƒBlood Hgb conc. <130 g/L (<13 g/dL)
or Hct<39%
◦Adult women-Blood Hgb conc. <120 g/L (<12 g/dL)
or Hct <37%
◦Limitations
◦Volume status
◦Special population
◦Volume status
◦RBC parameters are all concentrations and are
dependent on 2 factors
◦RCM
◦Plasma volume
◦Low-if the RCM is decreased and/or if the PV is increased
◦High-if the PV is decreased (ie, hemoconcentration).
◦Plasma volume in turn is subject for variation in certain
physiologic and pathologic conditions like:
◦Third trimester pregnancy
◦Acute bleeding e,g hematemesis
◦Volume depleted patients specially if underlying anemia
Special Population
◦Race
◦High altitude
◦Smokers
◦Environmental pollution
◦High prevalence of chronic diseases
◦Athletes
◦Elderly
 Erythropoiesis
◦ Erythropoiesis is a highly regulated process that begins
with the differentiation of small pool of pluripotent stem
cells in to early erythroid progenitor cells.

◦ These progenitors develop in to recognizable erythroid

precursors, which subsequently differentiate in to mature
erythrocytes
ERYTHROPOIESIS
◦Takes place in the bone marrow
◦Requirements
◦Sufficient nutrients
◦Stromal framework
◦Cytokines
◦Erythropoietin
Erythroid progenitor cells: are not

morphologically identifiable.

Erythroid burst forming unit (BFU-E) : is

the most primitive single lineage committed

erythroid progenitor cell.

Erythroid colony forming unit (CFU-E)

Erythroid precursor cells:

morphologically identifiable.

represent about 1/3rd of the marrow cell

population.

Proerythroblasts are the earliest

recognizable erythroid precursors.

Erythrocyte development….
ERYTHROID MATURATION SEQUENCE
 ERYTHROPOIESIS
◦About 10(10) cell per hour under steady state

◦Production can increase rapidly in the

presence of blood loss and hemolysis
through the influence of tissue hypoxia
◦Cytokines and growth factors involves
◦ Steel factor(SF)
◦ IL-3
◦ GM-CSF
◦ IGF-1 & Insulin
◦ Activin
◦ Hepatocyte growth factor
◦ Others besides Erythropoietin
 Regulation of Erythropoiesis

• Tissue oxygenation- most important regulator

• Erythropoietin
• Transcription factors (GATA1,FOG1)
• Iron
• Vitamins- B12 and folic acid
• Other factors ( SCF, IL-3, GM-CFU…) and
nutrients
ERYTHROPOIETIN
◦Produced largely in the kidney(>90%) and to a lesser extent in the
liver(<10%)
◦Produced by cells that sense adequacy of tissue oxygenation relative
to the metabolic need
◦ Interstitial fibroblasts in renal cortex
◦ Proximal tubules

◦Normal level 10–25 U/L

◦Hypoxia is the main stimulus
◦Acts through its receptor ( EpoR) in coordination with other factors
◦Affects the growth and differentiation of RBC progenitors
especially the terminal events(CFU-E)
RBC LIFE CYCLE
◦Under steady condition
◦Production = Destruction
◦The survival of RBC in the circulation
◦110 – 120days
◦100days for practical purposes
◦The Bone Marrow
◦Produces 1% of RBC/day
◦Vast potential to increase production by > 5fold
◦RBC survival of around 20 days can be tolerated
Reticulocytes
◦An immature erythrocyte that has lost its nucleus but
retains aggregates of RNA within its ribosomes
◦Last phase before turning in to mature RBC
◦Survive for 4days totally
◦3.5 days in BM
◦1day in the circulation
◦Stay in the BM can be shorter
◦Need special stain in the blood smear-supravital stains
◦New Methylene Blue(NMB)
◦Brilliant Cresyl Blue (BCB)

◦Normal range/reticulocyte count-can be used to assess

bm erythropoietic activity
◦Absolute retic count
◦Corrected retic count
◦Reticulocyte production index
 CONSEQUENCES OF ANEMIA
◦These are physiologic responses and others which come
into the picture as the level of hemoglobin progressively
falls.
◦Bohr effect
◦Increase in cardiac output
◦Bohr effect
◦Increased extraction of oxygen by tissues with shift of the curve
via changes in
◦ pH
◦ CO2 Level
◦ Intracellular 2,3-DPG
CONSEQUENCES OF ANEMIA
◦Increase in cardiac output
◦Hyperdynamic state by increasing
◦Heart Rate
◦Stroke Volume
◦Responsible for the majority of clinical features
 CLINICAL MANIFESTATIONS
◦Clinical Features of anemia per se depend on
◦Degree of anemia
◦Rate of the decline in HGB
◦Oxygen demands of the patient
◦Other features
◦Manifestation of acute blood loss
◦Sn &Sx of the underlying diseases
◦Associated presentation of specific anemias
◦Anemia is just a sign not a diagnosis by itself
◦Any degree of anemia is never normal
◦Major features
◦Fatigue
◦Dyspnea (exertional/at rest)
◦Sn & sx of hyperdynamic state
◦Bounding pulse
◦Palpitation
◦tinnitus
◦In more severe cases
◦Lethargy & confusion
◦CHF
◦Arrhymthmia
◦Angina/MI
◦Due to bleeding
◦Easy fatiguability
◦Lassitude
◦Muscle cramps
◦Postural dizziness
◦Lethargy
◦Syncope
◦Hypotension/shock/death
CLASSIFICATION OF CAUSES OF
ANEMIA

◦Two approaches

◦Kinetic

◦Morphological
 Kinetic Approach
◦Deals with the kinetics of RBC loss & production
◦One of the following independent mechanisms
 Marrow production defects (hypoproliferation)

◦Some of the situations

◦Deficiency of nutrients, eg, Iron
◦BM disorders/DAMAGE INFILTRATION/FIBROSIS
◦Aplastic anemia, pure RBC aplasia,MDS
◦Bone marrow suppression
◦Drugs, infiltration
◦Low level of trophic hormones-STIMULATION
◦EPO, androgen, thyroid
◦Anemia of chronic illness/INFLAMMATIONSTIMULATION
Maturation disorder
• Cytoplasmic defects
• Iron deficiency (severe)
• Thalassemia
• Sideroblastic
• Nuclear defects
• ƒ Folate deficiency
• Vitamin B12 deficiency
• Drug toxicity
• Methotrexate
• Alkylating agents
• Alcohol
• Refractory anemia
ƒ Myelodysplasia
BLOOD LOSS
◦Obvious(trauma, melena, hematemesis, severe
menometrorrhagia)
◦Occult(slowly bleeding ulcer or carcinoma)
◦Induced( hemodialysis losses, excessive blood
donation
◦Subtle
◦Factitious
◦Retroperitoneal
◦After surgery
◦Chronic blood loss
◦A different entity
Increased RBC destruction

◦RBC life span shorter than 100days by

definition is hemolysis
◦Hemolytic Anemia
◦Survival less than 20days or >5% of RBC/day
◦Inherited or acquired
◦Intravascular vs extravascular
◦Intrinsic vs extrinsic RBC defect
MORPHOLOGIC APPROACH
◦Based on RBC size and other morphologic features as
determined by
◦Peripheral blood smear examination
◦Automated machines
◦Other morphologic features
◦Anisocytosis
◦Poikilocytosis
◦hemoglobinization
◦Normal values
◦MCV 80-90fL
◦Diameter-7-8microns= nucleus of mature lymphocyte
◦Central pallor of 1/3rd of the diameter of RBC
◦3 Categories according to morphologic(size)
approach
◦Macrocytic
◦Microcytic
◦Normocytic
Macrocytic Anemia
◦MCV > 100fL
◦Typical example
◦Megaloblastic anemias
◦Folate deficiency
◦Vitamin B12 deficiency
◦Not all macrocytosis is necessarily associated
with megaloblastic anemia
◦AZT, alcohol, dyslipidemia--MACROCYTIC -NON
MEGALOBLASTIC
Microcytic Anemia
◦MCV < 80fL
◦Always associated with hypochromia
◦Typical examples
◦IDA
◦Thalassemias
◦ACD-late
Normocytic Anemia
◦Normocytic & Normochromic cells
◦Vast and heterogeneous group
◦Of little diagnostic significant
◦Kinetic approach more important for Dx in NN
anemias
◦Typical examples
◦Aplastic anemia
◦Early IDA
◦Certain proportion of ACD
EVALUATION OF THE ANEMIC
PATIENT
◦Principles
◦Anemia is just a major sign of disease
◦Any degree of anemia is Never Normal
◦Hx, P/E & Laboratory
◦Questions to answer
◦Is the patient bleeding(anytime)?
◦Is the BM suppressed?
◦Is there evidence of destruction? IV?EV?
◦Is there deficiency state? Why?
History
◦Hx or Sxs of anemia or medical condition related to anemia
◦Duration (recent origin, subacute, or lifelong?)
◦Family history of anemia/ethnicity/country-INHERITED INTRA
CORPUSCULAR DEFECTS
◦Blood loss/ previous transfusion/liver disease
◦Hx of pregnancy/ Detailed menstrual hx
◦Dietary hx, alcohol
◦Use of medication & exposure to chemicals
◦URINE COLOR
◦VALVES,AS,MARCHING-MECHANICAL HEMOLYSIS
Physical Examination

◦Aim
◦Severity, Cause
◦Other related hematologic or medical conditions
◦Important examinations & Sns to look for
◦Vital signs & signs of infection
◦Pallor. Jaundice LAP, cvs, HSM, DRE, Bone tenderness
◦Integumentary system Petechiae ecchymoses,
Laboratory Evaluation
Serial determination of HGB &
HCT
Evaluation of specific anemias
IDA
HEMOLYTIC ANEMIAS
Megaloblastic anemias
Hemoglobin electrophoresis
Flowcytometry & cytogenetic
studies
NORMAL VALUES FOR RBC PARAMETERS IN MEN & WOMEN
RETICULOCYTE COUNT
◦ Red cells that have been recently released from the BM
◦ key to the initial classification of anemia
◦ Reticulocyte count 1% to 2% and reflects the daily replacement of
0.8–1.0% of the circulating red cell population
◦ Production rate increases to two to three times normal within 10
days following the onset of anemia.
◦ In the face of established anemia, a reticulocyte response less than two to
three times normal indicates an inadequate marrow response.
RETICULOCYTE COUNT
◦Normal range/reticulocyte count-can be used to
assess bm erythropoietic activity
◦Absolute retic count
◦Corrected retic count
◦Reticulocyte production index
◦CRC=RETICULOCYTE %X ACTUAL HCT
45%(NORMAL HCT)
HGB CAN BE SUBSTITUTED FOR HCT
EG A pt with a retic count of 2.5% and a hct of
37%
CRC=2.5 X 37/45=2.05%
Reticulocyte production
index
◦ The raw reticulocyte count is
misleading in anemic patients.
◦ Reticulocyte production index=
Reticulocyte index X correction factor
◦ It provides an estimate of marrow
production relative to normal

◦ where correction factor is applied as

follows
HCT Correction factor
36-45 1.0
26-35 1.5
16-25 2.0
< 15 2.5
 the RBC indices
◦MCV defines the size of the RBCs
◦MCH quantifies the amount of hemoglobin per RBC.
◦MCHC indicates the amount of hemoglobin per unit volume.
◦In contrast to MCH, MCHC correlates the hemoglobin
content with the volume of the cell. It is expressed as g/dl
of RBCs or as a percentage value
◦MCHC reflects defects in hemoglobin synthesis
(hypochromia).
◦spherocytosis or in other congenital hemolytic
anemias=HIGH
Red Cell Volume distributionwidth (RDW)
◦RDW represents the coefficient of variation of the RBC distribution
(size) and is expressed as a percentage.
◦The normal value for RDW is 13 ± 1.5%.
◦normal range indicates that the size distribution of RBCs has the
normal degree of variation (ie, a relatively homogenous population
of cells).
◦normal RDW is relatively insensitive for eliminating the possibility of
RBC abnormalities
◦An increased RDW suggests greater-than-normal variation in RBC
size; however, it is not highly specific or sensitive for making or
excluding any diagnoses
◦FA,B12,HEMOLYSIS,BLOOD TRANSFUSION
◦There is no condition that regularly yields a RDW less than normal.
White blood cell count and differential

◦A low WBC count (leukopenia)

 Bone marrow suppression or replacement
Hypersplenism
Deficiencies of cobalamin or folate
◦High total WBC count (leukocytosis)
Presence of infection, inflammation, or a hematologic
malignancy
Neutrophil
Hypersegmentation
◦ >5 % of neutrophils with ≥5 lobes and/or the presence of ≥ neutrophils with ≥6
lobes Impaired DNA synthesis, vitamins B12 and folate.
Tests of Iron Supply and
Storage
◦SI,TIBC,TS
◦SI = 9-27 μmol/L (50–150 μg/dL),
◦TIBC=54–64 μmol/L (300–360μg/dL);
◦TS 25 to 50%.
◦TS=SI X1 00/TIBC
◦Serum ferritin used to evaluate total body iron stores
50-200ug/L
 Peripheral blood smear
◦Important information about defects in red cell production
◦variations in cell size (anisocytosis)
◦Shape (poikilocytosis).-defect in the maturation of RBC
precursors in the BM or fragmentation of circulating RBCs
◦Polychromasia—red cells that are slightly larger than normal
and grayish blue
◦ Nucleated red blood cells severe of hemolysis ,profound
stress or hypoxemia, a myelophthisic condition, such as
myelofibrosis
Bone Marrow Examination
◦Marrow examination (not usually indicated)
◦Indications-hypoproliferative anemia in the presence of
normal RFT, normal iron status, PANCYTOPENIA,
ABNORMAL CELLS BLASTS
◦Aspirate
ƒ Myeloid to erythroid precursors ratio
ƒ Cell morphology
ƒ Iron stain
◦ Biopsy
ƒ Cellularity
ƒ Morphology
◦ It is preferred to perform the biopsy before the aspirate.
 summary
◦In addition to mild to moderate iron-deficiency
anemia, the
hypoproliferative anemias can be divided into four
categories:
◦(1)chronic inflammation,
◦(2) renal disease,
◦(3) endocrine and nutritional deficiencies
(hypometabolic states), and
◦(4) marrow damage
◦1-3-endogenous EPO production is inadequate for the
degree of anemia observed
ACI-
◦LOW endogenous EPO production –inadequate BM
stimulation--occasional/no polychromatophilic
(“shift”) reticulocyte(reticulocytopenia)
◦BM also responds inadequately to stimulation, due in
part to(defective iron reutilization).
◦IDA OR BM damage-↑endogenous EPO –reticulocyte-
↑ (“shift”) reticulocyte
 SUMMARY
◦Hemolytic disease -↑reticulocyte response RPI >3 will have an
M/E ratio of at least 1:1
◦erythroid hyperplasia
◦Hypoproliferative anemia and a RPI <2 will demonstrate
an M/E ratio of 2 or 3:1
◦If the reticulocyte response is inadequate and the
Bm shows erythroid hyperplasia, this suggests the
presence of ineffective erythropoiesis MATURATION D/O
◦discrepancy between the M/E ratio and the reticulocyte
production index
Marrow production defects (hypoproliferation)

◦~75% of all cases of anemia

◦Nc Nc red cells
◦A normal red cell indices
◦A low reticulocyte production index <2
◦ M/E ratio 2 or 3:1.
Hypoproliferative anemias
◦Key tests in distinguishing among various forms of
hypoproliferative anemia
o Iron pannel, RFT,TFT
o BMA/BX to detect marrow damage or infiltrative
disease IF normal RFT,IRON STUDY-BM EXAM
o Iron stain of the marrow, to determine the pattern
of iron distribution (occasionally)
◦Mild to moderate iron deficiency anemia shows:
o Low serum iron level
o High TIBC
o Low percent transferrin saturation
o Low serum ferritin level
ACD/ACI
• Anemia of acute or chronic inflammation shows a
distinctive pattern of:
o Low serum iron
o Normal or low TIBC
o Low percent transferrin saturation
o Normal or high serum ferritin
Hemolysis
Laboratory features of HA
◦Laboratory features of HA are related to :
(1) Hemolysis per se and
(2) The erythropoietic response of the bone marrow
◦Serum
◦Increased unconjugated bilirubin,
◦ Increased lactate dehydrogenase (LDH),
◦ Increased aspartate transaminase,
◦ And reduced haptoglobin.
◦ Urobilinogen will be increased in both urine and stool
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◦Abnormalities on the ◦Abnormalities which
peripheral blood smear suggest that the hemolysis
suggesting extravascular is intravascular include:
hemolysis include:
◦ ◦Presence of free
◦Spherocytes hemoglobin in plasma or
◦Fragmented red cells urine
◦"Bite" or blister cells ◦A urine sediment positive
◦Acanthocytes, and for iron (hemosiderinuria),
◦Teardrop red cells and
◦In rare cases, presence of
circulating red cell "ghosts"
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◦The main sign of the erythropoietic response by the BM is :
◦An increase in reticulocytes
◦% age of reticulocytes and the absolute reticulocyte count
◦The increased number of reticulocytes is associated with an :
◦Increased mean corpuscular volume (MCV) in the blood count.
◦Macrocytes, polychromasia and nucleated red cells on blood smear

85
◦The increased red cell turnover :
◦Has metabolic consequences.
◦In normal subjects : iron from effete red cells : recycled by the body
◦Chronic Intravascular Hemolysis:
◦Persistent Hemoglobinuria
◦Cause considerable iron loss
◦Needing replacement

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◦Chronic Extravascular Hemolysis : opposite problem :
◦Iron overload is more common
◦Especially if patient needs frequent blood transfusions
◦Chronic iron overload :
◦Cause Secondary Hemochromatosis
◦Damage to :
◦Liver = cirrhosis
◦Heart Muscle =heart failure

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THANK YOU !!!
 SPECIFIC ANEMIAS
WILL FOLLOW IN THE
NEXT LECTURE
IRON DEFICIENCY
ANEMIA
92
◦ Normal body iron content — 3 to 4
grams.
Iron containing proteins (eg, myoglobin,
cytochromes, catalase) — 400 mg
◦ Storage iron in adult men = 10 mg/kg,
and is found mostly in liver, spleen, and
bone marrow
◦ Adult women have less storage iron,
depending upon the extent of menses,
pregnancies, deliveries, lactation, and
iron intake
Basic Iron Metabolism

◦ Total body iron is controlled by modulating dietary iron absorption

◦ Dietary iron inorganic non heme iron
◦ Organic iron heme iron- distinct absorption mechanism
◦ Homeostasis takes place at gi, blood and cellular level
◦ Dcytb,DMT-1,FERROPORTIN/HEPHAESTIN/CERULOPLASMIN/APOTRANSFERRIN
◦ HEPCIDIN
◦ Ferritin/Transferrin/hemosiderin
Basic Iron Metabolism

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Role of hepcidin

97
Iron deficiency anemia
◦ Iron deficiency is one of the most prevalent forms of malnutrition
◦ Globally, 50% of anemia is attributable to iron deficiency
◦ Accounts for approximately 1MLN deaths annually worldwide
◦ Africa and parts of Asia bear 71% of the global mortality burden

98
IDA-Causes

99
STAGES OF IRON DEFICIENCY

Three stages
◦ STAGE 1-negative iron balance
◦ demands for (or losses of) iron exceed the body’s ability to absorb
◦ iron deficit must be made up by mobilization of iron from RE storage sites
◦ ↓iron stores—↓ serum ferritin level or stainable iron (BM)
◦ SI, TIBC and red cell protoporphyrin levels remain within normal limits. At this stage,
◦ Red cell morphology and indices are normal.

100
Stage 2 Iron-deficient erythropoiesis
◦ iron stores are already become depleted but not completely exhausted
◦ hemoglobin synthesis becomes impaired
◦ 1st appearance of microcytic cells
Stage 3 Iron-deficiency anemia
102
 Clinical Presentation of Iron Deficiency
◦Increased likelihood- Pregnancy, adolescence, periods of rapid
growth, and an intermittent history of blood loss of any kind

◦Iron deficiency in an adult male or postmenopausal female

means GI blood loss until proven otherwise

◦usual signs of anemia—fatigue, pallor, and reduced exercise

capacity

103
C/F…
◦ In advanced state,
Cheilosis (fissures at the corners of the mouth)
 koilonychia (spooning of the fingernails)

Atrophic glossitis -red, glazed, smooth

tongue.
◦ Pica and pagophagia — perverted appetite to clay
or dirt (geophagia), paper products, or starch
(amylophagia), ice

104
Diagnosis of IDA
1) Red cell morphology and indices

105
ddx
107
Treatment: Iron-Deficiency
Anemia
◦Approach to treatment determined by :
severity and cause of iron-deficiency anemia
◦symptomatic elderly patients with severe iron-deficiency
anemia and cardiovascular instability may require red cell
transfusions
◦ Younger individuals who have compensated for their anemia -
iron replacment

108
Treatment…

◦Three major therapeutic approaches

1) Red Cell Transfusion

2) Oral Iron Therapy

3) Parenteral Iron Therapy

109
 1. Red Cell Transfusion

Reserved for:
◦Hemodynamically unstable because of active bleeding
and/or shows evidence for end-organ ischemia
◦ hemoglobin level is <7 g/dL

◦ Transfusions of RBCs correct the anemia acutely and provide a source of iron for
reutilization
◦ 1 unit packed RBC(300ml)-200 mg of iron, raise hct by 3% and Hgb by 1g/dl

110
2. Oral Iron Therapy
Goal of therapy
1) Repair the anemia
2) 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

111
 2. Oral Iron Therapy
◦Provides a safe, cheap and effective means of restoring iron balance
◦Dose- up to 300 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 of the day
◦should be taken on an empty stomach, since food may inhibit iron
absorption
◦A dose of 200–300 mg of elemental iron per day should result in the
absorption of iron up to 50 mg/d.
◦supports a red cell production level of two to three times

112
Side effect
◦ 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.

113
 Expected response
◦Pica will disappear almost as soon as oral iron therapy is
begun
◦Improved feeling of well-being : first few days
◦Reticulocytosis will be seen, maximal in ~7 to 10 days
◦Hemoglobin concentration
will rise slowly
 usually beginning after about 1-2 wks
 will rise approximately 2 g/dL over the ensuing three weeks
Return to normal by 6 to 8 weeks

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3. PARENTERAL IRON THERAPY
Indications
1) Level of continued bleeding exceeds GI absorption
2) Patients with IBD(severe intolerance to oral iron
preparations)
3) In dialysis patients
4) Anemic cancer patients receiving treatment with
erythropoiesis-stimulating agents (eg, erythropoietin,
darbepoetin) who have failed to respond adequately to
oral iron preparations

116
3. PARENTERAL IRON THERAPY…
Available preparations

◦Iron dextran (cosmofer - imferon)

 Good efficacy but more side effects.
 Giving IM, or IV infusion.
 Amp 2 ml = 100mg.
 Side effects:
 Local pain, staining inflammation, abscess formation
 General: hypersensitivity reaction, fever, rigor, hypotension

N.B: Test dose is required prior to the use of iron therapy.

In administering iv iron dextran, anaphylaxis is a concern

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 3. PARENTERAL IRON THERAPY…
◦Ferric gluconate
◦Iron sucrose ( ferrosac – venofer)
 Good safety and efficacy profile.
 Given IV or slowly IV infusion.
 Amp: 5ml = 100 mg.
◦ Ferumoxytol

◦ 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.

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 ANEMIA OF
CHRONIC DISEASE
119
120
PATHOGENESIS of ACD
◦Inflammation, infection, tissue injury, cancer...)
◦Primarily reflect a reduction in RBC production by the BM.
1) Abnormal iron metabolism with trapping of iron in macrophages
low fe reutilization
◦inadequate iron delivery to the marrow, despite the presence of
normal or increased iron stores.

2) Inability to increase erythropoiesis in response to anemia

3) A relative decrease in EPO production
4) Decreased red cell survival(mild to moderate contribution)

121
Pathogenesis…
◦The role of cytokines-↓BM responsiveness to EPO is
mediated by inflammatory cytokines, especially IL-6
◦Hepcidin
◦Hepcidin is the predominant negative regulator of iron
absorption in the small intestine, iron transport
◦Increased hepcidin production seen in patients with
infections, malignancy, or inflammatory states

122
Role of hepcidin

123
Anemia of Chronic Disease
Lab findings:
◦ Hypoproliferative anemia (low reticulocyte count)
◦ Typically a normocytic anemia, though 25% of cases are microcytic
◦ Inadequate iron delivery to the marrow, despite the presence of normal
or increased iron stores.

◦ labs –***Norm. or ↑↑ Se ferritin, and low serum Fe and TIBC. i↑↑ red cell
protoporphyrin, a hypoproliferative marrow, low transferrin saturation in
the range of 15–20%
*****The most distinguishing feature bn true IDA & ACD
◦ Bm stores of iron are normal (though testing for this is not indicated)
Treatment: Treat underlying cause

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ACD +/- Fe def.
ACD Fe def. ACD + Fe def

Serum iron Low Low Low

TIBC Low - normal High Normal
Transferrin Low Low Low
saturation
Ferritin Normal – high Low Low - normal
Soluble Normal High Normal - High
transferrin
receptor(sTf
R)
Ratio of Low High High
soluble
transferrin
receptor to
log ferritin
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Transfusions
◦ When to transfuse?
◦ General rule: Hct <21%, consider at <25% in pt’s with multiple medical problems
◦ Other times to consider: on-going rapid blood loss, highly symptomatic patients, patient with low Hct
and severe cardiovascular disease
◦ You expect the Hct to increase 3% for each unit of blood transfused

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ANEMIA OF CHRONIC KIDNEY DISEASE (CKD)

◦ Primarily due to a failure of EPO production by the diseased kidney and a reduction
in
red cell survival
◦ usually associated with moderate to severe
hypoproliferative anemia
◦ the level of the anemia correlates with the stage of CKD
◦ Red cells are typically normocytic and normochromic,
and reticulocytes are decreased
◦ CKD usually present with normal serum iron, TIBC, and ferritin levels.
◦ Those on Chronic HD may develop IDA from blood loss (dialysis procedure)
Anemia Summary
◦ Evaluation:
◦ CBC – eval. RBC data alongside WBC and Plt counts, RBC indices
◦ Reticulocyte count – if bone marrow is responding appropriately
◦ Smear – morphologic clues to etiology

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Anemia Summary
◦ Most common etiologies:
◦ Females – Iron deficiency
◦ Men – Anemia of chronic disease
◦ Hx and labs, possibly including soluble transferrin receptor will help you differentiate

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Anemia by size
◦ Microcytic: iron def., thalassemia trait, thalassemia intermedia
◦ Normocytic: anemia of chronic disease (25% microcytic), chronic renal failure,
hemolytic anemia, acute blood loss
◦ Macrocytic anemia: Folate def., B12 def.

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Thank You

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