ANEMIAS
Nazzal Bsoul,MD
Al Bashir Hospital
DEFINITION
Anemia: Is defined as a reduction in one or more
of major RBC measurements.
Hemoglobin (Hb).
Hematocrit (HTC).
Red blood cells count (RBCs) .
Anemia is not a disease by itself but is one of
the major signs of disease.
May be the first manifestation of a systemic
disease,along with other nonspecific complaints
such as fever,weight loss,anorexia.
HEMOGLOBIN (Hb)
Hb Concentration: measures the major
oxygen-carrying pigment in whole blood.
Values are expressed as grams of Hb per
dL of whole blood (g/dL).
Normal range: M 13-16,5 g/dL
F 12-15,5 g/dL
HEMATOCRIT
Hematocrit (HTC): Is the percent of a
volume of whole blood occupied by intact
RBCs.
Values are expressed as a percentage.
Normal range: M 41-51%.
F 37-47%.
RED BLOOD CELL COUNT
(RBCs)
RBC Count: Is the number of RBCs
contained in a unit of whole blood.
Values are expressed as millions of cells per
uL of whole blood.
Normal range: M 4,5-6,5 millions/uL
F 3,8-5,8 millions/uL
VOLUME STATUS
The three measurements are all
concentrations.
As such they are dependent upon both the
RBC mass and the plasma volume.
1.In acute bleeding, anemia develops only
after 36-48 hours.
2.Pregnancy: RBC mass is increased by
25% and plasma is increased by
50%.Normal values in pregnancy are
diffirent.
SPECIAL POPULATIONS
1.Living at high altutute.
2.Smoking and air pollution.
3.African-Americans—lower values.
4.Populations with a high incidence of
ch.diseases.
5.Athletes.
6.The elderly:should not have a lower
normal range for fear of missing a serious
underlying disorder.
ERYTHROPOESIS -1
Erythropoesis takes place in adults within the BM
under the influence of the stromal framework,a
number of cytokines,and the eryrhroid specific
growth factor,erythropoietin(EPO).
EPO is a true endocrine hormone produced in the
kidney.
EPO enhances the growth and differentiation of
the 2 erythroid progenitors.
1.Burst Forming Units-erythroid/BFU-E/.
2.Colony Forming Units-erythroid/CFU-E/.
ERYTHROPOESIS-2
The rate of RBC production equals the
rate of RBC destruction.
Approximately 1% of RBCs is removed
from the circulation daily.
The rate of RBC production can be
increased markedly (5-7 folds).
CLINICAL CONSEQUENCES OF
ANEMIA
The signs and symptoms induced by anemia
are dependent upon the degree of anemia
as well as the rate at which the anemia
has evolved.
Symptoms of anemia can result from two
factors:
1.Decreased O2 delivery to tissues.
2.Hypovolemia (acute bl.loss).
COMPENSATORY
MECHANISMS
Signs and symptoms depend also on the
compensatory mechanisms.
1.Extraction of O2 by the tissues can increase
from 25% to 60%.
2.Cardiac compensation: stroke volume and heart
rate (cardiac output).
Thus normal O2 delivery can be maintained by
1and 2 at rest at HBG as low as 5g/dL,assuming
that the intravasc.volume is maintained.
Thus symptoms will develop when HBG falls below
this level at rest or at higher HBG during
exersion or when cardiac compensation is
impaired.
SYMPTOMS AND SIGNS
Symptom:is a sensation or change in health
function experienced by the patient.
It is a subjective report.
Fatigue/tiredness
Pain.
Nausea.
Dizziness.
SYMPTOMS AND SIGNS-cont’d
Sign: is an objective evidence of the
presence of a disease or disorder.
Signs are discovered and reported by
the physician,not by the patient.It is
an objective report.
Elevated BP.
Skin rash.
Tachypnea.
Tachycardia.
SYMPTOMS AND SIGNS OF
ANEMIA
Dyspnea/S.O.B.:on exersion/at rest.
Fatigue/tiredness.
Signs and symptoms of hyperkinetic state:
1.bounding pulses.
2.palpitations.
3.roaring in ears.
In more severe anemia:Lethargy,confusion,CHF,angina,MI.
Pallor.
Headache.
Complications of extracellular volume depletion (in acute
bleeding).
CAUSES OF ANEMIA
There are 2 interrelated approaches one can
use to help identify the cause of anemia.
1.Kinetic approach.
2.Morphologic approach.
KINETIC APPROACH
Anemia can be caused by one or more of 3
independent mechanisms.
1.Decreased RBC production.
2.Increased RBC destruction.
3.RBC loss.
Decreased RBC PRODUCTION
If less than 1% of the circulating RBCs is
replaced by the BM.
1- Lack of nutrients such as iron,B12,or
folate.
2- Primary involvement of the BM such
as aplastic anemia,PRCA,MDS,or
tumor infiltration.
3- Low levels of trophic hormones,such
as EPO in CRF,thyroid hormones,and
androgens.
INCREASED RBC DESTRUCTION
A RBC life span below 100 days is the
operational definition of hemolysis.
Anemia will ensue when the BM is unable
to keep up with the need to replace
more than 5% of the RBC mass daily.
1-Inherited hemolytic anemias: hereditary
spherocytosis,SCD,and thalassemia
major.
2-Aquired hemolytic anemias: AIHA,TTP.
RBC LOSS
Blood loss is the most common cause of anemia
Forms of bleeding:
1-Obvious bleeding: trauma,melena,
hematemesis,or menometrorrhagia.
2-Occult bleeding:a slowly bleeding
colonic polyp or carcinoma.
3-Iatrogenic bleeding: Excessive bl.
donations,or repeated venesection.
MORPHOLOGIC APPROACH
According to RBC size.
Mean Corpuscular (Cell) Volume (MCV).
RBC size (MCV) is 80-96 femtoliters(fL).
Microcyte.
Macrocyte.
Normocyte.
ANEMIAS ACCORDING TO THE
RBC SIZE
1.Microcytic anemia.
2.Macrocytic anemia.
3.Normocytic anemia.
MICROCYTIC ANEMIAS
Are associated with an MCV below 80 fL.
1-Iron Deficiency Anemia (IDA)
2- Anemia of Chronic Disease (ACD)
3-Thalassemias.
IDA,ACD,and thalassemias are the most
3 common causes of microcytosis in
clinical practice.
Since all 3 have hypochromic and microcytic RBCs on blood film (smear),other
factors must be used to establish the
diagnosis.
IRON DEFICIENCY
ANEMIA (IDA)
Important discriminating features are:
1-Low serum iron concentration.
2-Increased total iron binding capacity
(TIBC)
3-Low serum ferritin concentration.
4-High RDW.
It is mandatory to determine the cause of
iron deficiency.
ANEMIA OF CHRONIC DISEASE
(ACD)
The hallmarks of this condition are:
1-Low serum iron.
2-Low TIBC.
3-Normal to increased serum ferritin
concentration.
The causes are usually related to the
presence of chr.infection (TB),
inflamation (RA),or malignancy.
ALPHA OR BETA THALASSEMIA
MINOR
Adults with thalassemia are most often
heterozygotes for the alpha or beta
forms of this syndrome,and may not be
anemic.
Family history is often negative.
P/E may reveal splenomegaly.
Blood film: microcytosis,hypochromia,
target cells,tear-drop forms,and
basophilic stippling.
MACROCYTIC ANEMIAS
Are characterized by an MCV above 100 fL.
Reticulocytosis.
Vit.B12 def.
Folate def.
MDS.
Hypothyroidism
NORMOCYTIC ANEMIAS
By definition the MCV is normal.
ACD.
MDS.
MULTIPLE CAUSES OF ANEMIA
In pediatric practice anemia is commonly
caused by a single disorder.
In adults,mainly older adults,multiple
causes are frequently present.
1-Ca colon: IDA and ACD
2-AIHA on steroids and GI
bleeding.
3-RA and NSAIDs: ACD and IDA
EVALUATION OF THE PATIENT
WITH ANEMIA-1
Anemia is one of the major signs of
disease.
It is never normal and it`s cause should
be always be sought.
History.
Physical examination.
Simple lab.tests.
Other investigations.
EVALUATION OF THE ANEMIC
PATIENT-2
The workup should be directed towards
answering the following questions:
1.Is the patient bleeding (now or in the past) ?
2.Is there evidence of increased RBC
destruction?
3.Is the BM suppressed?.
4.Is the patient iron deficient? if so,why?.
HISTORY
Symptoms related to anemia
(melena,CRF,RA)
Etnicity and country of origin
(Hemoglobinopathies).
Drug history (NSAIDS).
PHYSICAL EXAMINATION
Pallor.
Jaundice.
Tachycardia.
Lymphadenopathy.
Hepatosplenomegaly.
Bone tenderness.
LABORATORY EVALUATION-1
Complete blood count (CBC): HBG,HCT,
RBC count,RBC indices,and
WBC count.
WBC differential,PLT count,and
reticulocyte count.
Blood film (Blood smear).
Red cell distribution width.
LABORATORY EVALUATION-2
Red cell indices:
1-Mean corpuscular volume.MCV 80-100
femtoliter.
2-Mean corpuscular hemoglobin.MCH
27,5-33,2 picograms of hemoglobin
per RBC.
3-Mean corpuscular hemoglobin
concentration.MCHC.33,4-35,5
grams of hemoglobin per dL of RBCs.
Red Cell Distribution Width(RDW)
RDW is a measure of anisocytosis or variation in
red cell size.
Increased RDW is commonly found when
there is a nutritional deficiency(eg,iron
,folate,and Vit.B12).
Increased RDW is not specific for any one
abnormality.
An increased RDW is the mathematical equivalent of the term”anisocytosis”,but is not
diagnostic of any particular morphologic finding.
LABORATORY EVALUATION-3
Reticulocyte count: helps to distinguish
among the different types of anemia.
0,5-1,5 percent.
Absolute reticulocyte count.25,00075,000/uL.
Reticulocytes normally survive for 4 days,of which 3 days in
the BM and one day in the peripheral circulation.
White blood cell count (WBC count).
Neutrophil hypersegmentation.
Platelet count (PLT count).
OTHER INVESTIGATIONS
Bone marrow aspirate and trephine
biopsy.
Radiological studies.
Genetic studies.
Immunological studies.
BONE MARROW EXAMINATION
BM examination generally offers little
additional diagnostic information in the
more common forms of anemia.
Although the absence of stainable iron in
BM is considered the “gold standard”
for the diagnosis of ID,this diagnosis
is usually established by lab.tests alone.
BONE MARROW EXAMINATIONCont’d
Indications for BM examination in anemic
patients include:
1-Pancytopenia.
2-The presence of abnormal cells in the
circulation (blast forms).
EVALUATION FOR ID
History: menometrorrhagia,symptoms of
PUD.
Preliminary lab.data: Low MCV,low MCH,
high RDW,high PLT count.
More complete evaluation is needed:
Serum iron
TIBC
serum ferritin
Clinical Manifestations of Iron
Deficiency (ID)-1
The presenting symptoms of ID are
caused primarily by anemia:
Weakness,headache,irritability,fatigue,
exercise intolerance.
Koilonychia (Spoon nails),blue sclerae,
glossal pain.
Cognitive functions-verbal learning,
memory,and concentration.
Clinical Manifestations of ID-2
Physical performance- ID impairs exercise
capacity and causes easy fatiguability
PICA and Pagophagia:
PICA:is a perverted apetite for substances
not fit as food,such as clay or paper
products.
Pagophagia: is PICA for ice.
Causes of ID
Blood loss:Common cause.Overt or occult.
Decreased iron absorption: Relatively
uncommon cause.
Intravascular hemolysis: Hematuria (PNH).
Pulmonary hemosiderosis:
Administration of erythropoietin: In anemia
of chronic renal failure.
Diagnosis of ID-1
History and physical examination.
Laboratory investigations: CBC,RBC
indices,and blood film(smear)→presumptive diagnosis of ID.
Therapeutic trial of oral iron→positive
response (reticulocytosis,followed
by an increase in Hb at a rate of
about 2-4 g/dL every 3 weeks
Diagnosis of ID-2
No positive response ?
The following lab.investigations are
needed at the beginning:
1-Serum Iron (SI)
2-Total Iron Binding Capacity (TIBC)
3-Transferrin Saturation: (SI ÷TIBC)%
4-Serum ferritin level.
Search for Source of Bleeding and
Iron Loss
Diagnosing the cause of ID is much more
important than diagnosing ID.
History and physical examination.
Other investigations: Upper and lower
endoscopy.
Classic Presentation of IDA
A multigravid woman in her 40’s,presents
with tirednes and fatigue and chronic
blood loss from menometrorrhagia.The following lab.
findings were noted:
1-The hemoglobin was 8 g/dl,with MCV of 75 fL.
2-The MCH and MCHC were both low.
3- Blood film showed microcytic,hypochromic
red blood cells(RBCs)
4-The serum iron was low and the total iron binding
capacity(TIBC) was elevated,resulting in transferrin
saturation < 15%.The plasma ferritin
concentration was reduced.
Classic presentation of IDA-Cont’d
Iron stores were absent after performing
the “gold strandard” test for estimating
iron stores via bone marrow aspirate of
the patient.
Finally,the patient responded briskly to
oral iron therapy with a reticulocytosis
followed by elevations in the hemoglobin concentration.
VITAMIN B12 AND FOLATE
DEFICIENCY ANEMIAS
Dr.Nazzal Bsoul
Vitamin B12
Vitamin B12 (Vit.B12),also called cobalmin
is a water-soluble vitamin with a key
role in normal functioning of the brain
and nervous system,and for erythropoiesis.
It is normally involved in the metabolism of
every cell of the body.
It is structurally the most complicated vitamin
and it contains the rare element cobalt.
• It is absorbed,mainly in the terminal ileum.
Classical Presentation of Vit.B12
and Folate Deficiency
The patient usually presents with severe
anemia,and macrocytosis,with or without varying neurologic disturbances.
However,many patients with B12 deficiency
exist who have no or only mild anemia,
and macrocytosis may be masked by a
concurrent disorder,such as IDA or
thalassemia.
Diagnosis of B12 and/or Folate
Deficiency
B12 or folate deficiency should be suspected in
patients with one or more of the
following findings:
1-Oval macrocytic RBCs on blood film,with
or without anemia.
2-The presence of hypersegmented neutrophils.
3-Pancytopenia of uncertain cause.
4-Unexplained neurologic signs and symptoms,
(dementia,weakness,and parasthesia)
Diagnosis of B12 or/and Folate
Deficiency-cont’d
Special populations are at increased risk:
1-Older adults.
2- Alcoholics.
3- Patients with malnutrition.
4- Vegeterians.
Vit.B12 and folate deficiency often coexist
and are not easily diffirentiated on a
clinical basis.
The first step is to test for serum Vit.B12 and
folate level.
Methylmalonic Acid and
Homocysteine
Patients with low-normal or even normal
serum B12 values may be truly Vit.B12
deficient.
Measurement of the homocysteine and
methylmalonic acid appears to be
more sensitive for the diagnosis of
these deficiencies than serum Vit.B12
and folate levels.
Methylmalonic Acid and
Homocysteine-cont’d
Vit.B12 deficiency: Both serum homocysteine and methylmalonic acid (MMA)
are elevated.
Folate deficiency: Only homocysteine level
is elevated.
EVALUATION OF HEMOLYSIS
Hemolysis should be considered if the pt.
has a rapid fall in Hb ,reticulocytosis,
and/or abnormally shaped RBCs
(specially spherocytes or fragmented
RBCs) on bl.film.
Lab.findings in hemolysis:
High LDH
High indirect bilirubin.
Low serum haptoglobin.
Positive direct coombs’ test (only in case of
autoimmune hemolytic anemia).
General Causes for Hemolysis
1-Hemolysis due to intrinsic defects (intracorpuscular).
2-Hemolysis due to causes extrinsic to
the RBC (extracorpuscular).
Diagnosis of Active Hemolysis
Recognizing overt hemolysis is not difficult
in a classic patient with:
New onset of Pallor
Jaundice
Splenomegaly
Anemia
Circulating spherocytes.
Accurate histrory and physical examination
should always be the cornerstone of the
patient’s evaluation.
Laboratory Findings in Hemolysis
Serum lactate dehydrogenase (LDH) and
Haptoglobin are the major serum tests
in the diagnosis of hemolysis.
Reticulocyte count.
Other tests:Indirect bilirubin.
Coombs’ test.
Blood film (smear).
Serial evaluation of Hb and Ht
Atypical Presentations
Hemolysis without anemia: if the rate of
RBCs destruction falls within the bone
marrow’s compensatory ability.Indirect
bilirubil, LDH,and reticulocyte count are
high, but without anemia.
Hemolysis without reticulocytosis:
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