HEMATOLOGY

cours

Prof. Univ. Dr. Coralia Cotoraci

ANEMIAS
 DEFINITION

• Anemias (A) are diseases of the

erythrocyte (E), which are defined by a
• decrease in red blood cell parameters such
as: decreased hemoglobin (Hb) less than
12 g% in F, less than 13 g% in men (main
criterion), of hematocrit (Ht) less than 35%
in females and 42% in males and the
number of red blood cell (H) in the
peripheral blood
 DEFINITION
• Anemia is not a diagnosis in itself but a
manifestation of a disease in most cases.

• The correct terminology of the diagnosis must

therefore include the cause of anemia.

• The reason of specifing this into the diagnosis

is simple and fundamental: the right treatment
requires knowledge and understanding of the
pathogenesis of this clinical condition
 DEFINITION
• Parameters evaluated quantitatively the
erythrocytes in circulation are:
– hemoglobin
– hematocrit
– number of erythrocytes
 Normal red cell parameters

Parameter Men Women

Hemoglobin g/dl 14-17.4 12.3-15.3
Hematocrit % 41.5-50.4 36-45
Number of erithrocytes mil/mm3 4.5-5.9 4.5-5.1
Number of leucocytes /mm3 4400-11300 4400-11300
VEM fl 80-96 80-96
HEM pg 27.5-33.2 27.5-33.2
CHEM g/dl 33.4-35.5 33.4-35.5
Number of platelets /mm3 150000-450000 150000-450000
Reticulocytes % 0.5-2 0.5-2
Reticulocytes /mm3 22500-1475000 22500-1475000
RDW 12.4 (11.5-13.4) 4. (11.5-13.4)

*VEM- volum eritrocitar mediu;

**HEM-cantitate medie de Hb/E;
*** CHEM- concentraţie medie a Hb/E;
Erythrocyte characteristics 1
• Erythrocyte morphology – it is a biconcave
disc (diameter 8 microns app, app 2 microns
thick)
• Erythrocyte has a great plasticity, which
gives the possibility to pass through
capillaries
• Contain hemoglobin, a protein consisting of
HEM (iron + protoporphyrin) + globin
 Erythrocyte characteristics 2
• Erythrocyte function is to carry oxygen to tissues

• Therefore, if anemia occurs, it automatically

installs the tissue hypoxia (the most sensitive
organs to hypoxia will be the first to give symptoms
of anemia)
• Erythrocyte hemoglobin can adapt spontaneously
to the need for oxygen by changing the oxygen-
hemoglobin dissociation curve
 Complete blood count
• Hemoglobin - is determined by
spectrophotometric methods by chemical
lysis of erythrocytes which release it;
although the method is usually used with
good results, some circumstances may
affect the turbidity / color of plasma and
can result in artificial elevated values of
plasma Hb and MCHC
• The number of red blood cells - cells flow passes the
electrodes; electrical impedance caused by the
passage determines the number of erythrocytes. Each
unit has its own protocol by which it makes a
differentiation between the erythrocyte and
leukocytes, platelets, based on cell size, shape,
osmotic lysis resistance etc. There are situations
when it is difficult to assess differentiation (hemolysis,
marked leukocytosis which may result in falsely
elevated erythrocyte)
• Hematocrit - monitors component E; is calculated as
MCVxRBC
formulas for erythrocyte
indices:

– VEM=Ht (%) / Nr eritr (mil/microl) x 10

– HEM= Hb (g/dl) / Nr eritr (mil/microl) x 10
– CHEM= Hb (g/dl) / Ht (%) x 100
• erythrocyte indices - characterize deviations
occurring in the amount or concentration of Hb
in the erythrocyte

– MCV (mean corpuscular volume) - value

obtained directly by electrical impedance
techniques; without significant changes if
abnormal cells are present in small numbers;
Normal MCV = normocitosis, low MCV =
microcytosis; Increased MCV = macrocytosis or
megalocytosis
– MCH - mean corpuscular hemoglobin
– MCHC (mean concentration of hemoglobin /
erythrocyte) - values> 36 fmol are
characteristic for spherocytosis; low =
hypochromia
– RDW - measures the dynamic of size
changes in erythrocyte population; elevated
in anisocytosis
 Abnormalities of erythrocytes
on the blood smears
• variations in size (anisocytosis)
– Microcytosis
– Macrocytosis
– Megalocytosis
Anisocytosis
• color variations (POLICROMATOFILIA)
– Hypocromia
– Anulocytes
– Target cells etc
 Policromazia /
policromatofilia
Abnormalities of erythrocytes
on the blood smears

• variations in shape (poikilocytosis):

ovalocytes, schistocytes, spherocytes, drop
cells, drepanocyte, acantocyte, leptocyte
Poikilocytosis
Abnormalities of erythrocytes
on the blood smears
• erythrocyte inclusions: Howell-Jolly
bodies (nuclear debris), basophil
inclusions (precipitated
ribonucleoprotein), Cabot rings - come
from proteins of mitotic spindle, Heinz
bodies (intracellular aggregated of
oxidative denatured hemoglobin)
 Incluzii eritrocitare

Corpi Howell Jolly

Inel Cabot

Corpi Heinz
 What can cause artifacts in
determining blood count?
• RBC – extreme leukocytosis; agglutination or
cold agglutinins;
• Hb – hyperlipidemia; hemoglobin due to
intravascular haemolysis; extreme leukocytosis;
hyperbilirubinemia;
• MCV- leucocitoza; autoaglutinine; deshidratare
• MCH – factorii care interferă cu MCV sau RBC;
• MCHC - factorii care interferă cu MCV sau RBC
Frotiu de sange periferic: hipocromie, anulocite.
http://health.allrefer.com/health/peripheral-smear-pictures-images.html
Frotiu de sange periferic: anulocite, schizocite.
http://health.allrefer.com/health/peripheral-smear-pictures-images.html
Frotiu de sange periferic: hipocromie, anulocite.
http://health.allrefer.com/health/peripheral-smear-pictures-images.html
Frotiu de sange periferic: hipocromie marcata.
http://health.allrefer.com/health/peripheral-smear-pictures-images.html
acantocytosis
Tear drop cells
stomatocytes
echinocytes
Target cells
Sickle cells
Red cells rouleau
basophilic stipping
 Various aspects of
erythrocyte depending on
the type of anemia

Anemia - microcytes hypocromia

microsferocytes

Anemia - megalocytes http://www.google.ro/imgres?imgurl=http://

http://health.allrefer.com/health/peripheral-smear-pictures-images.html
 CLASSIFICATION OF
ANEMIA
• To make an initial classification of
anemia, three main aspects are available
for the clinician

• - Erythrocyte indices
• - Blood smear
• - Index of erythrocyte distribution
KINETICS CLASSIFICATION
OF ANEMIA
• I. Low production of red blood cells (reticulocyte
production index <2):
• 1. HYPOPROLIFERATIVE ANAEMIAS
• A. ineffective erythropoiesis
• - low iron deposits
• - Anemia of chronic disease

• B. erythropoietin deficiency
• - Kidney diseases
• - Endocrine disorders
KINETICS CLASSIFICATION
OF ANEMIA
• C. hypoplastic anemia
• - Aplastic anemia
• - Pure erythroid aplasia

• D. infiltration
• - leukemia
• - metastases
• - myelofibrosis
KINETICS CLASSIFICATION
OF ANEMIA
• 2. ineffective production (megaloblastic,
microcytic, normocytic)
• - Vitam B12 deficiency
• Thalassemia
• - Folate deficiency
• sideroblastic anemia
• Other causes
KINETICS CLASSIFICATION
OF ANEMIA
• II. Increased production of red blood cells
(reticulocyte production index> 3)
• 1. hemolytic anemia
• - hereditary
• - acquired

• 2. NUTRITIONAL ANAEMIAS
 ETIOPATHOGENESIS
• A classification based on pathogenic mechanism:
• Anemia caused by reduced production of red blood
cells (anemia of central nature)
• Anemia associated with bone marrow failure
hypoproliferation (aplastic anemia / hypoplastic)
• anemia in bone marrow failure associated with ineffective
erythropoiesis:
• -Impairment of Hb synthesis: hypochromic anemia
• -Impairment of DNA synthesis: megaloblastic anemia

• Increased erythrocyte loss anemia (anemia peripheral

nature)
• acute and chronic posthaemorrhagic anemia
• hemolytic anemia
– intraerytrocitar
– extraerytrocitar
 How to approach a patient
with anemia?

• Clinical symptoms and signs of anemia =

• Paraclinically = a complex protocol which

determines the etiology of anemia
How do we describe anemia?
• Severity: mild / moderate / severe

• Depending on erythrocyte indices

• VEM - microcytic / normochromic / macro or
megalocytic
• HEM / CHEM - hypochromic / normochromic

• Function of reticulocytes
• Hipor- / normo- / hyper-regenerative
• Example:

• mild normocytic normochromic hypo-

regenerative anemia
 What are the steps?
• Complete blood counts + peripheral blood
smear (to see different forms of
erythrocytes)
• No of reticulocytes
• Examination of bone marrow

• Complex etiological investigations

 How is the bone marrowto
examined?
• Sternal / coxal aspirate

• bone marrow biopsy – the marrow

architecture can be clearly seen
 How to perform a bone marrow
aspirate and biopsy?

• Sternal aspiration is the technique by which a needle is

inserted into the sternum cavity (which contains the bone
marrow) in II intercostal space and, using a syringe, the
doctor aspirates a few ml of bone marrow. Immediately
after, the marrow is spread on smears slides (minimum
5), then they are colored (May-Grumwald-Giemsa or
special stains) and examined under a microscope.

• bone marrow biopsy is the method by using special

biopsy needle (the hip bone) take a bone fragment
(containing unaltered architecture of bone marrow)
Aspirate needle

Bone marrow biopsy needle

Coxal aspirat
 Selected references
• 1. Wintrobe, Hematology, 11th Edition
• 2 Colita, Tratat de hematologie, Bucuresti, 2003
• 3. Lupu Roxana, Bazele hematologiei clinice, edit MAST,
BUCURESTI,
• 4. Harison, Principles of Internal Medicine, Mc Graw Hill, Inc, 1990
• 5. Chanarin; the Megaloblastic Anemias; 3rd edition, Oxford, 1990
• 6. LindenbaumJ, Allen RH; Clinical spectrum and diagnosis of
folate deficiency; Folate in health and disease; New York, 1995
• 7. Kaptan K, Beyan C, Ural AU et all; Helicobacter pylori-is it a
novel causative agent in vitamin B12 deficiency? Arch Inren Med
2000; 160; 1349-1353
• 8. Dahele A; Ghosh S; Vitamin B12 deficiency in untreated celiac
disease, Am J Gastroenterology 2001; 96; 745-750
 Take home messages
• CBC is of inestimable value in anemia!
• The first orientation and etiologic
diagnosis is made after erythrocyte
indices!
• We must always look for the cause of
anemia!