Anaemias

1.1. EryhtropoiesisEryhtropoiesis
2.2. Erythrocytosis and erythropenia.Erythrocytosis and erythropenia.
3.3. Anaemia. Classifications of anaemias.Anaemia. Classifications of anaemias.
4.4. Etiology and pathogenesis of acuteEtiology and pathogenesis of acute
and chronic posthemorrhagic anaemia.and chronic posthemorrhagic anaemia.
5.5. Etiology and pathogenesis ofEtiology and pathogenesis of
hemolytic anaemias.hemolytic anaemias.
6.6. Anaemias with disorders ofAnaemias with disorders of
erythropoesis.erythropoesis.

ActualityActuality
 Alterations of erythrocyteAlterations of erythrocyte function involve
either insufficient or excessive numbers of
erythrocytes in the circulation or normal
numbers of cells with abnormal components.
 AnemiasAnemias are conditions in which there are too
few erythrocytes or an insufficient volume of
erythrocytes in the blood.
 PolycythemiasPolycythemias are conditions in which
erythrocyte numbers or volume is excessive.
 Each of these conditions has many causes and
is a pathophysiologic manifestation of a variety
of disease states.

Eryhtropoiesis is a process of structural, metabolic
and functional differentiation from polypotent cell to the
differentiated erythrocytes. Life-span of erythrocyte is
100-130 days. Than they destroy mainly in a spleen, liver
and marrow.
The norm amount of erythrocytes in peripheral blood is
3,7- 4,7×1012/l for women, 4,2-5,2×1012/l - for men.
Haemoglobin accordingly - 120-140 g/l and 135-165 g/l.
The color index (degree of saturation of erythrocytes
by hemoglobin) is 0.85-1.05
Production of erythrocytes:
Erythropoiesis

Red blood cell count
Male: 4.32-5.72 trillion cells/L* (4.32-5.72 million cells/mcL**)
Female: 3.90-5.03 trillion cells/L (3.90-5.03 million cells/mcL)
Hemoglobin
Male: 13.5-17.5 grams/dL***(135-175 grams/L)
Female: 12.0-15.5 grams/dL (120-155 grams/L)
Hematocrit
Male: 38.8-50.0 percent
Female: 34.9-44.5 percent
White blood cell count
3.5-10.5 billion cells/L
(3,500 to 10,500 cells/mcL)
Platelet count
150-450 billion/L
(150,000 to 450,000/mcL**)
The following are normal
complete blood count
results for adults:
* L = liter
** mcL = microliter
*** dL = deciliter
Index Normal Value
Mean cell volume (MCV) = (hematocrit ×
10)/
(red cell count × 10⁶)
90 ± 8 fL
Mean cell hemoglobin (MCH) =
(hemoglobin × 10)/(red cell count × 10⁶)
30 ± 3 pg
Mean cell hemoglobin concentration =
(hemoglobin × 10)/hematocrit, or
MCH/MCV
33 ± 2%

 1. Mean corpuscular volume (1. Mean corpuscular volume (MCVMCV) =) =
PCV in L/LPCV in L/L
RBC count/LRBC count/L
 2. Mean corpuscular haemoglobin (2. Mean corpuscular haemoglobin (MCHMCH) =) =
Hb/LHb/L
RBC count/LRBC count/L
 3. Mean corpuscular haemoglobin concentration3. Mean corpuscular haemoglobin concentration
Hb/dlHb/dl
MCHCMCHC ==
PCV in L/LPCV in L/L
Erythrocyte Volume Hemoglobin Content
Normal Normocytic Normochromic
Increased Macrocytic (higher mean
corpuscular volume [MCV])
Hyperchromic (higher mean corpuscular Hb
concentration [MCHC])
Decreased Microcytic (lower MCV) Hypochromic (lower MCHC)
(femto- is 10−15
)
(pico- is 10−12
)
(deci- is 10−1
)

Normally, MCV is expressed in femtoliters (fL, or 10−15
L), and [RBC] is the quantity
expressed in millions per microliter (106
/ μL). The normal range for MCV is 80–100 fL.
For example, if the Hct = 42.5% and [RBC] = 4.58 million per microliter (4,580,000/μL),
then
Use of volume-sensitive automated blood cell counters, such as the Coulter counter.
In this type of apparatus, the red cells pass one-by-one through a small aperture and
generate a signal directly proportional to their volume. Other automated counters
measure red blood cell volume by means of techniques that measure refracted,
diffracted, or scattered light
To calculate MCV, the hematocrit (Hct) isTo calculate MCV, the hematocrit (Hct) is
divided by the concentration of RBCs ([RBC])divided by the concentration of RBCs ([RBC])
HIGHHIGH
LOWLOW
Pernicious anemiaPernicious anemia,,
MCV up to 150 fLMCV up to 150 fL
Vit B12Vit B12 and/orand/or
folic acidfolic acid deficiencydeficiency
AlcoholismAlcoholism, as are, as are  CGTCGT
& a ratio of AST:ALT of& a ratio of AST:ALT of
2:12:1
Iron deficiency, MCVIron deficiency, MCV  60-7060-70
fL due to dietary intake, GITfL due to dietary intake, GIT
or menstrual blood lossor menstrual blood loss
ChronicChronic
diseasedisease
Thalassemia,Thalassemia,
sideroblasticsideroblastic
anemiaanemia

The system of red blood (erythron)
is presented:
a)by the organs of hemopoiesis
(mainly, by marrow);
b)by blood;
c)by the organs of hemodieresis
(basic by spleen).
The spleen and liver can also resume
their foetal haematopoietic role in certain
pathologic conditions and is called
extramedullary haematopoiesis.
In the bone marrow, developing blood
cells are situated outside the marrow
sinuses, from where after maturation
they enter the marrow sinuses, the
marrow microcirculation and thence
released into circulation.

Erythropoietin MechanismErythropoietin Mechanism
Imbalance
Reduces O2
levels in blood
Erythropoietin
stimulates red
bone marrow
Enhanced
erythropoiesis
increases RBC
count
Normal blood oxygen levels Stimulus: Hypoxia due to
decreased RBC count,
decreased availability of O2
to blood, or increased
tissue demands for O2
Imbalance
Start
Kidney (and liver to a
smaller extent) releases
erythropoietin
Increases
O2-carrying
ability of blood

a)a) increase (increase (erythrocytosis)erythrocytosis)
Various changes are in the system ofVarious changes are in the system of erythronerythron, which arise, which arise
up in physiology terms and at pathological processes,up in physiology terms and at pathological processes,
can be accompanied running the number ofcan be accompanied running the number of
erythrocytes in blood:erythrocytes in blood:
ErythrocytosisErythrocytosis is multiplying the amount ofis multiplying the amount of
erythrocytes higher as norm.erythrocytes higher as norm.
Distinguish the followings types of erythrocytosis:Distinguish the followings types of erythrocytosis:
A. PrimaryA. Primary (independent forms of illness):(independent forms of illness): 1)1) erythremiaerythremia
[polycythemia vera, Osler's disease, Vaquez' disease],[polycythemia vera, Osler's disease, Vaquez' disease], 2)2)
«familiar»«familiar» (inherited) erythrocytosis.(inherited) erythrocytosis.
B. SecondaryB. Secondary (symptoms of other illnesses or(symptoms of other illnesses or
pathological processes):pathological processes): 1)1) absoluteabsolute,, 2)2) relativerelative..
b)b) diminishing (diminishing (anemiaanemia))

ErythremiaErythremia is a disease of tumor nature, which relative to the group ofis a disease of tumor nature, which relative to the group of
chronic hemoblastosis.chronic hemoblastosis.
The amount of erythrocytes is multiplied considerable inThe amount of erythrocytes is multiplied considerable in
peripheral blood. Reticulocytes, neutrophiles, monocytes,peripheral blood. Reticulocytes, neutrophiles, monocytes,
platelets increase also. Haemoglobin grows also. Inplatelets increase also. Haemoglobin grows also. In
marrow are signs ofmarrow are signs of tumor hyperplasia of myeloid linestumor hyperplasia of myeloid lines..
Displays:Displays:
a)a) multiplying viscosity of blood;multiplying viscosity of blood;
b)b) aggregation and agglutination of erythrocytes,aggregation and agglutination of erythrocytes,
c)c) diffuse thrombosis which leads to violation ofdiffuse thrombosis which leads to violation of
microcirculation and results in capillarotrophicmicrocirculation and results in capillarotrophic
insufficiency.insufficiency.
 •• Family erythrocytosisFamily erythrocytosis usually have inheritedusually have inherited
 character, also accompanied multiplying mass ofcharacter, also accompanied multiplying mass of
 circulating erythrocytes and volume of blood.circulating erythrocytes and volume of blood.
 •• Primary (absolute) erythrocytosisPrimary (absolute) erythrocytosis connect with increasing the amount ofconnect with increasing the amount of
stimulators of erythropoiesis (in particular, erythropoietin) and arise up:stimulators of erythropoiesis (in particular, erythropoietin) and arise up:
a)a) at chronic hypoxia of different origin;at chronic hypoxia of different origin; b)b) at the local ischemia ofat the local ischemia of
kidneys,kidneys,
c)c) some types of tumors of kidneys or liver.some types of tumors of kidneys or liver.
 •• Second (relative) erythrocytosisSecond (relative) erythrocytosis is linked with:is linked with:
a)a) hemoconcentration -hemoconcentration - diminishing of volume of plasma of blood indiminishing of volume of plasma of blood in
conditions loss of liquid (diarrhea, vomit, plasmorrhea at burn illness)conditions loss of liquid (diarrhea, vomit, plasmorrhea at burn illness)
b)b) by a redistribution of blood –by a redistribution of blood – supply exit of the deposited erythrocytessupply exit of the deposited erythrocytes
(stress, acute hypoxia, increase the amount of catecholamines).(stress, acute hypoxia, increase the amount of catecholamines).

Hematological attributes of anemias areHematological attributes of anemias are
subdivided on quantitative and qualitativesubdivided on quantitative and qualitative
N = 36-48%N = 36-48%
AnemiasAnemias are diminishing of amount of erythrocytes and/orare diminishing of amount of erythrocytes and/or
hemoglobin in unit of volume of blood with the high-qualityhemoglobin in unit of volume of blood with the high-quality
(morphologic and functional) changes of erythrocytes.(morphologic and functional) changes of erythrocytes.
Hematological attributes of anemias are subdivided onHematological attributes of anemias are subdivided on
quantitativequantitative andand qualitativequalitative..
1. The quantitative displays include:1. The quantitative displays include:
1)1) reductionreduction of the maintenance of erythrocytesof the maintenance of erythrocytes in unit ofin unit of
blood volume:blood volume:
•inin menmen isis lower than 4×10lower than 4×101212,,
•inin womenwomen isis lower than 3,5×10lower than 3,5×101212 in 1L of blood;in 1L of blood;
2)2) reduction of hemoglobinreduction of hemoglobin concentrationconcentration::
inin menmen isis lower than 130 g/llower than 130 g/l,,
• inin womenwomen isis lower than 120 g/llower than 120 g/l;;
3)3) reduction of hematocrit (Htc),reduction of hematocrit (Htc), also known as packed cell
volume (PCV) or erythrocyte volume fraction (EVF)
in men is lower than 0,43 (43%), in women is lower than 0,40 (40%);in men is lower than 0,43 (43%), in women is lower than 0,40 (40%);
4)4) change of achange of a color indexcolor index – is– is not lower thannot lower than 0,850,85 andand

2. Qualitative attributes of anemias are presence in2. Qualitative attributes of anemias are presence in
blood of:blood of:
 1)1) regenerativeregenerative, but not mature forms of erythrocytes;, but not mature forms of erythrocytes;
 2)2) degenerativedegenerative changes of erythrocytes;changes of erythrocytes;
 3) cells of3) cells of pathological regenerationpathological regeneration..
 Regenerative forms of erythrocytesRegenerative forms of erythrocytes (cells of physiological(cells of physiological
regeneration) are young immature cells of red blood sproutregeneration) are young immature cells of red blood sprout
appearance of which in peripheral blood testifies to amplificationappearance of which in peripheral blood testifies to amplification
of regeneration of cells erythroid lines in red bone marrow orof regeneration of cells erythroid lines in red bone marrow or
increase of medullar barrier permeability.increase of medullar barrier permeability.
11). Regenerative forms include:). Regenerative forms include:
a)a) reticulocytesreticulocytes are nuclear-free cells of brown-green colorare nuclear-free cells of brown-green color
with the black including (granules). In a norm their maintenance in blood is 0,2-with the black including (granules). In a norm their maintenance in blood is 0,2-
2%. During the increased regeneration of cells of red line of blood their amount2%. During the increased regeneration of cells of red line of blood their amount
can grow to 50%;can grow to 50%;
b)b) polychromatophilespolychromatophiles are nuclear-free cells with a cyanotic tint whichare nuclear-free cells with a cyanotic tint which
distinguishes them from mature erythrocytes;distinguishes them from mature erythrocytes;
c)c) normoblastsnormoblasts (acidophilic polychromatophilic, basophilic) are nuclear(acidophilic polychromatophilic, basophilic) are nuclear
precursors of erythrocytes. In a norm in peripheral blood are absent, containedprecursors of erythrocytes. In a norm in peripheral blood are absent, contained
only in red bone marrow. Sometimes, at hyperregenerative anemias, in blood itonly in red bone marrow. Sometimes, at hyperregenerative anemias, in blood it
is possible to find erythroblasts (precursors of normoblasts).is possible to find erythroblasts (precursors of normoblasts).
ReticulocytesReticulocytes

Changes of erythrocytes, which testify about inferiority of these cells, named
degenerative. Such changes are characterized by the following phenomena:
а) anisocytosis – change in the size of the erythrocytes. Occurrence of macrocytes
and microcytes;
b) poikilocytosis – change in the form of the erythrocytes. In conditions of a pathology
may occur pear-shaped, extended, sickle-cell, oval erythrocytes, and also erythrocytes
with the spherical form (spherocytes);
c) change in the staining of the erythrocytes, that depends on the contents of
hemoglobin in them. Erythrocytes, intensively colored, are named hyperchromatic, with
pale staining – hypochromatic.
d) presence of pathological inclusions. They include Jolly’s bodies are the rests of
nuclear substance; Cabot’s rings – the rests of nuclear environment having the form of ring
or eight; basophilic granularity – the rests basophilic substances of cytoplasm significative
of toxic defeat of red bone marrow.
3). Cells of pathological regeneration3). Cells of pathological regeneration occur when there is changed ofoccur when there is changed of
erythropoesis from erythroblastic to megaloblastic:erythropoesis from erythroblastic to megaloblastic:
аа) megaloblasts) megaloblasts are big cells with basophilic, polychromatophilic or acidophilicare big cells with basophilic, polychromatophilic or acidophilic
cytoplasm, containing large, located usually eccentrically nucleus with soft chromatin gridcytoplasm, containing large, located usually eccentrically nucleus with soft chromatin grid
((diameter of 12-15 mkmdiameter of 12-15 mkm),), ;;
b) megalocytesb) megalocytes – denuclearized cells which are formed during maturing of– denuclearized cells which are formed during maturing of
megaloblasts. They usually intensively stained, some the oval form, non an brighten up inmegaloblasts. They usually intensively stained, some the oval form, non an brighten up in
the central part (the central part (diameter of 10-12 mkm and morediameter of 10-12 mkm and more))..
Occurrence of the specified cells in red bone marrow and blood is typical forOccurrence of the specified cells in red bone marrow and blood is typical for
megaloblastic anemias, in particular of the B12-deficiency anemia.megaloblastic anemias, in particular of the B12-deficiency anemia.

AnisocytosisAnisocytosis
AnisocytosisAnisocytosis
MicrocytosisMicrocytosis
MacrocytosisMacrocytosis
MegalocytosisMegalocytosis

ShuistocytesShuistocytes DacriocytesDacriocytes
EliptocytesEliptocytes
SpherocytesSpherocytes
Drepa-Drepa-
nocytesnocytes
PoikilocytosisPoikilocytosis

Anemia: a condition in which the blood is deficient in red blood cells,
in hemoglobin, or in total volume –
see APLASTIC ANEMIA, HYPERCHROMIC ANEMIA, HYPOCHROMIC ANEMIA,
MEGALOBLASTIC ANEMIA, MICROCYTIC ANEMIA, PERNICIOUS ANEMIA, SICKLE-CELL
ANEMIA; compare OLIGOCYTHEMIA

Symptom checkerSymptom checker

Symptom checkerSymptom checker
ADULT SYMPTOMS
Because a low red blood cell count decreases oxygen
delivery to every tissue in the body, anemia causes many
signs and symptoms.

CLASSIFICATION OF ANEMIASCLASSIFICATION OF ANEMIAS
CriteriaCriteria Types of anemiaTypes of anemia RangeRange
I. By etiologyI. By etiology 1. Hereditary1. Hereditary
2. Acquired2. Acquired
II. By pathogenesisII. By pathogenesis
1. Posthemorrhagic1. Posthemorrhagic
2. Hemolytical2. Hemolytical
3. Diserythropoietic3. Diserythropoietic
III. By the type ofIII. By the type of
hemopoiesishemopoiesis
1. Normoblastic1. Normoblastic
2. Megaloblastic2. Megaloblastic
IV. By regeneratoryIV. By regeneratory
ability of bone marrowability of bone marrow
1. Regeneratory1. Regeneratory
2. Hyperregeneratory2. Hyperregeneratory
3. Hyporegeneratory3. Hyporegeneratory
4. Aregeneratory4. Aregeneratory
5. Aplastic5. Aplastic
0,2-1%0,2-1%
More than1%More than1%
Less than 0,2%Less than 0,2%
0%0%

CriteriaCriteria Types of anemiaTypes of anemia RangeRange
V. By color indexV. By color index
1. Normochromic1. Normochromic
2. Hyperchromic2. Hyperchromic
3. Hypochromic3. Hypochromic
0.85-1.050.85-1.05
more than 1.05more than 1.05
less than 0.85less than 0.85
VI. By the sizes ofVI. By the sizes of
erythrocyteserythrocytes
1. Normocytary1. Normocytary
2. Microcytary2. Microcytary
3. Macrocytary3. Macrocytary
4. Megalocytary4. Megalocytary
7.2-8.3 mcm7.2-8.3 mcm
less than 7.2 mcmless than 7.2 mcm
8.3-12 mcm8.3-12 mcm
more than 12-15 mcmmore than 12-15 mcm
VII. By the clinicalVII. By the clinical
coursecourse
1. Acute1. Acute
2. Chronic2. Chronic

Classifications of anemiasClassifications of anemias
Pathogenetic classification:Pathogenetic classification:
АА. Posthemorrhagic anemias:. Posthemorrhagic anemias: a)a)acute posthemorrhagic anemia;acute posthemorrhagic anemia;
b)b) chronic posthemorrhagic anemia.chronic posthemorrhagic anemia.
B.B. Hemolytic anemias:Hemolytic anemias:
1.1. Acquired:Acquired:
аа) toxic-hemolytic;) toxic-hemolytic;
b) immune;b) immune;
c) mechanical;c) mechanical;
d) acquired membranopathy.d) acquired membranopathy.
CC. Anemias as a result of erythropoiesis disorders. Anemias as a result of erythropoiesis disorders
(Dyserythropoietic).(Dyserythropoietic).
1. Deficient:1. Deficient: аа)) iron deficient;iron deficient; b)b) B12-deficient;B12-deficient; c)c) protein deficient.protein deficient.
2. Hypo-, aplastic.2. Hypo-, aplastic.
3. Metaplastic.3. Metaplastic.
4. Dysregulative.4. Dysregulative.
2.2. Hereditary:Hereditary:
аа) hereditary membranepathy;) hereditary membranepathy;
b) enzymopathy;b) enzymopathy;
c) hemoglobinopathy.c) hemoglobinopathy.

Morphology ofMorphology of
remaining erythrocytesremaining erythrocytes
Name and Mechanism of AnemiaName and Mechanism of Anemia Primary CausePrimary Cause
Macrocytic-
normochromic
anemia: large,
abnormally shaped
erythrocytes but
normal hemoglobin
concentrations
Pernicious anemia: lack of vitamin
B12 (cobalamin) for erythropoiesis;
abnormal deoxyribonucleic acid
(DNA) and ribonucleic acid (RNA)
synthesis in the erythroblast;
premature cell death
Folate deficiency anemia: lack of
folate for erythropoiesis; premature
cell death
Congenital or acquired deficiency
of intrinsic factor (IF); genetic
disorder of DNA synthesis
Dietary folate deficiency
Microcytic-
hypochromic
anemia: small,
abnormally
shaped erythrocytes
and reduced
hemoglobin
concentration
Iron deficiency anemia: lack of iron
for Hb production; insufficient Hb
Sideroblastic anemia: dysfunctional
iron uptake by erythroblasts and
defective porphyrin and heme
synthesis
Thalassemia: impaired synthesis of
α- or β-chain of hemoglobin A;
phagocytosis of abnormal
erythroblasts in the marrow
Chronic blood loss; dietary iron
deficiency, disruption of iron
metabolism or iron cycle
Congenital dysfunction of iron
metabolism in erythroblasts,
acquired dysfunction of iron
metabolism as a result of drugs
or toxins
Congenital genetic defect of
globin synthesis

MORPHOLOGIC CLASSIFICATION OFMORPHOLOGIC CLASSIFICATION OF
ANEMIASANEMIAS
Morphology ofMorphology of
remaining erythrocytesremaining erythrocytes
Name and Mechanism of AnemiaName and Mechanism of Anemia Primary CausePrimary Cause
Normocytic-
normochromic
anemia: normal size,
normal hemoglobin
concentration
Aplastic anemia: insufficient
erythropoiesis
Posthemorrhagic anemia:
blood loss
Hemolytic anemia: premature
destruction (lysis) of mature
erythrocytes in the circulation
Sickle cell anemia: abnormal
hemoglobin synthesis,
abnormal cell shape with
susceptibility to damage,
lysis, and phagocytosis
Anemia of chronic disease:
abnormally increased demand for
new erythrocytes
Depressed stem cell
proliferation resulting in bone
marrow aplasia
Acute or chronic hemorrhage
that stimulates increased
erythropoiesis, which
eventually depletes body iron
Increased fragility of
erythrocytes
Congenital dysfunction of
hemoglobin synthesis
Chronic infection or
inflammation; malignancy

The characteristic of posthemorrhagic anemiasThe characteristic of posthemorrhagic anemias
Posthemorrhagic anemiaPosthemorrhagic anemia is an anemia which develops as a result ofis an anemia which develops as a result of
hemorrhage. There arehemorrhage. There are two typestwo types of anemias of this groupof anemias of this group according to theaccording to the
character of hemorrhagecharacter of hemorrhage:: 1)1) acuteacute posthemorrhagic andposthemorrhagic and
2)2) chronicchronic posthemorrhagic anemia.posthemorrhagic anemia.
Acute posthemorrhagic anemiaAcute posthemorrhagic anemia develops as a result of the massive externaldevelops as a result of the massive external
or internal (in the cavities of human body) bleeding.or internal (in the cavities of human body) bleeding.
Etiology:Etiology: a)a) various traumas;various traumas;
b)b) bleeding from a gastro-intestinal tract [alimentary canal];bleeding from a gastro-intestinal tract [alimentary canal];
c) c) gynecological pathology and others.gynecological pathology and others.
PathogenesisPathogenesis of acute posthemorrhagic anemia consists of tree periods:of acute posthemorrhagic anemia consists of tree periods:
1)1) Reflex vascular periodReflex vascular period - develops at once after- develops at once after hemorrhagehemorrhage..
Accompanied:Accompanied:
a)a) by the spasm of vessels; by the spasm of vessels;
b)b) by the redistribution of blood;by the redistribution of blood;
c)c) exit of deposited erythrocytes.exit of deposited erythrocytes.
Analysis of peripheral bloodAnalysis of peripheral blood : Er, Hb, color index, Ht – all is a near norm.: Er, Hb, color index, Ht – all is a near norm.
2)2) Hydremic period after 2-3 daysHydremic period after 2-3 days - there is compensation of circulating- there is compensation of circulating
plasma volume:plasma volume: a)a) diminishing of excretion by kidneys;diminishing of excretion by kidneys;
b)b) increase transport intertissue liquid and lymph to a lumen of vessels.increase transport intertissue liquid and lymph to a lumen of vessels.
Analysis of peripheral bloodAnalysis of peripheral blood : Er and Hb are lesser as norm, color index, Ht: Er and Hb are lesser as norm, color index, Ht
is near the norm, may be decreasing.is near the norm, may be decreasing.
3)3) Regenerative (bone-marrow) periodRegenerative (bone-marrow) period is on 5-7 days.is on 5-7 days.
Analysis of peripheral bloodAnalysis of peripheral blood : Er, Hb, color index are decreasing. Increase: Er, Hb, color index are decreasing. Increase
amount of Ht. May appearance normoblasts.amount of Ht. May appearance normoblasts.
Complete renewal of basic indexes of red blood after acuteComplete renewal of basic indexes of red blood after acute hemorrhagehemorrhage isis

Chronic posthemorrhagic anemiaChronic posthemorrhagic anemia
Chronic posthemorrhagic anemiaChronic posthemorrhagic anemia runs across on the type ofruns across on the type of
asiderotic [iron-deficiency] anemia and develops as a resultasiderotic [iron-deficiency] anemia and develops as a result
of small, but protracted repeated hemorrhage at:of small, but protracted repeated hemorrhage at:
a)a) different diseases (ulcerous illness, pathology of kidneys,different diseases (ulcerous illness, pathology of kidneys,
breathing organs, gynaecological pathology);breathing organs, gynaecological pathology);
b)b) at pathology of vessels;at pathology of vessels;
c)c) at violations of thrombocyte-vascular and coagulativeat violations of thrombocyte-vascular and coagulative
hemostasis.hemostasis.
DuringDuring chronic posthemorrhagic anemiachronic posthemorrhagic anemia after theafter the loss of ironloss of iron
hematologic attributes of iron deficiency anemia develop:hematologic attributes of iron deficiency anemia develop:
► concentration of hemoglobin and color index decrease;concentration of hemoglobin and color index decrease;
► in blood smear there are degenerate forms of erythrocytes (micro- andin blood smear there are degenerate forms of erythrocytes (micro- and
poikilocytosis, hypochromy);poikilocytosis, hypochromy);
► quantity of erythrocytes and hematocrit may remain without changes.quantity of erythrocytes and hematocrit may remain without changes.

Petechiae of the gastric mucosaPetechiae of the gastric mucosa Ecchymosis
Metrorrhagia
Ruptured
esophageal varix

Hemolytical anemias
Acquired (secondary) Hereditary or congenital (primary)
immune toxic mechanical membranopathy
enzymopathy
Hb-pathy
alloimmune
transimmune
heteroimmune
autoimmune
1.Protein dependent
- mykrospherocytosis
- stomatocytosis
- Ovalocytosis etc.
2.Lipid dependent
- acantocytosis
1.Glycolysis
-hexokinase
- Piruvatkinase etc.
2.Pentosphosphate cycle
- G-6-PhDH etc.
3. Glutathione system
- glutathionsynthetase
- GSH-reductase
- GSH-peroxidase
1.Thalassemia
• α- thalassemia
• β -thalassemia
2.Dysorder of
globin chains
primary structure
• sickle cell
anemia etc.
membranopathy

The characteristic of hemolytic anemiasThe characteristic of hemolytic anemias
Hemolytic anemias arise up as a result of destroying (to hemolysis) of erythrocytes.Hemolytic anemias arise up as a result of destroying (to hemolysis) of erythrocytes.
► T y p e s ofT y p e s of Hemolytic anemias:Hemolytic anemias:
► I. By origin:I. By origin:
1)1) Acquired (secondary).Acquired (secondary).
2)2) Inherited or innate (primary);Inherited or innate (primary);
Intravascular hemolysisIntravascular hemolysis arises up in the vessels of bloods under the action ofarises up in the vessels of bloods under the action of
hemolytic factors which damage erythrocytes, in particular:hemolytic factors which damage erythrocytes, in particular:
a)a) physical factors (mechanical trauma, ionizing radiation, ultrasound, temperature);physical factors (mechanical trauma, ionizing radiation, ultrasound, temperature);
b)b) chemical agents (hemolytic poisons);chemical agents (hemolytic poisons);
c)c) biological factors (exciters of infectious diseases, toxins, enzymes);biological factors (exciters of infectious diseases, toxins, enzymes);
d)d) immune factors (antibodies).immune factors (antibodies).
Mechanisms of intravascular hemolysis.Mechanisms of intravascular hemolysis.
► I.I. MechanicalMechanical hemolysishemolysis - arises up as a result of mechanical destruction ofarises up as a result of mechanical destruction of
erythrocytes (at squashing [crushing] of erythrocytes in the vessels of foot).erythrocytes (at squashing [crushing] of erythrocytes in the vessels of foot).
► II.II. OsmoticOsmotic hemolysishemolysis - arises up subject to the condition, when osmotic pressure- arises up subject to the condition, when osmotic pressure
into erythrocytes more than osmotic pressure of plasma of blood → increaseinto erythrocytes more than osmotic pressure of plasma of blood → increase
moving of water inside of erythrocyte → enlargement → rapture of membrane.moving of water inside of erythrocyte → enlargement → rapture of membrane.
► IIIIII.. OxidizingOxidizing hemolysishemolysis - develops as a result of FOL and albumens of plasmatic- develops as a result of FOL and albumens of plasmatic
membrane of erythrocytes. That led to increase permeability of membrane ofmembrane of erythrocytes. That led to increase permeability of membrane of
erythrocytes → than osmotic mechanism.erythrocytes → than osmotic mechanism.
► IV.IV. DetergentDetergent hemolysishemolysis – connect with to dissolution of lipidic components of– connect with to dissolution of lipidic components of
membrane of erythrocytes by detergents. This type ofmembrane of erythrocytes by detergents. This type of hemolysishemolysis is caused byis caused by
bilious acids (bilious syndrome), liposoluble chemical agents, some toxins ofbilious acids (bilious syndrome), liposoluble chemical agents, some toxins of
bacteria (lecithinase).bacteria (lecithinase).
► V.V. Complement-dependentComplement-dependent hemolysishemolysis – conditioned destruction (by a perforation)– conditioned destruction (by a perforation)
of membrane of erythrocytes by active complement. This mechanism lies in basisof membrane of erythrocytes by active complement. This mechanism lies in basis
of immuneof immune hemolysishemolysis..
II. By the mechanisms of hemolysis:II. By the mechanisms of hemolysis:
11)) anemias with intravascular hemolysis;anemias with intravascular hemolysis;
2)2) anemias with intracellularanemias with intracellular hemolysis.hemolysis.

IntravascularIntravascular hemolysishemolysis is accompanied theis accompanied the
exit of hemoglobin from cells in plasma ofexit of hemoglobin from cells in plasma of
blood, where it connect with the albumenblood, where it connect with the albumen
(haptoglobin).(haptoglobin).
 1)1) The complex of hemoglobinThe complex of hemoglobin -haptoglobin-haptoglobin
phagocytes by macrophages and causes productionphagocytes by macrophages and causes production
and excretion erythropoietin → stimulatesand excretion erythropoietin → stimulates
erythropoiesis.erythropoiesis.
 2)2) Albuminous part of haemoglobinAlbuminous part of haemoglobin chip off tochip off to
amino acid, and from a heme will appear bilirubin whichamino acid, and from a heme will appear bilirubin which
contacts with albumins and enters into bloodcontacts with albumins and enters into blood
(unconjugated [indirect] bilirubin). Hemolytic jaundice(unconjugated [indirect] bilirubin). Hemolytic jaundice
develops.develops.
 3)3) Part of unconnected from haptoglobinPart of unconnected from haptoglobin
hemoglobin is filtered by kidneys →hemoglobin is filtered by kidneys → appearanceappearance
of hemoglobin in urines (hemoglobinuria) andof hemoglobin in urines (hemoglobinuria) and
"obstructions" of nephrons of kidney with development"obstructions" of nephrons of kidney with development
of signs of acute kidney insufficiencyof signs of acute kidney insufficiency..

IntracellularIntracellular hemolysishemolysis develops as a result ofdevelops as a result of
absorption and overcooking of erythrocytesabsorption and overcooking of erythrocytes
by macrophages.by macrophages.
 Reasons:Reasons:
a)a) appearance ofappearance of imperfect erythrocytesimperfect erythrocytes which delay in thewhich delay in the
venous sinus of spleen ("splenic filter"), where theyvenous sinus of spleen ("splenic filter"), where they
contact with macrophages;contact with macrophages;
b)b) appearance on theappearance on the surface of erythrocytessurface of erythrocytes of chemicalof chemical
groups, capable specifically to co-operate with thegroups, capable specifically to co-operate with the
receptors of macrophages;receptors of macrophages;
c)c) hypersplenismhypersplenism is increasing phagocytic activity ofis increasing phagocytic activity of
macrophagesmacrophages of spleen.of spleen.
 Increased phagocytosisIncreased phagocytosis of erythrocytes causes theof erythrocytes causes the
followings changes:followings changes:
a)a) production and excretion of erythropoietinproduction and excretion of erythropoietin
b)b) increase unconjugated [indirect] bilirubin. Hemolyticincrease unconjugated [indirect] bilirubin. Hemolytic
jaundice developsjaundice develops
c)c) proliferation of macrophages. That lead toproliferation of macrophages. That lead to
splenomegaly.splenomegaly.

MacrophageMacrophage
phagocytosesphagocytoses
Globin chainsGlobin chains amino acidsamino acids
HemeHeme
Iron (stored)Iron (stored)
ProtoporphyrinProtoporphyrin
UnconjugatedUnconjugated
bilirubinbilirubin (Jaundice)(Jaundice)
Principal features :
anemia & jaundice;
Hemoglobinemia &
hemoglobinuria are
not observed
Principal features :
Hemoglobinemia ,
hemoglobinuria,
jaundice &
hemosiderinuria

TYPES EXAMPLES
Microangiopathic
Platelet thrombi
Hemolytic uremic syndrome
Thrombotic thrombocytopenic purpura
Fibrin thrombi
Disseminated intravascular coagulation;
HELLP syndrome: H - hemolytic anemia; EL - elevated
transaminases; LP – low platelets; associated with
preeclampsia
Macroangiopathic Aortic stenosis (most common cause)
Prosthetic heart valves

I.I. Acquired hemolytic anemiasAcquired hemolytic anemias
Depending on the reasons of development is allocated the followingDepending on the reasons of development is allocated the following
kinds of acquired hemolytic anemias.kinds of acquired hemolytic anemias.
 1.        1.        ToxicToxic hemolytic anemias.hemolytic anemias.
InfectiousInfectious hemolytic anaemias.hemolytic anaemias.
 2.        2.        ImmuneImmune hemolytic anemias.hemolytic anemias.
 3.        The anemias caused by3.        The anemias caused by mechanical damagemechanical damage ofof
erythrocytes.erythrocytes.
 4.        4.        Acquired membranopathyAcquired membranopathy ..
11.. Toxic hemolytic anemiaToxic hemolytic anemia may be caused by:may be caused by:
 аа)) exogenousexogenous chemical agents: phenylhydrasin, lead, copper salts, chemical agents: phenylhydrasin, lead, copper salts,
arsenous hydrogen etc.;arsenous hydrogen etc.;
 b)b) endogenousendogenous chemical factors: bile acids, products formed at chemical factors: bile acids, products formed at
burn desease, uraemia;burn desease, uraemia;
 c) poisons of c) poisons of biological originbiological origin : snake, beer, poison of some kinds: snake, beer, poison of some kinds
of spiders, number of infectious agents, in particular, hemolyticof spiders, number of infectious agents, in particular, hemolytic
streptococcus, malarial plasmodium, toxoplasma, leishmania.streptococcus, malarial plasmodium, toxoplasma, leishmania.
Infectious hemolytic anaemiasInfectious hemolytic anaemias - caused a number of infectious- caused a number of infectious
agents, in particular, by a hemolytic streptococcus, malaria,agents, in particular, by a hemolytic streptococcus, malaria,
toxoplasmosis and others.toxoplasmosis and others.

2. Immune Hemolytic Anemias2. Immune Hemolytic Anemias
Immune hemolytic anemiasImmune hemolytic anemias arise due to participation of specific immunearise due to participation of specific immune
mechanisms.mechanisms. They are caused by interaction of humoral antibodies with theThey are caused by interaction of humoral antibodies with the
antigenes fixed on a surface of erythrocytesantigenes fixed on a surface of erythrocytes (II type of allergic reactions)(II type of allergic reactions) and dividedand divided
on:on:
 1) Isoimmune1) Isoimmune, reason of which is:, reason of which is:
 a) receipt from outside of antibodies against own erythrocytes (hemolytic illness ofa) receipt from outside of antibodies against own erythrocytes (hemolytic illness of
babies);babies);
 b) entering organism of erythrocytes against which there are antibodies in plasmab) entering organism of erythrocytes against which there are antibodies in plasma
(transfusion of incompatible is after a group or Rh of blood).(transfusion of incompatible is after a group or Rh of blood).
 2) Autoimmune2) Autoimmune - conditioned education in the organism of antibodies against own- conditioned education in the organism of antibodies against own
erythrocytes.erythrocytes. Reasons: primary changes of erythrocytes (appearance ofReasons: primary changes of erythrocytes (appearance of
autoantigen), changes in the immune system (abolition of immunological toleranceautoantigen), changes in the immune system (abolition of immunological tolerance
and appearance of "prohibitive" clones of lymphocytes).and appearance of "prohibitive" clones of lymphocytes).
 3) Heteroimmune3) Heteroimmune - arise up during fixing on the surface of erythrocytes of foreign- arise up during fixing on the surface of erythrocytes of foreign
antigens (haptens),antigens (haptens), in particular, medicinal preparations (penicillin,in particular, medicinal preparations (penicillin, sulfonamidessulfonamides) or) or
viruses.viruses.
 Hemolytic illness of newbornsHemolytic illness of newborns arises up as a result of hemolysis of erythrocytes ofarises up as a result of hemolysis of erythrocytes of
embryo and baby, caused the antibodies of mother.embryo and baby, caused the antibodies of mother. Most often meet 2th variants ofMost often meet 2th variants of
this illness: a) rhesus incompatibility and b) AB0- incompatibility.this illness: a) rhesus incompatibility and b) AB0- incompatibility.
 Rhesus-incompatibilityRhesus-incompatibility - develops in the case of pregnancy of Rh(-)mother- develops in the case of pregnancy of Rh(-)mother
Rh(+)fetus (more frequent in case of the repeated pregnancy).Rh(+)fetus (more frequent in case of the repeated pregnancy). At first there isAt first there is
immunization of mother Rh+Er of fetus, which can get in the organism of motherimmunization of mother Rh+Er of fetus, which can get in the organism of mother
during births or at the defects of placenta. In reply to the receipt of Rh+Er in theduring births or at the defects of placenta. In reply to the receipt of Rh+Er in the
organism of mother antibodies are synthesized against to the D-antigen. Theseorganism of mother antibodies are synthesized against to the D-antigen. These
antibodies (IgG) are able to penetrate through a placenta in the organism of fetusantibodies (IgG) are able to penetrate through a placenta in the organism of fetus
and to cause hemolysis of erythrocytes.and to cause hemolysis of erythrocytes.
 AB0- incompatibilityAB0- incompatibility - arises up in instances where mother have 0(I), and fetus – A(II)- arises up in instances where mother have 0(I), and fetus – A(II)
or B(III).or B(III).

TYPE OF IMMUNETYPE OF IMMUNE
HEMOLYTIC ANEMIAHEMOLYTIC ANEMIA
EXAMPLESEXAMPLES
AutoimmuneAutoimmune
Warm antibodies (IgG)
Cold antibodies (IgM)
Chronic lymphocytic leukemia
Primary or idiopathic (no underlying cause)
Secondary (e.g., SLE)
Primary or idiopathic
Secondary:
 Mycoplasma pneumoniae (anti-l antibodies)
Infection: mononucleosis (anti-I antibodies)
Warm and cold immune hemolytic anemia
Drug-induced
Drug adsorption (e.g., penicillin): IgG antibody directed
against the drug attached to the RBC membrane
Immunocomplex (e.g., quinidine): drug-IgM
immunocomplex deposits on the RBC causing
intravascular hemolysis
Autoantibody induction (e.g., α-methyldopa): drug
alters Rh antigens on RBCs causing synthesis of
autoantibodies against Rh antigens
AlloimmuneAlloimmune
Hemolytic transfusion reaction
ABO hemolytic disease of newborn
Rh hemolytic disease of newborn
SLE, systemic lupus erythematosus.

ABO Blood GroupABO Blood Group
• Anti-A and anti-B antibodies are
produced when an antigen is absent
from the cell membrane
• Type A plasma contains anti-B antibodies
• Type B plasma contains anti-A antibodies
• Type AB plasma contains no antibodies,
universal recipient
• Type O plasma contains anti-A and anti-B
antibodies, universal donor

Rh Blood GroupRh Blood Group
 Rh positiveRh positive indicates presence of antigenindicates presence of antigen
D, one of the Rh antigensD, one of the Rh antigens
 Rh negativeRh negative indicates absence of Antigenindicates absence of Antigen
DD
 Rh antigens, like A and B antigens areRh antigens, like A and B antigens are
inherited and present from birthinherited and present from birth
 Anti-D antibodies are not producedAnti-D antibodies are not produced
until after an individual is sensitizeduntil after an individual is sensitized
to antigen Dto antigen D

33.. The anaemias caused by mechanicalThe anaemias caused by mechanical
damage of erythrocytesdamage of erythrocytes
Anaemias, conditioned by mechanical damage of erythrocytes:Anaemias, conditioned by mechanical damage of erythrocytes:
1)1) Mechanical hemolysis after prosthesis of vessels or valves of heart.Mechanical hemolysis after prosthesis of vessels or valves of heart.
2)2) March hemoglobinuria – trauma of erythrocytes in capillaries of feetMarch hemoglobinuria – trauma of erythrocytes in capillaries of feet
during protracted march.during protracted march.
44.. Acquired membranopathy.Acquired membranopathy.
Acquired membranopathyAcquired membranopathy arise due to the acquired defectsarise due to the acquired defects
of erythrocytes membranes. As an example may be paroxysmal nightlyof erythrocytes membranes. As an example may be paroxysmal nightly
hemoglobinuria (hemoglobinuria ( illness of Markiafavi-Mikeliillness of Markiafavi-Mikeli ) is a somatic mutation of) is a somatic mutation of
erythropoietic cells with defects of membrane.erythropoietic cells with defects of membrane. It is considered that disordersIt is considered that disorders
of membranes are connected withof membranes are connected with changes of ratio of fat acids which are part of theirchanges of ratio of fat acids which are part of their
phospholipidsphospholipids. Erythrocytes of abnormal population get ability to fix complement and. Erythrocytes of abnormal population get ability to fix complement and
hemolyse. The erythrocytes of anomalous population obtain ability to fix complementhemolyse. The erythrocytes of anomalous population obtain ability to fix complement
which is pre-condition ofwhich is pre-condition of complement-depended hemolysiscomplement-depended hemolysis, and, and diminishing of pHdiminishing of pH
environment is a factor which provokes intravascularenvironment is a factor which provokes intravascular hemolysishemolysis. This feature explains. This feature explains
the destruction of erythrocytes is observed more frequent at night (in the night-timethe destruction of erythrocytes is observed more frequent at night (in the night-time
рНрН of blood some diminishes).of blood some diminishes).
► The picture of bloodThe picture of blood of acquired hemolytic anemias is characterized byof acquired hemolytic anemias is characterized by
reduction of erythrocytes quantity and hemoglobin. The color index inreduction of erythrocytes quantity and hemoglobin. The color index in
norm, however may be higher than 1 unit that is connected withnorm, however may be higher than 1 unit that is connected with
extraerythrocytic hemoglobin. In blood smear the significant amountextraerythrocytic hemoglobin. In blood smear the significant amount
regenerative forms of erythrocytes is found out:regenerative forms of erythrocytes is found out: reticulocytes,reticulocytes,
polychromatophils, normocytes.polychromatophils, normocytes.

ІІ.ІІ. Hereditary hemolytic anemiasHereditary hemolytic anemias
1.1. Membranopathies.Membranopathies. Defects of erythrocytes membranes are in basis of this Defects of erythrocytes membranes are in basis of this
anemias group.anemias group.
2.2. Enzymopathies.Enzymopathies. Anemias of this group are caused by disorder of erythrocytesAnemias of this group are caused by disorder of erythrocytes
enzymes .enzymes .
3.3. Hemoglobinopathies.Hemoglobinopathies. Arise after qualitative changes of hemoglobin.Arise after qualitative changes of hemoglobin.
Hereditary membranopathiesHereditary membranopathies may be caused by two groups of defects erythrocyticmay be caused by two groups of defects erythrocytic
membranes:membranes:
1.1. MembranopathiesMembranopathies, caused by disorders of membrane proteins:, caused by disorders of membrane proteins:
аа)) microspherocytic anemia Minkovsky-Shoffar’s;microspherocytic anemia Minkovsky-Shoffar’s;
b)b) ovalocytic hemolytic anemia;ovalocytic hemolytic anemia;
► Anemia Minkovsky-Shoffar’sAnemia Minkovsky-Shoffar’s is hereditary, endoerythrocyticis hereditary, endoerythrocytic
(membranopathy) hemolytic anemia with endocellular hemolysis. Type of(membranopathy) hemolytic anemia with endocellular hemolysis. Type of
inheritance – autosomal dominant. Hereditary defect mentions membraneinheritance – autosomal dominant. Hereditary defect mentions membrane
proteins of erythrocytes,proteins of erythrocytes, in particularin particular
spectrinspectrin. Therefore permeability. Therefore permeability
of erythrocytic membranes for ions sodium isof erythrocytic membranes for ions sodium is
considerably increased.considerably increased. Sodium and waterSodium and water
pass from plasma inside of erythrocytes.pass from plasma inside of erythrocytes.
At passing in the sinus of spleen theyAt passing in the sinus of spleen they
lose part of erythrocytes membrane andlose part of erythrocytes membrane and
turn into microspherocytes.turn into microspherocytes.
Life expectancy of erythrocytes decreasesLife expectancy of erythrocytes decreases
untilluntill 8-12 (10-14) days instead of 120.8-12 (10-14) days instead of 120.

Schematic representation of the red cell membrane cytoskeleton andSchematic representation of the red cell membrane cytoskeleton and
alterations leading to spherocytosis and hemolysis. Mutations weakeningalterations leading to spherocytosis and hemolysis. Mutations weakening
interactions involvinginteractions involving αα-spectrin,-spectrin, ββ-spectrin, ankyrin, band 4.2, or band 3-spectrin, ankyrin, band 4.2, or band 3
all cause the normal biconcave red cell to lose membrane fragments andall cause the normal biconcave red cell to lose membrane fragments and
adopt a spherical shape. Such spherocytic cells are less deformable thanadopt a spherical shape. Such spherocytic cells are less deformable than
normal and therefore become trapped in the splenic cords, where they arenormal and therefore become trapped in the splenic cords, where they are
phagocytosed by macrophages.phagocytosed by macrophages.

2. Hereditary enzymopathies
Hereditary enzymopathies arise due to defect of erythrocytes fermental systems:
 1) deficiency of enzymes pentose cycle.deficiency of enzymes pentose cycle. The most widespread enzymopathy is glucose-6-
phosphatedehydrogenase deficiency anemia, caused by absence or significant decrease
(reduction) of glucose-6-phosphatedehydrogenase activity;
 2) deficiency of enzymes of glycolysis.deficiency of enzymes of glycolysis. The most widespread is deficiency of
pyruvatekinase which results to disorders of energy provision Na-K-pumps of plasmatic
membranes. Erythrocytes thus turn into spherocytes which are exposed to phagocytosis
by macrophages;
 3) deficiency of enzymes of glutathion cycledeficiency of enzymes of glutathion cycle (glutathionsynthetase, glutathionreductase,
glutathionperoxidaza) results in oppression antioxidant systems of erythrocytes, barrier
properties of erythrocytic membranes to ions and osmotic hemolysis;
 4) deficiency of utilizationdeficiency of utilization АТАТP enzymes.P enzymes. An example is deficiency of albuminous
components Na-K-pump of erythrocytic membranes. Thus concentration of sodium that
results them to hemolysis is increased in a cell.
As metabolic reactions in erythrocytes are
interdependent, quite often the blockade of one of
links brings to violation of vital important functions
cells over in connection with the deficit of energy
or ionic disbalance.
On the whole it:
a) reduces viability of erythrocytes,
b) multiplies their sensitiveness to the action
of unfavorable factors which over brings to
development of hemolysis.
Hereditary hemolytic anemia.
Reticulocytoses

33.. Hemoglobinopathies - related to violations ofHemoglobinopathies - related to violations of
synthesis of molecule of haemoglobin.synthesis of molecule of haemoglobin.
Sickle-cell anemia
The molecules of haemoglobin are heterogeneous of the adult healthy man. 95 % factionThe molecules of haemoglobin are heterogeneous of the adult healthy man. 95 % faction
of haemoglobin, which is reflected a letter A, makes (“standard”) (from word "adult").of haemoglobin, which is reflected a letter A, makes (“standard”) (from word "adult").
About 3,5-4 % it is haemoglobin on faction of A2 and 1-1,5% - on haemoglobin of F (fetus).About 3,5-4 % it is haemoglobin on faction of A2 and 1-1,5% - on haemoglobin of F (fetus).
Every faction consists of 574 amino acid which form polypeptidic chains. The molecule ofEvery faction consists of 574 amino acid which form polypeptidic chains. The molecule of
haemoglobin consists of 4 polypeptidic chains which are reflected by letter of the Greekhaemoglobin consists of 4 polypeptidic chains which are reflected by letter of the Greek
alphabet:alphabet: α,β,γ,δα,β,γ,δ..
Basic forms: 1)Basic forms: 1) drepancytic anemia [sickle-cell, Herrick's, sicklemiadrepancytic anemia [sickle-cell, Herrick's, sicklemia]]
2) thalassemia.2) thalassemia.
Qualitative and quantitative changes of hemoglobin lay in basis of development ofQualitative and quantitative changes of hemoglobin lay in basis of development of
hereditaryhereditary
hemoglobinopathies.hemoglobinopathies.
The most widespreadThe most widespread
clinical form isclinical form is sickle-cellsickle-cell
anemiaanemia at which inat which in
β-chain of a molecule ofβ-chain of a molecule of
hemoglobin glutaminehemoglobin glutamine
acid is replaced onacid is replaced on
valine (HbS).valine (HbS).

Spleen in sickle cell anemia (low power). Red pulp cords and sinusoids are markedly congested; between
the congested areas, pale areas of fibrosis resulting from ischemic damage are evident. B, Under high
power, splenic sinusoids are dilated and filled with sickled red cells. (Courtesy of Dr. Darren Wirthwein,
Department of Pathology, University of Texas Southwestern Medical School, Dallas, TX.)
Pathophysiology of sickle cell anemiaPathophysiology of sickle cell anemia

SCD is
characterized by its
presentation:
1- Vaso-occlusive
crises
2- Sequestration
crises
3- Hemolytic crises
4- Aplasic crises
Crewcut appearance

Thalassemias.Thalassemias. In contrast to sickle cell anemia, the thalassemias resultIn contrast to sickle cell anemia, the thalassemias result
from absent or defective synthesis of the α or thefrom absent or defective synthesis of the α or the β chains of hemoglobin. Theβ chains of hemoglobin. The
β-thalassemias represent a defectβ-thalassemias represent a defect in β-chain synthesisin β-chain synthesis, and the, and the α-thalassemiasα-thalassemias
represent a defectrepresent a defect in α-chain synthesisin α-chain synthesis. The defect is inherited as a mendelian. The defect is inherited as a mendelian
trait, and a person may be heterozygous for the trait and havetrait, and a person may be heterozygous for the trait and have a mild form ofa mild form of
the disease or be homozygous and have thethe disease or be homozygous and have the severe form of the disease. Likesevere form of the disease. Like
sickle cell anemia, the thalassemiassickle cell anemia, the thalassemias occur with high degree of frequency inoccur with high degree of frequency in
certain populations.certain populations. TheThe β-thalassemiasβ-thalassemias, sometimes called, sometimes called Cooley’s anemiaCooley’s anemia oror
Mediterranean anemia,Mediterranean anemia, are most common in the Mediterraneanare most common in the Mediterranean populations ofpopulations of
southern Italy and Greece, and thesouthern Italy and Greece, and the α-thalassemias are most common amongα-thalassemias are most common among
Asians. Both α- andAsians. Both α- and β-thalassemias are common in Africans and blackβ-thalassemias are common in Africans and black
Americans.Americans.
Thalassemia
HemoglobinHemoglobin PolypePolype
ptidesptides
HemoglobinHemoglobin
A1 (Adult)A1 (Adult)
22αα 22ββ
A2A2
22αα 22δδ
F (Fetal)F (Fetal)
22αα 22γγ

TypeType HbHb Hb-Hb-
electrophoresiselectrophoresis
GenotypeGenotype Clinical SyndromeClinical Syndrome
α-THALASSAEMIAS
1. Hydrops
foetalis
3-10 gm/dl
Hb Barts (γ4)
(100%)
Deletion of four
γ-genes
Fatal in utero or in early
infancy
2. Hb-H disease 2-12 gm/dl
HbF (10%), HbH
(2-4%)
Deletion of three
α-genes
Haemolytic anaemia
α-Thalassaemia
trait
10-14 gm/dl Almost normal
Deletion of two
α-genes
Microcytic hypochromic
blood picture but no
anaemia
β-THALASSAEMIAS
1. β-
Thalassaemia
major
< 5 gm/dl
HbA (0-50%),
HbF(50-98%)
βthal/βthal
Severe congenital
haemolytic anaemia,
requires blood
transfusions
2. β-
Thalassaemia
intermedia
5-10 gm/dl Variable
Multiple
mechanisms
Severe anaemia, but
regular blood
transfusions not required
β-Thalassaemia
minor
10-12 gm/dl
HbA2 (4-9%),
HbF (1-5%)
βA/βthal Usually asymptomatic

2-The clinically significant haemoglobinopathies
are listed in following Table

ANEMIAANEMIA PATHOGENESISPATHOGENESIS DISCUSSIONDISCUSSION
Reticulocytosis < 3%
Acute blood loss Loss of whole blood
Initial Hb and Hct normal
Infusion of normal saline
uncovers anemia
Signs of volume depletion
(c,g„ absolute neutrophilic
leukocytosis) commonly
present; positive tilt test
Early iron deficiency
Decreased iron
stores
Normocytic before
microcytic
Iron studies abnormal
(  serum ferritin)
Early ACD
Iron trapped in
macrophages by
hepcidin
Normocytic before
microcytic
Iron studies abnormal
(  serum ferritin)
Aplastic anemia
Suppression or
deficiency of
myeloid stem cells
Pancytopenia
Hypocellular marrow
Chronic renal failure Deficiency of EPO Presence of burr cells

Reticulocytosis ≥ 3%
Hereditary
spherocytosis
AD disorder
Defect in ankyrin
Extravascular hemolysis
Increased osmotic fragility
Treat with splenectomy
Hereditary
elliptocytosis
AD disorder
Defect in spectrin and band 4.1
Elliptocytes > 25%
Paroxysmal nocturnal
hemoglobinuria
Loss of anchor for DAF in myeloid
stem cell
Complement destruction of
hematopoietic cells
Intravascular hemolysis
Defect on hematopoietic cells
Pancytopenia
Positive sugar water test (screen)
and acidified
serum test (confirmatory test)
Sickle cell anemia
AR disorder
Valine substitution for Glutamic
acid β-globin chain
HbAS: HbA 55-60%;
HbS 40-45%
HbSS: HbS 90-95%;
HbF 5-10%; no HbA
C6PD deficiency
XR disorder
Deficiency GSH causes oxidant
damage to Hb and RBC membrane
Heinz body preparation: screen
during active hemolysis
Enzyme assay: confirmatory test
when hemolysis subsides

Pyruvate kinase
deficiency
AR disease
 ATP synthesis
 2,3.BPG right shifts OBC
Dehydrated RBCs with
thorny projections
(echinocytes)
Acute blood loss Loss of whole blood
Reticulocytosis 5-7 days
 Hb, Hct, RBC count
Warm AIHA IgG with or without C3b
Positive direct Coombs' test
SLE most common cause
Cold AIHA IgM with C3b
Extravascular or Intravascular
hemolysis
Association with
Mycoplasma pneumoniae;
EBV
Drug-induced
Immune hemolytic
anemia
Drug hapten; penicillin
Immunocomplex: quinidine
Autoantibody: methyldopa

Alloimmune
hemolytic
anemia
Antibodies against foreign
RBC
antigens
Hemolylic transfusion
reaction
ABO and Rh HDN
Micro- and
macroangiopathic
hemolytic anemia
Mechanical destruction of
RBCs with formation of
schistocytes
Calcific aortic stenosis most
common cause
Chronic hemoglobinuria
causes iron deficiency
Malaria Transmitted by female
Anopheles mosquito
Rupture of RBCs
corresponds with fever
ACD, anemia of chronic disease; AD, autosomal dominant; AIHA, autoimmune hemolytic
anemia; AR, autosomal recessive; ATP adenosine triphosphate: BPG,
bisphosphoglycerate; DAF, decay accelerating factor; EBV, Epstein-Barr virus; EPO,
erythropoietin; G6PD, glucose-6-phosphate dehydrogenase; GSH, glutathione; Hb,
hemoglobin; HbAS, sickle cell trait; HbSS. homozygous for sickle cell disease; Hct,
hematocrit; OBC, oxygen-binding curve; Rh HDN. Rhesus hemolytic disease of the
newborn; SLE, systemic lupus erythematosus: XR, X-linked recessive

The reasons of anemias with disorders of erythropoiesis mayThe reasons of anemias with disorders of erythropoiesis may
be:be:
► 1)1) disorder of formation of erythrocytesdisorder of formation of erythrocytes : deficiency of: deficiency of
hemopoietic cells due to their damage or replacement,hemopoietic cells due to their damage or replacement,
disorder of cells maturation of hemopoiesis (disorders of DNAdisorder of cells maturation of hemopoiesis (disorders of DNA
resynthesis), defects of erythrocytes maturing and theirresynthesis), defects of erythrocytes maturing and their
output(exit) into blood flow (deficiency erythropoiesis);output(exit) into blood flow (deficiency erythropoiesis);
► 2)2) disorders of hemoglobin synthesisdisorders of hemoglobin synthesis : deficiency of: deficiency of
iron, disorder of synthesis porphyrines (hereditary disordersiron, disorder of synthesis porphyrines (hereditary disorders
of enzymes, poisonings by lead, deficiency of vitamin B6,of enzymes, poisonings by lead, deficiency of vitamin B6,
frustration of albuminous chains synthesis of hemoglobinfrustration of albuminous chains synthesis of hemoglobin
molecules).molecules).
Anemias as a resultAnemias as a result
of erythropoiesis disorderof erythropoiesis disorder

Deficiency anemiasDeficiency anemiasIrondeficiency anemiaIrondeficiency anemia arises as a result of:arises as a result of:
1)1) Insufficient receipt of ironInsufficient receipt of iron with organism:with organism:
 аа) an) an alimentary anemiaalimentary anemia in the infants (feeding with cow or goat milk);in the infants (feeding with cow or goat milk);
 b)b) disorder of iron absorbtiondisorder of iron absorbtion (resection of stomach, intestines, gastritises, enteritis);(resection of stomach, intestines, gastritises, enteritis);
2)2) HemorrhageHemorrhage. It is the most widespread reason of iron deficiency in organism;. It is the most widespread reason of iron deficiency in organism;
3)3) Strengthened use of ironStrengthened use of iron – pregnancy, lactation.– pregnancy, lactation.
Insufficiency of iron in organism results in disorder of ferriferous proteins synthesis andInsufficiency of iron in organism results in disorder of ferriferous proteins synthesis and
consequently to the following disorders:consequently to the following disorders:
 1) disorder of heme synthesis,1) disorder of heme synthesis,
 2) disorder of cytochromes formation and tissue hypoxia,2) disorder of cytochromes formation and tissue hypoxia,
 3) decrease of catalase activity hemolysis of erythrocytes and development of3) decrease of catalase activity hemolysis of erythrocytes and development of
dystrophic changes in cells,dystrophic changes in cells,
 4) reduction of synthesis myoglobin and decrease (reduction) of resistance to hypoxia.4) reduction of synthesis myoglobin and decrease (reduction) of resistance to hypoxia.
Decrease of hemoglobin concentration in peripheral blood andDecrease of hemoglobin concentration in peripheral blood and reduction of color indexreduction of color index
are typical for iron deficiency anemia. The quantity of erythrocytes decreases a little.are typical for iron deficiency anemia. The quantity of erythrocytes decreases a little.
In blood smear the quantity regenerative forms of erythrocytes (reticulocytes,In blood smear the quantity regenerative forms of erythrocytes (reticulocytes,
polychromatophils) decreases and their degenerative forms (anulocytes, microcytosis,polychromatophils) decreases and their degenerative forms (anulocytes, microcytosis,
poikilocytosis).poikilocytosis).
Iron refractory anemiaIron refractory anemia results from disorder of iron inclusion in heme at decrease ofresults from disorder of iron inclusion in heme at decrease of
enzymes activity, which catalase synthesis of porphyrines and heme. The reasons mayenzymes activity, which catalase synthesis of porphyrines and heme. The reasons may
be:be:
 1) genetic down turn of decarboxylase activity of coproporphyrinogen – the enzyme1) genetic down turn of decarboxylase activity of coproporphyrinogen – the enzyme
providing one of final stages of heme synthesis (it is inherited recessively, is linked toproviding one of final stages of heme synthesis (it is inherited recessively, is linked to
the X-chromosome);the X-chromosome);
 2) reduction of the maintenance pyridoxalphosphate – the active form of vitamin B6 and2) reduction of the maintenance pyridoxalphosphate – the active form of vitamin B6 and
as a result of this iron is not taken from mitochondria of erythroblasts and is not includedas a result of this iron is not taken from mitochondria of erythroblasts and is not included
in heme;in heme;
 3) lead blockade of sulfhydryl groups of the enzymes participating in synthesis of heme.3) lead blockade of sulfhydryl groups of the enzymes participating in synthesis of heme.

Iron Deficiency AnaemiaIron Deficiency Anaemia
 Symptoms:Symptoms:
 weakness, fatigue, or lack of stamina
 shortness of breath
 headache – frontal
 difficulty concentrating
 irritability, apathy
 dizziness
 pale skin
 craving substances that are not food (pica)
 Signs:Signs:
 rapid heart beat
 brittle nails (also spoon nails)
 cracked lips (angular stomatitis)
 smooth sore tongue (Glossitis)
 decreased appetite (especially in children)
 decreased rate of growth
 delay in skills like walking, talking ..
and relatively later 
Blue scleraBlue sclera

Glossitis. Tongue
of individual with
iron deficiency
anemia has bald,
fissured
appearance
caused by loss of
papillae and
flattening.
Koilonychia.
The nails are
concave,
ridged,
and brittle.
A siderocyte containing Pappenheimer bodies, a
normal sideroblast and a ring sideroblast.

CLASSIFICATIONCLASSIFICATION CAUSESCAUSES DISCUSSIONDISCUSSION
Blood lossBlood loss
Gastrointestinal loss
Menorrhagia
Meckel's diverticulum (older children)
PUD (most common cause in adult men)
Gaslritis (e.g., NSAID)
Hookworm infestation
Polyps/colorectal cancer (most common cause in
adults > 50years of age); positive stool for blood
Most common cause in women < 50 years of age
IncreasedIncreased
utilizationutilization
Pregnancy/lactation
Infants/children
Daily iron requirement in pregnancy is 3.4 mg and
2,5-3 mg in lactation
Net loss of 500 mg of iron if not on iron supplements
Iron required for tissue growth and expansion of
blood volume
DecreasedDecreased
intakeintake
Prematurity
Infants/children
Elderly
Loss of iron each day fetus is not in utero
Blood loss from phlebotomy
Most common cause of iron deficiency in young
children
Restricted diets with little meat (lack of hemic iron)
DecreasedDecreased
absorptionabsorption
Celiac sprue
Post-gastric surgery
Absence of villous surface In the duodenum
Rapid transit; absent acid, which helps in iron
reabsorption
IntravascularIntravascular
hemolysishemolysis
Microangiopathic
hemolytic anemia
PNH
Chronic loss of Hb in urine leads to iron deficiency

Iron deficiency anemiaIron deficiency anemia
Normal tongue
Iron deficiency anemia: bald tongue with
atrophied papillae and angular inflammation

2.76
Iron
deficiency
anemia with
bald tongue
and angular
stomatitis
2.77
Iron and vitamin B
12 deficiency:
glossitis with
angular stomatitis
2.78
Undernutrition with
multiple vitamin
and iron deficiency:
bald, fiery tongue
2.79
Peutz-Jeghers
syndrome:
mucosal lentigines
and pigmentation

TESTTEST
IRONIRON
DEFICIENCYDEFICIENCY
ANEMIA OFANEMIA OF
CHRONICCHRONIC
DISEASEDISEASE
αα-THAL/-THAL/ββ--
THALTHAL
MINORMINOR
LEADLEAD
POISONINGPOISONING
MCV    
Serum iron   Normal 
TIBC   Normal 
Percent
saturation
  Normal 
Serum ferritin   Normal 
RDW  Normal Normal Normal
RBC count    
Hb
electrophoresis
Normal
Normal Α-Thal. trait:
normal
_
Ringed
sideroblasts
None None None Present
Coarse
basophilic
stippling
None None None Present
Hb – hemoglobin; MCV - mean corpuscular volume; RDW - red blood cell distribution width;
Thal – thalassemia; TIBC - total iron-binding capacity

B12-(folate)deficiency anemiaB12-(folate)deficiency anemiaThe reasons of vitamin B12 insufficiency in an organism:The reasons of vitamin B12 insufficiency in an organism:
1.1. Exogenous (alimentary) insufficiency –Exogenous (alimentary) insufficiency – insufficient receipt in an organism with foodinsufficient receipt in an organism with food
stuffs. May develop in small children as a result feeding goat milk or dry dairy mixes.stuffs. May develop in small children as a result feeding goat milk or dry dairy mixes.
2.2. Disorders of vitamin B12 absorbtion:Disorders of vitamin B12 absorbtion:
аа)) disorder of formation and secretion of gastromucoprotein (internal Castle’s factor).disorder of formation and secretion of gastromucoprotein (internal Castle’s factor). It happens atIt happens at
hereditary caused disorders, an atrophy of a mucous membrane of stomach, autoimmune damages ofhereditary caused disorders, an atrophy of a mucous membrane of stomach, autoimmune damages of
parietal cells of stomach mucous, due to gastrectomy or removal of more than two thirds of stomach;parietal cells of stomach mucous, due to gastrectomy or removal of more than two thirds of stomach;
b)b) disorder of small intestine function:disorder of small intestine function: chronic diarrheas (celiac disease, sprue), resection of the bigchronic diarrheas (celiac disease, sprue), resection of the big
parts of intestine;parts of intestine;
c)c) competitive use of vitamin B12 by helmints and microflora of intestines (competitive use of vitamin B12 by helmints and microflora of intestines (diphyllobothriasisdiphyllobothriasis).).
3.3. Disorder of transcobalamines formation in liver.Disorder of transcobalamines formation in liver.
4.4. Disorder of vitamin B12 deposition in liver.Disorder of vitamin B12 deposition in liver.
5.5. Increased use of vitamin B12 (at pregnancy).Increased use of vitamin B12 (at pregnancy).
Deficiency of vitamin B12 results in development of the frustration connected with formation disorderDeficiency of vitamin B12 results in development of the frustration connected with formation disorder
of its two coenzyme forms: methylcobalamine and 5-desoxyadenosilcobalamine. In a red bone marrowof its two coenzyme forms: methylcobalamine and 5-desoxyadenosilcobalamine. In a red bone marrow
erythroblastic type of hemopoiesis is replaced on megaloblastic, inefficient erythropoesis increases, lifeerythroblastic type of hemopoiesis is replaced on megaloblastic, inefficient erythropoesis increases, life
expectancy of erythrocytes is shortened. The anemia with the expressed degenerate shifts not only in aexpectancy of erythrocytes is shortened. The anemia with the expressed degenerate shifts not only in a
bone marrow, but also in blood develops. Changes in cells of myeloid and megacariocytic lines arebone marrow, but also in blood develops. Changes in cells of myeloid and megacariocytic lines are
shown by reduction of leukocytes quantity and thrombocytes, expressed by atypia of cells (hugeshown by reduction of leukocytes quantity and thrombocytes, expressed by atypia of cells (huge
neutrophils, megacaryocytes with degenerative changes in a nucleus). Occurrence of atypic mitosis andneutrophils, megacaryocytes with degenerative changes in a nucleus). Occurrence of atypic mitosis and
huge cells of epithelium digestive tract results in development of inflammatory-atrophic processes inhuge cells of epithelium digestive tract results in development of inflammatory-atrophic processes in
mucous membrane of its parts (mucous membrane of its parts (glossitis, stomatitis, esophagitis, achylic gastritis, enteritisglossitis, stomatitis, esophagitis, achylic gastritis, enteritis).).
As a result of theAs a result of the second coenzyme forms insufficiencysecond coenzyme forms insufficiency of vitamin B12 –of vitamin B12 – 5-desoxyadenosilcobalamine5-desoxyadenosilcobalamine
in organismin organism propionic and methylmalonic acids, which are toxic for nervous cellspropionic and methylmalonic acids, which are toxic for nervous cells. Besides fatty acids. Besides fatty acids
with the changed structure are synthesised in nervous fibres results in disorder formation of myeline andwith the changed structure are synthesised in nervous fibres results in disorder formation of myeline and
to damage of axones.to damage of axones. The degeneration of back and lateral columns of a spinal cord developsThe degeneration of back and lateral columns of a spinal cord develops
((funicular myelosisfunicular myelosis), cranial and peripheral nerves are damaged.), cranial and peripheral nerves are damaged.
TheThe color index is increasedcolor index is increased, that is explained by the big saturation of cells by, that is explained by the big saturation of cells by
hemoglobin. The phenomenon of degeneration erythrocytes is typical: anisocytosishemoglobin. The phenomenon of degeneration erythrocytes is typical: anisocytosis
(macrocytosis), poikilocytosis (occurrence of the oval form cells), pathological inclusions(macrocytosis), poikilocytosis (occurrence of the oval form cells), pathological inclusions
(Jolly’s bodies, Cabot’s rings).(Jolly’s bodies, Cabot’s rings).

Megaloblastic anemiaMegaloblastic anemia

CLASSIFICATIO
N
CAUSES DISCUSSION
Decreased
intake
Pure vegan diet
Malnutrition
Breast-fed infants of pure vegans may
develop deficiency
May occur in elderly patients
Malabsorption
 Intrinsic factor
 Gastric acid
 Intestinal
reabsorption
Autoimmune destruction of parietal cells
(i.e., pernicious anemia)
Cannot activate pepsinogen to release
vitamin B12
Crohn's disease or celiac disease involving
terminal ileum (destruction of absorptive
cells)
Bacterial overgrowth (bacterial utilization of
available vitamin B12)
Fish tapeworm
Chronic pancreatitis (cannot cleave off R-
binder)Increased
utilization
Pregnancy/lactation Deficiency is more likely in a pure vegan

Pathogenesis of vitamin BPathogenesis of vitamin B1212 deficiency anaemiadeficiency anaemia
Deficit of vitamin B12
Deficit of methylcobalamin – coenzyme form of vitamin B12
Deficit of tetrahydrofolic acid
Deficit of 5,10-methyltetrahydrofolic acid (coenzyme type
of folic aside)
Deficit of thymidynphosphate
Delay of DNA synthesis
Inhibition of erythropoiesis

CLASSIFICATION CAUSES DISCUSSION
Decreased intake
Malnutrition
Infants/elderly
Chronic alcoholics
Goat milk
Decreased intake most common
cause of folate deficiency
Malabsorption
Celiac disease
Bacterial overgrowth
Deficiency usually occurs in
association with other
vitamin deficiencies (fat and water
soluble)
Drug inhibition
5-Fluorouracil
Methotrexate,
trimethoprim-
sulfamethoxazole
Phenytoin
Oral contraceptives, alcohol
Inhibits thymidylate synthase
Inhibit dihydrofolate reductase
Inhibits Intestinal conjugase
Inhibit uptake of monoglutamate in
jejunum
Alcohol also inhibits the release of
folate from the liver
Increased
utilization
Pregnancy/lactation
Disseminated malignancy
Severe hemolytic anemia
Increased utilization of folate in
DNA synthesis

Occurrence in blood and red bone marrow of
pathological regeneration cells – megaloblasts,
megalocytes is the most typical feature of this anemia.
B12-(folate)deficiency anemia. Blood
B12-(folate)deficiency anemia. Red bone marrow

Such syndromes are observed forSuch syndromes are observed for
B12-(folate)deficiency anemia:B12-(folate)deficiency anemia:
 1. Hematologic syndrome:1. Hematologic syndrome:
аа) anemia; b) leukopenia; c) thrombocytopenia.) anemia; b) leukopenia; c) thrombocytopenia.
 2. Damages of the digestive tract which are2. Damages of the digestive tract which are
shown by development inflammatory –atrophicshown by development inflammatory –atrophic
changes in mucous membrane.changes in mucous membrane.
 3. Damages of the central and peripheral3. Damages of the central and peripheral
nervous system: funicular myelosis, degenerationnervous system: funicular myelosis, degeneration
of peripheral nerves.of peripheral nerves.

LABORATORY/LABORATORY/
CLINICAL FINDINGCLINICAL FINDING
PERNICIOUPERNICIOU
S ANEMIAS ANEMIA
OTHER VITAMINOTHER VITAMIN
B12B12
DEFICIENCIESDEFICIENCIES
FOLATEFOLATE
DEFICIENCYDEFICIENCY
Achlorhydria Present Absent Absent
Autoantibodies Present Absent Absent
Chronic atrophic
gastritis
Present Absent Absent
Gastric carcinoma
risk
 None None
Hypersegmented
neutrophils
Present Present Present
Mean corpuscular
volume
  
Neurologic disease Present Present None
Pancytopenia Present Present Present
Plasma homocysteine   
Serum gastrin level  Normal Normal

Hypoplastic anemiasHypoplastic anemias
 Hypoplastic (Hypoplastic (ааplastic)plastic) anemia is characterized byanemia is characterized by
oppression hemopoietic functions of red bone marrowoppression hemopoietic functions of red bone marrow
and shown by insufficient formation of erythrocytes,and shown by insufficient formation of erythrocytes,
granulocytes and throrombocytes or only erythrocytes.granulocytes and throrombocytes or only erythrocytes.
 There are acquired and is hereditary caused forms ofThere are acquired and is hereditary caused forms of
hypoplastic anemia. The type of hereditary ishypoplastic anemia. The type of hereditary is
autosomal-recessive type of inheritance concerns.autosomal-recessive type of inheritance concerns.
 TheThe acquired formsacquired forms may be caused by the followingmay be caused by the following
reasons:reasons:
1)1) physical factorsphysical factors (ionizing radiation);(ionizing radiation);
2)2) chemical agentschemical agents (benzene, lead, steams of mercury,(benzene, lead, steams of mercury,
medical products: cytostatic agents, chloramphenicol,medical products: cytostatic agents, chloramphenicol,
sulfanilamids);sulfanilamids);
3)3) biological factorsbiological factors (virus of hepatites).(virus of hepatites).
 Essential formsEssential forms of anemia, which reason is notof anemia, which reason is not
established belongs to acquired anemias.established belongs to acquired anemias.

CLASSIFICATlON EXAMPLES AND DISCUSSION
Idiopathic Approximately 50-70% of cases are idiopathic
Drugs
 Most common known cause of aplastic anemia
 Dose-related causes are usually reversible (e.g.,
alkylating agents)
 Idiosyncratic reactions are frequently irreversible
(e.g., chloramphenicol)
Chemical agents Toxic chemicals in industry and agriculture (e.g.,
benzene, insecticides-DDT, parathion)
Infection
May involve all hematopoietic cell lines (pancytopenia)
or erythroid cell line alone (pure RBC aplasia)
Examples—EBV; CMV; parvovirus; non-A, non-B
hepatitis, HCV
Physical agents Whole-body ionizing radiation (therapeutic or nuclear
accident)
Miscellaneous Thymoma (may be associated with pure RBC aplasia)
Paroxysmal nocturnal hemoglobinuria
CMV, cytomegalovirus; EBV, Epstein-Barr virus; HCV, hepatitis C.

Hypoplastic anemias
 Reduction of erythrocytes maintenance and concentration of
hemoglobin when color index is within the limits of norm is
characterised for the peacture of peripheral blood. Regenerative
of erythrocytes (reticulocytes, polychromatophils) as a role are
not found in a blood smear.The maintenance of granulocytes
(especially neutrophils) and thrombocytes decreases.The
quantity of lymphocytes may remain without changes.
 In a red bone marrow the quantity of hemopoietic cells
decreases with increase of maintenance of fatty tissue (picture of
devastation red bone marrow). Because of iron is not used for
the purposes hemopoiesis, its maintenance in erythroblasts and
extracelulary is increased.
 Appearence of hypoplastic anemias are connected with
reduction of three kinds formation of form blood elements:
erythrocytes, granulocytes and thrombocytes. It results in
development of the following clinical syndromes:
1. The anemia and connected to it hypoxic syndrome.
2. Hemorrhagic syndrome.
3.The inflammatory processes caused by infectious agents
(pneumonia, otitis, pyelitis etc.).

Metaplastic anemiasMetaplastic anemias
TheThe metaplastic anemiametaplastic anemia is the result of hemopoieticis the result of hemopoietic
tissue replacement on tissues: leucosis cells, connectivetissue replacement on tissues: leucosis cells, connective
tissue (fibrosis), metastasises of tumor.tissue (fibrosis), metastasises of tumor.
Dysregulative anemiasDysregulative anemias
Dysregulative anemiasDysregulative anemias arise as a result ofarise as a result of
erythropoiesis regulation disorders (infringement of ratioerythropoiesis regulation disorders (infringement of ratio
between erythropoietins and inhibitors of erythropoiesis duebetween erythropoietins and inhibitors of erythropoiesis due
to insufficiency of kidneys, damage of strome elements –to insufficiency of kidneys, damage of strome elements –
microenvironments of erythropoietins cells, hypofunction ofmicroenvironments of erythropoietins cells, hypofunction of
hypophysis, thyroid gland).hypophysis, thyroid gland).

1- Pallor1- Pallor  looked forlooked for
 in the skin in general, at palms, morein the skin in general, at palms, more
precise in the palmar creasesprecise in the palmar creases
 at the conjunctiva of the eyesat the conjunctiva of the eyes
 Mouth mucosaMouth mucosa
 nail bedsnail beds
2- Jaundice as in Haemolysis2- Jaundice as in Haemolysis  Skin, Eye Sclera, MucousSkin, Eye Sclera, Mucous
MembraneMembrane
3- Hyperpigmentation, café au-lait spots3- Hyperpigmentation, café au-lait spots  Fanconi AnaemiaFanconi Anaemia

1- Frontal Bossing1- Frontal Bossing  ThalassaemiaThalassaemia
2- Microcephaly2- Microcephaly  Fanconi AnaemiaFanconi Anaemia

1- Glossitis1- Glossitis  Vit. B12 deficiency, Fe deficiencyVit. B12 deficiency, Fe deficiency
2- Angular stomatitis2- Angular stomatitis  Fe deficiency anemiaFe deficiency anemia

Chest:Chest:
Chest PainChest Pain
MurmerMurmer  Severe anemia, EndocarditisSevere anemia, Endocarditis
Rapid BreathingRapid Breathing
Rapid Heart RateRapid Heart Rate

Abdomen:  Abdominal pain
 Hepatomegaly, Splenomegaly

Extremities:Extremities:
 brittle nails, Spoon Nailsbrittle nails, Spoon Nails 
Iron deficiencyIron deficiency

Nerves:Nerves:  Ataxia, PeripheralAtaxia, Peripheral
neuropathy (Vitamin B12)neuropathy (Vitamin B12)

Neuropathy:Neuropathy:
(A)erythema(A)erythema
chronicumchronicum
migransmigrans
(Lyme(Lyme
disease),disease),
(B)Reynaud's(B)Reynaud's
phenome-phenome-
non,non,
(C) purpuric(C) purpuric
rash (eg,rash (eg,
vasculitis)vasculitis)
andand
(D)depigmen-(D)depigmen-
tationtation
(leprosy).(leprosy).

General:General:
 Poor weight gain or Weight lossPoor weight gain or Weight loss
 Short StatureShort Stature  ThalassaemiaThalassaemia
 Sickle cell diseaseSickle cell disease

1. General and clinical pathophysiology/ Edited by Anatoliy V. Kubyshkin –
Vinnytsia: Nova Knuha Publishers – 2011.
2. Robbins and Cotran Pathologic Basis of Disease 8th
edition / Kumar, Abbas, Fauto
2006. – Chapter 12.
3. Essentials of Pathophysiology: Concepts of Altered Health States (Lippincott
Williams & Wilkins), Trade paperback (2003) / Carol Mattson Porth, Kathryn J
Gaspard. – Chapter 13.
4. Russell J. Greene. Pathology and Therapeutics for Pharmacists. A basis for clinical
pharmacy practice / Russell J. Greene, Norman D. Harris // IL 60030-7820, 3rd
edition, USA. – 2008. – Chapters 11.
5. Corwin Elizabeth J. Handbook of Pathophysiology / Corwin Elizabeth J. – 3th
edition. Copyright В. – Lippincott Williams & Wilkins – 2008. – Chapters 12.
6. Copstead Lee-Ellen C. Pathophysiology / Lee-Ellen C. Copstead, Jacquelyn L.
Banasik // Elsevier Inc, 4th edition. – 2010.
7. Pathophysiology, Concepts of Altered Health States, Carol Mattson Porth, Glenn
Matfin. – New York, Milwaukee. – 2009.
8. Silbernagl S. Color Atlas of Pathophysiology / S. Silbernagl, F. Lang // Thieme.
Stuttgart. New York. – 2000.
9. Gozhenko A.I. Pathophysiology / A.I. Gozhenko, I.P. Gurcalova // Study guide for
medical students and practitioners. Edited by prof. Zaporozan, OSMU. – Odessa.
– 2005.

Anaemias

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Viewers also liked

Viewers also liked (6)

Similar to Anaemias

Similar to Anaemias (20)

More from Ivano-Frankivsk National Medical University

More from Ivano-Frankivsk National Medical University (20)

Recently uploaded

Recently uploaded (20)

Anaemias

Editor's Notes