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formation
1-Intrautrine life:
Blood cells are formed in the liver and
SITES
STEPS
Blood
formation
3-Adulthood
The active bone morrow will be:
Restricted to axial skeleton : flat bones,
SITES
Pleuri-potent cells
Blood
formation
SITES
BFU-E
BFU-E
CFU-E
CFU-E
Proerythroblast
Proerythroblast
Basophilic
Basophilic
erythroblast
erythroblast
Polychromatic
Polychromatic
erythroblast
erythroblast
Othrochromatic
Othrochromatic
erythroblast
erythroblast
Reticulocytes
Reticulocytes
CFU-G
CFU-G
Myleloblast
Myleloblast
Promyelocyte
Promyelocyte
Myelocyte
Myelocyte
Metamgelocyte
Metamgelocyte
Juvenil
Juvenil
Granulocyte
Granulocyte
(PML)
(PML)
CFU-Mega
CFU-Mega
Megakaryoblast
Megakaryoblast
Megadaryocyte
Megadaryocyte
Platelet
Platelet
STEPS
Erthrocytopoiesis
Granulocytopoiesis
Thrambocytopoiesis
Blood
formation
STEPS
Blood
formation
Blood Constituents
Organelles (formed elements):
RBCs
WBCs
Thrombocytes
Fluid components: plasma in which the above
elements
fibrinogen.
are
suspended
and
contain
Blood
formation
Erythrocytopoiesis
Normal erythrocytopoiesis depends on:
Healthy
BM:
normal
stem
cells
and
architecture.
Elements
essential
for
erythropoies:
(Maturation factors )
Regulatory hormones: GPO, Androgen
thyroxin, cortisol and ACT.
Nutritional
elements:
Protein
(high
biological value),
Mineral (Iron, cupper, znic, selenium )
Vitamins (B, Folic acid, vit c)
Anemia
Definition
Types
C/P
Anemia
AETIOLOGICAL CLASSIFICATION
Definition
A-Dyshaemopoietic
(Decreased
Types
pyridoxine
C/P
Hormonal
diseases,
deficiency:
pituitary,
anaemia
thyroid
deficiency.
Protein deficiency : high class
or
of
renal
suprarenal
Anemia
AETIOLOGICAL CLASSIFICATION
I- Decrease red cell production.
B- Hypoproliferative anaemias (BM failure ):
Aplastic anaemia.
Myelophthisic anaemia (BM replacement
Types
anaemia).
Anaemia of chronic diseases.
Anemia
AETIOLOGICAL CLASSIFICATION
II- Haemolytic anaemia:
Short life-span of RBCs
III- Acute post haemorrhagic anaemia:
Loss of RBCs
Types
Anemia
MORPHOLOGICAL CLASSIFICATION
A. Microcytic-hypochromic anaemias:
Thalassaemia.
Iron deficiency anaemia.
Types
Anemia
MORPHOLOGICAL CLASSIFICATION
B-Normocytic-normochromic anaemias:
Acute post haemorrhagic anaemia.
Hemolytic anaemia.
Types
Aplastic anaemia.
Myelophthisic anaemia.
Anaemia of chronic diseases .
Anemia
MORPHOLOGICAL CLASSIFICATION
C- Macrocytic- normochromic anaemias:
Megaloblastic anaemia.
Marked reticulocytosis.
Myelodysplastic syndromes.
Types
Myxoedema.
Acquired sideroblastic anaemia.
Anemia
Definition
I- PATHOPHYSIOLOGY
The clinical feature of the anaemia could be
explained by the following factors.
1-Tissue Hypoxia
Impaired functions of the tissues, the
Types
C/P
Anemia
I- PATHOPHYSIOLOGY
The clinical feature of the anaemia could be
explained by the following factors.
2- Compensatory mechanisms
Increased COP.
Increased O2 delivery from HB to the tissue.
Increased
erythropoietin
production
with
stimulation of erythropoiesis
C/P
Anemia
I- PATHOPHYSIOLOGY
The clinical feature of the anaemia could be
explained by the following factors.
3-Rate of blood loss:
The rapid the rate of blood loss, the more the
severe symptoms will occur especially in
elderly. While the slowly falling HB allows for
haemodynamic
C/P
symptom.
4- Cause:
compensation
with
less
Anemia
C/P
Anemia
4-GIT:
Dyspepsia and anorexia
5-Gental
Loss of libido & impotence
Menstrual abnormalities as amenorrhea.
6-May be polyuria.
C/P
Anemia
C/P
Anemia
C/P
Loud HS
S3 over mitral or tricuspid area
Haemic murmur: ejection systolic,
hearted allover the precordium
Raised jugular venous pressure.
Anemia
and
impairment
of
the
C/P
CAUSE
Microcytic
Anemia
Dietary sources :
Red meat and liver, bread, eggs and green
vegetables, mainly in ferric form,
Daily minimum requirement 10-12mg of which
about 1mg is absorbed.
Microcytic
Anemia
Microcytic
Anemia
Microcytic
Anemia
Transport
There is a diurnal rhythm with higher level in
the morning, iron is transported in the
plasma bound to transferrin.
Utilization : incorporation into Hb, myoglobin
and tissue enzymes.
Microcytic
Anemia
Microcytic
Anemia
Aetiology
C/P
Lab
DD
TTT
Microcytic
Anemia
Aetiology
Microcytic
Anemia
Aetiology
C/P
Lab
DD
TTT
Microcytic
Anemia
C/P
Microcytic
Anemia
Aetiology
C/P
Lab
DD
TTT
Microcytic
Anemia
Lab
Microcytic
Anemia
Lab
Stool analysis:
Occult blood , ankylstoma & Bilharizasis .
GI cause:
Imaging : barium swallow, meal or
enema.
Endoscopic studies: upper and lower.
Achlorhydria
Haemostatic profile.
Microcytic
Anemia
Aetiology
C/P
Lab
DD
TTT
Microcytic anaemia
Anaemia of chronic disease
Microcytic
Anemia
Aetiology
C/P
Lab
DD
TTT
Microcytic
Anemia
TTT
Parenteral iron:
Indication :
General intolerance of oral preparation
even at low dose.
Severe malabsorption and those who
have gastrointestional diseases.
Rapid iron loss.
Preparation
Iron sucrose ( ferrosac venofer)
Good safety and efficacy profile.
Given IV or slowly IV infusion.
Amp: 5ml = 100 mg.
Microcytic
Anemia
Iron dextran (cosmofer - imferon)
Good efficacy but more side effects.
Giving IM, or IV infusion.
Amp 2 ml = 100mg.
Side effects:
Local pain, staining inflammation,
abscess formation
General:
hypersensitivity
reaction,
fever, rigor, hypotension
N.B: Test dose is required prior to the use of
iron therapy.
TTT
Microcytic
Anemia
Transfusion therapy :
It should be packed RBCs.
Indications:
Sever (Hb < 7 gm/dl) andsymptomatizing
anemia/dl)
Complicated anaemia:-HF
TTT
Microcytic
Anemia
Aetiology
Type of anaemia
may be microcytic
Mechanism
Endocrinal
disorders
hypothyroidism,
Lab
Chronic
infection:
as
TB,
oestomylitis .
Neoplastic diseases .
TTT
Malabsorption.
Organ failure, liver and kidney
sarcoidosis,
Microcytic
Anemia
Aetiology
Mechanism
Lab
TTT
Microcytic
Anemia
Aetiology
Mechanism
Lab
TTT
Microcytic
Anemia
Aetiology
Mechanism
Lab
TTT
Microcytic
Anemia
It is a refractory microcytic hypochromic
Definition
inside
which
iron
Aetiology
Microcytic
Anemia
Inherited:
X-linked
disease
transmitted
by
females.
Definition
Acquired :
Primary:
one
of
the
myelodysplastic
syndromes
Secondary:
Other types of myelodysplasia
Aetiology
Myeloproliferative disorders
Myeloid leukemia
Drugs as isoniazid, alcohol, lead
Microcytic
Anemia
Iron
deficiency
Anaemia of
Chronic disease
Thalassaem
ia
Sideroblastic
anaemia
MCV
Reduced
Low normal or
normal
Very low
Low in
inherited but
in acquired
type
Serum iron
Reduced
Reduced
Normal
Raised
Serum TIBC
Raised
Reduced
Normal
Normal
Serum ferritin
Reduced
Normal or
raised
Normal
Raised
Iron in BM
Absent
Present
Present
Present
Iron in
erythroblasts
Absent
Absent or
reduced
Present
Ring forms
Macrocytic
Anemia
MACROCYTIC ANAEMIAS
:This can be divided into
.Megaloblastic type-1
Non megaloblastic types depending on bone-2
.marrow findings
Macrocytic
Anemia
MEGALOBLASTIC ANAEMIA
Megaloblastic anaemia
This anaemia in which DNA syntheses is impaired with delayed
nuclear maturation. This will lead to formation of
megaloblast i.e. large cells with large immature nucleic
( cellular gigantism). The cells affected are those rapidly
.developing: haematopoietic cells, GI mucosa, and skin
Megaloblastic changes occur in
Vitamin B12 deficiency or abnormal vit. B12 metabolism- 1
Folic acid deficiency or abnormal folate metabolism- 2
Congenital enzyme deficiencies in DNA synthesis or drugs- 3
. interfering with DNA synthesis (hydroxyurea, azathioprine)
.Myelodysplasia due to dyserythropoiesis-4
Macrocytic
Anemia
Hematological values
MCV>96 Fl unless there is a coexisting cause-1
. of microcytosis
The peripheral blood film shows macrocytes-2
with hypersegmented polymorphs with six or
more lobes in the nucleus. If severe there may
.be leucopenia and thrombocytopenia
Macrocytic
Anemia
12 VITAMIN B)COBLAMIN(
Vit B12 is synthesized by certain micro-*
.organism
Sources: meat, fish, eggs, and milk but not*
plants
.
It is not destroyed by cooking*
.Daily requirement is 1-2 mg / day*
Storage : the average adult stores 2-3 mg in*
the liver, it may take two years or more
before B12 deficiency, develops as the daily
.losses are small (1-2mg)
Macrocytic
Anemia
Macrocytic
Anemia
Macrocytic
Anemia
. Malabsorption syndrome-2
: Ileal diseases-3
Terminal ileum resection
*
. TB enteritis
*
.Chrons disease
*
. Blind loop syndrome with bacterial over-growth
Infestation by fish tape worm Diphyllobothrium
.
latum
*
*
Macrocytic
Anemia
B-Decreased utilization:
*Rare congenital enzyme deficiency.
*Lack of transcoblamin II.
III-Relative deficiency : (increased demand)
*Infancy, pregnancy, lactation
*Haemolylsis and active haematopoiesis
*Malignancy.
*Thyrotoxicosis
IV- Increased loss: Hemodialysis
V- Decrease of stores. Far advanced chronic liver
diseases
Macrocytic
Anemia
PERNICIOUS ANAEMIA
(ADDISONIAN ANAEMIA)
DEFINITION
Pernicious anaemia (PA) is a condition in which
there is atrophy of the gastric mucosa with
consequent failure of intrinsic factor production and
vitamin B12 malabsorption.
Macrocytic
Anemia
AETIOLOGY
Most probably autoimmune disease with genetic-1
.tendency
There is an association with other autoimmune disease-2
.(Thyroid disease, vitiligo and Addisons disease)
Atrophic gastritis (decrease HCL + IF) associated with -3
production of parietal cell antibodies
Intrinsic factor antibodies which are specific for the-4
diagnosis and are of two types, blocking antibodies
which inhibit the binding of IF to B12 and precipitating
antibodies which inhibit the binding of B12-IF complex to
.its receptor sites in the ileum
It is common in the elderly over 60 years in fair haired-5
. and blue eyed people and in females than males
The relatives may have clinical features of autoimmune-6
disease
Macrocytic
Anemia
PATHOPHYSIOLOGY
Both vit Bi2 and folic acid are essential for DNA
synthesis and maturation.
In cases of megaloblastic anaemia there is a
deficient DNA synthesis, so the rate of cell
division of many cells in the body is rate. The
most affected cells are those with rapid rate
of division and growth. i.e. haematoportic
cells (RBC, WBC, platelet ) and, gastric
mucosa + inability to form myelin sheath
Macrocytic
Anemia
Macrocytic
Anemia
Macrocytic
Anemia
WBCs: (leucopenia)
Myeloid megaloblasts are present in BM and give
hypersegmented PNL to the peripheral blood.
Leucopenia due to deficient DNA synthesis
Thrombocytopenia
Due to deficient DNA synthesis .
NB : Since the three blood elements are effected in
megaloblastic anaemia, it is better to call it
megaloblastic pancytopenia.
GIT
Is affected in the same manner, with secondary atrophy
epithelial cells of the tongue, stomach and even
intestine.
Nervous system
Only with B12 deficiency., failure of synthesis of myelin
synthesis
Macrocytic
Anemia
CLINICAL FEATURES
The onset is insidious.
1- Haemtological manifestations
-General manifestation of anaemia .
-Thrombocytepenia Bleeding tendencies
-Leucpenia risk of infection
-Hepatosplenomegaly.
-Colour of the skin is lemon yellow owing to combination
of pallor and jaundice.
Macrocytic
Anemia
2- GIT manifestations
-Atrophic
-Angular stomatitis .
-Gastric atrophy dyspepsia, anorexia nausea,
vomiting .
-Intestinal atrophy diarrhoea and malabsorption
Cancer stomach on top of atrophic gastritis
Macrocytic
Anemia
Macrocytic
Anemia
Macrocytic
Anemia
INVESTIGATIONS:
I- CBC
a- RBCs:
Marocytic normochromic anaemia .
Poikilocytosis and anisocytosis
Howell-Jolly bodies may be present
b-WBCs:
Moderate Leucopenia.
Shift to the right
Giant hyperpigmented neutrophil.
C -Platelets
Moderate thrombocytopenia.
Giant platelets
d-Reticulocyte
are decreased but increased by treatment with vit
B12 or folic acid
Macrocytic
Anemia
Macrocytic
Anemia
Macrocytic
Anemia
Macrocytic
Anemia
TREATMENT
Treatment of the cause : if possible .
Replacement therapy .
Initial treatment is often as the 1000 mg B12
IM/day for 2 weeks then in a dosage of 1000
mg twice/week till correction of anaemia.
Maintenance therapy 1000 mg IM every 3
months.
Neurological damage can be precipitated by
treating incorrectly with folic acid.
Transfusion therapy by packed RBCs in the flowing
conditions
sever anaemia (Hb < 7 gm/dl )
Heart failure .
Marked symptoms .
Macrocytic
Anemia
FOLATE DEFICIENCY
Basic nutritional features and metabolism of folate***
Dietary folate source :
***Important sources are liver, kidney and fresh green
vegetables, nuts, yeast, cooking probably destroys,
at least half the folate in food,
***Minimum daily requirements 100-200 ug.
Absorption is chiefly in the jejunum.
Total body store is about 10 mg mainly in the liver
Store is sufficient for 4 months.
Function
It is essential for nucleic acid synthesis maturation. It
is deficiency lead to
Nuclear maturation defect., of blood cells and
megaloblastic erythropoiesis.
GIT: mucosal cells.
Macrocytic
Anemia
Macrocytic
Anemia
II- Relative deficiency (increased demand)
Physiological: pregnancy, lactation, prematurity
Pathological:
Haematological disease with excess red cells
production e.g haemolysis.
Malignant disease with increased cell turnover
Inflammatory disease e.g. rheumatoid arthritis,
Crohns disease.
Metabolic disease e.g. homocystinuria (rare
congenital defect in the conversion of
homocysteine to cystathion folate).
Macrocytic
Anemia
Macrocytic
Anemia
CLINICAL FEATURES
* May occur at any age, degrees of folate deficiency
are very common and mild deficiency states are
frequently unrecognised.
* The clinical picture is multivarious because of the
variety of possible underlying causes.
* The onset may be insidious or rapid as when
negative folate balance is precipitated by e.g infection
* Anaemia and sometimes slight jaundice.
* Glossitis.
* No defined neurological changes.
Macrocytic
Anemia
INVESTIGATIONS
* Essentially as in vit B12 deficiency .
* Howell Jolly bodies and target cells in the blood
film would suggest splenic atrophy (coeliac disease)
* Bone marrow show megaloblastic changes.
* Reduced folate levels: (N= 2.5-25mg/ml) serum
levels are labile and red cell levels are better
reflection of tissue folate by radioisotope dilution or
immunological methods
N.B Microbiological methods were used in the past
but has the disadvantage that antibiotic therapy
could lead to falsely low results.
Macrocytic
Anemia
Treatment
1) Folic acid therapy is contraindicated if there is
any suspicion of B12 deficiency (Neurololgical
changes may be precipitated or worsen).
2) Folic acid: 5mg daily is more than adequate.
3) Prophylactic folic acid is also given in chronic
hematological disorders where there is rapid
cell turnover 5mg each week.
4) Prophylactic folic acid (400ug daily) is
recommended in pregnancy.
Macrocytic
Anemia
MACROCYTOSIS WITHOUT
MEGALOBLASTIC CHANGES
A raised MCV with macrocytosis on the
peripheral blood film can occur with a normablastic
BM. In all these conditions, the level of Vit B12 and
folate are normal.
The exact mechanisms are uncertain, but it
seems there is increased lipid deposition in the red
cell membrane.
Macrocytic
Anemia
CAUSES
1) Physiological : pregnancy and newborn.
2) Pathological
*
*
*
*
*
Alcohol excess
Liver disease
Reticulocytosis
Hypothyroidism
Some haematological disorders (e.g aplastic
anaemia, sideroblastic anaemia
* Drugs (e.g cytotoxics as azathioprine)
* Agglutinated red cell measured on red counters.
* Cold agglutinis due to autoagglutination of red cells,
MCV decreases to normal with warming of the
sample to 37OC.
An increased number of reticulocytes lead to a raised
MCV because they are large cells.
Macrocytic
Anemia
HAEMOLYTIC ANAEMIAS
:Definition
The haemolytic anaemias are a group of diseases
in which red cell life span is shortened.
Macrocytic
Anemia
PATHOPYSIOLOGY:
* Haemolysis of RBC can occur either .
1) Intravascular ie within the circulation .
2) Extra vascular ie : by phagocytes in RES in the
liver, bone, spleen.
* Bone marrow compensatory reactions:
Erythriod hyperplasia in BM, can increase
erythropoiesis several times, so that anaemia
may not develop till RBCs life span is less than
20 days
Reticuylocytosis is hallmark.
Slight macroytosis in the peripheral blood
Macrocytic
Anemia
Consequences
1) Excess haemolysis increases bilurbin since the liver
can increase its capacity several time, the jaundice is mild
if hot at all.
2) The intravascular librated Hb is bound to &-2 globulin
(haptoglobin) and Hb haptoglobin is rapidly cleared from
the circulation by REs, and plasma level of haptoglobin is
reduced, In cases of excessive IV haemolysis,
haptoglobin is depleted, there is haemoglobinanemia and
haemoglobinuria and dark urine
3) Extramedullary erythropoiesis will cause specific bone
charges .
Macrocytic
Anemia
:CAUSES
:A - CORPUSCULAR CAUSES
:Congenital Abnormalities) 1
: Membrane defects
* Hereditary spherocytosis
* Hereditary elliptocytosis
Hereditary stomatocytosis
Haemoglobinopathies:
* Sickle cell anaemia
* Thalassaemia
Enzymopathies
1) Abnormal aerobic glycolysis e.g. G6PD deficiency
2) Abnormal anerobic glycolysis e.g pyruvate kinase
deficiency
3) Non glycolytic enzymopathies
Haemolytic
Anemia
2) Acquired Abnormalities
1- Paroxysmal nocturnal haemoglobinuria
2- Vitamin E deficiency
B- EXTRACORPUSCULAR CAUSES:
1- Immune mechanisms
a ) Alloimmune antibodies (iso-immune):
* Incompatible blood transfusion
* Haemolytic disease of the newborn
* After allogenic BM or organ transplantation
b) Autoimmune haemolytic anaemias
1-Warm reactive antibodies (react at 37 oC and does not
bring
agglutination type of AB= IgG ).
* Idiopathic
* Secondary to CLL, Lymphoma, SLE and rheumatoid
disease
* Secondary to drugs e.g methyldopa.
Haemolytic
Anemia
drug
Haemolytic
Anemia
2- Mechanical injury
* Cardiac haemolytic anaemia (valve prosthesis).
* Microangiopathic haemolytic anaemias.
March haemoglobinuria.
3- Chemicals and Drugs
* Snake venom
* Lead
* Naphthaline
* Phenacetin
* Sulpha drugs
* Hypophosphataemia
Haemolytic
Anemia
4- Infections
* Clostridium welchii septicemia (Secondary to
septic abortion)
* Malarial infestation (Black water fever)
5- Metabolic causes
* A betalipoproteinemia : A canthocytosis
* Liver porphyria :
* Spurr cell anaemia
* Zieves syndrome
* Wilson disease
* Severe hypophosphataemia
6- Secondary to systemic disease :
* Renal and liver failure
* Burn
7-Hyperslenism
Haemolytic
Anemia
Haemolytic
Anemia
Haemolytic
Anemia
C- Sequestration crisis
Trapping and pooling of RBCs in the spleen (mainly
and liver).
D- Megaloblastic crisis
* Anaemia severe without jaundice .
* Decreased reticulocytic count
* Macrocytic anaemia.
* BM : megabloblastic
Cause: folic acid deficiency.
E- Vaso-occlusive crisis (Thrombotic
phenomenon)
* Painful.
* Only in cases of sickle cell anaemia.
Haemolytic
Anemia
Features or the cause
e.g thalassaemia, sickle cell anaemia.
COMPLICATIONS
* Haemolytic crisis:.
* A plastic crisis:
* Folate deficiency caused by increased BM requirement
* Gall stones
*In sickle cell anaemia: signs and symptoms of thrombotic
phenomena.
Haemolytic
Anemia
Haemolytic
Anemia
2- Short life span of RBCs:
Measured by radioactive corium labeled RBCs
3- Bone marrow
* Hypercellular normabloastic marrow.
* Hypocellular in a plastic crisis.
* Megaloblastic in folate deficiency.
4-Increased serum LDH
5-Incresesd
serum
biliurbin,
fecal
stercobilinogen and urinary urobilinogen.
Haemolytic
Anemia
Haemolytic
Anemia
HEREDITARY SPHEROCYTOSIS
Pathogenesis:
A hereditary autosomal dominant disorder in
which the corpuscular membrane is abnormally less
deformable and more permeable to sodium. This is
due to an abnormality of the protein as pectrin in the
corpuscular membrane which causes water
imbibition and rupture or red blood cells.
Haemolytic
Anemia
CLINICAL PICTURE:
1) Symptoms usually appear during the first decade of
life, but may be delayed .
2) Common features of haemolytic anaemia .
3) Slight or moderate enlargement of the spleen .
4) Pigment biliary stones in long standing cases .
5) Chronic leg ulcers.
Haemolytic
Anemia
INVESTIGATIONS:
1- CBC
* Spherocytosis, red cells are spherical instead of being ]
biconcave.
* Reticulocytosis .
* Anaemia of moderate degree.
2- Osmotic fragility
is characteristically increased, haemolysis usually begins
at podium chloride concentration of 0.6 % or even higher
3- Direct coombs test is negative, excluding an
autoimmune cause of spherocytosis and haemolysis.
Haemolytic
Anemia
TREATMENT :
The principal form of treatment is splenectomy
although this should not be performed unless
clinically indicated because of anaemia.
Splenectomy lengthens the life span of redcells,
correct anaemia, prevents haemochromatosis, but
does not affect the character of red cells.
Haemolytic
Anemia
ELLIPTOCYTOSIS
This has similar clinical and laboratory
features to hereditary spherocytosis except for the
appearance of the blood film, but is usually a
clinically milder. Occasional patients require
splonectomy.
Haemolytic
Anemia
PAROXYSMAL NOCTARAL HAEMOGLOBINURIA
AETIOLOGY
* The only one of corpuscular causes of haemalysis
which is acquired .
* The exact a etiology is unknown.
* It results from increased sensitivity of RBCs
membrane to be damage by the complement system
Haemolytic
Anemia
CLINICAL FEATURE
1) Feature of haemolytic anaemia
- Haemolysis occurs mainly after sleep by night
leading haemoglobin anemia and haemoglobinuria.
2) Abnormal platelets thrombi
3) Abnormal WBCs inspection
4) Abdominal pain due visceral ischemia caused
by
micro thrombi.
Haemolytic
Anemia
COMPLICATIONS
1) Thrombosis
2) Plastic anaemia .
3) Acute myeloid leukaemia
Haemolytic
Anemia
INVESTIGATIONS
1) General investigation of haemalytic anaemia .
2) Activation of complement to cause haemolysis .
- Hams test haemalysis by adding acid to the blood
Haemolytic
Anemia
TREATMENT :
1- Symptomatic
2- Prodinisone .
3- BMT .
Haemolytic
Anemia
HAEMOGLOBINPATHIES
Normally haemoglobin consists of .
* Globin :protein which is formed from 4 polypeptide
chain
* Haem : iron-protoporphyrin complex
Haemoglobinopathies:
These are clinical syndromes resulting from
abnormalities in the structure of globin molecule, with
the production of abnormal haemoglobin.
There are three main categories :
1 )Structural variant of Hb: e.s HbS.
2) Failure to synthesize Ht: e.g thalassemia.
3)Failure to switch from fetal Hb (HbF) to adult Hb
(HbA) : Heridetary persistence of Fetal Hb
(HPFH).
Haemolytic
Anemia
Type of Hb
Hb
Normal %
Structure of globin
Normal
A
A2
F
97-98
1-2
1-2
2 2 (2 alpha + 2 Beta)
2 2 (2 alpha+ 2 Deta)
2 2 ( 2alpha + 2 gamma)
Abnormal
production
H
Barts
4 (-thalassaemia)
4(Homozyqous - thalassaemia)
Abnormal chain
structure
S
C
2 2 (abnormal -chain)
2 2.
Haemolytic
Anemia
Haemolytic
Anemia
CLINICAL FEATURES :
1) The disease is more common among negros.
2) General manifestations of haemolytic anaemia
3) In the older patients, vaso-occlusive problems
occur
owing to sickling in the small vessels of any organ,
typical infarctive sickle crises include
Haemolytic
Anemia
* Bone pain (most common)
- The hand and foot syndrome due to infarcts of
small bones is quite common in children and may
result in digits of varying lengths.
- Avascular necrosis of the fumoral or humoral
head
* Chest: pleuritic pain, pulmonary infarction
* Cerebral: hemiparesis, fits
* Kideny: papillary necrosis causing hematuria
renal tubular defect resulting in lack of
concentration
of the urine
Haemolytic
Anemia
* Spleen: painful
fibrosis,
hyposplenism.
infarcts,
self
splenectomy,
Haemolytic
Anemia
4) Attacks of generalized and abdominal pain with low
grade fever last from a few hours to a few days during a
crisis Hb does not fall unless there is one or more of the
following different crisis.:
* Aplasia due to decreased erythropoiesis associated
with viral infections
* Acute sequestration, the liver and spleen become
engorged with sickle cells
* Haemolysis due to drugs, acute infection or
associated (G6PD) deficiency.
5) Increased susceptibility to infection hyposplenisim)
e.g viral, pneumococcal) salmonella.
Haemolytic
Anemia
COMPLICATIONS
1) Susceptibility to infections
2) Chronic leg ulcers due to ischemia
3) Gall stones pigment stones from persistant haemolysis
4) A septic necrosis of bone particularly of the femoral
heads
5) Blindness due to retinal detachment and / or
proliferative retinopathy
6) Chronic renal disease.
Haemolytic
Anemia
Investigations:
1) CBC
The level of Hb is in the range 6-8gm/dl with high
reticulocytic count (10-20%).
* Blood films show features of hyposplenism
* Sickling of red cells on a blood film can be induced in
the presence of sodium metabisulphite which cause
hypoxia.
2) Hb electrophoresis:
* There is no Hb A, 80-85% Hb S and 2-20% HbF.
* The parents of the affected child will show features of
sickle cell trait
Haemolytic
Anemia
TREATMENT :
a) prophylaxis
* Genetic counseling
* Prenatal diagnosis
* Prevent exposure to hypoxia
* Vaccination
b) Active treatment
1) The steady state anaemia requires no treatment
2) Acute attacks require supportive therapy intravenous
fluids, oxygen, antibiotics and adequate analgesia.
3) Folic acid (5mg/day) is given to prevent megalobastosis.
Haemolytic
Anemia
4) Regular transfusion of packed RBCs are given if there
is severe anaemia or if patients are having frequent
crises in order to suppress the production of HbS
5) Exchange transfusions may be necessary in patient
with severe or recurrent crises
6) Transfusion and splenectomy may be life saving for
young children with splenic sequestration
7) Hydroxyurea increases HbF production by an unknown
mechanism and reduced the frequency of painful crises.
Haemolytic
Anemia
Sickle cell trait (Heterozygous sickling disorder)
These individuals have no symptoms unless
extreme circumstances cause anoxia such as flying
in non-pressurized aircraft or problems with
anaesthesia.
* Sickle cell trait protects against plasmodium
falciparum malaria.
* 60% Hb A and 40% Hb S
* The blood count and film are normal
* The diagnosis is made by a positive sickle test or
by Hb electrophoresis.
Haemolytic
Anemia
THE THALASSAEMIAS
The thalassaemia are anaemias originally found
in people living on the shores of the Mediterranean, now
known to affect people throughout the world.
The defective synthesis of globin genes in
thalassaemia leads to imbalanced globin chain
production leading to precipitation of globin chains within
the red cell precursors and resulting in ineffective
erythropoiesis. Precipitation of globin chains in mature
red cell leads to haemolysis.
Haemolytic
Anemia
TYPES:
Two types named after the chain which is missed.
A- Alpha thalassaemia
Production of alpha chain is decreased. It is replaced by
gamma or beta chain with for motion of Hb Bart (4g) or Hb
H (4b) types.
1- a-Thalassaemia major
- Homozygosis (2abnormal gene)
- Hb Bart & Hb H are 80-90%.
- In compatible with life and results in intrauterine fetal
death from hydrops foetalis
2- a-Thalassaemia minor
- Heterozygous (only one abnormal gene).
- H B Barts & Hb H are 10-20%.
- Presented by mild Microcytic hypochromic anaemia,
jaundice, and splenomegaly
3- a- Thalassaemia silent carrier or trait,
-Asymptomatic
Haemolytic
Anemia
B- Beta- thalassaemias
There is defective production of beta-chain with
excess production of Hb F and Hb A2
Types
1- b-thalassaemia major
-Homozygous (2 abnormal gene)
-Hb F > 80-90%
2- b- thalassaemia minor (trait)
- Heterozygous (only one abnormal gene)
- Both Hb F (10%) and Hb A2 (10%) .
- Presented in adults by mild Microcytic hypothermic
anaemia and splenomegaly.
-Commonly symptomatic and require treatment.
3- b Thalassaemia intermedia
-Mild anaemia
-Rarely requiles treatment.
Haemolytic
Anemia
b- THALASSEMIA
Thalassemia minor (Trait):
This common carrier state is asymptomatic,
anaemia is mild or absent, the red cells are
hypochromic and microcytic with a low MCV and MCH.
DD: * Iron deficiency anaemia.
* Thalassaemia trait the serum ferritin and the iron
stores are normal,
* Hb electrophoresis usually show a raised Hb A2 and
often a raised HbF.
*Iron should not be given to these patients unless they
develop coincidental iron deficiency.
Haemolytic
Anemia
Thalassaemia intermedia
* Patients are symptomatic with moderate anaemia and
who do not require transfusions.
* Patients may have splenomegaly and bone
deformities recurrent leg ulcers, gall stones and
infection.
Haemolytic
Anemia
b- THALASSAEMIA MAJOR (COOLEYS ANAEMIA
MEDITERRANEAN ANEAMIA)
CLINICAL PICTURE:
1) The onset is during the first year of life (3-6 mouth )
2) The children fails to grow, (stunted growth)
mongoloid faces, bone deformities .
3) Feature of haemalytic anaemia jaundice and huge
splenomegaly
4) Extramedullary haematopoiesis: that soon cause
hepatosplenomgaly, bone expansion giving rise to
classical thalassaemic facies (mongoloid facies).
Haemolytic
Anemia
Haemolytic
Anemia
INVESTIGATIONS
1) CBC
* Blood film show hypochromic microcytic picture and
target cells.
* The reticulocyte count is raised and nucleated red cells
are present in the peripheral blood.
* The WBC and the number of platelets are normal unless
hypersplenism is present.
Haemolytic
Anemia
2) Serum iron
decreased serum iron binding capacity and high serum
iron and ferritin levels are caused by multiple blood
transfusion.
3) Hb electrophoresis
shows an increase in HbF, reduced or absent HbA and
Hb A2 is normal or slightly increased.
4) X-ray
* Skull X-ray show the characteristic hair on end
appearance of bony trabeculae as a result of
expansion of bone marrow and thinning of bone
cortex .
* Long bone : thin cortex and wide medulla
Haemolytic
Anemia
TREATMENT
A) Prophylaxis
- genetic counseling
- prenatal diagnosis
B) Active treatment
1. Repeated packed RBCs transfusion to keep Hb > 1011gm/dl, Febril transfusion can be prevented by the
use of leucocyte depleted blood.
2. Folic acid supplements are required and regular
transfusions should be given to keep the Hb above 10
gm / dl
3. Splenectomy should be delayed until after the age of 6
years because of the risk of infection, prophylaxis
against infection is required
Haemolytic
Anemia
4. Iron overload caused by repeated transfusions treated
by iron chelating agent as desferrioxamine, it is given
as
an overnight subcutaneous infusion on 5-7 nights each
week. High doses of desferrioxamin may cause
catarcts, retinal damage and nerve deafness.
5. Ascorbic acid 200 mg daily is given as it increase the
urinary excretion of iron in response to desferroixamine.
6. Bone marrow transplantation has been used in young
patients with HLA-matched siblings
7. Hydroxyurea to increase HbF production
Haemolytic
Anemia
- THALASSAEMIA
In contrast to -thalassaemia it is caused by gene
deletions, the gene for -chains is duplicated on both
chromosomes 16. Deletion of one chain gene (+)
or both chain (o).
* If all four genes are absent there is no -chain
synthesis and Hb Barts (4) is present. Hb. Barts can
not carry oxygen and is incompatible with life and
infants are either stillborn or die very shortly after
birth. (hydrops fetalis)
* If three genes are deleted there is moderate anaemia
and splenomegaly (Hb H disease). Hb A, Hb Barts and
Hb H (B4) are present, Hb A2 is normal or reduced
* If two genes are deleted (-thalassaemia trait), there
is microcytosis with or without mild anaemia.
Haemolytic
Anemia
ENZYMOPATHIES
1- GLUCOSE -6- PHOSPHATE DEHYDROGENASE
DEFICIENCY.
Glucose-6- phosphate dehydrogenase (G6 PD)
Functions to reduce nicotinamide adenine dinucleotide
phosphate
(NADPH)
while
oxidizing
glucose-6phosphate. It is the only source of NADPH in red cells and
as NADPH is needed for the production of reduced
glutathione, a deficiency renders the red cell susceptible
to oxidant stress, and cause oxidation of NADPH which
permits oxidation of protein SH groups I the red cell
membrane and eventually causes irreversible oxidative
denaturation of Hb which becomes attached to red cell
membrane to form Heinz bodies. Red cells containing
such inclusion bodies become destroyed in the lifer and
spleen
Haemolytic
Anemia
Haemolytic
Anemia
CLINICAL PICTURE
Rapidly developing intravascular haemolysis with
haemoglobinuria precipitated by infecting and other acute
illness, drugs or the ingestion of fava beans.
Haemolytic
Anemia
DIAGNOSIS:
* Between crises the blood count is normal
* Direct enzyme assay.
* During crisis, the blood film may show contracted
and fragmented cells bite cells and blister cells
which have Red Heinz bodies removed by the
spleen.
* Haemoglobinaemia and haemoglobinuria in
acute stag .
Haemolytic
Anemia
TREATMENT
-Withdrawal of the drug or toxic substance
-Blood transfusion is life saving in severe
cases.
Haemolytic
Anemia
2- PYRUVATE KINASE DEFICIENCY.
This is inherited as an autosomal recessive,
the affected patients being homozygous or les
common heterozygous . the red cells become rigid as
result of reduced adenosine triphosphate (ATP)
formation. Direct enzyme asay is needed to make the
diagnosis .
Haemolytic
Anemia
Haemolytic
Anemia
Haemolytic
Anemia
INVESTIGATIONS
1) Intra vascular haemolysis
2) Hams test. Cells from a patient with PNH lyse
more readily in acidified serum than do normal
cells.
Haemolytic
Anemia
TREATMENT
1) Blood trans fusion for patients with severe anaemia
2) Long tern anticoagulation may be necessary for
patients with recurrent thrombotic episodes
3) BMT but only in patients under so years with an hlaidentical sibling.
Haemolytic
Anemia
APLASTIC ANAEMIA
DEFINITION
A condition associated with acellular or
hypoellular bone marrow. A number of patients have
failure of production of one or two cell lines e.g red cell
aplasia (Blackfan diamond syndrome) or aplastic crisis
in haemolytic anaemia,
Haemolytic
Anemia
Haemolytic
Anemia
Haemolytic
Anemia
Haemolytic
Anemia
Haemolytic
Anemia