Blood

formation
1-Intrautrine life:
Blood cells are formed in the liver and
SITES spleen up to the fifth months.
After 5th month : bone marrow share in the
formation of these cells.
2-After birth:
Formation of these cells will be restricted
to the bone morrow.
STEPS
 Blood 3-Adulthood
formation
The active bone morrow will be:
Restricted to axial skeleton : flat bones,
vertebrae, ribs, sternum, ilia .
SITES
Some extension to the proximal ends of
long bone mainly femur.
Extramedullary haemopoiesis: When demand for
blood formation is increased:
The active red BM extends into the shafts of
the long bones.
The spleen and liver will regain their ability
to produce blood elements when bone
morrow is affected by some diseases.
 Blood Pleuri-potent cells
formation

BFU-E
CFU-E CFU-G
Proerythroblast Myleloblast
SITES Basophilic Promyelocyte CFU-Mega
erythroblast Myelocyte Megakaryoblast
Polychromatic Metamgelocyte Megadaryocyte
erythroblast Juvenil Platelet
Othrochromatic Granulocyte
erythroblast (PML)
Reticulocytes

STEPS
Erthrocyto- Granulocyto-
Thrambocytopoiesis
poiesis poiesis
 Blood
formation

STEPS
 Blood
formation Blood Constituents

Organelles (formed elements):

RBCs
WBCs
Thrombocytes
Fluid components: plasma in which the above
elements are suspended and contain
fibrinogen.
 Blood
Erythrocytopoiesis
formation
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
Anaemia = reduction of O2 carrying capacity

of the blood with inadequate O2 supply to

Definition
tissue .
Anaemia is diagnosed when there is a

Types reduction of (RBCs number, or HBLO or

PCV) below the reference range for age and
sex of the individual .
C/P More accurately is defined as reduction in
the red cell mass
Anemia AETIOLOGICAL CLASSIFICATION
I- Decrease red cell production.

Definition A- Dyshaemopoietic anaemia: (Decreased

maturation due to deficiency of maturation
factors essential for erythropoiesis).
Mineral deficiency: iron, zinc, selenium, cupper
Types
Vitamin deficiency: B12, folic acid ; Vit C &
pyridoxine
Hormonal deficiency: anaemia of renal
C/P
diseases, pituitary, thyroid or suprarenal
deficiency.
Protein deficiency : high class
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 IV- Mixed anaemia.
eg. Megalobastosis associated with haemolysis
V: Dilutconal anaemia: (raised plasma volume)
Pregnancy
Oliguric RF
Volume-overload
Anemia MORPHOLOGICAL CLASSIFICATION

A. Microcytic-hypochromic anaemias:
Thalassaemia.
Iron deficiency anaemia.
Types Anaemia of chronic disease.
Sideroblastic anaemia:
Hereditary
Chronic lead poisoning.
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.
 I- PATHOPHYSIOLOGY
Anemia
The clinical feature of the anaemia could be
explained by the following factors.
Definition

1-Tissue Hypoxia
Impaired functions of the tissues, the
Types degree of impairment depends an the need
of the tissue to O2 so CVS, CNS and
skeletal muscles are much affected.
C/P
 I- PATHOPHYSIOLOGY
Anemia
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 Increased plasma volume.

Redistribution of the blood from less to more
vital organs.
 I- PATHOPHYSIOLOGY
Anemia
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 compensation with less

C/P symptom.
4- Cause:
 II- GENERAL SYMPTOMS OF ANAEMIA:
Anemia
1-Neurological
Dizziness, fainting, lack of concentration
Blurred or diminished vision
Headache, tinnitus
Paraesthesia in the fingers and toes
Insomnia, irritability.
2-CVS:
• Angina, dyspnea, palpitation and intermittent
claudication by exertion
C/P • HF in severe cases or presence of other
organic cardiac disease, it is high COP failure.
3-Musculo skeletal:
Easy fatigability.
Tiredness and lassitude.
 II- GENERAL SYMPTOMS OF ANAEMIA:
Anemia

4-GIT:
Dyspepsia and anorexia
5-Gental
Loss of libido & impotence
Menstrual abnormalities as amenorrhea.
6-May be polyuria.

C/P
 III- PHYSICAL SIGNS:
Anemia
Pallor of the skin and mucous membranes
The colour of the skin is unreliable
because it depends upon the degree of
skin pigmentation and the amount of fluid
in the subcutaneous tissues.
Best examined : palmer creases, nail bed,
and mucous membrane .
Peripheral oedema :
Slight oedema of the legs probably due to
increase in the capillary permeability
C/P
secondary to hypoxia.
High COP failure.
Fever :
Mild fever may occur in sever anaemia but
other causes should be excluded
 III- PHYSICAL SIGNS:
Anemia
Fundal changes:
Retinal hemorrhages of the flame shape
type, exudates and rarely papilloedema.
The cardiovascular system:
Increased velocity with decreased
viscosity of the blood in addition to
capillary dilation:
Pulse; tachycardia, bounding pulse
Cardiac examination :
C/P Loud HS
S3 over mitral or tricuspid area
Haemic murmur: ejection systolic,
hearted allover the precordium
Raised jugular venous pressure.
 III- PHYSICAL SIGNS:
Anemia
Proteinuria and impairment of the
concentrating power of kidneys due to anoxia
of renal tubules.

IV: SPECIAL MANIFESTATIONS RELATED TO THE

C/P CAUSE
Microcytic
Anemia
Basic nutritional features and metabolism of iron

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
Basic nutritional features and metabolism of iron
Absorption

In the stomach the iron is released from its

complex form and is reduced to ferrous form
(action of gastrin and Hcl).
Iron absorption takes place in the duodenum
and proximal jejunum.
Factor controlling iron absorption
Iron absorption is under regulatory system
(Apoferritin-Transferrin system ) present in the
intestinal mucosa and regulate absorption of the
iron according to body requirement .
Microcytic
Anemia
Basic nutritional features and metabolism of iron
Absorption
Factors enhancing iron absorption
Pregnancy
Iron deficiency anaemia
Increased erythropoiesis
Vit. C.
Factors decrease iron absorption :
Excess phosphate, tannates, phytate in diet
Iron overload haemochromatosis
Decreased erythropoies eg a plastic anaemia
Malabsorption syndrome
Decreased HCI atrophic gastritis .
Microcytic
Anemia
Basic nutritional features and metabolism of iron

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
Basic nutritional features and metabolism of iron

Storage :
About two-thirds of the total body iron is in the
circulation as haemoglobin.
Iron is stored in reticulo-endothelial cells,
hepatocytes, spleen, bone marrow and skeletal
muscle about two thirds as ferritin and one-
third as haemosiderin.
Iron loss: (0.5 mg/day). Via
Hair and nail growth
Epithelium of the skin and mucus membrane.
body excreta : stool and urine
Microcytic
Anemia
True deficiency (defective intake) Rare:
 Prolonged starvation and famines.
Aetiology  Infancy (milk is poor in iron)
Conditioned deficiency (normal demand and
intake but there are defective absorption and
C/P utilization) Not common:
 Ferric form cause.
 Decreased HCL
Lab  Iron binder: phosphate, phytate, tannates
 Malobsorption syndrome.
Relative deficiency : (increased requirement )
DD common cause.
 Menstruating females.
 Pregnancy, labor.
 Growing children .
TTT
 Convalescence from disease.
Microcytic
Anemia
Chronic blood loss : the commonest cause
 Frank blood loss
Aetiology
 Menorrhagia
 Repeated GI bleeding, haemeptysis,
epistaxis, haematuria
 Bleeding tendencies
 Repeated blood donation
 Occult blood loss via GIT:
 Anckylstoma & schistomiasis
 Oozing OV, PU.
 Neoplasm.
 Inflammatory bowel disease ulcerative
colitis
 TB enteritis.
Microcytic
Anemia
General manifestations of anaemia
Especial manifestations of iron deficiency
Aetiology anaemia .
Epithelial changes:
GIT manifestations
C/P Angular stomatitis.
Atrophic glossitis (red, glazed, smooth
tongue).
Lab Atrophy of the gastric mucosa
Small splenomegaly
Dermatological changes
DD Brittle nails thinning and ridging and loss of
luster.
Koilonychia; spoon-shaped nails in severe
cases:
TTT
Brittle hair
Microcytic
Anemia
Features of special types:
1- Plummer-Vinson –syndrome:
 Common in middle aged female
 Postcricoid esophageal web cause
dysphagia
C/P 2- Ankylostoma infestation:
 Perverted appetite: (pica) eating mud,
stones and chalk.
 Epigastric pain (DD= D. ulcer ), altering
bowel habits
 Endemic parasites (trapezoid face)
 The symptoms are mild and to variable.
 Investigations:
 Stool: Ova.
 CBC: eosinphilia.
Microcytic
Anemia
A.To diagnose iron deficiency anaemia

Aetiology CBC:
 The red cells are microcytic, (MCV<80f1)
and hypochromic (MCH < 27pg)
C/P anisocytosis and poikilocytosis
(variation in size and shape).
 Eosinophilia is present in cases of
Lab ankylostoma infestation.
Bone Marrow:
 Absent iron store,
DD  Normoplastic hyperplasia,
  Hb in maturely erythroblasts.

TTT
Microcytic
Anemia
A.To diagnose iron deficiency anaemia
Serum iron study
 Decreased serum iron (n=70-170 mg%).
 Increased total iron binding capacity
(TIBC).(n=250-450mg%).
 Decreased serum ferritin levels .
 Reflect iron stores.
 The normal values are 30-300 mg/L in
Lab males and 15-200 mg/L in females and
investigation of gastrointestinal tract
are often required.
 Falsely raised value in cases of acute
phase reactant e.g malignancy .
 Decreased transferrin saturation (n=25-
50%)
Microcytic
Anemia
B- Investigation for the causes

Stool analysis:
 Occult blood , ankylstoma & Bilharizasis .
 GI cause:
 Imaging : barium swallow, meal or
enema.
Lab  Endoscopic studies: upper and lower.
 Achlorhydria
Haemostatic profile.
Microcytic
Anemia

Aetiology

C/P
Microcytic anaemia
Anaemia of chronic disease
Lab

DD

TTT
Microcytic
Anemia
The aim of the treatment is to correct the
Aetiology anaemia and build up iron stores
 Correction of underlying cause if
possible
C/P  Iron replacement
Oral iron:
 200 mg anhydrous ferrous sulphate three
Lab times daily.
 The response is a rise in Hb
concentration of 1 gm/dl per week,
DD  Side effects nausea, abdominal pain,
diarrhea or constipation.

TTT
Microcytic
Anemia
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.

TTT
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) and symptomatizing
anemia/dl)
 Complicated anaemia:- HF

TTT
Microcytic
Anemia

Aetiology Type of anaemia may be microcytic

hypochromic or more common normocytic
normochromic .
Endocrinal disorders : hypothyroidism,
Mechanism
hypocorticalisin, hypogonadism in male .
Inflammatory diseases : collagenosis, chron’s
disease.
Lab Chronic infection: as TB, sarcoidosis,
oestomylitis .
Neoplastic diseases .
Malabsorption.
TTT
Organ failure, liver and kidney
Microcytic
Anemia

Aetiology

Not clear: Seems to be mediated by

Mechanism
inflammatory cytokines IL-1, TNF, and INF.

Lab

TTT
Microcytic
Anemia

Aetiology

Decreased serum iron and TIBC.

Mechanism
Normal or raised serum ferritin
Normal BM iron.

Lab

TTT
Microcytic
Anemia

Aetiology

Mechanism
Should be targeting the cause.

Lab

TTT
Microcytic
Anemia

It is a refractory microcytic hypochromic

Definition anaemia (peripheral blood) characterized by

the presence of sidroblasts in the bone
marrow.
Sidroblasts are:
 Erythroblasts inside which iron
accumulate into the mitochondria of
Aetiology erythroblasts owing to disordered haeme
synthesis .
 A ring of iron granules is formed around
the nucleus.
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 Differential diagnosis of Microcytic anaemia:
Anemia
Sideroblast Anaemia of Iron
Thalassae
ic Chronic deficienc
mia
anaemia disease y
Low in
inherited
Low normal
but in Very low Reduced MCV
or normal
acquired
type

Raised Normal Reduced Reduced Serum iron

Serum
Normal Normal Reduced Raised
TIBC
Normal or Serum
Raised Normal Reduced
raised ferritin

Present Present Present Absent Iron in BM

Iron in
Absent or
Ring forms Present Absent erythroblast
reduced
s
Macrocytic
Anemia

MACROCYTIC ANAEMIAS

:This can be divided into

.Megaloblastic type-1

Non megaloblastic types depending on bone-2

.marrow findings
Macrocytic MEGALOBLASTIC ANAEMIA
Anemia 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
Absorption: Vit. B12 is liberated in the
stomach, bound by intrinsic factor
(IF) and absorbed through the
terminal ileum, transported by
transcobalamin I and to lesser extend
.by transcobalamin II and III

:It is essential for

haematopoiesis-1
GIT mucosa integration-2
Formation of myelin of nervous-3
.system
Macrocytic CAUSES OF VIT. B12 DEFICIENCY
Anemia
I- True deficiency: (Decreased intake)
-Poor socioeconomic status.
-Vegetarians, alcoholic

II-condition deficiency
A-Decreased absorption .
1-Decreased intrinsic factors commonest cause.
*Pernicious anaemia.
*Total or partial gastrectomy
*Atrophic gastritis.
*Gastric cancer.
*Non- Addisonian pernicious anaemia
a- In association with hypogammaglobulinemia,
gastric atrophy, achlorhydria and absent intrinsic
factor but no antibodies
b-In infancy: Selective failure of IF, normal mucosa.
C- Juvenil PA failure of IF secretion with gastric
atrophy rarely with antibodies
Macrocytic
Anemia
.Malabsorption syndrome-2

:Ileal diseases-3
Terminal ileum resection *
.TB enteritis *
.Chron’s 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 AETIOLOGY
Anemia Most probably autoimmune disease with genetic-1
. tendency

There is an association with other autoimmune disease-2

.(Thyroid disease, vitiligo and Addison’s 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 RBCs (Megaloblastosis = cellular gigantism)

1-Megaloblasts (cell gigantism ): these are

large cells (megalo) with relatively small
nucleus (blasts). The cytoplasm is markedly
in crease because RNA synthesis is normal
while the nucleus is slowly growing because
deficient DNA synthesis.

2-In BM, the normblast are replaced by these

megaloblasts. Some of these abnormal cells
are destroyed in BM. (intramedullary
haemolysis)
Macrocytic 3-Some of these erythroid megaloblasts lose
Anemia
their nuclei and joined peripheral blood as
macrocytes, irregular shape with remnant of
the nucleus . these cells are hatched and
destroyed by the spleen. During its
circulation.

So anaemia is multifactorial-4
Defective erythropoiesis -
.Intramedullary haemolysis -
. Destruction by the spleen -

Increased Serum bilirubin-5

.Increased medullary haemolysis-
.Increased splenic destruction of RBCs-
Macrocytic WBCs: (leucopenia)
Anemia 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 2- GIT manifestations
Anemia
-Atrophic glossitis, (red – glozed tongue)

-Angular stomatitis .

-Gastric atrophy dyspepsia, anorexia nausea,

vomiting .

-Intestinal atrophy diarrhoea and

malabsorption

Cancer stomach on top of atrophic gastritis

Macrocytic
Neuropsychatice manifestations (only with -3
Anemia .vit B12 deficiency)

:A-Neurological manifestations (3Ps)

Peripheral neuropathy (LMNL)

.Pyramidal tract affection (UMNL) spastic paraplegia

Posterior column affection  loss of deep sensation and

. sensory ataxia

NB: Combination of the two lessons is called sub acute

combined degeneration of the spinal cord (SCD)

b- Dementia

c- Optic atrophy

d- psychosis rare
Macrocytic
Anemia
Association with other autoimmune -4
features: (in pernicious anaemia)

Thyrotoxcoais -1

.Hashimoto’s disease -2

Vitiligo-3

Rheumatoid disease-4

Primary billiard cirrhosis-5

Macrocytic INVESTIGATIONS:
Anemia 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 :II- Bone marrow

Show megaloblastic erythropoiesis. The most

characteristic is dissociation between nuclear
& cytoplasmic development in erythroblasts
with the nucleus maintaining a primitive
appearance despite maturation and
.haemoglobinization of the cytoplasm

Erythroid hyperplasia, maturation defect in

erythropoiesis, giant metamyelocytes, atypical
.megakaryocytes with hypersegmented nuclei
Macrocytic
Anemia
III- Estimation of serum B12 level
is low using radioisotope dilution or immunological
assays.
IV. Biochemistry
Serum iron is high, more than 175 mcg/100 ml.
Increased serum indirect bilirubin reflect mild
haemolysis and ineffective erythropoiesis.
Increased serum lactic dehydrogenase (LDH)
reflecting ineffective megaloblastic erythropoiesis.
V. Immunology
Parietal cells antibodies and gastrin receptor
antibodies, present in 70% of patients. (not specific)
Intrinsic factor antibodies type I blocking (more
specific) and type II precipitating antibodies.
 VI- other investigations
Macrocytic .Gastric biopsy: proximal 2/3 of stomach atrophic***
Anemia .Augmented histamine test: achlorhydria***
.Schilling test***
Aim*
.Diagnosis of pernicious anaemia -1
To detect its cause whether malabsorption or IF -2
.deficiency

Methodology*
Large dose of unlabelled B12 (1000ug) is given IV to
.saturate body sores
Radiolabelled B12 (lug) is given orally, the amount of
.radio labellol B12 on the urine
Urine of the next 24 hours is measured
Results

If radiolabelled B12 excretion is low there may be

Malabsorption -1
.Pernicious anaemia -2
Repeated the test after giving IF orally if it increase in the
.urine, this means that the cause is IF deficiency
Macrocytic
TREATMENT
Anemia
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 FOLATE DEFICIENCY
Anemia
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

CAUSES OF FOLATE DEFICIENCY:

I- True deficiency (decreased intake)

Poor intake particularly in infancy, old age, poor social
conditions, starvation alcohol excess.
Poor intake due to anorexia as in GIT disease e.g. Partial
gastrectomy, coeliac disease, Crohn’s disease, cancer.
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,
Crohn’s disease.
Metabolic disease e.g. homocystinuria (rare
congenital defect in the conversion of
homocysteine to cystathion folate).
Macrocytic
Anemia
III - Conditioned deficiency normal intake and
requirement but their may be :

a) Decreased absorption
* Malabsorption: in small bowel disease.
* Drugs : pill or anticonvulsant.

b) Decreased utilization

* Antifolate drugs. anticonvulsants, methotrexate,

pyrimethamine and trimethoprim

IV- Increased loss

* Haemodialysis or peritoneal dialysis closely bound

to plasma protein, so easily removed.
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 CAUSES
Anemia
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 :CAUSES
Anemia
: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 2) Acquired Abnormalities
Anemia 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
2- Cold reactive antibodies (react at 32oC and
usually agglutinates and haemolyse red cells,
type of AB = IgM).

* Cold haemoagglutinin disease

- Idiopathic
-Secondary (mycopolasma pneunemia infection,
infectious mononucleosis, lymphomas.

* Paroxysmal cold haemoglobinuria

- Idiopathic
-Secondary (some viral infections congenital &
tertiary syphilis).

c) Immunochemical mechanisms: drug

induced haemolytic anaemias
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 4- Infections
Anemia
* Clostridium welchii septicemia (Secondary to
septic abortion)
* Malarial infestation (Black water fever)

5- Metabolic causes

* A betalipoproteinemia : A canthocytosis
* Liver porphyria :
* Spurr cell anaemia
* Zieve’s syndrome
* Wilson disease
* Severe hypophosphataemia

6- Secondary to systemic disease :

* Renal and liver failure
* Burn

7-Hyperslenism
 CLINICAL FEATURES OF HAEMOLYTIC ANAEMIA
Haemolytic General features of anaemia
Anemia General features of haemolytic anaemia
1)Haemalytic jaundice .
* Mild degree.
* Skin is lemon yellow
* Sclera tinge of jaundice .
* Dark stool.
* Normal urine which darken on exposure to air
2)Heapatosplenomegaly:
* Common in chronic haemolysis except in cases of
sickle cell anaemia where there self-splenectomy
3) Biliary obstruction and /or gall bladder stones.
* Pigment stones: extra hepatic obstruction .
* Viscid bile: intrahepatic obstruction.
NB. In this situation jaundice becomes, mixed
( haemolytic + obstructive) and abdominal pain my be
present.
4- Leg ulcer:
Chronic leg ulcer surrounded by pigmentation cause
by extra vascular iron deposition . Ulcers develop on the
malleoli
Haemolytic 5-Different types of crisis:
Anemia a) Heamolytic crisis
* Fever, rigors: pyrogen release from RBCs .
* Generalized bone pain
* Acute abdominal pain, backache, may be vomiting.
* Aggravation of anaemia (pallor), deepening as jaundice,
and dark colouration of urine
* Investigations:
- Dark urine: haemoglobinuria.
- Increased serum biliurbin
- Reticulocytosis
- BM erythroid hyperplasia.
* Cause may be infection
B- A plastic crisis
* Inability of BM to replaced the destructed RBCs
- Severe anaemia without jaundice.
- Reticulocytopenia .
- BM erythroid hypoplasia.
* Cause: viral infection especially parvovirus B19 and
HBV.
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 INVESTIGATION FOR CASE OF HAEMOLYTIC
ANAEMIA

1) Diagnosis of Haemolytic anaemia

1- CBC

* Normocytic normochromic anaemia with reticulocytosis

* Microcytic anaemia: thalassaemia, spherocytosis.
* Macrocytic + reticulocytosis: megaloblastic crisis
* Reticytopenia: a plastic crisis .
* Morphological evidence of RBC damage: as red cell
fragment, cell containing malarial parasites.
* Morphology of RBCs: eg spherocytes & sickle cells
* WBCs thrombocytes are normal but may increase due to
bone marrow stimulation.
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 Tests for detection the site of
haemolysis.
In intravascular haemolysis vs. extravascular the
following parameters are presents.

* Haemoglobin anemia, Haemoglobinuria and

haemosideringuria
* Reduced plasma haptoglobin and haemopexin
* Presence of met haemalbumin in plasma.

Tests for the cause

* RBC morphology.
* Osmotic fragility .
* Hb electrophoeresis.
* Estimation of G6 PD.
* Coomb’s test.
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
INVESTIGATIONS:
Anemia
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 coomb’s 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 .

- Ham’s test haemalysis by adding acid to the blood

Haemolytic
Anemia

TREATMENT :

1- Symptomatic

2- Prodinisone .

3- BMT .
 HAEMOGLOBINPATHIES
Haemolytic
Anemia
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

Structure of globin Normal % Hb Type of Hb

2 2 (2 alpha + 2 Beta) 97-98 A

 2 2 (2 alpha+ 2 Deta) 1-2 A2 Normal
 2 2 ( 2alpha + 2 gamma) 1-2 F

4 (-thalassaemia) - H Abnormal
4(Homozyqous - thalassaemia) - Barts production

 2 2 (abnormal -chain) - S Abnormal chain

 2  2. - C structure
Haemolytic
Anemia SICKLE CELL ANAEMIA

Symptoms vary from a mild asymptomatic

disorder to severe haemolytic anaemia and recurrent
severe painful crises.

A herediatary autosomal recessive disorder.

The homozgotic form is due to the presence of the
abnormal haemoglobin, (Hbs), which on exposure to
hypoxia, the deoxygenated Hbs forms in soluble
aggregates that distort the erythrocytes and increase
their rigidity causing sickling deformation and
subsequent fragmentation. In addition, the unyielding
elongate crescentic erythrocytes form aggregates that
block terminal arterioles, capillaries and veins, resulting
in tissue infractions and perivascular oedema in the
involved organs (vascular occlusion)
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 infarcts, self splenectomy,

fibrosis,
hyposplenism.

* Penis: priapism and impotence.

* Liver: pain with abnormal biochemistry

* Intestine, ischaemia, infarction, abdominal and

fever .

* Ischemic cardiomyopathy

* Eye: retinal detachment and blindness

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 TYPES:
Anemia 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 (COOLEY’S 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

5) Feature of haemochromatosis: liver cirrhosis, bronze

skin, cardiomegaly.

6) The disease is more common among Mediterranians.

7) Positive family history.

8) Usually recurrent bacterial infection.

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 > 10-

11gm/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 (γ4) 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 PDH)

Functions to reduce nicotinamide adenine dinucleotide
phosphate (NADPH) while oxidizing glucose-6-
phosphate.
phosphate 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

A gents which may cause haemolysis in (g6PD)

deficiency

* Infections and other acute illnesses e.g diabetic

ketoacidosis
* Drugs

1- Sulphonmides e.g co-trimoxazole

2- Ant. Bacterial e.g into furans, chloramphenicol
3- Analgesics e.g aspirin phen a cetin
4- Anti malarial e.g primquine and quinine
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 ACQUIRED NON IMMUNE HAEMOLYTIC ANAEMIA

Paroxysmal nocturnal haemoglobinuria (PNH)

This is rare acquired red cell defect in which a

lone of red cells is particularly sensitive to destruction by
activated complement. These cells are continually
haemolysed intravascularly .

The underlying defect is an inability of PNH cells

to make glycosyl-phosphatidylinositol (GPI) which anchors
surface proteins such as delay accelerating factor (DAF)
membrane inhibitor of reactive lysis (MIRL) to cell
membranes. DAF and MIRL and other proteins are
involved in complement degradation and in their absence
the hemolytic action of complement is not regulated.
Haemolytic
Anemia

CLINICAL PICTURE:-

1) Haemolysis which may be precipitated by infection or

surgery.

2) Urine voided at night and in the morning on waking is

dark in colour, the reason for this phenomenon is not
clear.

3) Venous thrombotic episodes are very common

Haemolytic
Anemia

INVESTIGATIONS

1) Intra vascular haemolysis

2) Ham’s 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 hla-

identical 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

a
Haemolytic
Anemia

a
Haemolytic
Anemia

a
Haemolytic
Anemia

a
Haemolytic
Anemia