ANAEMIA

Is present where there is a decrease in the number of circulating

red cells, a decrease in the amount of haemoglobin in the blood or a
haematocrit below the normal range.

DEFINITIONS IN HAEMATOLOGY
Mean corpuscular Haematocrit
= N = 80 – 96 μ
volume (MCV) Red cells count

Mean corpuscular Haemaglobin x 10

= N = 27 – 33 pg
haemaglobin (MCH) Red cells count

Mean corpuscular Haemaglobin x 10

= N = 32 – 35 g/dL
haemaglobin Haematocrit
concentration (MHCH)
 Clinical features

Symptoms (all non - specific):

– fatigue
– headaches
– faintness
– breathlessness
– angina of effort
– intermitent claudication
– palpitations
Signs:
2. Non / specific signs include:
– pallor
– tachycardia
– a full pulse
– systolic flow murmur
– cardiac failure
– ankle oedema
– rarely papilloedema and retinal haemorrhage in an acute
bleed

3. Specific signs:
– koilonychia – spoon-shape nails seen in iron deficiency
anaemia
– jaundice – haemolytic anaemia
– bone deformities – thalassemia major
– leg ulcers – sickle cell disease
 Classification:
2. Hypochromic microcytic with low mean corpuscular volume
(MCV)
3. Normochromic normocytic with a normal MCV
4. Macrocytic with a high MCV

Special investigations:
– bone marrow aspiration from the sternum or posterior illiac
crest is performed to:
– confirm a diagnostic made from peripheral blood count
– determine the cellularity of the marrow
– determine the type of erythropoiesis
– determine the proportion of the various lines
– see wether the marrow is unfiltrated
– determine the size of the iron stores
 MYCROCYTIC ANAEMIA

– small cells (microcytes)

– low MCV (< 80 μL)
– ↓ iron content
–ragged normoblasts
} Iron deficiency anaemia

}
– small cells (microcytes)
Thalassaemia
– low MCV (< 80 μL)
– normal iron content hyperplastic Sideroblastic anaemia
 1.IRON DEFICIENCY

– the commonest cause of mycrocitic anaemia

– the average daily diet contains 15 – 20 mg of iron, but only 10%
is absorbed
– absorption:
 duodenum and jejunum
 ferrous iron is absorbed better than ferric
 gastric acidity helps to keep iron in the ferrous state and
soluble in the upper gut
– transport in the blood:
 transported in the plasma bound to transferin, beta globuline
synthesized in the liver
– iron stores – in the tissues as ferritin and haemosiderin (1000 –
1500 mg)
– requirements:
 each day 0.5 – 1 mg of iron are lost in the faeces, urine and
sweat
 menstruating women lose 0.7 mg iron / day of menstruation
 pregnancy and groth ↑ iron demand
 CAUSES OF IRON DEFICIENCY
2. Poor intake
3. Decreased absorption
4. Increased demands
5. Blood loss

The commonest cause of iron deficiency:

 Blood lost from G.I. tract
 Menstruation
Clinical features:

– brittle nails
– spoon – shaped nails (koilonychia)
– atrophy of the papillae of the tongue
– angular stomatitis
– brittle hair
– dysphagia and glossitis (plummer – Vinson or Paterson Brown
Kelly syndrome)
– parotid gland enlargement, splenomegaly and failure to grow
investigations:
– the red cells are microcytic (MCV < 80 fL) and hypochromic
(MCV < 27 pg)
– poikilocytosis (variation in shape) and anisocytosis (variation in
size)
– target cells
– hypersegmentation of polymorphs
– serum iron falls
– iron blinding capacity ↑
– bone marrow – erythroid hyperplasia with ragged normoblasts
– ring sideroblast

other investigations:
– the G.I. tract - endoscopy
Bone marrow in iron deficiency
 1.sideroblastic anaemia
Classification:
A. Congenital:
– “X” linked disease – transmitted by females
B. Acquired:
– primary or idiopathic
– secondary:
 drugs
 alcohol
 lead
 myeloproliferative disorders
 leukaemias
 secondary carcinoma
 other systemic disorders (connective tissue
disease)
 1.thalassaemia
Deficiency in the synthesis of the globin chains of haemoglobin
in addition, the accumulation of abnormal chains within the red
cell leads to its early destruction.

The severity of the thalassaemia will depend on the amount of

the haemoglobin A2 and F present.

Clinically β-thalassaemia can be divided into:

–thalassaemia mayor, with severe anaemia
–intermedia, with moderate anaemia rarely requiring
transfusion
–minor, the symptomless heterozygous carrier state
symptoms:

– failure to thrive
– intermittent infection
– severe anaemia
– extramedullary haemopoiesis → hepatosplenomegaly and bone
expansion thalassaemic facies
investigation:

– blood count:
 moderate to severe anaemia (↓MCV, MCH↓)
 reticulocyte ↑
 white cells and platelets = N
– blood film:
 hypochromic and microcytic picture
 Howell – Jolly bodies
– high ferritin levels
– haemoglobin electrophoresis (HbF ↑; HbA absent)
β-Thalassaemia trait (minor)
– asymptomatic
– no anaemia, red cells hypochromic and microcytic

α-Thalassaemia
– two main form:
 deletion of only alpha chain gene
deletion of both alpha chain genes → no alpha chains are
produced
 Thalassemia major

Thalassemia minor
 Macrocytic anaemia
The presence in the bone marrow of erytroblasts with delayed
nuclear maturation because of defective DNA synthesis
(megaloblasts).

Occurs in:
–vitamin B12 deficiency
–folic acid deficiency
–diseritropoetic anaemia
Haematological values:
–anaemia
–MCV > 96 fL
–blood film (peripheral): macrocytes and hypersegmented
polymorphs
–neutropenia
–thrombocytopenia
 vitamin b12 (Addison – Biermer anaemia)
– average daily diet 5 – 30 μg B12
–average adult stores 1000 μg – liver
–absorption and transport:
gut → binder complex (R binder + B12) → intrinsec
factor (glycoprotein from the gastric juice)
Transcobalamin
Ileum → → → → → → → → → → Marrow
Pernicious anaemia (Addison – Biermer) affect:
– particularly nordic people: fair – haired; blue – eyed.
–association with other autoimmune diseases: thyroid disease,
Addison’s disease, vitiligo
– higher incidence of gastric carcinoma
 Causes of vitamin b12 deficiency:
– low dietary intake (vegans)
– impaired absorption:
A. stomach (gastrectomy)
B. small bowel:
– coeliac disease
– tropical sprue
– bacterial overgrowth
– ileal disease or resection
C. pancreas:
– chronic pancreatic disease
– Zollinger – Ellison syndrome
D. miscellaneous and rare:
– fish tape worm (diphyllobothrium latum)
– congenital deficiency:
– intrinsec factor
– transcobalamin III
– nitrous oxide (inactivates B12)
 Clinical features:
2. Anaemic syndrome
3. Neurological syndromes:
 Peripheral neuropathy progressively involving the
posterior and lateral columns of the spinal cord:
– symmetrical paraesthesia in the fingers and toes
– loss of vibration sense and proprioception
– progressive weakness and ataxia
– paraplegia
 Mental changes:
– somnolence
– irritability
– psychosis
– dementia
1. Digestive syndrome:
– glossitis (red sore tongue)
– angular stomatitis
– hepatosplenomegaly
– gastric atrophy and achlorhydria
2. Others:
– skin – lemon-yellow tint due to hyperbilirubinaemia
– heart – failure
– fever
 Investigations:

–peripheral blood film shows features of megaloblastic

anaemia: ↓ reticulocytes
–the serum bilirubin ↑
–bone marrow → megaloblastic erythropoiesis
–the Schilling test (a radioactive dose of B12 is given orally
and the total body activity is measured)
–G.I. investigations → endoscopy
Bone marrow
pernicious anaemia
 Folic acid
Daily requirement 100 μg
Causes of folate deficiency:
– poor intake:
– old age
– poor social conditions
– starvation
– alcohol excess
– poor intake due to anorexia:
– G.I. disease (partial gastrectomy, coeliac disease, Crohn’s
disease, cancer)
– excess utilization
 clinical features:
B. Physiological:
 pregnancy
 lactation
 prematurity
C. Pathological:
 haemolysis
 malignant disease
 inflammatory disease
 metabolic disease
 haemolysis
– malabsorption
– antifolate drugs
 Normocytic anaemia

1. Acute blood loss

2. Aplastic anaemia
3. Anaemia of chronic disease
4. Haemolytic anaemia
 1.Acute blood loss
Stage I:
– Hb, Ht, Rc, N or ↑
– white cells ↑
– platelets ↑

Stage II (2 – 4 days):
– Hb, Ht, Rc ↓
– reticulocytosis
– ↓ white cells
Stage III (2 – 3 weeks):
– ↓ platelets
–Hb, Ht, Rc
–Wc
–Platelets
} N
 1.Aplastic anaemia
Aplasia of the bone marrow with peripheral blood pancytopenia.
Causes:
– congenital: Fanconi’s anaemia
– acquired:
– chemicals, drugs, insecticides
– ionizing radiation
– infections: viral hepatitis measles
– miscellaneous infection: tuberculosis
– tyhmona
– pregnancy
– unknown
clinical features:
– anaemia
– bleeding (ecchymoses, bleeding gums and epistaxis)
– infection (fungal infections)

investigations:
– elevated serum iron
– low haemoglobin
– white cell
– count 500 / mmc
– platelet 20,000 / mmc
– reticulocytes virtual absent
– hypocellular or aplastic bone marrow
 1.Haemolytic anaemia
The red cells normally survives about 120 days, but in
haemolysis the cell survival times are considerably shortened.
Causes of haemolytic anaemia:
D. Inherited:
1. red cell membrane defect:
– hereditary spherocytosis
– hereditary eliptocytosis
2. haemoglobin abnormalities:
– thalassaemia
– sickle cell disease
3. metabolic defects:
– glucose 6 phosphate dehydrogenize deficiency
– pyruvate kinase deficiency
 (Causes of haemolytic anaemia)
B. Acquired:
1. immune:
– autoimmune
– isoimmune (Rh or ABO incompatibility)
2. non-immune:
– membrane defects: paroxysmal nocturnal
haemoglobinuria, liver disease, renal disease
– mechanical: damaged vessels, valve prosthesis, march
haemoglobinuria
3. miscellaneous:
– infections
– drugs and chemicals
– hypersplenism
 site of haemolysis:

3. Intravascular – red cells are rapidly destroyed within the

circulation, haemoglobin is liberated;
4. Extravascular – red cells are removed from the circulation by
macrophages in the reticuloendothelial system (liver and
spleen)
 evidence for haemolysis:
Increased red cell breakdown leads to:
– iron ↑
– stercobilinogen ↑
– elevated serum bilirubin (unconjugated)
– excess urinary urobilinogen
– reduced plasma haptoglobin
– abnormal red cell fragments in peripheral blood

Increased red cell production leads to:

– reticulocytosis
– erythroid hyperplasia of the bone marrow
 clinical findings:
– skin – jaundice
– splenomegaly
– abdominal pain (infarction or acute sequestration as in sickle
syndromes)
– gall stones
– growth impaired (e.g. spherocytosis)
– ulcers on the leg
– dark urine (in haemolytic crises)
– black in pmn
– septic necrosis of the bone (sickle sdr.)
– papillary necrosis affecting the kidney → haematuria (S.S.)
– painful priaprism
– cerebral damage
Peripherical blood in
hemolytic anaemia
 Polycythaemia

Is defined as a haemoglobin level greater than 18 g/dL, a red

cell count above 6x1012/L. The red cell volume is greater than
36 mL/kg in males and 32 mL/kg in females.

Causes of polycythaemia
Primary:
– Polycythaemia vera
Secondary:
A. due to an appropriate increase in erythropoetin:
– high altitude
– lung disease
– cardiovascular disease (right left shunt)
– heavy smoking
B. due to an inappropriate increase in erithropoetin:
– renal disease, carcinoma, Wilms tumor
– hepatocellular carcinoma
– adrenal tumors
– cerebellar haemangioblastoma
– massive uterine fibroma
Relative:
– stress or spurious polycythaemia
– dehydration
– burns
 Policitemia vera
Caused by chronic sustained proliferation of the erithroid
population of the bone marrow.

↑ red cell volume

↑ blood viscosity

Ht ↑ ↑ ↑
compensated by an
increase plasma
volume and  myocardial infarction
cardiac output stroke
 clinical findings:

 tiredness
 depression
 vertigo
 tinitus and visual disturbance
 hypertension
 angina
 intermitent claudication
 tendency to bleed
 itching after bath
 peptic ulcerations
 investigations:

 ↑ Hb, ↑ Ht, ↑WBC, ↑platelets

 erythroid hyperplasia and abnormal megakaryocytes in bone
marrow
 red cell volume ↑
 serum uric acid levels ↑
 leucocyte alkaline phosphatase (LAP) ↑
 vitamin B12 binding protein is ↑
 The white cell
The five types of leucocytes found in peripheral blood are:
• polymorphonuclear leucocytes (neutrophil leucocytes)
• eosinophil leucocytes
• basophil granulocytes
• lymphocytes
• monocytes

Polymorphonuclear leucocytes originate in the bone marrow and

are carried to tissues via the blood, where they are involved in
immune defense and may continue to circulate between the
lymphatic tissue and blood stream.
 neutrophilis

The neutrophil granulocyte originates in the bone marrow as

myeloblast → promyelocyte → myelocyte (stored up to 10 days)
Function
– ingest and kill bacteria
– accumulation of degenerate neutrophils gives rise to pus

Neutrophil luecocytosis
 rise in the number of neutrophils to > 10x105/l in bacterial
infection or tissue damage
 exercise
 corticosteroid administration
Neutrophil leucocytosis
 leukaemia
 myeloproliferative disease
 leukaemoid reaction
 leucoerytroblastic anaemia
 the leucocytosis may be accompanied by a pyrexia due to
the production of a leucocyte pyrogen
 a leukaemoid reaction (the overproduction of white cells,
many of them primitive) may occur in - severe infections
- tuberculosis
-malignant infiltration
 neutrophilis
Neutropenia and agranulocytosis
 defined as a circulatory neutrophil count below 1,5x109/l
 the absence of heutrophilis is called agranulocytosis

causes of neutropenia
 rasial (neutropenia is common in black rases)
 viral infection
 severe bacterial infection (typhoid)
 Felty’s syndrome
 megaloblastic anaemia
 drugs
 pancytopenia from any cause
 Clinical features:
 infections
 glazed mucositis occurs in the mouth and ulceeration is
common
 septicaemia

investigation
 blood film shows neutropenia
 bone marrow – absence of cells from the neutrophil
granulocyte series
 eosinophils
– Occur when the number of eosinophils is > 1x109/l

causes of eosinophils
 Parasitic infestation
– ascaris
– strongyloides

 Allergic disorders
– hayfever (allergic rhinitis)
– other hypersensitivity reactions, including drug reactions

 Skin disorders
– urticaria
– eczema
– pemphigus
 Pulmonary disorders
– bronchial asthma
– tropical pulmonary eosinophilia
– allergic bronchopulmonary aspergillosis
– polyarteritis nodosa (Churg – Strauss syndrome)

 Malignant disorders
– lymphoma
– carcinoma
– melanoma
– eosinophilic leukemia

 Miscellaneous
– sarcoidosis
– hypoadrenalism
– eosinophilic gastroenteritis
– hypereosinophilic syndrome
 lymphocytes
• Form nearly the circulating white cells
• Originate in the lymph glands, spleen, Peyer’s patches, bone
marrow, thymus
2 types:
 thymus dependent or T lymphocytes concerned with
cellular immunity
 “bursa – dependent” or B lymphocytes concerned with
humoral immunity

Lymphocytosis occurs in:

• viral infections: Epstein – Barr, cytomegalvirus
• chronic infections: syphilis, tuberculosis
• acute viral infections: pertussis, brucellosis
 The leukaemias
Characterized by the proliferation of a single malignantly
transformed progenitor cell in the haemopoietic system.

clasification
There are TWO MAJOR of acute leukemia:
F. Acute lymphoblastic leukaemia
G. Acute non-lymphocytic leukaemia (called also acute
myelogenous leukaemia)
The CHRONIC FORMS of these conditions are:
Chronic granulocytic leukaemia
Chronic lymphatic leukaemia
 incidence
– the commonest childhood leukaemia is acute lymphoblastic in
type (80%)
– adults B and in elderly – chronic forms

aetiology
– remains unknown
Genetic factors:
– are important: low frequency of all in black children
– a high incidence of leukaemia in the identical twin
– ↑ risk of developing acute leukaemia in children with Down’s
syndrome (who have chromosomal abnormalities)
Enviromental factors:
 radiation (in survivors of the atomic bomb of Hiroshima)
 chemicals
 drugs and chemotherapeutic agents
 viruses (human leukaemia virus type I) which was first
discovered in Japanese with T cell leukaemia and
hypercalcaemia
 Acute leukaemia
Cellular types
3. Acute lymphoblastic leukaemia
– blast cells involved may vary
– histologically: L1, L2 and L3 types
– the phenotypic markers have proved to be of considerable
importance assessing the likelihood importance of
response and the long-term outlook
4. Acute non-lymphocytic leukaemia
 classification
Acute myelocytic • predominant myeloblasts, distinct
M1 leukaemia without nucleoli
differentiation• few granules Auer rods – rare
Acute myelocytic • myeloblasts and promyelocytes
Leukaemia with predominant
M2 Differentiation • further maturation abnormal
• auer rods – many
Acute • promyelocytes predominate
M3 promyelocytic hipergranular
leukaemia • auer rods – rare
Acute • myelocytic and monocytic maturation
M4 myelomonocytic evident may be peripheral
leukaemia • auer rods – rare
Acute monocytic • promonocytes predominant with
M5 leukaemia differentiation
Acute monoblastic • completely with differentiation
M5 leukaemia • undifferentiated blast cells
A
• bizzare, multinucleated megaloblasted
M6 Erytroleukaemia erythroblasts predominate
• myeloblasts also present
 Acute leukaemia
clinical features
Hystory short
 symptoms of anaemia and maladive
 acute infections such as mouth ulceration, sore throat,
pneumonia, perianal and skin infections
 painful and enlarging lymphadenopathy
 bruising and bleeding
 bone pain (particularly common in children with all)
 symptoms due to infiltration of tissues with leukaemic blast
cells, marked gum hypertrophy
 headache, nausea, vomiting and blurred vision (raised
intracranial pressure)
Signs
These may be relatively few, but commonly they are:
 pallor
 bruising, petechial haemorrages, bleeding gums and gum
hypertrophy
 lymphadenopathy
 splenomegaly and hepatomegaly
 haemorrhages in the optic fundi with characteristic central
white deposit in the middle of the fundal haemorrhage →
leukaemic retinopathy
 meningeal leukaemia
 boys – hard enlarged testicles (infiltrated with leukaemic
tissue)
 investigation
2. Peripheral blood film and bone marrow
– normochromic and normocytic anaemia
– the white cell count may be normal or raised; rarely a few
blast cells may be seen in the peripheral blood, or none at
all
– the platelet count is usually reduced
– hypercellular bone marrow with characteristic blasts in the
trail of the fragments on the microscope slide
3. The CSF should be examined – will contain blasts cells if
meningeal leukaemia is present
4. Test of renal function
5. Serum uric acid
6. Serum calcium
7. Serum electrolytes (potassium)
8. Blood cultures
9. Chest X ray (to determine the presence of a mediastinal mass)
Gum-hypertrophy ALL
Blasts-and-Auer-body
 ALL

ALL Blast
ALL-L1-Marrow
 Chronic granulocytic leukaemia
– occurs in middle-aged and elderly people
– it occurs in the myeloproliferative syndromes, which include:
polycythaemia vera, myelofibrosis, essential trombocytosis
– it is characterised by the presence of Philadelphia
chromosome

Clinical features
 often of insidious onset (may only be discovered on a routine
blood count)
 anaemia
 bruising and bleeding manifestations
 pain or discomfort due to a very large spleen →
gastrointestinal disturbance
 sweating, fever and loss of weight as the result of a high
metabolic rate
 Phisical signs
 anaemia
 lymphadenopathy (uncommon)
 a large spleen (common)
 haemorrhage and thrombosis; bruising, bleeding, priapism
may occur
 gout
 Investigations

 normal Hb (initially), than a normocytic, normochromic

anaemia
 white cell count is greater than 100 000 /mmc (100 000 – 500
000 /mmc)
 blood film: abundance of neutrophils, mielocytes and even a
few blast cell are present
 platelets count: N or ↑
 bone marrow: hypercellular marrow with the granulocyte
precursors markedly increased
 a chromosome preparation shows the Philadelphia
chromosome
 the leucyte alkaline phosphatase (lap) is very low
 levels of serum vit. B12 and B12 binding proteins are elevated
 Chronic lymphatic leukaemia
 disease of late middle-aged and elderly people
 disorder of B cells, with accumulation of mature lymphocytes
in the tissues and peripheral blood
 few cases the lymphocytes are T cells and skin involvement
can occur (mycosis fungoides, the Sézary syndrome,
peripheral T cell lymphoma)

clinical features
• the onset is insidous
• lethargy
• fever and sweating
• loss of weight
 signs
 moderate enlargement of lymph nodes in the neck, axilla and
groin
 splenic and hepatic enlargement, but not usually massive

investigations
 mild anaemia, normochromic, normocytic
 white cell count > 15x109 &l, which more than 40%
lymphocytes
 platelet count is usually normal as the disease progresses,
anaemia may become severe due to Coombs positive
haemolysis and the number of lymphocytes ↑