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ANAEMIA

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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

volume (MCV) Red cells count

Mean corpuscular Haemaglobin x 10

haemaglobin (MCH) Red cells count

Mean corpuscular Haemaglobin x 10

haemaglobin Haematocrit

concentration (MHCH)

N = 80 96 =

=

=

N = 27 33 pg

N = 32 35 g/dL

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Clinical features

Symptoms (all non - specific):

fatigue

headachesfaintness

breathlessness

angina of effort

intermitent claudication

palpitations

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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 deficiencyanaemia

jaundice haemolytic anaemia bone deformities thalassemia major

leg ulcers sickle cell disease

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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 illiaccrest 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

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MYCROCYTIC ANAEMIA

small cells (microcytes)

low MCV (< 80 L)

iron content

ragged normoblasts

small cells (microcytes)

low MCV (< 80 L)

normal iron content hyperplastic

Iron deficiency anaemia

Thalassaemia

Sideroblastic anaemia

}

}

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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 andsoluble in the upper gut

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transport in the blood:

transported in the plasma bound to transferin, beta globulinesynthesized 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 andsweat

menstruating women lose 0.7 mg iron / day of menstruation

pregnancy and groth iron demand

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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. tractMenstruation

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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

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investigations:

the red cells are microcytic (MCV < 80 fL) and hypochromic(MCV < 27 pg)

poikilocytosis (variation in shape) and anisocytosis (variation insize)

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

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Bone marrow in iron deficiency

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1.sideroblastic anaemiaClassification:

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 tissuedisease)

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1.thalassaemia

Deficiency in the synthesis of the globin chains of haemoglobin

in addition, the accumulation of abnormal chains within the redcell leads to its early destruction.

The severity of the thalassaemia will depend on the amount othe haemoglobin A2 and F present.

Clinically -thalassaemia can be divided into:

thalassaemia mayor, with severe anaemia

intermedia, with moderate anaemia rarely requiring

transfusion

minor, the symptomless heterozygous carrier state

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symptoms:

failure to thrive

intermittent infection

severe anaemia

extramedullary haemopoiesis hepatosplenomegaly and boneexpansion thalassaemic facies

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investigation:

blood count:

moderate to severe anaemia (MCV, MCH)

reticulocyte

white cells and platelets = N

blood film:

hypochromic and microcytic picture

Howell Jolly bodieshigh ferritin levels

haemoglobin electrophoresis (HbF ; HbA absent)

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-Thalassaemia trait (minor)

asymptomatic

no anaemia, red cells hypochromic and microcytic

-Thalassaemia

two main form:

deletion of only alpha chain gene

deletion of both alpha chain genes no alpha chains are

produced

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Thalassemia major

Thalassemia minor

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Macrocytic anaemia

The presence in the bone marrow of erytroblasts with delayednuclear maturation because of defective DNA synthesis(megaloblasts).

Occurs in:

vitamin B12 deficiency

folic acid deficiencydiseritropoetic anaemia

Haematological values:

anaemia

MCV > 96 fL

blood film (peripheral): macrocytes and hypersegmentedpolymorphs

neutropenia

thrombocytopenia

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vitamin b12 (Addison Biermer anaemia)

average daily diet 5 30 g B12

average adult stores 1000 g liver

absorption and transport:

gut binder complex (R binder + B12) intrinsec

factor (glycoprotein from the gastric juice)

Transcobalamin

Ileum Marrow

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Pernicious anaemia (Addison Biermer) affect:

particularly nordic people: fair haired; blue eyed.

association with other autoimmune diseases: thyroid disease,

Addisons disease, vitiligo

higher incidence of gastric carcinoma

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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 resectionC. 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)

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Clinical features:

2. Anaemic syndrome

3. Neurological syndromes:

Peripheral neuropathy progressively involving theposterior 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

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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

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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

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Bone marrow

pernicious anaemia

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Folic acid

Daily requirement 100 g

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, Crohns

disease, cancer)

excess utilization

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clinical features:

B. Physiological:

pregnancy lactation

prematurity

C. Pathological:

haemolysis

malignant disease

inflammatory disease

metabolic disease

haemolysis

malabsorption

antifolate drugs

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Normocytic anaemia

1. Acute blood loss

2. Aplastic anaemia

3. Anaemia of chronic disease

4. Haemolytic anaemia

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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 platelets

Stage III (2 3 weeks):

Hb, Ht, Rc

Wc N

Platelets

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1.Aplastic anaemia

Aplasia of the bone marrow with peripheral blood pancytopenia.

Causes:

congenital: Fanconis anaemia

acquired:

chemicals, drugs, insecticides

ionizing radiation

infections: viral hepatitis measles

miscellaneous infection: tuberculosis tyhmona

pregnancy

unknown

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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

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1.Haemolytic anaemia

The red cells normally survives about 120 days, but inhaemolysis 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

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(Causes of haemolytic anaemia)

B. Acquired:

1. immune:

autoimmune

isoimmune (Rh or ABO incompatibility)

2. non-immune:

membrane defects: paroxysmal nocturnalhaemoglobinuria, liver disease, renal disease

mechanical: damaged vessels, valve prosthesis, marchhaemoglobinuria

3. miscellaneous:

infections

drugs and chemicals

hypersplenism

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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

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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

li i l fi di

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clinical findings:

skin jaundice

splenomegaly

abdominal pain (infarction or acute sequestration as in sicklesyndromes)

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

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Peripherical blood in

hemolytic anaemia

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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 polycythaemiaPrimary:

Polycythaemia vera

Secondary:

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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 fibromaRelative:

stress or spurious polycythaemia

dehydration

burns

Policitemia era

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Policitemia veraCaused by chronic sustained proliferation of the erithroid

population of the bone marrow.

red cell volume

blood viscosity

compensated by an

increase plasmavolume and

cardiac output

Ht

myocardial infarctionstroke

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clinical findings:

tiredness

depression

vertigo

tinitus and visual disturbance

hypertension

angina

intermitent claudication

tendency to bleed itching after bath

peptic ulcerations

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investigations:

Hb, Ht, WBC, platelets

erythroid hyperplasia and abnormal megakaryocytes in bonemarrow

red cell volume

serum uric acid levels

leucocyte alkaline phosphatase (LAP)

vitamin B12 binding protein is

h hi ll

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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.

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neutrophilis

The neutrophil granulocyte originates in the bone marrow asmyeloblast 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 bacterialinfection or tissue damage

exercise

corticosteroid administration

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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

t hili

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neutrophilis

Neutropenia and agranulocytosis

defined as a circulatory neutrophil count below 1,5x10

9

/l the absence of heutrophilis is called agranulocytosis

causes of neutropenia

rasial (neutropenia is common in black rases)

viral infection

severe bacterial infection (typhoid)

Feltys syndrome

megaloblastic anaemia

drugs

pancytopenia from any cause

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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

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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

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y

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

l h

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lymphocytes

Form nearly the circulating white cells

Originate in the lymph glands, spleen, Peyers patches, bonemarrow, 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

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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 acutemyelogenous leukaemia)

The CHRONIC FORMS of these conditions are:

Chronic granulocytic leukaemia

Chronic lymphatic leukaemia

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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 Downssyndrome (who have chromosomal abnormalities)

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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 andhypercalcaemia

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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 outlook4. Acute non-lymphocytic leukaemia

classification predominant myeloblasts distinctAcute myelocytic

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bizzare, multinucleated megaloblastederythroblasts predominate

myeloblasts also present

ErytroleukaemiaM6

completely with differentiation undifferentiated blast cells

Acute monoblasticleukaemiaM5

A

promonocytes predominant with

differentiation

Acute monocytic

leukaemiaM5

myelocytic and monocytic maturationevident may be peripheral auer rods rare

Acutemyelomonocytic

leukaemiaM4

promyelocytes predominatehipergranular

auer rods rare

Acutepromyelocytic

leukaemia

M3

myeloblasts and promyelocytespredominant further maturation abnormal auer rods many

Acute myelocyticLeukaemia withDifferentiation

M2

predominant myeloblasts, distinctnucleoli few granules Auer rods rare

Acute myelocyticleukaemia without

differentiation

M1

Acute leukaemia

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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

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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

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investigation2. Peripheral blood film and bone marrow

normochromic and normocytic anaemia

the white cell count may be normal or raised; rarely a fewblast cells may be seen in the peripheral blood, or none atall

the platelet count is usually reduced

hypercellular bone marrow with characteristic blasts in thetrail of the fragments on the microscope slide

3. The CSF should be examined will contain blasts cells ifmeningeal leukaemia is present

4. Test of renal function

5. Serum uric acid6. Serum calcium

7. Serum electrolytes (potassium)

8. Blood cultures

9. Chest X ray (to determine the presence of a mediastinal mass)

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Gum-hypertrophy ALL

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Blasts-and-Auer-body

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ALL

ALL Blast

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ALL-L1-Marrow

Chronic granulocytic leukaemia

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g y

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 Philadelphiachromosome

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 highmetabolic rate

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Phisical signs anaemia

lymphadenopathy (uncommon)

a large spleen (common) haemorrhage and thrombosis; bruising, bleeding, priapism

may occur

gout

Investigations

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g

normal Hb (initially), than a normocytic, normochromic

anaemia

white cell count is greater than 100 000 /mmc (100 000 500000 /mmc)

blood film: abundance of neutrophils, mielocytes and even a

few blast cell are presentplatelets count: N or

bone marrow: hypercellular marrow with the granulocyteprecursors markedly increased

a chromosome preparation shows the Philadelphiachromosome

the leucyte alkaline phosphatase (lap) is very low

levels of serum vit. B12 and B12 binding proteins are elevated

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Chronic lymphatic leukaemia

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y p

disease of late middle-aged and elderly people

disorder of B cells, with accumulation of mature lymphocytesin the tissues and peripheral blood

few cases the lymphocytes are T cells and skin involvement

can occur (mycosis fungoides, the Szary syndrome,

peripheral T cell lymphoma)

clinical features

the onset is insidous

lethargy

fever and sweating

loss of weight

signs

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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