Anaemia

Anaemia is a haematological condition in which there is

quantitative deficiency in the circulating haemoglobin,
often accompanied by a reduced number of erythrocytes
causing pallor, weakness and breathlessness
Anaemia is defined as a decrease in the circulating red
blood cell (RBC) mass; the usual criteria are a
haemoglobin (Hb) of less than 12g/dl(haematocrit less
than 36%) in women and less than 14g/dl( haematocrit
less than 46%) men
Anaemia is a condition in which the number of RBC or the
amount of haemoglobin is low

Physiology of the blood

The blood is a complex mixture of plasma, white blood cells(WBC),

RBC, and platelets
The blood functions as a transport system for carbondioxide
(CO2), oxygen, nutrients, hormones and waste other waste
products of metabolism
It also contains components that fight infections
The bone marrow the site for the production RBC, most WBC and
platelets.
T and B lymphocytes are also produced in the lymph nodes,
spleen.
Within the bone marrow all blood cells originate from a single type
of unspecialized cell called the stem cell.

 The

WBC last for a few hours to a few days

The platelets last for about 10 days
The RBC last for about 120 days

Approach to patients with anemia

clinical manifestations

Signs and symptoms of anemia vary depending on the

disorders etiology, degree, and rapidity of onset, but
generally with Hb of less than 7g/dl presents with
symptoms of tissue hypoxia suc has headaches,easy
fatigability, dyspnea, light headedness, angina.
Symptoms such as pallor, visual impairmnet, syncope,
and tarchycardia may signal anemic hypovolumia
which require immediate attention.

History and physical examination

The

acute or chronic onset of the anemia

should be assessed and clues to any
underlining systemic prosses should be sought
Physical findings that aid in diagnosis include
lymphoadenopathy, hepatic or splenic
enlargement, jaundice, bone tenderness,
neurologic symptoms and evidence of blood in
urine or stools

Laboratory evaluation

Hb and Hct
It serves as an estimate of the RBC mass but
their interpretation must take into consideration
the volume status of the person
The recticulocyte count
It reflects the rate of production of the RBC and
it is an indication of the bone marrow response
to the anemia

Laboratory evaluation ctn

The MCV
It is used in classifying anemia i.e whether microcytic,
normocytic and macrocytic .
Proper interpretation of MCV depends on the
examination of peripheral smear for the ff reasons
Small and large cells may be present simultaneously
resulting a normal MCV
The recticulocyte colud increase the MCV because they
are larger the RBCs
Abnormal cells may be present in numbers too small to
affect the MCV

Lab ctn
Examination

of peripheral smear
This is mandatory because
Heterogenicity in RBC size and shape may be
seen

Lab ctn
Additonal

testing should be guided the initail

findings eg G6PD and Hb electrophoresis

classification
Anaemia

is characterized by the MCV and the

recticulocyte count

Anemia associated with decreased

RBCs production

Iron deficiency anemia

Megaloblastic anaemias
Thalassemias
Anemia from chronic renal insufficiency
Anemia from chronic diseases
Aplastic anemia
Anemia associated with HIV infections
Myelodysplastic syndrome

Iron deficiency anemia

Laboratory

results;
Usually, the MCV is normal in early iron
deficiency. As the Hct falls below 30%,
anisocytosis increases, and hypochromic
microcytic cells appear, followed by a decrease
in MCV

Classifications of anaemia

Anaemia associated with decreased RBC production

Iron- deficiency anaemia
Thalassemias
Myelodysplastic syndrome(MDS)
Megaloblastic anaemia
Anaemia of chronic renal insufficiency
Anaemia associated with HIV infection
Aplastic anaemia
Vitamin C deficiency
Multiple myeloma
Leukemia
Lymphoma
Metastatic cancer

Classification ctn

Anaemia associated with increased RBC loss or destruction

Bleeding
Haemolytic anaemia
Sickle cell anaemia
G6PD deficiency
Autoimmune haemolytic anaemia
Enlarged spleen
Mechanical damage to RBC
Paroxysmal noctural haemoglobinuria
Hereditary spherocytosis
Hereditary elliptocytosis
Haemoglobin C, S-C, and E disease

Classification ctn
Excessive

bleeding

Sudden
Accidents
Surgery
Childbirth
Ruptured blood vessel

Classification ctn

Chronic
Nosebleeds
Hemorrhoids
Ulcers in the stomach or small intestine
Cancer or polyps in the GIT
Kidney or bladder tumors
Heavy menstrual bleeding

classification

Decreased RBC production

Iron- deficiency
Vitamin B12 deficiency
Folic acid deficiency
Vitamin C deficiency
Chronic disease
Aplastic anaemia

Iron deficiency anaemia

Iron

is a transition metal which is a key

component in the RBC
The ability of blood to carry oxygen to the
tissue is due to the presence of iron in the
haemoglobin
Iron is als ocontained in some enzymes and
other functional compounds such as myoglobin
and those of the cytochrome system

Physiological importance of iron

Erythropoiesis
Tissue

respiration
Several enzyme-catalyzed reactions

Symptoms of iron deficiency

Impaired work performance in adults

Low birth weight
Prematurity
Increased perinatal motrality
Impaired psychomotor behaviour, cognitive function in
infants and young children
Abnormalities of epidermal structures, heat production,
catecholamine turnover, mentation and resistance to
infection
Decreased academic achievement in children

Daily iron requirements

Body iron is usually kept constant by a delicate

balance between the amount lost and amount
absorbed
Iron requirements are determined by total losses from
the body and vary according to age, gender.
Requirements are higher for menstruating and
pregnant mothers and premature babies
Menstrual iron losses are reduced by 50% in women
taking oral contraceptives but increased by up to 100%
if they are using intrrauterine devices

Absorption or iron
Dietary

iron exist as a heme or non heme iron

Iron is absorbed in the ferrous state with heme
iron being the most readily absorbed form
It is found in a variety of food stuffs example
red meat, poultry, some dried beans and some
vegetables
Only part of dietary iron is absorbed

 Absorption

of iron is dependent on some

factors such as
The amount of iron in the diet
The physiologic status of the small bowel
where the iron is absorbed
The composition of the diet
The erythropoiesis rate

Factors that affect absorption

food

that reduce iron absorption include;

Coffee
Tea
Milk
Eggs
Any food contain carbonates, bicarbonates,
phosphates and oxalates

Factors affecting absorption ctn

Enhancers

of nonheme iron absorption include;

Meat
Food acids eg. Citric acid, lactic acid or
ascorbic acid

etiology

Primary cause of iron deficiency in adults is hemolysis

and pregnancy
Primary source of blood loss include the GIT caused
by;
NSAIDs
Noeplasms
PUDs
Oesophageal varices
Hookworm infestations
Ulcerative colitis

Etiology ctn
Menorrhagia(

heavy menstrual bleeding)

Sports and dilutional anaemias
Poor nutrition
Malabsorption
Gluten enteropathy
Gastrectomy

Clinical findings

Appearance
tired, lifeless appearance, listless
Skin and hair
pale skin, inelastic, and often dry, dry
and often scanty hair
Mouth papillary atrophy and erythema of the tongue,
angular stomatitis
Eye
pearly white, sclerea
Nails flattened, longitudinally rigid and concave
Cardiovascular system slight cardiomegaly,
tarchycardia, functional systolic mumur, ankle edema

Clinical findings ctn

haematology
MCV

decreased
MCHC
decreased
Marrow iron stores depleted
Serum iorn reduced
Serum ferritin reduced
Serum transferrin increased
Heamoglobin reduced

Clinical finding ctn

Half

pica

the sufferes of iron deficeincy experience

Laboratiory results

Usually, the MCV is normal in early iron deficiency .

As the Hct falls below 30%, anisocytosis increases and
hypochromic microcytosis cells apear, followed by a decrese in the
MCV
Serum ferritin levels of less than 10ng/gl for women and 20ng/dl
for men is indicative of low iron stores.
Ferritin is an acute phase reactant and normal levels may be seen
in inflammatory conditions despite low iorn stores
A bone marrow biopsy is the definite test for establishing iron
deficiency. This is used when serum ferritin levls fail to confirm the
diagnosis
Alternatively a therapeutic challenge with iorn may be use

therapy
Treatments

available include
Oral iron therapy
Parental iron therapy
Blood tranfusion

Oral iron therapy

Ferrous

sulphate ,containing 65mg elemantal

iron given tid in between meals will maximize
absorption will correct anaemia and restore
depleted iron in 6 months
Other salts of iron include
Ferrous fumarate
Ferrous glu

Side effects
These

include
Constipation
Cramping
Diarrhoea
nausea

Oral iron therapy

Ferrous

gluconate and fumarate may be more

tolerated
Ascorbic acid aids in the absorption of the iron
Enteric and slow-release preparations may
release less elemental iron because of site of
iron absorption

Parenteral iron therapy

This

may be used in patients with

Poor oral absorption( IBD, malabsorption)
Very high iron requirements that cannot be met
by oral therapy
Intolerance of oral peparation

Parenteral iron therapy

This formula may be used to approximate the amount of

iron required to restore the Hb to normal levels and
replenish the iron stores
Iron(mg)=0.3xbodywt(lb)x(100-{Hb(g/dl)/14.8]x100)
Most people require 1000-2000mg iron to correct the deficit
Iron dextran is the only available parenteral agent and may
be given either IV or IM.
A single dose of IV diluted in 250-500ml of normal saline
and infused at 6mg/min. has been used with few
coplications

Parenteral therapy
A 0.5ml

( 25mg) test dose IM or IV of undiluted

dextran should be given 1 hour before therapy
Delayed reactions to IV therapy may be seen
within 3 days of therapy and resolves
spontaneously or after treatment with NSAIDs

Blood transfusion
Blood

transfusion is not recommended for the

treatment in the absence of cereberal or
cardiopulmonary compromise

Megaloblastic anemia
A group

of disorders associsted with altered

morphology of hematopoietic cells and other
rapidly cells because of abnormalities in DNA
synthesis
Almost all cases result from from folic acid and
Vitamin B12 deficiency.

Sources of folic acid and Vit B12

Folic acid
Green leafy vegetables
Fruits
Organ meat such as liver and kidney
Vitamin B12
Fresh liver
Eggs
Meat
Kidney
Diary products
fish

Megablastic anaemia
folic acid deficiency
Causes

include;
Decreased intake( alcoholism)
Malabsorption
Increased use( hemolytic anemia, pregnancy)
Some drugs ( trimethoprim, methothrexate,
sulfsalazine, pyrimethamine, oral
contraceptives and anticolvosants) may lead to
a disturbed folate metabolism

Megaloblastic anemia
Vitamin B12 deficiency

Deficiency develops over years because very little of

the bodys store is used each day
Causes of Vit B12 deficiency include;
Pernicious anemia
Gastrectomy
Pancreatic insufficiency
Intestinal bacterial overgrowth
Ilietis or ileal resection
Intestinal parasites

History and physical examination

Symptoms are attributed to anemia although glossitis,
jaundice, and splenomegaly may be present
Vitamin B2 deficiency may cause;
Decreased vibratory and positional sense
Ataxia
Paresthesias
Confusion
Dementia
Folic acid deficiency does not cause neurological disease

Laboratory result

Laboratory findings include

A macrocytic anemia is present
Leucopenia and thrombocytopenia may also occur
Peripheral blood smear may show
Anisocytosis
Poikilocytosis
Macro-ovalocytes
Hypersegmented neutrophils

jh

Lab results

Lactate dehydrogenase(LDH) and indirect bilirubin are elevated

Serum vitamin B12 and folate levels should measured but RBC
folate is more accurate indicator of body folate stores
Serum methymalonic acid and homocysteine(HC) may be
helpful when the vit B12 or folate level is eqivocal. Both
serummethymalonic acid and HC levels are elevated in vitamin
B12 deficiency but only HC is elevated in folic acid deficiency
The schilling test may be useful in the diagnosis of pernicious
anaemia due to vitamin B12 deficiency but rarely affect the
therapeutic approach

Lab cont
Bone

marrow biopsy may be necessary to rule

out MDS and hematologic malignancy; these
disorders may present with findings similar to
megaloblasic anemia on blood smear

Treatment
goals;
The

replace the deficient factor

The treat the hypokaleamia which may occur
To identify and treat appropriately if possible
the underlining condition

treatment

Folic acid ;where possible folic acid should not be

given until Vit B12 or pernicious anemia has been
excluded
Although 5mg folic acid is able to restore folate levels,
in practice much lower doses can be used
Duration of therapy depends on the underlining
condition and it can take 3 to 4 months to clear folatedeficient blood cells from the system
Long-term therapy may be required in cases such as

Treatment ctn

Chronic hemolytic states

Mylofibrosis
Refractory malabsorption
Requirements may be increased inc onditions such as
Postgastrectomy states
Prolong stress or infection
Chronic fever
Persistent diarrhoea

Treatment ctn
Low

doses of folic acid can be given to patients

with megaloblastic anemia due to antiepileptic
agents
Prophylaxis is given to
Pregnant women with poor diet
Women with multiple pregnancies
Thalassemia minor

Treatment
Vitamin B12
The

goals of treatment include

Hematologic remission
Reversal or retardation of the nervous system
complication
Replenishment of B12 stores

Treatment ctn

Depending on the cause either oral or Parenteral B12 is used is used

In pernicious anemia or after totall gastrectomy or extecsive ileal
resection, parenteral therapy is required for life

In children with intracellular defects of B12 metabolism, hydroxocobalamin

is more effective for treatment than th cyanocobalamin

Higher doses are used in the management of the neurologic

manifestation

In severe cases of pernicious anemia the patient should be confined to

bed until the heamoglobin has increased to about 70g/l
The diet should be light, easily digested and must contain proteins, iron
and ascorbic acid

Treatment ctn
Oral

cyanocobalamin may be justified for

patients with beeding disrders or for those
allergicc to parenteral B12
Oral b12 is not useful in
small bowel
Malabsorption syndrome
Following gastric or illael resection

Treament ctn
Transfusion

is rearly indicated but are used

cautiously in patients how are
dyspneic at rest
Those not responding to b12
Those witth very low Hb levels

Anemia of chronic renal insufficiency

The anemia that complicate end stage renal disease is

genreally more severe than that associated with other
chronic diseases
Most patients with serum creatinine concentratoins of
morethan 3.5mg/dl and 97% of those on maintenance
dialysis are affected
The cells are normochromic, norcytic but frequently
irregular in shape
Although the hematocrit may fall not all patients
become symptomatic

symptoms
Generalised
Anorexia
Insomnia
depression

coldness

pathogenesis
This

is attributed primarily to decreased

indogenous erythropoetin(Epo) production
Other factors that contribute to the anemia are;
The accumulation of inhibitors or
erythropoiesis,
reduces red blood cell lifespan and
chronic blood loss

Laboratory findings
Hct

of 20-30%
Normal MCV
RBCs are normochromic
Occassional presence of echinocytes and
acanthocytes

Treatment
goals
Sujective

benefits include
Increase energy
Enhance appetite
Better sleep parterns
Improve sexual activity

Treament
goals
Objective

benefits
Enhanced exercise capacity
Improve cognitive function
Elinication of RBC transfusions and reduction
of iron overload

treatment

Androgens; this has been recommended in selected

patiens with end-stage renal disease
Androgens stimulate the synthesis of erythropoeitin
and/or the production of RBC in the bone marrow
Therapy with the injectable formulations nandrolone
decanoate and testesterone enanthate resulted in
significantly greater improvement than the oral
androgens, fluoxymesterone and oxymetholone

Treatment ctn
Patients

with lower pretreatment Hct

concentration, bilateral nephrectomies, intact
parathyroid glands have poorer response rate

Side effects of the androgens

Hirsutism
Changes

in external genitalia
Amenorrhoea
Acne
Voice deeping
Liver sysfunction
Hepatic cancer

Treatment ctn
Recombinant human erythropoeitin

( rHuEpo)

patients with end-stage renal disease with Hct

levels under 0.30 may be considered as
candidate for rHuEpo

Treatment ctn
Recombinant human erythropoeitin

( rHuEpo)

Therapy is indicated in both predialysis and dia;ysis

patients who are symptomatic
Treatment maybe given IV or SC
More than 97% of patients increase their Hct by 10
points or to level greater than 32% within 12 weeks of
therapy
Suboptimal responses occur with coexisting iron
deficeincies thus many patients benefit from iron
supplementations

treatment
Response

to Epo may be affected by

Chronic inflammatory conditoins
Acute or chronic bleding
Aluminium intoxication
Secondary hyperparathyroidism causes bone
marrow fibrosis and relative Epo resistance
may occur

Side effects
Myalgias
Headaches
Hypertension
Flank

pain
Seizures

Aplastic anemia
This

is an acquired abnormality of the bone

marrow stem cells
Most cases are idiopathic, although perhaps
20% is associated with drug or chemical
exposure and another 10% is associated with
viral illnesses

pathogenesis

In normal hematopoeisis three cells originate from the

pluripotential stem cell, producing erythrocytes, granulocytes and
platelets
Aplastic anemia develops when hematopoeisis is interrupted
because of defficient or defective stem cells
Pathophysiologic mechanisms resultiing in apalstic anemia
include;
Reduced number of progenitor cells
Immune mediated suppression of stem cell function
Disturbances in bone marrow micrenvironment
Alteration in the cellular or hmoral interractions that sustain
hematopoiesis

Etiology
Acquired

Drugs and chemicals

Acetazolamide
Anticonvulsants
Carbamazepine
Phenytoin
Primidone
Arsenic
Benzene
Chloramphenicol
Chorpromazine
Ethanol
Goldsalt
Insecticides
Sulphur drugs

Etiology
acquired
Viral

Cytomegalovirus
Hepatits
Herpes virecella zoster
Influenza
Rubella

Etiology
acquired
Other

Ionizing radiation
Pregnancy
Parosysmal nocturnal hemoglobiniria

Etiology
congenital
Dyskeratosis

congenita
Fanconis anemia
Schwarchman-Diamond syndrome

Treatment
goal
Removal

of potential etiologic agent

Supportive care
Restoration of normal hematopoesis

Treatment ctn
Pharmacologic

agents
Bone marrow transplant

Pharmacologic agents

Androgens such as oxymetholone may be used at a

dose of 1-5mg/kg daily for 3-6 months
Immunosuppressive agents such as cyclosporin,
glucocorticoids, anti lymphocyte globulins and
antithymocyte globulins
Antilymphocyte globulin given IV through a central line
over 12 -18 hours each day for 5 days produces a
response in about 50% of cases of acquired aplastic
anemia. Response rate may increase when cyclosporin
is given as well

Bone marrow transplant

This

has become the treatment of choice for

severe aplastic anemia with greater success
achieved in younger patients undergoing the
procedure soon after dialysis
Graft rejection may develop because of minor
antigenic differences between the donor and
recepient marrow. Therefore a course of
immunosuppressivetherapy is administered
immediately prior to transplant

Bone marrow transplant

Most commonly the treatment regimen consist of IV

cyclophosphamide 50 mg/kg daily for 4 days alone or
combined with total body or total lymphoid irradiation
Supprotive care should include
Isolation in a sterile environment
Transfusions of blood products as required
Close monitoring for signs of infection
Prophylactic antifungal therapy and bowel sterilization

Problems of bone marrow

transplant
Infections
Acute

graft versus host disease

Chronic graft versus host disease

Anemia associated with increase

RBC loss or destruction
Bleeding
Hemolytic

anemia
Autoimmune hemolytic anemia
Drug-induced hemolytic anemia
Micrangiopatic hemolytic anemia
Sickle cell anemia
Glucose 6 Phosphate Dehydrogenase
Deficiency (G6PD)