anaemias by DR KD DELE
DEPT. FAMILY MEDICINE
DORA NGINZA HOSPITAL

ANAEMIA:
“LACK OF
BLOOD”
Reduced concentration of
haemoglobin in the blood.
The number of red blood
cells in the blood is low.
If left untreated, can have
many serious implications

DEFINITION
A decrease in red blood cell (RBC) mass that can be detected by
haemoglobin (Hb) concentration, haematocrit (Hct), and RBC count
• adult males: Hb <13.5 gldL or Hct <41%
• adult femalc:s: Hb <12 gldL or Hct <36%
The World Health Organization (WHO) defines anaemia as hemoglobin
concentration <12 g/dL in women and <13 g/dL in men)

EPIDEMIOLOGY
Globally, anaemia is prevalent in most developing countries and of public health
significance
The global prevalence of anaemia for the general population is 24.8%
Women and young children are most vulnerable to anaemia.
The proportion of women and children is highest in the Africa region where:
 57% of pregnant women,
 48% of non-pregnant women, and
 68% of preschool children are anaemic
Anaemia is also a common, multifactorial condition among older adults.

EPIDEMIOLOGY, CONT.
Anaemia is associated with poorer survival in older adults
More than 10% of community-dwelling adults age 65 years and older are anaemic
After age 50 years, prevalence of anaemia increases with advancing age
In nursing homes, anaemia is present in 48–63% of residents.
Among older adults with anaemia, approximately:
 one-third have evidence of iron, folate, and/or vitamin B12 deficiency,
 another third have renal insufficiency and/or chronic inflammation, and
 the remaining third have anaemia that is unexplained.

PATHOPHYSIOLOGY

PATHOPHYSIOLOGY

PATHOPHYSIOLOGY
Erythropoietin – which is produced by peritubular capillary lining cells of the
kidney – is critical to the production of red blood cells.
Endogenously produced erythropoietin circulates in the plasma to act on specific
target cells in the marrow through cell surface receptors.
When the oxygen content of body tissues is low or the number of red blood cells
decreases, the kidneys produce and release erythropoietin, which stimulates the
bone marrow to produce more red blood cells.
Iron is bound to the iron transport protein transferrin, and the complex is
internalized, along with the transferrin receptor, by the developing erythroid cell.
Within the cell, the iron molecule is subsequently split off and either used for
haemoglobin synthesis or stored within the cytoplasm as ferritin.

REGULATION OF RED CELL
PRODUCTION

ERYTHROCYTE DIFFERENTIATION
It is the pathway
through which an
erythrocyte
matures from a
hemocytoblast into
a full-blown
erythrocyte.
01
Erythrocyte
differentiation takes
place in 8 stages.
02
The first seven all
take place within
the bone marrow.
03
After stage 7 the
cell is then released
into the
bloodstream as a
reticulocyte, where
it then matures 1-2
days later into an
erythrocyte:
04
Hemocytoblast,
Proerythroblast,
early & late
erythroblast,
Pronormoblast,
normoblast,
Reticulocyte
05

ERYTHROCYTE DIFFERENTIATION
P.S. Hemocytoblast is a pluripotent hematopoietic stem cell

RED CELL
PRODUCTION:
ORIGIN
Hemocytoblast:
generalized stem cell,
from which all blood cells
form including both
erythrocytes and
leukocytes.
(This is according to the
monophyletic theory of
blood cell formation)
It resembles a lymphocyte
and has a large nucleus; its
cytoplasm contains granule

PATHOPHYSIOLOGY CONT.
The primary role of red blood cells is the transport of respiratory
gasses.
In the lung, oxygen diffuses across the alveolar barrier from
inspired air into blood, where the majority is bound by haemoglobin
to form oxy-Hb, a process called oxygenation.
Haemoglobin is contained in the red blood cells, which, being
circulated by the cardiovascular system, deliver O2 to the periphery
where it is released from its Hb-bond (deoxygenation) and diffuses
into the cells.
In anaemia, there is decreased Haemoglobin which decreases
exercise performance despite a compensatory actions such as
increase in cardiac output.

CLINICAL FEATURES

CLINICAL FEATURES:
NON-SPECIFIC
Fatigue / malaise
Dizziness / faintness
Poor concentration
Headache
SOB
Palpitations
Angina

CLINICAL FEATURES:SPECIFIC
Blood loss (PR, PV bleeding)
Drugs (NSAIDS, chloramphenicol, phenytoin)
Diet (vegans, alcoholics, elderly)
Gastrectomy
Pregnancy
Chronic disease
Ethnicity – Thalassaemia

SYMPTOMS OF ANAEMIA, CONTD

SYMPTOMS OF ANAEMIA, CONTD

GENERAL ASSESSMENT

INVESTIGATIONS
Rule out dilutional anaemia (low Hb. due to increased effective circulating
volume)
FBC with differential (Hb, note WCC and platelets)
Note mean corpuscular volume (MCV) and Red Cell Distribution Width (RDW)
Reticulocyte count
Blood film
Rule out gastrointestinal disease in iron deficiency anaemia
Additional laboratory investigations as indicated (Microcytic Anaemia,
Normocytic Anaemia, Haemolytic Anaemia and Macrocytic Anaemia)

INVESTIGATIONS CONT.
Reticulocyte studies (marrow activity)
Reticulocyte count: N = 0.5 – 2 % of RBC’s
RPI (Retic Production Index )
 1-2 = adequate BM response
 <1 = inadequate BM response
 >3 = haemolysis, haemorrhage
Screen for (intravascular) haemolysis if suspected
 Raised LDH
 Decreased Haptoglobin
 Increased serum bilirubin (unconjugated) + urine urobilinogen

INVESTIGATIONS CONTD.
Iron studies
Folate and Vitamin B12 levels
Bone Marrow
 For further Investigation of abnormal blood results.
 Can tell cellularity of marrow,
 type of erythropoiesis (micro/macrocytic),
 cellularity of cell lines, iron stores.
Occult blood in stools
GI Endoscopy
Schilling test (macrocytic)
Microcytic

MEAN CORPUSCULAR VOLUME
(MCV)
The anaemia may be:
Microcytic (MCV <80 fL): serum iron studies should be performed
Normocytic (MCV 80-100 fL): the reticulocyte count should be examined
to determine whether the anaemia is hypoproliferative (<2%) or
hyperproliferative (>2%)
Macrocytic (MCV >100 fL): the peripheral smear should be examined for
megaloblasts and hypersegmented neutrophils. If these cells are present,
the anaemia is megaloblastic. If they are absent, the anaemia is non-
megaloblastic.

ALGORITHM

IRON STUDIES

PERIPHERAL SMEAR
Burr cells: irregularly shaped cells (uraemia)
Anisocytosis: variation in cell size (megaloblastic anaemia, thalassaemia)
Poikilocytes: variably shaped cells (Fe def anaemia)
Rouleaux formation: red cells stack on each other (high ESR)
Schistocytes: fragmented red cells (intravascular haemolysis)
Spherocytes: spherical red cells (haemolysis, hereditary spherocytosis)
Target cells: central staining, ring of pallor, outer rim of staining (liver dz.
Sickle cell dz. Small amounts in Fe def.)

NORMAL
A normal peripheral blood
smear indicates the
appropriate appearance of
red blood cells, with a zone
of central pallor occupying
about 1/3 of the size of the
RBC
See also Neutrophil and
few platelets

SEVERE IRON
DEFICINECY
Severe iron deficiency
anaemia showing
hypochromic pale
haemoglobin-deficient
microcytic small and
misshapen red blood
cells in human peripheral
blood smear
Variation in size
(anisocytosis) and shape
(poikilocytosis)

RETICULOCYTOSIS
Reticulocytosis
There is an increase in
reticulocytes, immature red blood
cells.
It is commonly seen in anaemia,
particularly in haemolysis.
They are seen on blood films when
the bone marrow is highly active in
an attempt to replace red blood
cell loss (N = 0.5-2%)

SCHISTOCYTES
The presence of schistocytes
(fragmented red blood cells) on
the peripheral blood smear.
It suggests red blood cell injury
from damaged endothelium
It is a characteristic feature of
microangiopathic haemolytic
anaemia.

SPHEROCYTOSIS
Spherocytosis is an auto-
haemolytic anaemia (a
disease of the blood)
characterized by the
production of spherocytes
(red blood cells (RBCs)) or
erythrocytes that are
sphere-shaped rather than
bi-concave disk shaped.
Usually hereditary or in
autoimmune conditions

Harrison’s Principles of Internal Medicine, 17th Edition
CALCULATION OF RPI

CLASSIFICATION

CLASSIFICATION: AETIOLOGICAL

CLASSIFICATION:
MORPHOLOGICAL

CLASSIFICATION:
MORPHOLOGICAL
3 Major Types
 Microcytic hypochromic
 Macrocytic normochromic
 Normocytic normochromic

CLASSIFICATION:
MORPHOLOGICAL CONT.

CLASSIFICATION:
MORPHOLOGICAL CONT.
Normochromic, normocytic anaemia (normal MCHC, normal MCV).
These include:
 anaemias of chronic disease
 haemolytic anaemias (those characterized by accelerated destruction of
RBC's)
 anaemia of acute haemorrhage
 aplastic anaemias (those characterized by disappearance of RBC precursors
from the marrow)
(The mean corpuscular haemoglobin concentration (MCHC) is the average
concentration of haemoglobin in the red blood cells. While Mean corpuscular
volume (MCV) is the average volume of red cells.)

CLASSIFICATION:
MORPHOLOGICAL CONT
Hypochromic, microcytic anaemia (low MCHC, low MCV).
These include:
 iron deficiency anaemia
 thalassemias
Normochromic, macrocytic anaemia (normal MCHC, high MCV).
These include:
 vitamin B12 deficiency
 folate deficiency

IRON DEFICIENCY
ANAEMIA

MICROCYTIC HYPOCHROMIC
MCV <80-100
MCHC <32-35
Causes:
 Fe-deficiency
 Anaemia of chronic disorders
 Thalassaemia
 Sideroblastic anaemia

IRON DEFICIENCY
ANAEMIA
Most common form of
anaemia
Iron deficiency anaemia
develops when body stores
of iron drop too low to
support normal red blood
cell (RBC) production.
Inadequate dietary iron,
impaired iron absorption,
bleeding, or loss of body
iron in the urine may be the
cause

AETIOLOGY
Increased demand
 Increased physiological need for iron in the body e.g. pregnancy
Increased losses
 haemorrhage
 obvious causes - menorrhagia in young women
 occult - peptic ulcer disease, GI cancer
 intravascular haemolysis
 paroxysmal nocturnal hemoglobinuria (PNH)
 cardiac valve RBC fragmentation

AETIOLOGY
Decreased supply:
 dietary deficiencies (rarely the only etiology)
 cow's milk (infant diet)
 "tea and toast" diet (elderly)
 absorption imbalances
 post-gastrectomy
 malabsorption (IBD of duodenum, celiac disease, atrophic gastritis)

CLINICAL FEATURES
iron deficiency may cause fatigue before
clinical anaemia develops
symptoms of anaemia:
fatigue, weakness, irritability, exercise
intolerance, syncope, dyspnoea, headache,
palpitations, postural dizziness, tinnitus,
feeling cold, confusion/loss of concentration

CLINICAL FEATURES
brittle hair, nail changes
[koilonychia (spoon-shaped)]
dysphagia
(e.g. oesophageal web, Plummer-Vinson ring)
pallor - conjunctiva, palmar creases
glossitis
angular stomatitis
(inflammation & fissuring at mouth corners)
pica
(appetite for non-food substances: ice, paint, dirt)

INVESTIGATIONS
History
Peripheral smear
 Poikilocytosis (variation in shape), anisocytosis (variation in size) and
target cells
Fe studies
 Fe: LOW
 Transferrin (iron transport protein): HIGH
 Transferrin saturation: LOW
 Ferritin (iron storage protein): LOW
Often, the platelet count is elevated (>450,000/µL); this elevation
normalizes after iron therapy

MANAGEMENT
Find and treat the cause
Oral ferrous iron salts most economical
and effective medication
Ferrous sulfate most commonly used
200mg po TDS
To promote absorption, patients should avoid tea and coffee and may
take vitamin C (500 units) with the iron pill once daily
Reserve parenteral iron for patients who are either unable to absorb oral
iron or who have increasing anaemia despite adequate doses of oral iron

ANAEMIA OF
CHRONIC DISEASE

ANAEMIA OF CHRONIC DISEASE
Causes include
 Chronic Infections: TB, IE, osteomyelitis
 Chronic inflammatory disease: RA, SLE
 Malignancy

MECHANISM
Decreased release of Fe
from BM stores to
developing erythroblasts
Inadequate EPO response
to anaemia
Decreased RBC survival -
Inflammatory cytokine
mediated

ANAEMIA OF CHRONIC DISEASE
Fe studies
 Serum Fe: LOW
 Ferritin: HIGH/N
 Transferrin: LOW/N
 Transferrin sat: LOW
Management:
 Cause

MANAGEMENT OF ANAEMIA OF CHRONIC
DISEASE IN PATIENTS WITH THE HUMAN
IMMUNODEFICIENCY VIRUS
Correct the underlying cause
Treatment of nutritional deficiencies (iron, folic acid, vitamin B12)
Treat opportunistic infections
If drug-induced, discontinue & equally effective alternative
Treatment with HAART improve anaemia in some patients with HIV
Symptomatic treatment for HIV-related anaemia of chronic disease
should be based on the patient's symptoms and cardiopulmonary status
rather than on a specific haemoglobin concentration
Blood transfusions and r-HuEPO (Recombinant Human Erythropoietin)

MACROCYTIC

MACROCYTIC NORMOCYTIC
ANAEMIAS

MACROCYTIC NORMOCYTIC
ANAEMIAS CONT
Megaloblastic – in BM, erythroblasts with
delayed nuclear maturation that defective
DNA synthesis.
Megaloblastic anaemia results from
inhibition of DNA synthesis during red blood
cell production.
When DNA synthesis is impaired, the cell
cycle cannot progress from the growth
stage to the mitosis stage

MACROCYTIC NORMOCYTIC
ANAEMIAS
Non-megaloblastic macrocytic anaemias are disorders associated with
increased red cell membrane surface area
Such as pathologies of the liver and spleen which produce codocytes or
"target cells" which have a central collection

MACROCYTIC ANAEMIAS

MEGALOBLASTIC: CAUSES
Vitamin B12 deficiency
 Malabsorption (need Intrinsic factor from stomach + intact terminal
ileum for absorption)
 Pernicious anaemia
 Intestinal lesions (malignancy, TB, coeliac disease)
2. Poor dietary intake

MEGALOBLASTIC: CAUSES
Folic acid deficiency
1. Poor dietary intake
2. Increased demand
Pregnancy
Incr. cell turnover (haemolytic anaemia)
3. Malabsorption
Resection of small bowel
4. Interference with utilization
Drugs: Phenytoin, Methotrexate, Pyrimethamine, Trimethoprim

PERNICIOUS ANAEMIA
Atrophy of gastric mucosa – failure of IF production – vit B12
malabsorption
Cause
Autoimmune
Parietal cell Ab in 90%
Familial factor
Schillings (absorption test)

MANAGEMENT
Vitamin B12 deficiency
 Hydroxocobalamine imi
 Vit B12 IMI
 Vit B12 PO
Folate deficiency
 Folic acid 5mg dly

NON-MEGALOBLASTIC
Normoblastic BM: Causes of normoblastic BM with macrocytic anaemia
Alcohol
Liver disease
Aplastic anaemia
Reticulocytosis
Marrow infiltration
Myxoedema
Myelodysplasia

NON-MEGALOBLASTIC
Normocytic Normochromic
Haematological disorders (aplastic anaemia, haemolytic anaemia)
Chronic disease
Endocrine disorders (hypothyroidism, hypoadrenalism)
Acute blood loss
Renal failure

PANCYTOPENIA

PANCYTOPENIA
Definition: a decrease in all hematopoietic cell lines
Anaemia, thrombocytopenia and leukopenia.
Clinical Features
• anaemia - fatigue
• leukopenia - recurrent infections
• thrombocytopenia - mucosal bleeding and ecchymoses

PANCYTOPENIA: CAUSES
BM failure
Ineffective haemopoesis (Megaloblastic anaemia)
BM Suppression (Cytotoxic drugs)
BM Infiltration (Malignancy)
Myelofibrosis(myelodysplasias)
Peripheral Consumption
Stem Cell Defect (Aplastic anaemia)
Hypersplenism

PANCYTOPENIA: INVESTIGATIONS
FBC and differential, blood film
investigate secondary causes: HIV test, serum B12, RBC folate, ANA
often requires bone marrow biopsy to determine cause

PANCYTOPENIA: INVESTIGATIONS

APLASTIC ANAEMIA

APLASTIC ANAEMIA
Syndrome of bone marrow failure characterised by peripheral
pancytopenia and marrow hypoplasia.

APLASTIC ANAEMIA
Clinical features
Anaemia
Neutropenia
Overt and/or recurrent infections
Thrombocytopenia
Haemorrhages, purpura
Gingival bleeding, petechial rashes

CAUSES
Acquired (more than 80% of cases are acquired)
Idiopathic factors
Infectious causes: Hepatitis, Epstein-Barr virus (EBV), HIV, parvovirus, and
mycobacteria
Toxic exposure to radiation and chemicals, such as benzene
Transfusional graft versus host disease (GVHD)
Pregnancy
Anorexia
Severe nutritional deficiencies (B12, folate)

CAUSES CONT.
Paroxysmal nocturnal haemoglobinuria (PNH)
Myelodysplastic syndrome (MDS
Acute lymphoblastic leukaemia (ALL)(rarely)
Drugs and elements (eg, chloramphenicol, phenylbutazone, gold)
Hereditary
Fanconi anaemia

INVESTIGATION & MANAGEMENT
Investigations
RPI: LOW
BM: hypoplastic /aplastic with almost no
haemopoietic precursors
Management
BM transplant
Immunosuppressive therapy (if immune mediated cause)

BLOOD TRANSFUSION

BLOOD TRANSFUSION

INDICATIONS FOR RED CELL
COMPONENTS: ANAEMIA
Anaemia
The aetiology of the anaemia should be investigated and, as far as possible, a definitive
diagnosis should be made in every case.
Medical management will be determined by the cause of the anaemia.
Appropriate alternatives to blood transfusion must be considered.
Consider transfusion in normovolaemic patients only if they are severely symptomatic
e.g. shortness of breath at rest, angina, incipient cardiac failure.
Patients with a Hb level below 8 g/dl should be considered for a transfusion.
In chronic nutritional anaemias, a Hb of 6 g/dl is often well tolerated without associated
medical complications and should respond well to treatment of the deficiency without
transfusion being required.

INDICATIONS FOR RED CELL
COMPONENTS
Acute blood loss
Acute blood loss of greater than 30% of blood volume (about 1 200-1 500
ml of blood in an adult) will often result in the need for a red cell
transfusion.
There must be no delay in ordering blood in situations where blood loss is
acute and rapid or where there is a possibility of recurrence or
continuation of bleeding.
Limited volumes of crystalloid solutions should be used initially in volume
resuscitation.

INDICATIONS FOR RED CELL
COMPONENTS
General surgery
Consider transfusion if:
• The pre-operative Hb level is less than 8 g/dl and the surgery is
associated with major blood loss (>500 ml).
• The intra- or post-operative Hb falls below 7 g/dl.
A higher Hb level may be indicated in patients who are at risk for
myocardial ischaemia or who are >60 years of age.
Pre-operative anaemia must be investigated in every case, as medical
management to raise the Hb level may be more appropriate than
transfusion.

INDICATIONS FOR RED CELL
COMPONENTS
Anaemia in Acute Coronary Syndromes (ACS)
In patients with ACS the guidelines cannot recommend for or against a liberal or
restrictive RBC transfusion threshold.
Transfusion to a Hb level between 8 and 10 g/dl should be considered
acceptable, but the effect of each unit transfused must be evaluated for the risk
of heart failure due to fluid overload.
Obstetric haemorrhage
During an obstetric haemorrhage, RBCs should be administered to maintain the
patient free of signs and symptoms of inadequate tissue oxygen delivery.
The Hb should be maintained between 6 and 10 g/dl during the resuscitation
phase.
Special attention must be given to maintaining adequate fibrinogen levels.

INDICATIONS FOR RED CELL
COMPONENTS
Cardiac surgery
Pre-operative clinical variables have been identified that independently predict the
likelihood of exposure to blood transfusion of patients undergoing cardiac surgery.
These variables include: pre-operative Hb, weight, female gender, age, non-elective
procedure, pre-operative creatinine levels, previous cardiac surgical procedure, and non-
isolated procedure (e.g. coronary artery bypass graft (CABG) and valve repair).
They constitute the clinical predictive index (TRUST).
Making use of this scoring tool enables clinicians to stratify patients according to their
likelihood of exposure to blood transfusion.
It provides patients with important information about their transfusion-related needs,
helps the medical team anticipate the patient’s transfusion needs, and guides the
clinician in the ordering of additional tests.

PROCEDURE
Collect blood for crossmatch
Identify that blood is correct for patient
and that blood is ideally at room temp.
Use a blood administration set
Close observation for 1st 10 min for any reactions and thereafter continue close
observation.
Transfusion of a unit should occur within 6hours
1 U will increase Hb by 1,5-2g/dl

COMPLICATIONS: EARLY
(<24HRS)
 Acute haemolytic reaction (ABO, Rh incompatibility)
 Anaphylaxis
 Bacterial contamination
 Febrile reaction (from HLA Abs)
 Allergic reactions
 Fluid overload
 Transfusion related lung injury (ARDS due to anti-leukocyte Ab in donor plasma.)

COMPLICATIONS: DELAYED
(>24HRS)
Infections (hep B/C, HIV, bacteria)
Fe overload
Graft vs host disease
Post transfusion purpura (decreased platelet count)

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