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ANAEMIA

Submitted By
• Dr. NAVDEEP GILL
B.D.S
INTRODUCTION
• It is defined as a Hb. Concentration in
blood below the lower limit of the normal
range for the age & sex of the individual
• Normal count:-
• In adults:For males-13.0 g/dl
For females-11.5 g/dl
In infants:15 mg/dl(lower limit)
CLASSIFICATION
• Pathophysiologic
• Morphologic
Pathophysiologic Classification
1.Anaemia due to increased blood loss
a)Acute post-haemorrhagic Anaemia
b)Chronic blood loss
2.Anaemia due to impaired red cell
production
a)Cytoplasmic maturation defects
Deficient haem synthesis:Iron deficiency
anaemia
Pathophysiologic Classification
• Deficient globin synthesis:Thalassaemia
b)Nuclear maturation defectsVit. B12 &/or
folic acid deficiency:Megaloblastic
anaemia
c)Defect in stem cell proliferation &
differentiation- Aplastic anaemia
Pure red cell aplasia
Pathophysiologic Classification
d) Anaemia of chronic disorders
e) Congenital anaemia
3. Anaemia due to increased red cell
destruction (haemolytic anaemia)
d) Extrinsic(extracorpuscular) red cell
abnormalities
e) Intrinsic(intracorpuscular) red cell
abnormalities
Morphologic Classification
A) Microcytic, Hypochromic
B) Normocytic, Normochromic
C) Macrocytic, Macrochromic
Sideroblastic Anaemia
• Comprise a group of disorders of diverse
etiology in the bone marrow, show
characterstic“ring sideroblasts”.
• Classification:
1. Hereditary (Congenital) sideroblastic anaemia
2. Acquired sideroblastic anaemia
E. Primary acquired sideroblastic anaemia
F. Secondary acquired sideroblastic anaemia
B. Secondary acquired sideroblastic anaemia
ii) Drugs and chemicals and toxins
e.g. isoniazide, cycloserine, chloramphenicol,
alcohol & lead.
iv) Haematological disorders
e.g. Myelofibrosis, polycythaemia vera, acute
leukaemia, myeloma & lymphoma.
vi) Misc.
e.g. Carcinoma, myxoedema & SLE.
Lab Investigation

- Moderate to severe degree of anaemia


- Blood picture shows Hypochromic
anaemia which may be microcytic or there
may be some nomocytic RBCs.
- Absolute values: (MCV, MCH, MCHC) are
reduced in hereditary type but MCV is
often raised in acquired type
Lab Investigation

- Bone marrow examination shows erythroid


hyperplasia usually macro-normoblastic
erythropoiesis. Marrow iron stores
areraised and ringed sideroblasts are
raised.
- Serum ferritin levels raised.
- Increased iron deposition in the tissue.
Megaloblastic Anaemia
• Are disorders caused by impaired DNA
synthesis & are characterized by a
distinctive abnormality in the
haematopoietic precursors in the bone
marrow in which the maturation of the
nucleus is delayed relative to that of the
cytoplasm.
Classification
1. Vitamin B12 deficiency
A) Inadequate dietary intake e.g. Breast fed
infants
C) Malabsorption
iv) Gastric causes:- pernicious anaemia,
gastrectomy, congenital lack of intrinsic
fectors.
v) Intestinal causes:- Tropical sprue, coeliac
disease, fish tapeworm infestation
Classification
2. Folate deficiency
A) Inadequate dietary intake e.g. in
alcoholics, infants, old age, poverty etc.
B) Malabsorption:-
e.g.:-Tropical sprue, coliac disease,
partial gastrectomy, crohn’s disease.
C)Exess demand
i)Physiological: Pregnancy, lactation, infancy
Classification
ii)Pathological: Malignancy, tuberculosis,
rheumatoid arthritis etc.
D)Excess urainary folate loss e.g. in active
liver disease, CHF.
3. Other causes
A) Impaired metabolism e.g. inhibitors of
DHF reductase such as methotrexate &
pyrimethamine ,alcohol etc.
Classification
• Unknown etiology :-
e.g.-In De Guglielmo’s syndrome, congenital
dyserythropoietic anaemia, refractory
megaloblastic anaemia.
Lab investigation of megaloblastic
anaemia
A. General lab findings :-
2. Blood –
iii) Red cell morphology:
- macrocytic red cell
v) Absolute values :
- MCV-elevated
- MCH-elevated
- MCHC-normal or less
iii) Leucocytes : WBCs count may reduced
Lab investigation of
megaloblastic
anaemia
iv) Platelets- Moderately reduced in severly
anaemic patients.
Bizzarre form of platelets seen.
2. Bone marrow findings:-
v) Marrow erythropoiesis- Megaloblastic
vi) Bone marrow stores- Increased
vii) Erythropoiesis :
Megaloblasts- Abnormal, large, nucleated
d erythroid precursors,
having
nuclear cytoplasmic asynchrony
(i.e. nuclei is less mature than
development of cytoplasm)
Lab investigation of megaloblastic
anaemia
iv) Marrow iron : Increase in number & size
of iron granules in erythroid precursors.
Iron in reticulum cells increased.
Lab investigation of megaloblastic
anaemia
3. Biochemical findings :
ii) Rise in serum unconjugated bilirubin &
LDH as a result of Ineffective
erythropoiesis causing marrow cell
breakdown.
iii) Serum iron & ferritin raised or normal.
Lab investigation of megaloblastic
anaemia
4) Special Test :-
ii) Serum Vitamin B12 assay
iii) SCHILLING TEST
iv) Serum enzyme level – Test performed in
3 stages
a. Without IF
b. With IF
c. Test for malabsorption
Haemolytic Anaemia
• Are defined as anaemias resulting from an
increases in the rate of red cell destruction
Classification
1. Acquired (Extacorpuscular)
A) Antibody : Immunohaemolytic Anaemias
i) Autoimmune haemolytic anaemia(AIHA)
a. Warm antibody AIHA
b. Cold antibody AIHA
ii) Drug induced Immunohaemolytic
Anaemia
iii) Isoimmune haemolytic anaemia
Classification
B) Mechanical Trauma: Microangiopathic
haemolytic anaemia
C) Direct toxic effects: Malaria, bacterial
infection & other agents.
D) Acquired red cell membrane
abnormalities: paroxysmal nocturnal
haemoglobinuria (PNH)
E) Splenomegaly
Classification
2. Hereditary (Intracorpuscular)
B) Abnormalities of red cell membrane
iii. Hereditary spherocytosis
iv. Hereditary ovalocytosis
v. Hereditary stomatocytosis
B) Disorders of red cell interior
vii. Red cell enzyme defects
a) Defects in the HMP-shunt:G6PD Deficiency
Classification
b) Defects in the glycolytic pathway :
Pyruvate kinase
ii) Disorders of haemoglobin:
c) Structurally abnormal
Hbs(haemoglobinopathies) , sickle
syndromes , other haemoglobinopathies
d) Reduced globin chain synthesis :
Thalassaemias
A c q u ir e d H a e m o ly t ic a n a e m ia

Im m u n e N o n Im m u n e

A u to im m u n e A llo im m u n e D r u g in d u c e d

Id io p a th ic S e c o n d a ry
Lab Findings Of AIHA
• Warm antibody AIHA
- Mild to moderate chronic anaemia
- Reticulocytosis
- Prominent spherocytosis in the PBF
- Positive direct Coombs’ (antiglobulin)
test for presence of warm antibodies on
the red cell, best detected at 37 C.
Lab Findings Of AIHA
• Cold antibody AIHA
- Chronic anaemia
- Low reticulocyte count since young red
cells are affected more.
- Spherocytosis is less marked
- Positive direct Coombs’ test
- Donath-Landsteiner test : Cold Ab. Titre is
very high at 4 C & very low at 37 C.
Lab Findings Of Hereditary
Haemolytic Anaemia
A) Hereditary abnormalities of red cell membrane –
- Anaemia : mild to moderate degree
- Reticulocytosis : usually 5-20 %
- Blood film : abnormality of RBCs in the form of
microspherocytes
- MCV : normal or decreased
MCHC : increased
- Osmotic fragility test : in testing the spheroidal
nature of RBCs ( lysing more readily in sol. of low
salt conc. ) i.e. osmotic fragility decreased.
- Autohaemolyses test negative
- Direct COOMB’s test negative
Lab Findings Of Hereditary
Haemolytic Anaemia
B) Hereditary disorders of red cell interior –
2. During period of acute haemolysis :
- Rapid fall in haematocrit by 25-30 %.
- Features of intravascular haemolysis :
rise in plasma Hb.
haemglobinuria
rise in unconjugated bilirubin
fall in plasma haptoglobin
Lab Findings Of Hereditary
Haemolytic Anaemia
- Formation of Heinz bodies called Heinz
body haemolytic anaemia .They aren’t
seen for first 2 days as they are removed
by spleen leading to formation of BITE
CELLS .
2. Between the crises –
- Affected patient has no anaemia
- Red cell survival shortened
Thalassaemia
• Thalassaemias are a group of hereditary
disorders in which there is reduced rate of
synthesis of one or more of the globin
polypeptide chains .
Classification
• α-Thalassaemias :-
2. Hydrops foetalis
3. Hb-H disease
4. α-Thalassaemia trait
• β-Thalassaemia :-
1. β-Thalassaemia major
7. β-Thalassaemia intermedia
8. β-Thalassaemia minor
Lab Investigations
• α-Thalassaemias :-
- Moderate anaemia ( Hb = 8-9 g/dl )
- Blood film :
Severe microcytosis
Hypochromia
Basophillic stippling
Target cells
Normoblasts
Lab Investigation
• β-Thalassaemia :-
- Anaemia severe
- Blood Film:
- Severe Microcytic hypochromic RBCs morphology
- Marked an isopoikilocytosis
- Basophilic stippling
- Presence of many target cells
- Tear drop cells
- Serum bilirubin (Unconjugated) raised
Lab Investigations
- Mild reticulocytosis
- HbH inclusions as Heinz bodies
- Hb electrophoresis –
2-4 % HbH
Remainder : HbA , HbA2 & HbF
• α-Thalassaemia trait :-
- Hb normal or reduced
- Blood film :
hypochromic red cell morphology
No evidence of haemolysis or anaemia
- MCV, MCH & MCHC INCREASED
- Hb ELECTROPHORESIS: Small amount of Hb-Bart’s in
neonatal period.
Lab Investigations
- Reticulocytosis present
- MCV, MCH & MCHC reduced
- WBC count raised
- Platelet Count normal or reduced in
patients with spleenomegaly
- Osmotic fragility decreased
- Hb electrophoresis: HbA2 increased , HbA
absent.
Lab Investigations
- Bone marrow examination :
Normoblastic erythroid hyperplasia with
predominance of intermediate & late
normoblasts
• β-Thalassaemia minor :-
- Mild anaemia
- Blood film shows anisopoikilocytosis ,
microcytes & hypochromia,basophilic
stippling with occasional target cells.
- Serum bilirubin normal or raised
Lab Investigations
- Mild reticulocytosis present
- MCV,MCH,MCHC reduced
- Osmotic fragility decreased
- Hb electrophoresis shows about two fold
increase in HbA2 & slight elevation in HbF
The Thalassaemias
• Management
– Regular transfusion
– Iron chelation
– Splenectomy
– Immunisation
– Bone marrow transplantation

– Reduced life expectancy


Aplastic Anaemia
• It is defined as pancytopenia ( i.e.
simultaneous presence of anaemia ,
leucopenia & thrombocytopenia )resulting
from aplasia of the bone-marrow
Lab Investigations
1. Anaemia :
Hb level moderately reduced
Blood picture shows normocytic normochromic anaemia
Reticulocyte count is reduced or 0.
2. Leucopenia :
Granulocyte count is low with lymphocytosis
3. Thrombocytopenia : Reduced
4. Bone marrow aspiration : Reveals patchy areas in a
hypocellular or aplastic marrow due to replacement by fat.
severe depression of myeloid cells , megakaryocytes or
erythroid cells. Marrowchiefly composed of lymphocytes &
plasma cells.
Lab Investigations
• A sample of bone marrow in a patient with
Aplastic Anaemia
Case history (1)
• 45yr old female
• 3 month history of fatigue and shortness
of breath on exertion
• O/E pallor ++
• FBC – Hb 6.2g/dl
Case history (1)
• What further results are important in the
full blood count?
• What further details are important in the
clinical history and examination?
• What further investigations should be
carried out?
• How should the patient be managed?
Full Blood Count
• What further results are important in the
full blood count?

• Hb 6.2 g/dl (12-16)


• WCC 7.0 x 109/l (4-11)
• Platelets 300 x 109/l (140-440)
• MCV 60fl (76-96)
• MCH 24 pg (27-32)

• WCC differential –N
• Blood Film
Some causes of microcytic
anaemia…..
• Acquired
– Iron deficiency
– Anaemia of chronic disease
– Myelodysplastic syndromes
– Lead poisoning
More causes of microcytic
anaemia…..
• Inherited
– Beta Thalassaemia trait
– Beta Thalassaemia major
– Alpha Thalassaemia trait
– Sickle cell trait
– Congenital sideroblastic anaemia
Hypochromic Anaemia

Ferritin

Reduced Normal Increased

Iron Sideroblastic
deficiency Haemoglobinopathy
Anaemia

Anaemia of
Chronic disorders Other causes of high
ferritin
What further details are
important in the clinical history?
• Dietary intake of iron
• Symptoms of malabsorption / weight loss
• Overt GI blood loss
• Menorrhagia
• Pregnancy
• Oral iron therapy
• Bleeding history/ family history of
bleeding disorder
Iron Requirements

• Males 0.5-1mg per day


• Menstruating females 1-2mg per day
• Pregnant females 1.5-2.5mg per day
• Children 1mg per day

• An adequate diet contains 15mg of iron,


10% of which is absorbed.
Dietary iron
• Red meat , liver
• Absorbed in the duodenum and jejunum
• Absorption enhanced by ascorbic acid,
citrus fruits
• Absorption reduced by phytates, alkalis,
tea, tetracyclines
Causes of iron deficiency
anaemia
• Inadequate intake • Dietary iron
• Iron supplements

• Failure of absorption • Gastrointestinal


symptoms
• Hx of Coeliac disease

• Increased blood loss


• Overt blood loss from
bowel or change of bowel
habit
• Menorrhagia
• Increased
Common causes of
gastrointestinal bleeding
• Oesophagus • Hiatus hernia
• Varices
• Stomach • Gastritis
• Ulcer
• Carcinoma
• Small bowel • Ulcer
• Meckels diverticulum
• Carcinoma
Common causes of
gastrointestinal bleeding
• Colon • Ulcerative colitis
• Carcinoma
• Diverticulitis

• Rectum • Haemorrhoids
• Ulceration
• Carcinoma
Iron loss in pregnancy
• Obligatory iron loss 150-200
mg
• Fetal iron 200-370 mg
• Iron in placenta and cord 30-170
mg
• Iron in blood lost at delivery 90-310 mg

• Total iron loss 470-


1050mg
What further investigations
should be carried out?
• Serum ferritin +/- serum iron
• B12 / folate
• FOBs
• Bioprofile
• +/- Coeliac screen
• +/- Gastroscopy and/or colonoscopy
• +/- Gynaecology referral
What further investigations
should be carried out?
If indicated:
• Coagulation screen
• VWD screen
• Haemoglobin electrophoresis
Causes of raised ferritin levels
• Acute inflammation
• Acute liver disease
• Lymphomas
• Solid tumours
• Haemochromatosis
How should the patient be
managed?
• Treat the underlying cause
• Oral iron supplements
– correct anaemia
– replenish iron stores
• IV iron
– malabsorption
– intolerance
• Is there a role for blood transfusion?
Failure to respond to oral iron
• Is the diagnosis correct?
• Is the patient taking the iron?
• Is there evidence of malabsorption?
• Is there evidence of persistent blood loss?
Anaemia of chronic disease
• Causes
– Chronic infection eg abscess, TB
– Rheumatoid arthritis
– Ulcerative colitis
– Malignancy
Anaemia of chronic disease
• Mechanisms
– Shortened red cell survival
– Impaired marrow response to anaemia
– Impaired erythropoietin production
– Defective iron transport
Anaemia of chronic disease
• Laboratory findings
– Hypochromic or normochromic cells
– Reduced serum iron
– Increased iron stores in RE system
– Low or high ferritin
Case History (2)
• History : This 13 month old cat presented
with pale mucous membranes, an
increased heart rate and general malaise.
Flea infestation was apparent
Lab abnormalities included
• PBF :-
Lab abnormalities included
• Reduced PCV of 22, lowered haemoglobin
of 6.1, reduced red cell count, redcued
MCV and abnormal blood film morphology
as above
Diagnosis: Iron Deficiency
Anaemia
• In iron deficiency, red cells do not develop the normal
complement of iron–containing haemoglobin and the cells that
form in the bone marrow are small (microcytic, low MCV) and
hypochromic (low MCH and MCHC). The process of red cell
maturation becomes prolonged so young red cells no longer
contain large amounts of RNA and therefore do not appear
polychromatic. As a result the anaemia is non- regenerative,
with inappropropriately low reticulocyte counts. There is often
a marked increase in variation in red cell shape (poikilocytosis)
and red cell fragments (schistocytes) are often seen, as above.
In cats, the red cells are often so small that platelets appear
larger than red cells and this overlap in sizing can contribute to
apparently very high platelet counts as some automated
counters include some small red cells in the platelet count. Iron
deficiency anaemia reflects chronic external blood loss, either
through the gut associated with bleeding tumours or ulcers or
occasionally with severe flea burdens and parasitic blood loss.