Transcript Document

ANAEMIA
BY
DR. C.C. OKANY
ANAEMIAS
• Definition
• Normal values
Adult males
Adult females
Neonates
1yr
6-12yr
15.00 + 2gms/dl
13.5 + 1.5gms/dl
18.0 + 4gms/dl
12.6 + 1.5gms/dl
13.5 + 2gms/dl
CLASSIFICATION OF ANAEMIA
2 types
Aetiological
morphological
AETIOLOGICAL CLASSIFICATION
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Blood loss
Impaired red cell production
a) Due to lack of nutrients essential for erythropoiesis
Iron def.
Vit B12 def
Folate def
Protein calorie malnutrition
b) Depression of erythropoietic activity
Anaemia of chronic disorders e.g infections, connective
tissue disorder, disseminated malignancies, anaemia of
chronic renal failure, Aplastic anaemia,
Anaemia due to replacement of normal marrow by
leukaemia, lymphoma, myeloproliferative disease,
myeloma, MDS
AETIOLOGICAL CLASSIFICATION (contd)
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Excessive or premature destruction of RBCs
(a) Due to intracorpuscular mechanism
Congenital
- Membrane defects
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Hereditary spherocytosis
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Haemoglobin defects
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Elliptocytosis
Haemoglobinopathies
Enzyme defects
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Pyruvate kinase deficiency or other enzymes of the Embden
Meyerhoff pathway
Due to 6GPD deficiency or other enzymes of the Pentose
Phosphate shunt
Drug induced haemolytic anaemia and favism
Acquired e.g. P.N.H
AETIOLOGICAL CLASSIFICATION (contd)
b) Due to extra corpuscular mechanisms
- Immune mechanism
Haemolytic disease of the newborn
Incompatible blood transfusion
Drug induced haemolytic anaemia
- Non-immune mechanism
Cardiac haemolytic anaemia
Microangiopathic haemolytic anaemia
March haemoglobinuria
Morphological classification
• Assessment of size of red cell
• Assessment of central pallor
Normocytic
microcytic
macrocytic
normochromia
hypochromia
EXAMINATION OF ANAEMIC PATIENT
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Skin
Nails
Conjuctiva and sclera
Retina
Mouth (tongue)
Abdomen (splenomegaly, hepatomegaly
abdominal masses)
• Superficial lymphnodes
• Bone tenderness
• Rectal examination
Evidence of increased haemoglobin breakdown
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Jaundice and hyperbilirubinaemia
Plasma haptoglobulin (2 glycoprotein, combines with Hb)
Plasma haemopexin  (-glycoprotein carries haem portion of Hb)
Plasma L.D.H 
 urinary urobilinogen
 fececal stercobilinogen
Haemoglobinaemia
Haemoglobinuria
Evidence of intravascular
Haemosiderinuria
haemolysis
Evidence of compensatory erythroid hyperplasa
• Reticulocytosis & erythroblastaemia
• Macrocytosis and polychromasia
• Erythoid hyperplasia of bone marrow
marrow space
• X-ray shows changes in skull and tubular
bone with thinning of cortex (congenital
anaemia only).
Evidence of damage to the red cell
• Spherocytosis and increased reduced
fragility.
• Fragmentation of red cells
• Heinz bodies (aggregates of denatured
globin)
Demonstration of shortened red cell life span
• Cr51 labelling used for this.
Anaemia of systemic Disorders
• These are anaemias that occur in association
with a number of well defined systemic
disorders. The peripheral blood in these
anaemias characteristically shows normocytic
and normochromic red cells, although
occasionally, a macrocytic or even microcytic
picture may be seen. Generally, these anaemias
are moderate with PCV usually ranging from
30-40, the degree being related to the activity of
the disease.
Anaemia of systemic Disorders (contd)
The main disorders normally associated with
these anaemias are:
– Infection
– Renal failure
– Malignant disease
– Liver disease
– Endocrine disease
– Connective tissue disorders
– Protein malnutrition
– Vitamin deficiencies
ANAEMIA OF INFECTION
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A mild to moderate anaemia usually occurs in most
chronic infections and in some acute infections. The
most common infections causing anaemias include the
following:
Pelvic inflammatory disease
Puerperal infection
Urinary tract infection
Lung abscesses, empyema, bronchiectasis
Pneumonias
Tuberculosis
Bacterial endocarditis
Chronic osteomyelitis
Typhoid
ANAEMIA OF INFECTION (Contd)
Except in septicaemias very severe anaemia
is rare in these conditions.
The degree of anaemia is usually directly
proportional to the degree of infection
PATHOGENESIS OF ANAEMIA
DUE TO INFECTIONS
a) There is a mild haemolytic element
with shortened red cell life span,
especially when the bone marrow is
unable to increase its production to
compensate for this. This impaired
marrow response is due to impaired
erythropoietin production or utilisation.
PATHOGENESIS OF ANAEMIA DUE
TO INFECTIONS (Contd)
b)
There is disturbance of iron metabolism
with impairment of iron flow from the
reticulo-endothelial cells to the
erythroblasts. This gives rise to the
paradoxical picture of increased stainable
iron in the marrow when there is
hypochromia – the so called “Starvation in
the midst of plenty”. Serum ferritin level is
typically raised in chronic infection.
PATHOGENESIS OF ANAEMIA DUE
TO INFECTIONS (Contd)
c)
Blood loss and acute haemolysis
occasionally contribute to anaemia of
patients with infection. Acute severe
anaemia may follow septicaemia or
virulent acute infections. This may be
due to toxic depression of erythropoiesis
or due to haemolysis. For example,
Clostridium Welchii septicaemia can
cause severe haemolysis.
PATHOGENESIS OF ANAEMIA DUE
TO INFECTIONS (Contd)
Occasionally,viral infections like Cytomegalovirus,
HIV, and infectious mononucleosis can cause
autoimmune haemolytic anaemia. In patients with
G6PD deficiency who have acute infections, a
haemolytic anaemia can be triggered off by the
infection per se or by the drugs used for treating the
infection.
Apart from causing anaemias by some of the
mechanisms listed above, tuberculosis can also cause
anaemia by causing:
a) Secondary myelofibrosis leading to a leuco-erythroblastic
anaemia
b) A splenomegaly which can lead to hypersplenism and
anaemia.
Anaemia of chronic renal failure
Anaemia is such a common feature of chronic
renal failure that renal function tests should be
part of the routine investigation of any patient,
especially on adult presenting with an uneasily
explained anaemia.
It is not uncommon for patient with chronic
renal failure to present for the first time with
symptoms of anaemia. The degree of anaemia
doe not depend on the type of disease causing
the renal failure but seems proportional to the
level of blood urea.
Anaemia of chronic renal failure (Contd)
The anaemia is characteristically of the normochronic
and normocytic type although occasionally slight
microcytosis, hypochromia or rarely macrocytosis may
occur. Neutrophil hypersegmentation can occur. The
anaemia of renal failure is attributable to several
mechanisms:
– Depression of erythropoiesis either due to retained metabolic
products or depressed plasma erythropoietin.
– Decreased red cell survival mainly due to extracorpuscular
mechanisms.
– Infection, like in acute pyelonephritis when the marrow will
also be depressed.
– Blood loss from haematuria, bleeding tendency in uraemia and
epistaxis.
– Anorexia – leading to folate deficiency
– Chronic dialysis
Anaemia of chronic renal failure (Contd)
Micro-angiopathic haemolytic anaemia is the
haematological picture seen in some forms of
progressive renal failure especially when the causative
disorder is associated with intravascular thrombosis or
deposition of fibrin clot. The peripheral blood film
classically shows fragemented red cells,
microspherocytes and Burr cells. Micro-angiopathic
haemolytic anaemia is usually seen in conditions
associated with disseminated intravascular coagulation
which will include the following.
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Haemolytic uraemic syndrome
Disseminated carcinoma
Malignant hypertension
Eclampsia
Anaemia in Malignant disorders
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Anaemia is a common accompaniment of malignant
disorders. A number of factors usually contribute to this
anaemia and include the following:
Blood loss
Infection
Bone marrow metastasis
Disturbance of nutrition (anorexia or malabsorption)
Impairment of renal function
Haemolytic anaemia (usually auto-immune as in
lymphoma)
Bone marrow depression from treatment.
Anaemia in Malignant disorders (Contd)
The type of anaemia depends on the dominant
underlying mechanism causing the anaemia.
Most of the time the anaemia is normochromic
and normocytic. Occasionally, a leucoerythroblastic blood picture, in which nucleated
red cells and granulocyte precursors are
prominent, is seen when there is marrow
metastasis. Other haematological changes often
seen occasionally in malignant disorders include
leucocytosis, thrombocytosis and eosinophilia.
Anaemia in Liver Disease
Anaemia is a frequent manifestation of liver disease and
occurs in about two-thirds of patients with liver
cirrhosis. It is usually moderate but occasionally severe.
Many aetiologic factors have been implicated in the
anaemia associated with liver disease. These include:
• Liver disease itself. The pathogenesis is not clear but is
somehow related to the impaired liver function. The
degree of the anaemia does not correlate with the
severity of the liver damage as estimated by the liver
function test, neither does it correlate with the duration
of liver disease. There is usually both depression of
erythropoiesis and accelerated red cell destruction. In
chronic alcoholic cirrhosis, alcohol exerts a toxic effect
on the bone marrow.
Anaemia in Liver Disease (Contd)
• Blood loss from oesophageal varices, peptic
ulcers and haemorrhoids can also worsen the
anaemia in chronic liver disease patients.
• Nutritional folate deficiency, especially in
chronic alcoholics is also a contributing factor
• Hypersplenism in patients with portal
hypertension and splenomegaly.
• Frank haemolytic anaemia can rarely occur,
either as part of Zieve’s syndrome (acute
haemolysis, alcoholic fatty liver and extreme
hyperlipidaemia) or auto-immune haemolytic
anaemia secondary to chronic active hepatitis
Anaemia in Liver Disease (Contd)
• Acute viral hepatitis especially one due to
hepatitis A, can on very rare occasions be
complicated by an irreversible aplastic anaemia.
Blood picture: The anaemia of liver disease is
usually normochromic and normocytic although
a macrocytic picture is also often seen.
Anaemia is Endocrine Diseases:
Many hormones (in addition to erythropoietin)
participate in the regulation of erythropoiesis, and
patients lacking such hormones often develop
hypoplastic anaemia. The hormones most often
involved in development of hypoplastic anaemia are
those of thyroid, pituitary, adrenal cortex and gonads.
Hypothyroidism: A mild to moderate anaemia occurs is
about one third of patients with myxoedema. The
anaemia is often normochromic normocytic but may be
microcytic – hypochromic due to iron deficiency
resulting from menorrhagia (a frequent complication),
achlorhydria and intestinal malabsorption of iron.
Anaemia is Endocrine Diseases:(Contd)
Occasionally hypothyroidism coexists with true
pernicious anaemia. The anaemia of hypothyroidism
normally responds well to thyroxin therapy.
Hyperthyroidism: Although the thyroid hormone has a
haemopoietic effect, on rare occasions patients with
hyperthyrodism may also have an associated pernicious
anaemia.
Hypopituitarism: Mild to moderate anaemia is usually
seen is most patients with hypopituitarism. This
anaemia is usually refractory to haematinics until the
hypopituitarism is adequately treated.
Addison’s Disease: The anaemia in patients with
Addison’s disease is often masked by the reduction in
plasma volume. The treatment is that of the primary
condition.
Anaemia in Connective tissue diseases
Rheumatoid arthritis: Mild to moderate anaemia
frequently accompanies rheumatoid arthritis with
haemoglobin ranging from 9 to 11gms/dl.
Two forms of anaemia are usually recognised:
a) A normochromic – normocytic anaemia due to
rheumatoid arthritis per se, with the severity varying
with the activity of the disease. This is due to poor
iron entry into the erythrocytes.
b) A hypochromic – microcytic anaemia usually
secondary to the gastric erosion and blood loss
complicating the medication with salicylates and other
NSAID.
Anaemia in Connective tissue diseases (Contd)
Aplastic anaemic is a rare complication of a drug
like phenylbutazone which is often used to treat
rheumatoid arthritis. Auto immune haemolytic
anaemia is also a rare complication. Secondary
amyloidosis can also contribute to the anaemia,
especially when it leads to chronic renal failure.
Felty’s syndrome (Splenomegaly, neutropenia in
a patient with rhematoid arthritis) is often
associated with significant anaemia.
Anaemia in Connective tissue diseases (Contd)
Systemic Lupus Erythematosis: Anaemia is
present in up to 75% of these patients and is
mostly of the normochromic – normocytic type,
although in 5% of these patients a Coomb’s Test
positive autoimmune haemolytic anaemia is
present. Other haematological features of these
patients include leucopenia, immune
thrombocytopenia and very high ESR.
Mild anaemia is also occasionally seen in other
connective tissue diseases like dermatomyositis
and scleroderma
Anaemia of Protein malnutrition
The human body has such a high priority for the
available protein for haemoglobin synthesis that
protein deficiency alone does not often act as a
limiting factor in haemoglobin synthesis and
cause anaemia. Very considerable depletion of
body protein must occur before interference in
haemoglobin synthesis occur. In the situations
where protein malnutrition exists, there are often
deficiencies of other nutrients, such as folic acid,
vitamin B12, riboflavin vitamin A and vitamin D.
Anaemia of Protein malnutrition (Contd)
Anaemia due to protein deficiency frequently
occurs in the tropics, particularly in pregnant
women, and in children with Kwashiorkor. The
anaemia is usually mild to moderate in degree
and often responds to high protein diet.
Anaemia of Scurvy
Scurvy is a deficiency of the C vitamin and usually
causes anaemia which in adults is normocytic or
slightly macrocytic. In children a hypochromic –
microcytic picture might be due to associated iron
deficiency caused by inadequate iron intake and blood
loss. Like folic acid, ascorbic acid is heat labile, so that
the two deficiencies often coexist in infantile anaemias
and in elderly people who live in institutions. The
anaemia is proportional to the severity of the scurvy.
Ascorbic acid tablets or fruits like oranges which are
rich in ascorbic acid promptly correct the anaemia in
these patients.
Treatment of anaemia of systemic disorders
The mainstay of management of the anaemia
secondary to these systemic disorders is the
correction of the primary disorders.
In cases, however, when the associated anaemias are
severe and the primary disorders are chronic and
irreversible, then blood transfusion often becomes
the only way to correct the anaemia. Blood
transfusion should be given only if the anaemia is
very severe and life threatening.
In recent times, however perenteral administration of
recombinant human erythropoietin is
revoluntionising the management of anaemia of
patients with chronic renal failure and malignant
disease.
Anaemia of Bone marrow
Failure
Causes of impaired marrow erythropoietic activity:
Quantitative
Haemopoietic cell defect
– Aplastic anaemia
• Erythropoietic factor
– Renal insufficiency
– Endocrine hypofunction (thyroid, pituitary)
• Marrow replacement
– Myelofibrosis
– Osteomyelosclerosis
– Malignant lymphomas & leukeamia
• Qualitative
– Dyserythropoiesis
Leuco-erythroblastic (myelophthistic) Anaemia
This term used to describe a form of anaemia in
which nucleated RBCs and granulocyte
precursors appear in the peripheral blood.
Red cells show anisocytosis and poikilocytosis
Nucleated RBCs often present in large numbers.
WBC is normal or mildly  with many immature
granulocytes.
Platelet counts normal or reduced.
Leuco-erythroblastic (myelophthisia) Anaemia (Contd)
Causes
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Metastatic Ca
Myelosclerosis
Myelofibrosis
Refractory anaemia
Haemolytic disease of newborn
Hodgkins disease
Myeloma
Primary lipid storage disease
– Gaucher’s disease
– Niemann Pick disease
– Hands Schuller – Christian disease
• Occasional causes
– After severe haemorrhage
– Some severe sepsis
– After irradiation
PANCYTOPENIA
This is the simultaneous presence of anaemia,
leucopenia and thrombocytopenia. Patients
with pancytopenia usually present with
symptoms attributable to anaemia,
thrombocytopenia and leucopenia.
Causes
– Aplastic anaemia
– Subleukaemic leukaemia
– Administration of cytotoxic agents
– Radiotherapy
– Myelodysplastic disorders
Causes Contd
– Marrow infiltration or replacement
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Hodgkins Disease
Multiple myeloma
Metastatic Ca in the marrow
Myelopfibrosis
Hypersplenism
Megaloblastic anaemia (especially severe ones)
S.L.E
Paroxysmal Nocturnal Haemoglobinuria (PNH)
Overwhelming infection
APLASTIC ANAEMIA
Defn: This is a disorder characterised
by pancytopenia, reduction in the no.
of redcells, neutrophils, and platelets in
the peripheral blood, a marked
decrease in the amount of
haemopoietic tissue in the bone
marrow and absence of evidence of
involvement of the marrow by diseases
such as leukaemia, myeloma or
carcinoma.
CLASSIFICATION OF APLASTIC ANAEMIA
Acquired of Causes
 Inevitable (if dose is sufficient)
 Ionising radiation
 Cytotoxic drugs
 Idiosyncratic
 Idiopathic
 Drug induced
 Viral (hepatitis, EB, vira, HIV dengue)
 Industrial
 Benzene (usually dose dependent, proliferative disorders more
common)
 Immune
 Drug Induced
 Viruses (e.g. EB virus)
 SLE
CLASSIFICATION OF APLASTIC ANAEMIA (CONTD)
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Miscellaneous causes
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Diffuse eosinophilic fascitis
Pregnancy
Simmond’s Disease
Sclerosis of the thyroid
Familial Causes
– Fanconi’s Anaemia
– Dyskeratosis congenita
– Schwachman – Diamond syndrome (Pancreatic
insufficiency and pancytopenia)
Drug associated with idiosyncratic Aplastic anaemia
Antibiotics
Anti-malarials
Anti-inflammatories -
Chloramphenicol*
Sulphonamides
Cotrimoxazole
Nitrofuradantoin
Quinacrine*
Chloroquin
Phenylbutazone*
Indomethacine
Sulindac
Diclofenac
Ibuprofen
Piroxicam
Drug associated with idiosyncratic Aplastic anaemia (Contd)
Anti-thyroids
Psychotropic/
Antidepressants
Anti-convulsants
Anti-diabetics
Miscellaneous
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Potassium perchlorate
Carbimazole
Methimazole
Methylthiouracil
Phenothiazines
Dothiapine
Carbamazepine
Phenytoin
Mesatoin*
Ethusuximide
Tolubutamide
Chlorpropamide
Gold salt*
Penicillamine
Allopurinol
Haematological findings in
Aplastic anaemias
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Normochromic, normocytic anaemia
Low absolute reticulocyte count
Neutropenia
Thrombocytopenia
 serum and urinary erythropoietin level
Markedly hypocellular marrow (majority of cells
seen are plasma cells, lymphocytes and
macrophages.
Pathogenesis of aplastic anaemia
There is evidence to suggest that aplastic anaemia may be
heterogenous in its pathogenesis.
- May develop as a result of a stem cell defect
Evidence –
Bone marrow culture experiments
confirms deficiency,
- Success of marrow transplantations in
some identical twins
- Chromosomal abnormalities found in
those with Fanconi’s anaemia
- Defects found in all the cell lines in PNH
- Defect in marrow environment
- Evidence from animal studies involving irradiation
Pathogenesis of aplastic anaemia (Contd)
- Impaired production or effectiveness of haemopoietic
growth factors
Cytokines with inhibitory activity on haemopoiesis
are usually increased in aplastic anaemia. -interferon,
interleukin-2, and -tumor necrosis factor are all known
to be increased.
- Immunologically mediated damage.
Alteration in cytokines as above may be taken as
evidence for an immune basis for aplastic anaemia.
In vitro culture of cells from patients could be enhanced
by T-cell depletion and depressed by T-cell restitution.
Management of aplastic anaemia
Supportive Treatment
– Blood products
Red cell Transfusion(White cell depleted)
Platelet transfusion
– Prophylactic Antibiotics
– Recombinant granulocyte colony stimuling factor
(G-CSF or GM-CSF)
Management of aplastic anaemia (Contd)
Restoration of marrow activity
– Antilymphocyte globulin
– Cyclosporin (alone or with ALG)
– Haemopietic growth factors
G.CSF
Erythropoietin (Ronferon A)
IL – 3
IL – 6
? Thrombopoietin
– Androgen
– Splenectomy
Marrow transplantation
FANCONIS ANAEMIA
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Rare
Autosomal recessive inheritance
Onset of the pancytopaemia between age 5-10yrs
Frequent association with other congenital abnormalities e.g.
skin pigmentation, short status, microcephaly, skeletal defects,
genital hypoplasia, and renal abnormalities.
Various chromosomal abnormalities (breaks, rearrangement,
exchanges etc).
Increased number of chromosomes per cell after culture with
alkylating agents.
Increased in incidence of acute leukaemia
Treatment – form response to androgens or corticosteroiod
marrow transplantation.
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