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Anaemia

Anaemia’s
• Anaemia is present when there is a decrease in the level of haemoglobin in the
blood < 13.5 g/dL in adult males or < 12 g/dL in adult females.

• There are two classifications of anemia:


1. Classification according to the aetiology.
a. Diminished RBC’s production.
i. Deficiency of essential factors (Iron, vitamin B12 or folate).
ii. Toxic factors (Inflammatory disease, hepatic and renal failure, drugs).
iii. Endocrine deficiencies (Hypothyroidism, hypoadrenalism, hypopituitarism,
hypogonadism, and reduced production of erythropoietin).
iv. Invasion of bone marrow (Leukemia, secondary carcinoma, fibrosis).
v. Disorders of developing red cells (Sideroblastic anemia, neoplastic disorders of
erythropoiesis, hereditary disorders of Hb synthesis like thalassaemia).
vi. Failure of stem cells (Hypoplastic and aplastic anemia).
b. Blood loss anemia.
i. Acute (due to acute hemorrhage).
ii. Chronic (due to GIT bleeding, menorrhagia).
c. Excessive destruction of RBC’s.
i. Haemolysis.
2. Classification according to the morphology
a. Microcytic (MCV < 100 fl)
i. Iron deficiency anaemia.
ii. Thalassemia minor.
iii. Sideroblastic anemia.
iv. Lead poisoning.
b. Macrocytic (MCV > 100 fl)
i. Megaloblastic (due to vitamin B12 & folic acid deficiency).
ii. Macrocytic without megaloblastic (due to alcohol excess, cirrhosis of liver,
hypothyroidism and reticulocytosis, marrow infiltration and myelodysplastic
syndrome.
C. Normocytic (MCV 80-100 fl)
i. Aplastic anemia (bone marrow failure).
ii. Myelodysplastic syndrome.
iii. Anemia of chronic disease such as connective tissue disease, tuberculosis, chronic
renal failure.
iv. Endocrine disorders e.g hypothyroidism, hypopituitarism & Addison’s disease.
v. Hymolytic anemias.
vi. Malignancy.
vii. Malnutrition.
Clinical features of Anemia
Symptoms
• Fatigue.
• Headache.
• Faintness.
• Breathlessness.
• Angina of effort.
• Palpitation.
• Intermittent claudication.

Signs
a. Non-specific
• Paler skin, conjunctiva & mucous membrane.
• Tachycardia.
• High volume pulse.
• Ankle edema.
• Cardiac failure.
• Systolic flow murmur.
b. Specific
• Koilonoychia in iron deficiency.
• Jaundice (in haemolytic)
• Bone deformities (In thalassaemia major)
• Leg ulcers (in sickle cell anaemia)
Causes of Microcytic Anemia
1. Iron deficiency anemia
Iron deficiency anaemia develops when there is an inadequate amount of iron for
hemoglobin synthesis.
Causes
1. Deficient diet .
2. Decreased absorption Increased requirements.
3. Pregnancy.
4. Lactation Blood loss.
5. Gastrointestinal.
6. Menstrual.
7. Blood donation.
8. Hemoglobinuria.
9. Iron sequestration.
10. Pulmonary hemosiderosis.

Clinical features
1. Features of anemia.
2. Features due to iron deficiency in the tissues producing epithelial changes are:
o Brittle nails and nail cracking and koilonychias may be present.
o Atrophy of the papillae of the tongue.
o Angular stomatitis.
o brittle hair.
o Plummer-Vinson Syndrome (which is iron deficiency anemia with dysphagia due to
esophageal webs usually in middle aged women)
• Diagnosis
I. History
By asking the patient about dietary intake, regular self medication with aspirin,
presence of blood in faeces, and in women about the duration and flow of
menstruation.
II. Examination
By looking for features of iron def. anaemia, palpating the spleen to find out
chronic liver disease as a cause of chronic blood loss, PR examination and
proctoscopy.
III. Investigations
a. Blood picture: RBC’s are microcytic (MCV<80 fl), hypochromic (MCH<27 pg),
poikilocytosis, anicytosis.
b. Serum Ferritin: 30-300 microgram/L (which indicates nearly absent iron stores).
c. Serum iron &iron-binding capacity: Serum iron falls and the total iron-binding
capacity rises as compared to normal.
d. Plasma transferrin: raised.
e. Leucocyte count differential: normal.
f. Platelet count: normal or raised.
g. Bone marrow: Erythroid hyperplasia with ragged normoblast, and bone marrow
stain indicates iron depletion.
Management

• Treatment of the cause.


• Iron replacement:
o Tab. Ferrous sulphate (Iberet) 500 mg daily.
o Cap. Ferrous gluconate (Sangobion) 250 mg daily.
o Intramuscularly : Inj. Jectofer (75 mg), 1.5mg/kg/day (in the gluteal maximus)
o Intravenous infusion: Inj. Venofer given by slow IV injection or IV infusion.
2. Sideroblastic Anaemia

The sideroblastic anemias are a heterogeneous group of disorders in which


hemoglobin synthesis is reduced because of failure to incorporate heme into
protoporphyrin to form hemoglobin( due to defects in ezymes involved) Iron
accumulates, particularly in the mitochondria of erythroblasts. A Prussian blue stain
of the bone marrow will reveal ringed sideroblasts, cells with iron deposits
encircling the red cell nucleus.
Patients have no specific features other than those related to anaemia.

Causes of Sideroblasatic Anaemia


1. Inherited: X-linked diseases.
2. Acquired:
a. Primary: one type of myelodysplastic syndrome.
b. Secondary: drugs (isoniazid, phenacetin), alcohol abuse, lead toxicity,
myeloproliferative disorders, myeloid leukemias, other disorders like carcinoma, RA,
megaloblastic and haemolytic anaemias, malabsorption
Diagnosis

1. The peripheral blood smear characteristically shows a dimorphic population of red


blood cells, one normal and one hypochromic. In cases of lead poisoning, coarse
basophilic stippling of the red cells is seen.
2. Examination of the bone marrow: Characteristically, there is marked erythroid
hyperplasia, a sign of ineffective erythropoiesis (expansion of the erythroid
compartment of the bone marrow that does not result in the production of
reticulocytes in the peripheral blood).
The iron stain of the bone marrow shows a generalized increase in iron stores and the
presence of ringed sideroblasts. Other characteristic laboratory features include a
high serum iron and a high transferrin saturation. In lead poisoning, serum lead levels
will be elevated.

Management
- Blood tranfusion in severe anaemia.
- The withdrawal of drugs or alchol if they are causative agents. In some cases folic
acid or pyridoxine may improve iron utilization.
3. Anaemia of chronic disease
This type of microcytic anaemia develops in patients with chronic infections such as
infective endocarditis, tuberculosis, osteomyelitis, RA, SLE, polymyalgia rheumatica
and malignancy.

Mechanism
• Theirs is decreased release of iron from bone marrow to developing erythroblasts.
• Decreased response to erythropiotein.
• Decreased red cell survival.

Investigations
• Serum iron and TIBC.
• Serum ferritin (normal or high due to inflammation)
• Iron is present in the marrow but not in developing erythroblasts.

Treatment
• Treatment of underlying cause
• No response to iron therapy
Causes of Macrocytic Anemia
1. Pernicious Anaemia
After being ingested, vitamin B12 is bound to intrinsic factor, a protein secreted by
gastric parietal cells. The vitamin B12–intrinsic factor complex travels through the
intestine and is absorbed in the terminal ileum by cells with specific receptors for
the complex. It is then transported through plasma and stored in the liver.
Since daily losses are 3–5 mcg/d, the body usually has sufficient stores of vitamin B12
so that vitamin B12 deficiency develops more than 3 years after vitamin B12
absorption ceases.
PA is megaloblastic anaemia due to vitamin B12 deficiency as a result of failure of
secretion of intrinsic factor by stomach due to atrophy of gastric mucosa.
It’s a hereditary disease.

Causes of vit. B12 deficiency


• Low dietary intake (in vegans).
• Impaired absorption from the stomach (intrinsic factor deficiency due to
pernicious anaemia, gastrectomy, or congenital deficiency) or from the small
bowel (Crohn’s disease, ileal resection, bacterial overgrowth in stagnant loops,
parasites such as the fish tapeworm).
Symptoms
1. Insidious onset.
2. Features of anaemia e.g pallor, weakness, tachycaardia, and dyspnoea. Anaemia may
be severe.
3. Yellow discoloration: due to milid jaundice caused by excessive breakdown of
hemoglobin due to ineffective erythropoiesis in the BM.
4. Mucosal changes: Red sore tongue due to glossitis and anguar stomatitis may be
present. Diarrhoea and anorexia due to changes in GI mucosa.
5. Neurological features: Polyneuropathy, posterior column of the spinal cord becoome
impaired causing loss of vibration and proprioconception and patients complain of
difficulty with balance, cerebral function may be altered with progressive weakness
and ataxia, and paraplegia, dementia.

Sings
1. Anaemia.
2. Skin with lemon yellow tint due to unconjugated hyperbilirubinaemia.
3. Spleen may be palpable
4. Purpura due to thrombocytopenia.
5. Low grade fever due to anaemia itself or infection.
6. Red sore tounge (glossitis) and angular stomatitis.
7. CNS examination shows signs of polyneuropathy or subactue combined degeneration
of the spinal cord
Investigations
1. Complete CBC
• Low Hb.
• MCV is raised (110-140 fl.)
• Peripheral film shows anisocytosis and poiklocytosis.
• WBC and platelet count may be low showing pancytopenia.
• Neutrophils are hypersegmented (6 lobes).
• Reticulocytes count is low.
2. Bone marrow
• Shows marked erythroid hyperplasia, abnormally large cell size, giant metamyelocytes.
3. Serum vit.. B12 is usually low below the normal level (150-350pg/ml)
4. LDH is elevated
5. Serum Unconjugated bilirubin is increased.
6. Vitamin b12 absorption test (schilling test)
Treatment
• Blood tranfusion (when Hb is very low)
• Treatment of infection.
• Packed platelets.
Inj vitamin b12 100 microgram daily for first week, weekly for first month, and then
monthly for life.
Iron : tab. Ferrous sulphate 200 mg.
2. Folic acid Deficiency anaemia
The most common cause of folic acid deficiency is inadequate dietary intake, malabsorpton
of folic acid is rare because it is absorbed from the entire GIT
Causes
1. Nutritional: poor intake (old age, starvation, and alcoholic excess, anorexia due to GIT
disease)
2. Antifolate drugs (Phenytoin, methotrexate, pyrimethamine, trimethoprim.
3. Excess utilization ( physiological like pregnancy, lactation, prematurity)
4. Pathological (haemolysis, malignat disease, inflammatory disease, haemocystinuria,
dialysis).
5. Malabsorption (small bowel disease)
• Clinical features
1. Features of anaemia and underlying cause.
2. Glossitis may occur.
3. Unlike B12 deficiency there is no neuropathy.
Investigations
1. Low serum folate level, fasting blood sample.
2. Red cells folate levels are low (but maybe normal if folate deficiency is of very recent
onset).
3. Macrocytic dysplastic blood picture, megaloblastic marrow.
Treatment
1. Tab. Folic acid 5mg orally/day.
2. Maintenance dose 5mg/day.
3. Prophylactically in pregnant women where there’s rapid cell turnover and in
patients taking methatrexate.
4. Folic acid should never be given before vit. B12 in B12 deficiency anaemia because
folic acid can aggrevate or precipitate neurological features of B12 depletion.
Causes of normocytic anaemia.
1. Aplastic Anaemia.
Defined as peripheral blood pancytopenia (low RBC’s. WBC’S, and platelets) with aplasia (inability to
produce blood cells) of the bone marrow.
It’s due to reduction in the number of pluripotential stem cells. Failure of one cell line may occur. A full
blood count demonstrates pancytopenia. Neutropenia is the most marked aspect of leukopenia;
anemia is normocytic normochromic and often marked; platelet production is often severely
affected and the last to recover.
Causes
1. Congenital: Fancol’s anemia.
2. Acquired:
• Idiopathic or primary aplastic anemia: cause unknown, may be due to autoimmune process.
• Secondary aplastic anemia due to
 chemicals like benzene
 drugs like sulfonamides, chloramphenicol, penicillamine, phenylbutazone, antithroid drug,
antiepileptic drugs, chemotherapy
 Insecticides.
 Ionizing radiation.
 Infections (viral hep. , TB, EBV, HIV)
 Pregnancy.
 SLE.
 Paroxysmal nocturnal hemoglobinuria.
Clinical features
a. Anemia due to low RBC count.
b. Infection due to low WBC count.
c. Bleeding due to low platelet count.
d. Fatigue, pallor , dyspnoea due to anaemia.
e. Persistant minor infection e.g fungal infection of mouth, sore throat and fever due to
low WBC count.
f. Petichiae and ecchymosis, bleeding disorders due to low platelet count.

Investigation
1. Blood complete picture
• Pancytopenia ( virtual absence of reticulocytes, anemia is normocytic normochromic type,
platelet count is very low, leucopenia)
2. Bone marrow biopsy
• Shows a hypocellurlar or aplastic bone marrow with increased fat spaces.
Management
I. Supportive masures:
Packed cell volume and platelet tranfusion for bleeding, vigorous antibiotics for infection, severe
aplastic anemia is defined by the presence of neutophils less than 500 /micro litres, platelets less
than 20000/ micro litres, reticulocytes count less than 1% and bone marrow cellularity less than
20%
II. Bone marrow transplantation.
III. Immunosuppressive therapy
IV. Treatment to stimulate hemopoiesis (androgenic steroids).
2. Haemolytic Anaemia
Haemolytic anaemias are caused by increased destruction of red cells. Shortening of reed
cell survival stimulates bone marrow to compensatory increase in red cell production
manifested as reticulocytosis and erythoid hyperplasia. If red cell loss is more than bone
marrow capacity, anaemia manifests.
Mechanisms of Haemolysis.
• Abnormalities of the red-cell membrane (in hereditary spherocytosis)
• Abnormal Hb. (Sickle cell anaemia and thalassemia).
• Abnormalities of vessel wall
• Sites of Haemolysis
1. Intravascular haemolysis: when red cells are rapidly destroyed within the destoyed
within the circulation.
Evidence of intravascular haemolysis.
• Raised level of plasma Hb..
• Haemoglobinuria or hemosiderenuria.
• Very low or absent heptoglobins.
• Presence of methamealbimin.
Causes of intravascular haemolysis.
• Falciparum malaria
• Transfusion reaction
• Microangiopathy.
2. Extravascular Haemolysis.
Here the red cells are removed from the circulation by macrophages in the reticuloendothelial system,
particularly the liver and the spleen.
Causes
A. Congenital
• Red cell membrane defect
Hereditary spherocytosis, hereditary elliptocytosis.
• Haemoglobin abnormalities
Thassemia, sickle cell disease.
• Metabolic defects
Glucose-6 phosphate dehydrogenase deficiency.
B. Acquired
• Immune
1. Alloimmune
Hemolytic transfusion reaction, hemolytic disease of new born, after transplantation.
2. Autoimmune
Warm antibody, cold antibody
3. Drug induced.
• Non-immune
1. Mechanical (burn, porsthetic valves)
2. Infections ( malaria, sepsis)
3. Hypersplenism
4. Drugs and chemicals
5. Systemic disease (renal or liver failure)
Inherited Haemolytic Anemias

• Hereditary spherocytosis.
• Hereditary elliptocytosis.
• Thalassemia.
• Sickle cell anaemia disease.
• Glucose-6-phosphate dehydrogenase deficiency.
Common investigations in blood disease.
Complete blood count (CBC) or complete picture (CP) is one of the most frequently
requested test by clinicians.

Main parameters measured


1. Hb concentration.
2. Red cell count (RCC).
3. MCV.
4. MCH.
5. MCHC.
6. Haematocrit (Hct) or PCV.
7. Red cell distribution width (RDW).
8. White cell count.
9. WBC differential.
10.Platelet count.
FBC parameters
Haemoglobin concentration (Hb)
Units: g/dL or g/L
Defines anaemia (Hb <lower limit of normal adjusted for age and sex).
Values differ between 9 and 3 since androgens drive RBC production and
hence adult male has higher Hb, PCV and RCC than adult female.
Red cell count (RCC)
Unit: × 1012/L.
Most clinicians pay little attention to the red cell count but this parameter
is useful in the diagnosis of polycythaemic disorders and thalassaemias (the
latter results in the increased production of red cells that are smaller than
usual and contain low quantities of haemoglobin, i.e. are microcytic and
hypochromic).
Causes of a low red cell count include
- Hypoproliferative anaemias, e.g. iron, vitamin B12 and folate deficiencies.
-Aplasias e.g. idiopathic or drug-induced (don’t forget chemotherapy).
-Parvovirus B19 infection-induced red cell aplasia resulting in transient
marked anaemia.
Causes of high red cell count
-PRV(polycythaemia rubra vera).
-Thalassaemia.
Mean cell volume (MCV)
Unit: femtolitre (fL), 10–15L.
Provided as part of the derived variables or can be calculated if you know
Irrespective of the method used to determine the MCV, this index provides
a useful starting point for the evaluation of anaemia
The MCV may suggest the cause of anaemia
• High MCV: B12 or folate deficiency, Myelodysplasia.
• Low MCV: Iron deficiency, B thalassaemia trait, sideroblastic anaemia.
• Normal MCV: Blood loss, myelodysplasia, anaemia of chronic disease.

Mean cell haemoglobin (MCH)


Unit: pg.
High
2 Macrocytosis.
Low
2 Microcytosis, e.g. iron deficiency anaemia.
Mean cell haemoglobin concentration (MCHC)
Unit: g/dL or g/L.
Of value in evaluation of microcytic anaemias.
High
2 Severe prolonged dehydration.
2 Hereditary spherocytosis.
2 Cold agglutinin disease.
Low
2 Iron deficiency anaemia.
2 Thalassaemia.
Haematocrit or PCV
The RBCs will
occupy about 40% of the blood in the tube—the blood will have a PCV of
0.4 (or 40%). The Hct is similar, but derived, using automated blood counters.
PCV unit: litres/litre (although the units are seldom cited on reports).
High PCV
2 Polycythaemia (any cause).
Low PCV
2 Anaemia (any cause).
Red cell distribution width (RDW)
Measures the range of red cell size in a sample of blood, providing information
about the degree of red cell anisocytosis, i.e. how much variation
there is between the size of the red cells. Of value in some anaemias:
e.g. 5 MCV with normal RDW suggests thalassaemia trait.
5 MCV with high RDW suggests iron deficiency.
(Probably noticed more by haematology staff than those in general medicine!)
White cells
The automated differential white cell count is provided as part of the FBC.
The red cells in the sample are lysed before the white cells are counted. A
typical FBC will show the total white cell count and the 5-part differential
white cell count, broken down into the 5 main white cell subtypes in peripheral
blood which include:
1. Neutrophils.
2. Lymphocytes.
3. Monocytes.
4. Eosinophils.
5. Basophils.
• Causes of neutrophilia
Infections (bacterial or fungal), inflammation( Gout, RA,IBD)
Infarction (MI, Pulmonary embolism), malignancy (polycythaemia, CML,
Lymphoma), physiological (exercise and pregnancy)
• Causes of neutropenia
Infections (viral, salmonella, malaria)
Drugs (NSAIDs, anti-thyroid, captopril, anticonvulsants, antimalarial,
sulphonamides)
Autoimmune (CT diseases)
Alcohol
• Causes of Esionphilia
Allergy (asthma, eczema)
Infections (parasitic)
Drug allergy (sulphonamide)
CT disease ( polyarteritis nodosa)
Malignancy (lymphoma)
• Basophilia
CML
Polycythaemia
allergy