ANAEMIAS

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Introduction & pathophysiology.

Haemolytic anaemia.
Anaemia of bone marrow failure.
Megaloblastic anaemia.
Iron deficiency anaemia.
Anaemia & pregnancy.

Introduction
Def. of anemia:
Reduction below what is expected in one of these parameters:
1. Haemoglobin percentage
a) In intrauterine life the fetus lives in a relatively hypoxic environment thus the
Hb % is very high at birth about 18 gm. It falls to half this value at 10 years old
then reaches the ideal figure of 15 gm at puberty.
b) are 1-1 gm less than at any age and can be explained
Before puberty by the effect of androgen on the bone marrow
After puberty by the effect of androgen on the bone marrow + menstruation
2. Haematocrite
Haematocrite is the packed cell volume. Normally RBCs occupy about 45% of
the bloods volume & plasma represents 55% of the same volume.
3. Red cell count
RBCs count varies from 4-6 millions/cm2. are < by 1 million/cm2 than .
- The term "below what is expected" is better than "below normal" because of
the wide range of the normal figure in every parameter regarding age & gender

Pathologic physiology
Four changes occur in the body to symptoms & bad effects of anaemia:
1) Shift of O2 dissociation curve to the right makes O2 delivery easier to tissues.
This is activated by excess production of 2,3 DPG "2, 3 diphosphoglycerate" which
makes the binding bet. O2 & Hb to be loose
2) Excess production of erythropoietin & erthyropoietic factor by the kidney.
Erthyropoietic factor secreted by the kidney change erythropoietenogen
formed by the liver into erythropoietin
Erythropoietin has a stimulant effect on the bone marrow:
a) It differentiates the stem cell into the red series.
b) It early denucleates the late normoblast by activating alkaline phosphatase
enzyme inside the red cell.
c) It early releases the reticulocyte
NB.: Hypoxia of the kidney as a sequence of anaemia is the main stimulus of this
excess erythropoietin and the amount of erythropoietin is related to the amount of
kidney tissue.
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3) Hyperdynamic circulatory state achieved by peripheral vasodilatation & leads to

short circulation time.
This hyperdynamic state has a bad effect on cardiac muscle if the heart is
decompensated it makes heart failure to be "refractory" which doesnt
respond to ordinary lines of treatment.
NB.: VD is also caused by hypoxia as a sequence of anaemia.
4) Redistribution of circulation occurs very late in anaemia with very low Hb level as the
blood is shifted to vital organs as brain by peripheral vasoconstriction.

Classification of anaemia
1. Classification based on red cell size:
Microcytic, normocytic & macrocytic
2. Classification based on the value of mean corpuscular Hb concentration:
Normochromic & hypochromic
3. Classification based on the value of the color index:
Anemia with >1, =1 & with <1
4. Aetiological classification: based on the cause of anemia
NB.: It may be used in one term more than one classification as hypochromic microcytic

1. Classification based on the size of the red cell:

Normally diameter of RBCs = 7.2 micron
If the majority of RBCs > 7.2 micron macrocytic anemia e.g. B12 & folic acid
deficiency.
If the majority of RBCs < 7.2 micron microcytic anemia e.g. iron deficiency.
Price Jhons curve is the method to determine this classification. It plots the diameter
against the number of RBCs
a) In normal curve most of RBCs are at the diameter of 7.2 micron
b) If Price Jhons curve showed normal pattern normocytic
c) Shift of the curve to the right macrocytosis
d) Shift of the curve to the left microcytosis
e) Plateau curve anisocytosis "means marked variations in the size of RBCs"

2. Classification based on the value of the mean corpuscular Hb concentration:

Any RBC cant accommodate Hb more than approximately its third so the normal
mean corpuscular Hb concentration is 35% & it may be low but cant be high
1) If anaemia is accompanied by a normal value normochromic
2) If accompanied by low value hypochromic
3) Hyperchromia is not a correct term bec. the mean corpuscular Hb concentration
cant exceed 35% except in the "microspherocyte" which is a cell shrinkage
phenomenon with a mean corpuscular Hb concentration > 35%

3. Classification based on the value of the color index:

The colour index is the relation bet. the Hb % & the RBCs count %
The normal Hb 15 gm = 100%, the normal RBCs count 5,000,000 = 100%, the normal
colour index = 1 (100/100)
Colour index reflects the degree of the reduction of each in comparison to the other
a) Anaemia with colour index = 1 the reduction in the RBCs = the reduction in Hb
b) Anaemia with colour index < 1 the reduction in the RBCs < the reduction in Hb
e.g. iron deficiency anemia as the reduced amount of Hb is divided on large
number of RBCs more than that expected to that level of Hb
c) Anaemia with colour index > 1 the reduction in the RBCs > the reduction in Hb.
4. Aetiological classification:
It is the nearest classification to the mind as it is based on the physiology
a) Dyshaemopoietic anaemia is present when there is deficiency in one of the
elements essential for erythropoiesis
1) Iron deficiency anaemia.
2) Megaloblastic anaemia due to deficiency of B12 &/or folic acid
3) Anaemia of scurvy due to deficiency of Vit. C
4) Renal anaemia due to deficiency of erythropoietin
5) Anaemia of myxedema due to deficiency of thyroxin
b) Anaemia of bone marrow failure due to the inability of the bone marrow to utilize
the already present elements
c) Haemolytic anaemia
d) Haemorrhagic anaemia
1) Acute blood loss
2) Chronic blood loss

Clinical picture of anaemia in general

Patients with anaemia irrespective to the cause or type usually have these findings
Symptoms:
- Symptommatology of anaemia depends upon how quickly the Hb is reduced
rather than the absolute figure of Hb
e.g.: Hb of 15 gm reduced to 13 gm in one day as after complicated labour may
result in symptoms more profound than those present in a patient with Hb 9 gm
due to ankylostoma which causes very gradual blood loss.
- All symptoms are usually those of low COP in spite that COP is high in anaemia
1) Dizziness, Giddiness
2) Easy fatigue, Lack of concentration
3) Dyspnea ... etc.

 Physical signs:
1) Pallor
2) Hyperdynamic circulatory state Big pulse volume, tachycardia, accentuation of
Ht sounds, murmurs over the Ht mostly systolic basal, systolic apical, diastolic
apical & rarely diastolic basal, 3rd Ht sound
3) Splenomegaly especially in chronic haemolysis, but not in bone narrow failure
4) Hepatomegaly in chronic haemolysis & anaemia of chronic illness
NB.: Hepatosplenomegaly may have nothing to do with anaemia & may be just an
association
5) Peripheral neuritis in various chronic types of anaemia
6) Leg ulcer in haemolytic types specially sickle cell anaemia

Investigations of anaemia in general

1) Blood picture is the most important of all investigations as the primary diagnosis of
anaemia is based on it
Three main items are looked for:
a) RBCs & their parameters + the Hb
b) WBCs count both the total and the differential
c) Platelet count
The parameters of the RBCs include:
a) The mean corpuscular Hb concentration.
b) The size of RBCs detected by Price Jhons curve.
c) The colour index.
2) Bone marrow picture is not done if the diagnosis is already established. It is of value
when aplasia of the bone marrow, myelofibrosis, myelosclerosis & leuckemias are
suspected
3) Estimation of some factors essential for erythropoiesis as iron, B12 & folic acid
4) Estimation of bilirubin & haptoglobin when hemolysis is the clinical diagnosis
5) Stool Analysis when ankylostoma is suspected as a cause of the anaemia

Treatment:
1) Essentially is the trt of the cause
2) Blood transfusion is indicated in acute blood loss & some hematologic disorders

A) Megaloblastic Anaemia
Def.: It is a hematological disorder characterized by:
1) Pancytopenia with evidence of macrocytosis & anisocytosis
2) Megaloblastic changes of the bone marrow
3) GI &/or neurological complications
4) Good response to B12 &/or folic acid
Pathophysiology:
- Before cell division, it must reduplicate its amount of DNA.
- DNA formation needs B12 & folic acid while Hb & cytoplasm dont need DNA.
- So in B12 &/or folic acid deficiency DNA formation is arrested & consequently
the cell isnt able to divide. At the same time, the growth of the cell runs normally
resulting in big cells.
- The only dividing somatic cells are those in the bone marrow, so B12 & folic acid
deficiency show their effect mainly in the bone marrow by forming megaloblasts
instead of normoblasts.
- Most of the megaloblasts undergo intramedullary haemolysis called ineffective
erythropoiesis.
- Some of these megaloblasts can escape from the bone marrow & appear in the
peripheral bl. as macrocytes which are rapidly sequestrated by the spleen.
- Leucopenia & thrombocytopenia are caused by the same mechanism.
- The cause of the neurological complications in megaloblastic anaemia is not
known.
- Injury of any cell in the body as in buccal mucosa, vagina or gastric wall is
replaced by giant cells in cases of B12 or folic acid deficiency.
Causes of megaloblastic anaemia:
1) B12 deficiency.
2) Folic acid deficiency.
The hematological picture of megaloblastic anaemia with the presence of
macrocytes in the peripheral blood must be differentiated from normoblastic
macrocytosis as in:
1) Myxedema.
2) Aplasia of the bone marrow.
3) Liver cirrhosis.
4) Chronic alcoholism.
5) Pregnancy.
Causes of B12 deficiency:
1) Diminished intake of B12 which present in animal & bacterial products.
2) Gastric causes:
- B12 has no receptors in the intestine to carry out the absorption
- So when B12 is found in the stomach the stomach secretes the intrinsic
factor which combines with B12 and its receptors are present in the terminal
ileum.
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- We absorb B12 by the amount secreted from intrinsic factor & not by the
amount ingested from B12 so any cause which affects intrinsic factor
secretion will in turn affect B12 absorption as:
a) Gastrectomy
b) Chronic gastritis
c) Idiopathic "pernicious anaemia"
d) Congenital
3) Intestinal causes:
- Malabsorption syndrome
- Chronic diarrhea
- Diphyllobothrium latum
4) Deficiency of the substance responsible for the transformation of B12 to the
bone marrow "transcobalamin II" which is usually congenital
Causes of folic acid deficiency
1) Diminished intake as in old age (most important & most common cause)
2) Diminished absorption occurs with malabsorption syndrome & chronic diarrhea
3) Increased demands as in:
- Pregnancy
- Malignancy
- Haemolysis
- Dialysis
4) Drugs interfering with folate metabolism as:
1) Antiepileptic drugs
2) Trimethoprim
3) Methotrexate
The following are examples for megaloblastic anemia
1) Pernicious Anemia
Aetiology: 2 theories
1) Genetically determined weakness of the mucosa of the stomach at middle age
2) Autoimmune disease in which antibodies are secreted against parietal cells
"anti-parietal cell antibodies"
The net result of the two theories is defective production of the intrinsic factor which
affects the absorption of B12.
Clinical manifestations: 2 groups of symptoms are present
- Group 1 of anaemia: fatigue, palpitation, dyspnea, headache & general ill health
- Group 2 of neurological manifestations: paraesthesia, numbness of limbs,
weakness of both lower limbs, unsteadiness
Physical Signs:
1) Those of anaemia as pallor
2) Purpura due to thrombocytopenia
3) Hepatosplenomegaly
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4) Glossitis & angular stomatitis

5) Neurological signs:
a) Glove & stocking hypoesthesia due to peripheral neuritis
b) Exaggerated knee & lost ankle reflexes due to affection the pyramidal tract
and peripheral nerve
c) Lost vibration sense over the anterior superior iliac spine
NB.: Subacute combined degeneration of the cord is a term used when the affected
parts of the nervous system are
- Peripheral nerve
- Pyramidal tract
- Posterior column
Investigations: The aims are
1) To prove that the anaemia is macrocytic by the ordinary blood picture:
a) Hb is low
b) The mean corpuscular volume > 95
2) To prove that macrocytic anaemia is megaloblastic & not normoblastic by both
the blood picture which shows pancytopenia & the bone marrow picture which
shows megaloblastic hyperplasia
3) To prove that the megaloblastic anaemia is caused by B12 deficiency & not folate
deficiency by serum estimation of B12 which is < 50 ug/L
4) To prove that B12 deficiency is caused by a gastric cause by Schilling test & in
some cases upper GI endoscopy
Schilling Test:
- The test is based on the fact that if B12 is absorbed it will appear in urine.
- Radioactive B12 is given orally & is tested for in urine
If the radioactive B12 appears in urine, this is a proof of its absorption,
if not, there are two possibilities are raised
a) No absorption occurs
b) The ingested B12 goes to the liver to be stored there but this is
excluded by injection of big amounts of B12 days before the test
- The negative test can be repeated by giving intrinsic factor with B12 if the
test changed from -ve to +ve, this is a good proof for gastric abnormality as
a cause of the megaloblastic anaemia.
5) To prove that this gastric cause is pernicious anaemia by estimation of the antiparietal cells antibody in the serum of the suspected patient
Treatment of pernicious anaemia:
- Hydroxycobalamine is the drug of choice and is given IM 1 mg/twice weekly for 3
weeks, then every 3 months for life.
- Hematological improvement which is known by reticulocytosis occurs within
days, but neurological manifestations take months to show improvement and
may not occur in neglected patients.
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2) Folate Deficiency Anemia

Folate deficiency is more common to cause megaloblastic anaemia than B12 deficiency
as B12 stores are very huge & need at least 5 years after failure of absorption to affect
the body
Also, the daily needs for folate are higher than those of B12.
Clinical Picture:
C/P is like that of B12 deficiency but usually lacking the neurological manifestations.
Investigations:
The results of investigations are like those in B12 deficiency but folate level both in
the plasma & in the RBCs is low
Treatment:
- Oral folic acid in a dose of 5 mg/day
- As B12 is essential for the transformation of folic acid to its active form folinic acid
so folic acid isnt given in B12 deficiency alone as it may aggravate the disease,
including neurological manifestations.

B) Haemolytic Anaemia
Def. of haemolysis:
Diminished life span of RBCs. Normally, their life span is about 120 days.
Pathophysiology of haemolysis:
1) Anaemia:
The BM can its activity regarding the formation of the RBCs into 8 folds thus
anaemia doesn't occur in haemolysis except when life span of the RBCs is < 15
days, except in hyporegenerative crisis in which haemolysis occurs with
simultaneous depression of the bone marrow.
2) Haemoglobinuria:
- There are 2 types of Hemolysis
a. Intra-vascular: occurs inside the bl. vessels.
b. Extra-vascular: at the level of reticuloendothelial system.
- When Hb escapes from the RBCs during haemolysis it rapidly binds to various
proteins aiming to prevent its filteration in the glomerulus. These proteins are
haptoglobin, haemopexin & albumin.
- So conditions for haemoglobinuria to occur:
Haemolysis must be intravascular.
The binding capacity of Hb to the proteins is lost.
- Effect of haemoglobinuria:
It may cause tubular damage
It may result in dark urine which may mislead for the diagnosis of another
type of jaundice as the haemolytic jaundice is associated with normal
colour of urine "acholuric"
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3) Hyperbilirubinaemia:
- When the life of RBCs comes to its end:
a) Most of them show extravascular haemolysis at the level of the
reticuloendothelial cells
b) 1 % of the RBCs show intravascular haemolysis which is the cause of the 1
mg% bilirubin in bl.
- Bilirubin coming out of the destroyed RBCs is called unconjugated "indirect or
haemobilirubin " and can't pass the glomerulus with glumerular filtrate.
- This type of bilirubin goes to the liver where 3 steps occur:
1) Uptake
2) Conjugation
3) Excretion
- The excreted bilirubin is called conjugated "direct or cholebilirubin" and If it is
present in the bl. it can pass the glomerulus with glomerular filtrate.
- The conjugated bilirubin passes with bile to the intestine where it is changed
to stercobilinogen and
1) Part of it comes out with the stool to be changed into stercobilin by the
process of oxidation and this is responsible for the normal colour of the
stool.
2) The other part is absorbed and
a) Part of it passes through the portal circulation causing enterohepatic
circulation which is essential for the process of uptake.
b) The other part escapes to be filtered in the kidneys to appear as
stercobilinogen in urine "urobilinogen" which changes to urobilin in air
In severe haemolysis:
1. Bilirubin
- Present in the bl. as unconjugated type
- Doesn't appear in urine
- Its level is not high bec. the liver can its capacity regarding excretion
of bilirubin 4 folds
2. Stool is rich in stercobilinogen & stercobilin
3. Urine is rich in urobilinogen & urobilin but free from bilirubin
4) Hepatosplenomegaly:
- Hepatosplenomegaly is due to activation of the reticuloendothelial system to
make all haemolysis to be extravascular
- Also as a result of haemolysis serum iron and is precipitated in liver cells
causing Hepatomegaly
C/P of haemolysis in general:
a) Acute haemolysis: presented by
Fever, rigor, loin pain, palpitation, dark urine & jaundice
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b) Chronic haemolysis:
1) May be asymptomatic
2) Symptoms: Fatigue, headache, palpitation, faintness, dyspnea, angina &
intermittent claudications.
3) Signs:
- Pallor, tachycardia, high pulse volume
- Murmurs over the heart, mainly systolic, commonly over the base
The commonest is systolic pulmonary murmur then systolic apical murmur
Diastolic mitral murmur is rare & diastolic aortic murmur is very rare
- Jaundice & lemon colour of the skin, which is a mixture of pallor &
yellowish discoloration of jaundice
- Splenomegaly, bone deformities & leg ulcers
Investigations of haemolysis in general:
1) Blood picture:
- Anaemia is not a rule in mild haemolysis & appears when the lifespan of the
RBCs < 15 days
- In acute haemolysis
a) Anaemia is normochromic & normocytic with normal mean corpuscular
haemoglobin concentration
b) WBC count is normal
c) The platelet count is normal
- DD: Haemolysis may occur in systemic disorders as SLE where the bl. picture
follows the primary disease with more reduction in the haemoglobin
2) Bone marrow picture: 3 possibilities
a) The most common picture is hypercellular bone marrow with normoblastic
hyperplasia to compensate for the red cell destruction
b) Hypocellular bone marrow occurs in simultaneous depression of the bone
marrow & haemolysis "hyporegenerative crisis"
c) Megaloblastoid changes due to secondary B12 & folic acid deficiency
3) Serum haptoglobin: is low as it is combined with Hb to prevent its passage
through the glomerulus.
NB: Haptoglobin is a protein formed by liver & is low in haemolysis & liver cirrhosis
4) Serum iron: is high as a result of destruction of RBCs & the release of their iron
into the circulation.
5) Liver function tests:
a) Serum bilirubin is mildly & of the unconjugated type
b) Stercobilinogen is excess in stool
c) Urobilinogen is excess in urine while Bilirubin is absent
d) Other liver functions are normal
6) Determination of the RBCs lifespan by isotopic methods
7) Special investigations to reach the cause of the haemolysis:
- Type of Hb
- Osmotic fragility test.
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 Treatment of haemolysis in general:

1) Bl. transfusion in acute & severe cases
2) Splenectomy in some cases
3) Bone marrow transplantation
Causes of haemolysis:
A) Congenital:
1) Membrane defect
- Hereditary spherocytosis
- Hereditary elliptocytosis
2) Abnormal haemoglobin
- Thalassemia
- Sickle cell disease
3) Enzymatic defect
- Glucose 6 phosphate dehydroenase deficiency "G6PD"
- Pyruvate kinase deficiency
B) Acquired:
1) Immunological
- Autoimmune haemolytic anaemia
- Rh incompatibility
- ABO incompatibility
2) Non-immunological
- Paroxysmal nocturnal haemoglobinuria
- Liver diseases
- Renal diseases
- Mechanical:
March haemoglobinuria
Valve replacement
Haemodialysis
- Miscellaneous:
Burns
Infection
Some drugs
Hereditary Spherocytosis
Def.: autosomal dominant condition in which the membrane of RBCs has 2 defects
causing the life span to be short
a) 1st defect: the membrane of RBCs is more rigid thus RBCs are trapped in small
sinusoids & rapidly destroyed.
b) 2nd defect: the membrane is freely permeable to sodium & water.
- Normally, the excess Na passed to RBCs is pumped out by Na pump
mechanism which needs energy.
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- Under certain conditions, this mechanism doesnt act keeping the Na in RBCs
with consequent withdrawal of excess H2O causing RBCs to take the sphere
shape & early destruction occurs.
C/P:
Haemolysis is usually chronic resulting in anaemia & jaundice with:
1) Splenomegaly
2) Leg ulcers
3) Skull deformity due to hypertrophy of their bones
4) Stunted growth
Investigations:
a) To prove the presence of haemolysis:
1) CBC
2) Serum haptoglobin
3) Bone marrow picture
b) To prove the cause of haemolysis:
1) Spherocytes in the peripheral bl. film
2) ed osmotic fragility:
Normally, RBCs stand diluted saline without haemolysis up to 0.4-0.3 %. But in
hereditary spherocytosis, haemolysis occurs earlier
TTT:
1) Bl. transfusion if Hb is markedly or in crisis.
2) Splenectomy which is better postponed after childhood.

Sickle Cell Anaemia

Def.: one of the haemolytic anaemia caused by presence of abnormal Hb inside RBCs
Types:
1) Homozygous sickle cell disease in which the phenomenon of sickling results from
mild hypoxia
2) Heterozygous sickle cell disease in which the phenomenon of sickling results
from severe hypoxia
Precipitating factors for the phenomenon of sickling:
1) Hypoxia
2) Cold
3) Infection
4) Dehydration
Type of Hb:
- The abnormal Hb present in this disease is called haemoglobin S in which amino
acid No. 6 on its side chain is substituted by valine instead of glutamine
- Under some precipitating factors, haemoglobin S becomes rod-like, changing the
red cells into sickle-shaped.

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 C/P:
- C/P of severe anaemia due to haemolysis of the sickle cells +
- C/P of arteriolar obstruction as sickle cells may form clumps obstructing the small
vessels resulting in:
1) Spleen: auto-splenectomy
2) Heart: myocardial damage
3) Kidneys: papillary necrosis
4) Brain: cerebral damage
5) Eye: retinal detachment
6) Penis: priapism
Types of crisis: 4 types
1) Painful crisis due to infarction in various organs
2) Aplastic crisis following infection & resulting in severe depression of BM
3) Haemolytic crisis which is differentiated from aplastic crisis by high
reticulocytic count while it is zero in aplastic crisis
4) Sequestration crisis which simulates haemolytic crisis but is due to trapping
of RBCs in liver & spleen
Investigations:
1) As ordinary case of haemolytic anaemia + demonstration of sickle cells in bl. film,
either spontaneously or artificially by adding sodium metabisulphite
2) Hb electrophoresis to demonstrate its abnormality
TTT:
1) Correction of the cause of disease by gene therapy (ideal ttt)
2) Avoid all precipitating factors.
3) Bl. transfusion aiming to:
- Correction of anaemia.
- of % of Hb S before elective surgery
- Exchange transfusion in emergency surgery
4) Pain is treated by analgesics.
NB.: No role for anticoagulants as occlusion of vessels occurs as a result of clumps of
RBC & not thrombosis
Glucose 6 Phosphate Dehydrogenase Deficiency "G6PD"
Sources of energy inside RBCs: 2 sources
1) Glycolytic pathway which utilizes about 90% of glucose
2) Hexose monophosphate shunt pathway which utilizes about 10% of glucose
- Glucose 6 phosphate dehydrogenose is essential for the hexose monophosphate
shunt pathway which doesnt act in absence of this enzyme
Deficiency of the enzyme glucose 6 phosphate dehydrogenose makes RBCs
vulnerable to death when exposed to severe oxidizing stress, which may be:
1) Infections
2) Fava Beans
3) Drugs as aspirin, anti-malarial, Vit K, quinidine, chloramphenicol, sulphonnamide
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 Types:
a) Negro or African type:
The recently-formed RBCs show normal enzymatic levels while deficiency is
present in aged RBCs only, so C/P is not marked
b) Mediterranean type:
The enzymatic deficiency affects all RBCs, so C/P is severe
C/P:
Haemolysis occurs when the patient is exposed to severe oxidizing stress
Investigations:
1) Estimation of the activity of glucose 6 phosphate enzyme will show its deficiency
2) Blood picture shows some characteristic phenomena:
a) Blister cells: Hb appears separated from the cell membrane
b) Bite cells: the cell membrane is bit "indented"
c) Heinz bodies: denaturated Hb
3) All tests for haemolysis are +ve during an attack
TTT:
- Prevention of any of precipitating causes
- The gene of G6PD is sex-linked carried on the x-chromosome so it affects & is
carried by apparently healthy so it is wise to estimate the enzymes in all boys in
a suspicious family

Paroxysmal Nocturnal Haemoglobinuria

Def.: RBCS, WBCs & platelets are sensitive to the circulating complement which
causes their destruction resulting in pancytopenia
For unknown reasons, haemolysis usually occurs during night
Thrombotic manifestation is known & better not to be treated by heparin as it
activates the complement
Aplasia of bone marrow or acute leukemia may terminate the disease
It can be proved by Ham's test in which rapid haemolysis occurs if the serum is
acidified
Immune Haemolytic Anaemia

Types:
1) Warm type "Coomb's test is +ve"
2) Cold type "Coomb's test is -ve"
Causes: No definite cause could be known in both types in many cases
1) Cause of warm type:
2) Cause of cold type:
- SLE
- Infectious mononucleosis
- Lymphoma
- Lymphoma
- Chronic lymphatic leukemia
- Paroxysmal cold haemoglobinuria
- Carcinomas
- Drugs as methyldopa
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C) Anaemia of Bone Marrow Failure

"Aplastic or hypoplastic anaemia"
Def: It is a type of anaemia caused by failure of one, two or three elements of the
bone marrow
Aetiology:
1. Depression of the BM may be primary with no evident cause but maybe by
cytotoxic T-cells
a) It may affect 1 element monocytopenia resulting in 1 of the following:
Anaemia
Leucopenia
Thrombocytopenia.
b) It may affect 2 elements dicytopenia causing 2 only of the above clinical
conditions
c) It may affect 3 elements pancytopenia
2. Depression of the BM may be secondary:
a) Replaced bone marrow:
1) Myelofibrosis.
2) Myelosclerosis.
3) Malignant tissue.
b) Depressed bone marrow:
1) Irradiation.
2) Drugs as
a) Drugs routinely causing depression of the BM as Anti-neoplastic drugs:
- Mercaptopurine
- Busulphan
- Methotrexate
b) Drugs occasionally causing depression of the BM as
1. Anti-inflammatory:
- Phenylbutazone
- Gold
- Non-steroidal anti-inflammatory
2. Anti diabetic:
- Tolbutamide
- Chlorpropamide
3. Anti-thyroid:
- Carbimazole
- Methylthiouracil
4. Antibiotic: Chloramphenicol
5. Chemotherapeutics: Sulphonamide
6. Tranquilizers: Chlorpromazine
- NB.: Any of the above-listed drugs may cause depression of the bone
marrow by single dose "hypersensitivity" or in a dose-related manner.
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c) Miscellaneous causes:
1. Insecticides
2. Viral infections
3. Tuberculosis
4. Pregnancy
5. Thymoma
6. Paroxysmal nocturnal haemoglobinuria
Clinical Picture:
- The usual form of BM depression is that resulting in pancytopenia
Anaemia
Agranulocytosis
Thrombocytopenia
- The onset may be acute after drug intake or gradual in other cases
- Throat infection is the usual presentation
Differential Diagnosis:
1. Acute leukemia
2. Agranulocytosis
3. Haemolytic anaemia
4. Thrombocytopenia
Investigations:
1) Blood picture shows pancytopenia. The presence of reticulocytes is against the
diagnosis of bone marrow failure as it indicates hyperactive marrow
- D.D. of the blood picture: other conditions that cause pancytopenia
1. Megaloblastic anaemia
2. Myelofibrosis
3. Myeloscelrosis
4. SLE
5. Paroxysmal nocturnal haemoglobinuria
6. Hypersplenism
7. Subleukemic leukemia
2) The bone marrow is hypocellular
Treatment:
1) Removal of the offending agent
2) Blood or platelet transfusion
3) Antibiotics for infection which must be safe to the bone marrow
4) Steroids especially in the congenital pure red cell aplasia
5) Thymectomy for adults in cases of pure red cell aplasia
6) Androgens may stimulate the bone marrow in some cases
7) Immunosuppression may help in some cases
8) Bone marrow transplantation is trt of choice in young patients below 20 years

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D) Iron Deficiency Anaemia

Def.: It is the type of anaemia due to iron deficiency
- It must be differentiated from sideroblastic anaemia in which there is failure of
combination of iron to prot-oporphyrin inside the red cell to form haemoglobin so
it simulates iron deficiency but iron is available & is normal in the plasma
Causes of iron deficiency:
1) Chronic bl. loss "the most common cause"
2) Diminution of iron intake "rare bec. iron is present in most of foods available for
everyone"
3) Gastric disorders where HCl is lacking "achlorhydria" as HCl of the stomach is
the agent responsible for transformation of Ingested iron "in ferric form" to
ferrous to be absorbed absorption of ingested iron
4) Diminished absorption from the intestine as in Coeliac disease
5) Milk is a very bad source of iron & iron stored in the baby is enough for 6 months
so if iron supplement is not added to the baby, he will develop iron deficiency
Clinical Picture:
1) The most characteristic sign is the nail changes which become brittle, flat or
spooned & ridged
2) Glazed tongue due to atrophy of its papillae
3) Angular stomatitis
4) Clinical picture of anaemia:
- Hyperdynamic circulation
- Splenomegaly
- Pallor
Plummer-Vinson syndrome:
Iron deficiency anaemia
Dysphagia
Glossitis
Searching during clinical examination should be done for a source of bleeding as
piles
Investigations:
1) Blood picture:
a) The RBCs count & Hb % are low
b) The RBCs are microcytic hypochromic
c) The mean corpuscular haemoglobin concentration is low
d) The white cell count is usually normal
e) Eosinophilia is present in ankylostoma cases
f) The platelet count is normal but may be low & could be the cause of the bl.
loss & iron deficiency
2) Serum iron is low
3) Total iron-binding capacity "TIBC" is high
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4) Serum ferritin which reflects the amount of stored iron is low

Normal in male is 30-300 ug/L & in females is 20-200 ug/L
5) Bone marrow picture is rarely needed & it shows normoblastic hyperplasia
6) Upper gastrointestinal endoscopy if bleeding varices or ulcer is suspected
Treatment:
1) TTT of the cause is more important than giving iron supplements
2) Ferrous sulphate 200 mg orally
3) Ferrous gluconate 200 mg orally
4) Iron Dextran 50-250mg/day deeply intramuscular
Successful treatment is known by:
- Reticulocytosis
- Rise of haemoglobin 1 gm/week

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