Clinical Haematology

2
Anaemia
T. Rashad Saleh M. Alkhwlany
MSc. Medical Microbiology
 Clinical Hematology T/ Rashad Saleh Alkhwlany

Disorders of Red cells

Disorders of RBCs may be:
1. Anemia
2. Haemoglobinpathies
3. Disorders due to red cell enzymes defects
4. Disorders due to red cell membrane defects
5. Polycythaemia.

Anaemia
(from Gk anaimia, from an- 'without' + haima 'blood')

Definition of Anemia
Anemia is defined as a decrease in RBCs, Hb, and Hct. In the peripheral blood below
the normal range (values).
Thus, adult male is said to be anemic when his Hb falls below 13.5 g/dl and adult
female her Hb falls below 11.5 g/dl.
‫فقز اىذً ھو اّخفاض ٍظروى خعاب اىذً (اىھََوجيوتَِ) ومزٍاخ اىذً اىذَزاء وٍنذاص اىذً ذذد اىَظروى‬
‫ وقذ ٍذراج‬، ‫ ٍشٍْا أو دادا‬، ‫ وقذ ٍنوُ ھذا االّخفاض تظَطا أو أُ ٍنوُ شذٍذا‬،‫اىطثَعٌ دظة اىعَز واىجْض‬
.‫إىٌ إعطاء دً ىيَزٍط ىشٍادذھا وٍْع عواقثھا اىوخََح‬

:Causes of anemia ‫ أسباب فقر الدم‬

ٌ‫ وف‬،‫ فئُ دجٌ مزٍاخ اىذً اىذَزاء ٍْخفط وٍذرواھا ٍِ اىھََوجيوتَِ ٍقو‬،َِ‫عْذ ّقص اىھََوجيوت‬
‫ فرصثخ قيَيح اىعذد أو ظعَفح اىْوع‬،‫ٍزديح الدقح ٍؤثز عيٌ عذد مزٍاخ اىذً اىذَزاء وذْخفط ھٌ األخزى‬
:‫ وھْاك أطثاب عذٍذج ىْقص اىھََوجيوتَِ ٍْھا‬،‫أو ميَھَا‬
‫ و داٍط اىفوىَل‬1١ ‫ فَراٍَِ ب‬،‫ ّقص اىذذٍذ‬:‫ ٍثو‬:Nutrition deficiency ٌ‫ اىْقص اىغذائ‬.1
‫ األَََّا اىَْجيَح‬:‫ خيو وراثٌ ٍؤدً إىٌ ذزمَثح غَز غثَعَح اىھََوجيوتَِ ٍثو‬:Genetic ‫ أطثاب وراثَح‬.١
.Eliptocytosis ‫ أو‬Spherocytosis ‫ أو‬Thalassaemia ‫ أو اىثالطَََا‬Sickle cell anaemia
.Haemolysis ً‫ سٍادج ذنظز اىذ‬.3
.‫ اىجزوح – اىْشٍف‬:Blood loss ً‫ فقذاُ اىذ‬.4
‫ ىعَوب فٌ ٍْاغق اإلّراج ٍثو‬:Decreased blood production ‫ قيح إّراج مزٍاخ اىذً اىذَزاء‬.5
.‫ اىعَوب اىخيقَح‬،‫ األشعح‬،ُ‫اإلصاتح تاىظزغا‬

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 Clinical Hematology T/ Rashad Saleh Alkhwlany

 Symptoms
Because a low red blood cell count decreases oxygen delivery to every tissue in
the body, anemia causes many signs and symptoms.
- Mild anemia (Hb 11.5-10 g\dL) normally produce no symptoms or clinical
sings.
- Moderate anemia (Hb 7-10 g/dL) may not produce clinical signs or symptoms
if the onset of anemia is slow. Depending on the patient's age and
cardiovascular state.
- Severe anemia (Hb < 7 g/dL) usually produce the symptoms of cardiovascular
and nervous system.
The most common symptoms are:
1. Pallor  looked for:
 in the skin in general, at palms, more precise in the palmar
creases
 at the conjunctiva of the eyes
 Mouth mucosa
 nail beds
2. Fatigue.
3. Dyspnea (shortness of breath) occurs on exertion. Although the respiratory
system in the anemic person is healthy, the tissues out in the body are starved
for oxygen, because there is not enough Hb to get it to them. When they need
even more oxygen, as in a period of strenuous exercise, they send signals to the
respiratory system to deliver more. The respiratory system responds by
increasing the depth and rate of breathing, which the anemic person experiences
as shortness of breath .
4. Palpitation.
5. Tachycardia or fast heart rate, results from the increased cardiac output.
6. Tinnitus means "ringing in the ears" . One possible explanation for this is that
the cardiac output is so increased that the rushing of the blood through the
vessels in the region of the ear is perceived as sound.

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7. Headaches can be a symptom of anemia, although the exact cause is unknown .

8. Loss of appetite.
9. Nausea.
10. Constipation.
11. Weakness.
12. Lethargy.

The history and physical examination are essential for establishing the clinical
diagnosis of anemia

 Classification of Anemia
There are two main methods of classification of anemia:
 The morphological classification, based on the morphology of RBCs.
 The pathphysiological and etiological classification, based on the causes of
the anaemia.

I. The morphological classification

In the morphologic classification, anemia is subdivided into three large groups
according to:
 The average of cell volume (MCV).
 The average of cell haemoglobin concentration (MCHC).
There are three types are recognized:
1. Normocytic, normochromic anemia:
Has an MCV in the range of 80-100 fl, and MCHC of 32-36%
- Defective formation of the blood cells or the presence of tumor cells in the
BM. (aplastic anemia, leukemia, multiple myeloma)
- Abnormal Hb, increases destruction of RBC.
(certain acquired hemolytic anemia, sickle cell anemia, HDN, anemia of
chronic renal insufficiency)

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2. Microcytic, hypochromic anemia:

Has an MCV less than 80 fl, and MCHC of less than 32%
- Iron deficiency anemia.
- Thalassemia.
- Sideroblastic anemia.
- Chronic blood loss.
- Anemia of chronic disorder
3. Macrocytic anemia:
Have an MCV higher than 100 fl, and MCHC higher than 36%
- Vit. B12 deficiency, folic acid deficiency
(Pernicious anemia, megaloplastic anaemia)
- Disease of the liver

II. The pathphysiological and etiological classification

Anemia result from three causes:
1. Blood loss.
2. Decreased or Impaired production of RBC.
3. Increased RBC destruction.
1. Blood loss
- Acute blood loss
- Chronic blood loss
2. Decreased or Impaired Production of RBCs
Decreased production of RBCs may be due to:
I. Disturbance of marrow function due to deficiency of substances of essential for
erythropoiesis (eg: iron, Vit. B12, folate and ascorbic acid). This due to:
- Inadequate intake.
- Inadequate absorption.
- Excess demand.
- Excess loss.
II. Disturbance of marrow function NOT due to deficiency of substances of
essential for erythropoiesis:

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- Anemia associated with infection.

- Anemia associated with renal failure.
- Anemia associated with liver disease.
- Anemia associated with bone marrow infiltration (leukaemia, malignant
lymphoma and multiply myeloma).
III. Ineffective red cell formation
- Chronic inflammation
- Thalassemia
- HbS, Hbsc and HbC.
3. Increased RBC Destruction
- Hemolytic anemia

 Incidence of anaemia:
- Anaemia are widly distribution.
- The incidence in female is about 4 times as high as in males. In female, the
anaemia is commenst in childbearing (pregnancy) period while in male, it is
commonest under the age of 10 years and over the age of 60 years.
- The commonest cases of anaemia is iron deficiency.

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 Clinical Hematology T/ Rashad Saleh Alkhwlany

Microcytic hypochromic anemia

 Appearance of microcytic hypochromic red cells is due to:
1. Lack of iron released from macrophage to serum.
2. Lack of iron.
3. Failure of globulin synthesis.
4. Lead poisoning (inhibit haem and globulin synthesis).
:ٌ‫مو ھذٓ األطثاب ذؤدً إىي خيو فٌ عَيَح تْاء اىھََوجيوتَِ مَا فٌ اىشنو اىراى‬

Iron Protoporphyrin
(Fe++)

 Iron deficiency anaemia Sideroblastic anaemia

 Chonic inflammation

Haem Globulin

Thalassemia (α or β)

Hb

ٌ‫ّقصاُ اىذذٍذ ھو ٍِ أمثز األطثاب اىَؤدٍح ىألَََّا فٌ جََع دوه اىعاى‬

The iron deficiency is the commenst cause of anaemia in every country of the word.
Metabolism of iron

Iron metabolism
Iron is one of the commonest elements in earth’s but it is deficiency is the commonest
causes of anaemia.
 Body iron distribution:
Total body content varies from 3-5 g, depending on sex and body weight the iron is
distributed in several forms:

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1. Haemoglobin iron:
- About 2/3 of body iron. Since the greater part of body’s iron is contained in
haemoglobin of RBCs, it is obvious that any major blood loss will lower
total iron content.
- The iron amount in Hb is from 1.5-3g.
2. Tissue iron:
- Can be divided in to:
1. Storage (available) iron.
2. Essential (non-available) tissue iron.
3. Plasma (transport) iron.

1. Storage (available) iron.

- Which can be give iron for heamoglobin synthesis, it is about 1.2-2g (which
sufficient to replace 1/3-1/2 of Hb).
- Storage iron occurs in two forms ferritin and haemosiderin.
- Ferritin:
o water soluble protein- iron complex of protein shell called apoferrtin
(consisting of 22 amino acid) and iron phosphate core.
o About 20% of it is MW is iron.
o Ferritin is the primary iron storage protein of body. Play role in the
regulation of iron and ferritin in the intestinal mucosa plays a significant role
in absorption.
- Haemosiderin:
o insoluble protein iron complex derived from partial lysosomal digestion of
aggregates of ferritin molecules. It is more stable, less mobilized than ferritin
with higher content of iron. At the later ages the haemosiderin being formed
gradually and aggregates into granules visible in tissue.

2. Essential (non available) tissue iron:

- This is made up of the iron in the muscle, myoglobulin, iron in enzymes for
cellular respiration (cytochromes, catalase and peroxidase).

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3. Plasma (transport) iron:

- Between 3 and 4 mg of iron are present in the plasma binding to protein, this is
a β-globulin, known as transferring, each molecules binds 2 atoms of the ferric
iron.

 Iron absorption
- In general iron from animal foods is better absorbed than that of vegetable
(plant) foods. The main dietary source is meat especially liver. Only 10% is
absorbed from dietary iron.
- Most of dietary iron present in food as ferric hydroxide or ferric protein
complex (haemoprotein complex).
- Before this iron is available for absorption it must released from these ferric
complex by the action of acids in stomach and then, the free ferric complex
(fe+++) are reduced to ferrous (fe++) form at an acid pH by reducing agent e.g.:
Vit. C (ascorbic acid).
- The vit. C reduces insoluble ferric iron to soluble ferrous form.
- There are several stages of normal iron absorption:
1. Luminal stage:
Iron from the food undergoes chemical processing in the lumine of gut,
mainly in the duodenum and jejunum, the relatively low pH in duodenum
facilitates absorption by preventing the oxidation of the ferrous iron to the
ferric iron state.
2. Mucosal stage:
When the iron is available for absorption it passes across the mucosal cell
by active transport into plasma.
3. Plasma stage:
Where iron is passed into transferrin of the plasma and the remaining is
deposited as ferritin.

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 Control of absorption:(mucosal black theory)

The mucosal cell play a controlling role in determining the amount of iron
absorbed.
 Excessive iron storage:
This occur in:
1. Transfusion hemosiderosis
2. Iron over load
3. Haemolytic anaemia.
 Excretion
- The amount of iron excreted by the body per-day is small between 0.5-1mg
under physiological condition.
- Loss of iron occur by menstruation in female and occur from desquamation of
epithelial cell mainly of alimentary tract.
- Excretion in urine and sweat and by growth of hair and nail.
- Unabsorbed iron from food and desquamated cell is excreted in faces.
 Iron transport:
By transferrin: the function of transferrin is to:
1. Transport iron absorbed from alimentary tract to tissue stores.
2. Transport iron from tissue stores site to other.
3. Transport iron from tissue stores to bone marrow for erythropoiesis.
- The binding of iron to plasma transferrin need ceruloplasmin (a copper-
containing enzyme) which catalyzes oxidation of the ferrous iron to the ferric
form for binding to plasma transferrin.
- The amount of transferrin in the serum is measured directly as the total iron
binding capacity (TIBC).
- TIBC= serum iron + unsaturated serum iron-binding capacity.

 Physiological increased of iron absorption:

Iron absorption is increased in:
1. Anoxia.

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2. Iron deficiency.
3. Increased erythropoiesis.
4. increased sucrose content of diet.
5. Large quantities of ascorbic iron enhance iron absorption by converting
ferric iron to ferrous iron in the food.
6. In women, who require more iron than men, to replace iron lost during
menstruation and to the fetus during pregnancy. There is a rapid mobiliz-
ation of iron from tissue stores with an early fall in serum ferritin during the
first trimester, and with a modest increase in serum erythropoietin in late
pregnancy. By 6-8 weeks postpartum most of tile iron has returned to the
body iron stores.
7. In infants, and especially pre-term infants - the body iron stores are used by
6 months and 200 mg of iron are required to expand the red cell mass (500
ml of blood contains about 250 mg of iron).
8. Growing children: 200-300 mg iron are required at adolescence.

 Physiological decreased of iron absorption:

Iron absorption is reduced by:
1. Low iron content of diet.
2. Alkalis in antacids raising the duodenal pH.
3. Phytates and phosphates in the diet block iron absorption.
4. Tannin in tea.
5. Decreased demand for iron is caused by:
o Decreased erythropoiesis.
o Acute and chronic disease.
o Pyrexia.
o Iron overload.
6. A high calcium content in a diet containing marginal amounts of iron is
associated with reduced iron absorption. i.e. iron deficiency is more frequent
in babies fed cows' milk than human milk.

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7. Atrophy of the gastric mucosa with increasing age is associated with iron
deficiency.
8. Intestinal malabsorption also causes decreased iron absorption.

 Iron turnover
Normal red blood cell life = 120 days. To maintain the normal haemoglobin level
the red cell iron turnover = 0.25-0.5 mg/day per kg body weight = 22 mg/day =
6.58 g haemoglobin replaced daily (in a 70-kg man, resulting in the excretion of
193-234 mg urobilinogen daily.
The total daily plasma iron turnover = 20-40 mg/day, i.e. 3-4 mg iron in serum
turns over 12 times each day (30 mg/day = 0.5 millimoles/day); 90% of the red cell
iron is recycled.

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Iron deficiency anemia (IDA)

When IDA occur, the iron stores (haemosiderin and ferritin) becomes completely
depleted before anaemia occurs.
Later, the patient may develop the general symptoms and signs of anaemia.
 Causes of IDA:
1. Depletion of RE stores of iron.
2. Blood loss (chronic):
a. Uterine blood loss: menstrual cycle and delivery.
b. Gastrointestinal blood loss:
i. Peptic ulcer
ii. Chronic aspirin use
iii. Parasite (e.g hook worm)
iv. Hiatal hernia
v. Esophageal varices
vi. Carcinoma of colon, gastric, esophageal or small intestinal.
3. Increased demands (increased iron requirements):
a. Infancy and adolescence (periods of rapid growth)
b. Pregnancy, lactation and delivery
4. Iron malabsorption:
a. Gastrectomy (Surgical removal of all or part of the stomach)
b. Coeliac disease (chronic failure to digest food is triggered by hypersensitivity of the

small intestine to gluten)

5. Inadequate iron intake (poor diet)
 Stages of IDA:
Three stages:
1. Iron depletion
2. Iron deficiency for erythropoiesis
3. Iron deficiency anaemia
 Symptoms:
1. Atrophic in the epithelium are the most feature of IDA:

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a. Oral lesion:
- Glossitis with atrophy of the tongue
- Stomatitis: inflammation and soreness of the tongue and mouth
b. Dysphagia: difficulty in ingestion
c. Nail lesion:
- Spoon-nail shaped (koilonychias)
- Flattening and thinning of the nails
2. Pica: the ingestion of non-nutritive substances (e.g: eating ice, clay in children)
 Laboratory diagnosis:
1. Peripheral blood findings:
- RBCs count, MCV, MCH, MCHC, Hb and PCV are reduced.
2. Peripheral blood smear:
- Microcytic, hypochromic red cell.
- Target cell, tear drop and spherocyte may be seen.
3. Blood count (other RBCs):
- Total and differential white cell count are normal.
- PLTs: normal or may be slightly increased in bleeding.
- Reticulocyte: normal or reduced.
4. Serum iron studies (biochemistry):
- Free erythrocyte protoporphyrin (FEP): increased before anaemia.
- Serum iron: reduced.
- TIBC: increased.
- UIBC: increased.
- Serum ferritin: reduced.
 Treatment of Iron Deficiency Anemia
a. Prophylactic
1. Adequate iron intake for pregnant mothers, a supplement of 30 mg/day
should be adequate.
2. Breast-feeding: Has a preventive effect during at least the first 6 months.

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3. Prophylactic iron supplementation after the 3rd Month, and earlier in

premature by fortified formulas or cereals during infancy.
4. Prophylactic needed after partial gastrectomy.
b. Curative
1. Specific treatment of the causes e.g. as Ancylostoma, or cow- milk protein
allergy etc.
2. Oral iron therapy: The best is ferrous sulphate in a dose of 6 mg/kg/day of
elemental iron (=30 mg/kg/day ferrous sulphate), in 3 divided doses. Better
absorption occurs if given between meals (on empty stomach). It is given for
4-6 weeks after correction of hematological values.
3. Parenteral iron therapy: Iron dextran complex (Imferon). It is not superior to
oral iron administration (50 mg iron/ml).
 The Expected effect of Iron Therapy
1. Within the first day: Repletion of intracellular iron containing enzymes which
leads to increase appetite and improved irritability.
2. Within the first 2 days; bone marrow shows erythroid hyperplasia.
3. At the 3rd day, reticulocytosis appears in peripheral blood, which peak, about
the 6th day.
4. From fourth to 30th day; gradual increase of Hb level.
5. From 1-3 months gradual repletion of body iron stores.

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Sideroplastic anaemia
Sideroplastic anaemia: is anaemia of a group of disorders of varying etiology in
which there are defect in Hb synthesis.
The term sideroblast anaemia is used to describe a dyshemopoietic anaemia, in which
defective hemoglobin synthesis is associated with excessive accumulation of iron
granules in immature red cell. This cell called Sideroblasts.
 Siderocyte and sideroblast
Siderocyte: are cells "red cell" containing granules of iron which give positive
prusien-blue reaction. The granules also stain with Romanowwsky stain, appearing
as basophilic granules which have been refered to as Poppenheimer bodies.
Sideroblast: immature red cell which containing granules of iron are found in
nucleated red cell (only those in which Hb is being formed).
Neucleated red cells containing these granules are known as sideroblast.
 Types of sideroblast
1. Normal sideroblasts:
Granules few in number, difficult to see, randomly distributed throughout the
cytoplasm.
2. Abnormal sideroblasts:
 Increased granulation directly proportional to percentage of saturation of
transferrin, granules are large and more numerous, easily visible with
normal distribution in cytoplasm.
 Increased granulation not directly proportional to percentage saturation of
transferrin. Granules are more numerous and usually large.
 Classification of sideroblastic anaemia:
1. Hereditary siderobastic anaemia:
 This are disorder of sex-linked.
 The affected male are anaemic, female are carriers.
 The anaemia is moderate indegree.

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 It is due to a congenital enzyme defect e.g Saminolaevulinic acid synthatase

or haem synthetase.
2. Acquired sideroblastic anaemia:
a. Primary:
This disorder occures in adults of both sexes, the anaemia is moderatly
severe, but many patient have Hb of 6-7 g/dl.
b. Secondary:
Due to exposureto:
1. Druge : antituberculosis e.g "isoniazid' , lead and ethanol.
2. Nutritional : malabsorption and malnutrition.
3. Marrow proliferative disorders:
 Leukaemia.
 Haemolytic anaemia.
 Treatment:
NO IRON THERAPY
1. Pyridoxine, folic acid.

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Anaemia of chronic disorder

Anaemia of chronic disorder (ACD): is a term used to describe atype of anaemia
seen in chronic inflammatory, infective and malignant diseases.
The term ACD should not be used to describe other causes of anaemia such as
haemolysis or bleeding.
 The causes of ACD:
a. Chronic inflammatory diseases:
1. Infectious: eg: tuberculosis, pneumonia and bacterial endocarditis.
2. Non-infectious: eg: Rheumatoid arthritis
b. Malignant diseases.

 These are many reason in which these diseases can causes this type of anaemia
such as:
1. Decreased red cell production.
2. Shortened red cell survival.
This reason for shortened red cell survival is unclear. One hypothesis is that red
cells are prematurely consumed due to over activity of reticuloendothelial system
in the presence of chronic inflammation.
 Also inflammation causes abnormalities of iron metabolism these abnormalities
include:
1. Reduced iron absorption from the GIT.
2. Decreased plasma iron concentration.
3. Excessive retention of iron in reticuloendothelial cells.
These abnormalities may be due to:
1. Lactoferrin (protein released from neutrophils) during inflammation bind serum
iron and transfers it to macrophage without transfers it to red cell precursors.
2. Increased levels of apoferrin (an acute phase reactant) produced during
inflammation lead to store of iron as ferritin.
3. Erythropoietin levels in some patients are lower.

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Many symptoms of ACD are due to the release of interleukin-1 produced by

macrophages and present in inflammatory exudates.

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Macrocytic anaemia
 In macrocytic anaemia the red cells are abnormally large (mean corpuscular
volume, MCV >95 fL).
 There are several causes but they can be broadly subdivided into megaloblastic and
nonmegaloblastic, based on the appearance of developing erythroblasts in the bone
marrow.

Megaloblastic anaemia
Megaloblastic anaemia: is a blood disorders, in which red cells are larger than normal.
In this type of anaemia, there are delay mature of nucleus thus immature RBCs
(erythroblast) die in the bone marrow or release in to peripheral blood with larger size.
 Causes of megaloblastic anaemia:
The main causes of megaloblastic anaemia are:
1. Vitamin B12 deficiency.
2. Folate deficiency.
3. Abnormalities in Vit.12 and folate metabolism.
Other causes:
1. Leukaemia.
2. Multiply myeloma.
3. Drugs that effect on DNA.
 Symptoms of megaloblastic anaemia:
1. Loss of appetite.
2. Diarrhea.
3. Tingling and numbness of hand and feet.
4. Pale skin colour.
5. Headaches.
6. Sore mouth and tongue.
7. The patient may be mildly jaw1diced (lemon yellow tint) (Fig. 4.6) because of
the excess breakdown of haemoglobin resulting from increased ineffective
erythropoiesis in the bone marrow.

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8. Glossitis (abeefy-red sore tongue).

9. Angular stomatitis.
10. Loss of weight may be present because of the epithelial abnormality.
11. Purpura as a result of thrombocytopenia.
12. Widespread melanin pigmentation (the cause of which is unclear).
Vitamin B12
- Vit.B12 is synthesized by microorganism in gastrointestinal tracts, (in human: it is
not absorbed from this site but is excreted in the faeces).
- The main sources of Vit.B12 is meat, liver, poultry and dairy product.
- Vit.B12 is not found in fruit or vegetable.
- Vit.B12 in diet is in from of deoxy adenosyl cobalamin which is bound to food
protein.
- In stomach is released from protein by the action of acid and proteolytic enzymes.
The Vit.B12 combines with IF.
- If (Intrinsic factor) is glycoprotein with MW 45000 secreted by parietal cells of the
stomach.
- The IF-Vit.B12 complex binds to receptors in the ilea mucosal cell. This attachment
require the presence of Ca+2 and pH above 6.
- In the ileum, Vit.B12 is absorbe into portal circulation which require transport it to
tissue for storage.
- Vit.B12 in plasma is mostly as methylcobalamin.
 Transport of Vit.B12:
There are two major Vit.B12 transport protein:
1. Transcobalamin I (TCI): (currently haptocorrin) is α-globulin, synthesized by
granulocytes, which carries 70-90% of circulating Vit.B12.
2. Transcobalamin II (TCII): is β-globulin, synthesized in liver, which transport
of Vit.B12 from one organ to other and in and out of cell.
TC deficiency causes megaloblastic anaemia because of failure of B12 to enter
marrow (and other cells) from plasma but the serum B12 level in TC deficiency
is normal.

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 Tissue storage:
 Mainly in liver, kidney, heart and brain.
 Vit.B12 in these storages is as deoxyadenosyl cobalamin.
 Excretion:
 The main route of excretion is through the bile, unabsorbed Vit.B12 through
stool.
 Function of Vit.B12:
Two biochemical reaction require Vit.B12 as coenzymes:
1. Synthesis of succinyl CoA from methylmalonyl CoA.
2. Synthesis of methionine from homocysteine.

 Vit.B12 deficiency:
 Etiology: Vit.B12 deficiency may be due to:
1. Some disorders of the alimentary tract such as:
a. Lack of IF.
b. Impairment of the absorption capacity of the intestinal mucosa.
c. Gastrectomy (total or partial).
d. Coeliac disease.
2. Inadequate dietary intake.
3. Malabsorption.

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Pernicious anaemia
This form of the megaloblastic anaemia, in which there are lack of IF.
 Etiology:
 There are autoimmune (autoantibody) attack the gastric mucosa leading to
atrophy of the stomach and the secretion of IF is absent.
Folate
- Folic acid (Pteroylglutamic) is found in liver, greens.
- Folate in the diet is converted to methyl THF, during absorption through the upper
small intestine (especially in the duodenum and jejunum).
- Once, inside the cell they are converted to folate polyglutamates.
 Function of folate:
 Folates is needed in a variety of biochemical reactions in the body especially in
the synthesis of purine or pyrimidine of DNA.

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 Folate deficiency:
 Etiology: Deficiency of folate may be from:
1. Inadequate intake.
2. Intestinal malabsorption.
3. Increased demand:
a. Physiological: Pregnancy, lactation and prematurity.
b. Pathological: Haemolytic anaemia, leukaemia, lymphoma and
inflammatory disease.
4. Excess urinary folate loss:
a. Active liver disease.
b. Congestive heart failure.

Causes of macrocytosis other than megaloblastic anaemia

There are many non-megaloblastic causes of macrocytic anaemia. The exact
mechanisms creating large red cells in each of these conditions is not clear although
increased lipid deposition on the red cell membrane or alterations of erythroblast
maturation time in the marrow may be implicated.
 Causes:
1. Alcohol (is the most frequent cause of a raised MCV in the absence of
anaemia)
2. Liver disease
3. Myxoedema
4. Myelodysplastic syndromes
5. Cytotoxic drugs
6. Aplastic anaemia
7. Pregnancy
8. Smoking
9. Reticulocytosis (Reticulocytes are bigger than mature red cells and so
haemolytic anaemia is an important cause of macrocytic anaemia)
10. Myeloma and paraproteinaemia
11. Neonatal

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