Hematopathology

RBC disorders
WBC disorders
Coagulation disorders
Transfusion
Learning outcomes:

After this session you should be able to:

1.Have a basic understanding of hemopoiesis and blood formation.

2.Basic principle of erythropoiesis.
3. General hematological investigations particularly to anemic patient.
4.Definition, classification, and clinical presentations of anemias.
5.Iron metabolism and iron deficiency anemia.
6. Differential diagnosis of hypochromic anemia.
7. B12, FA metabolism and megaloblastic anemia.
8. Bone marrow failure and aplastic anemia.
 LO1
Blood formation

Blood is suspension of non-dividing end stage cells in plasma.

Haemopoiesis: is process of proliferation, differentiation and mature

blood cell release. It include erythropoiesis, leucopoiesis and
thrombopoiesis processes.

Sites of hemopoiesis:
Fetus 0-2 m (yolk sac)
2-7 m (liver, spleen)
5-9 m (Bone marrow)
Infant Bone marrow (all bones)
Adult Bone marrow (axial skeleton and proximal end of long bones).
 LO1

Blood composition

What is the difference between

plasma and serum ?

• Plasma contain all coagulation proteins while the serum lack most of
them mainly the fibrinogen loss in clot formation.
• Plasma obtain from blood collected in tube contain anticoagulant
while serum collected from blood in plain tube.
• Plasma mainly use in investigations of coagulation disorders while
serum mainly use in biochemical and hormonal investigations.
 LO1
Structure of BM:

• Bone marrow consist of hemopoietic and fat tissue. Hempoietic

tissue including stem, progenitor, precursor and mature cells.

• Stem cells can give rise all cell lines, able to self-renewal (proliferation)
and differentiation, present in few and constant number and required
certain growth factors and suitable microenvironment to work.

• Progenitor cells present in early and late types, and consider

intermediate stage of multi-lineage or uni-lineage cells with increase
differentiation over the proliferation.

• Precursor cells specific for single line and morphologically recognizable

in the bone marrow.
 LO1
Stem cells

Progenitor cells

Precursors cells

Mature cells
 LO1
Structure of BM:

Percentage of active hemopoiesis will differ according to the age of the

patient and gradually reduce with progression of the age in compare with
percent of fat tissue:
• In adult (fat: haemopoietic tissues) 50%:50%
• In child (fat: haemopoietic tissues) 25%:75%
• In elderly (fat: haemopoietic tissues) 75%:25%

Red marrow is active marrow and consider site of hemopoiesis, while

yellow marrow is inactive marrow consist mainly of fat cells. Fat
marrow (yellow marrow) able to reverse into red marrow (active marrow)
in many diseases when function of active marrow is required.

Extramedullary hemopoiesis mean process of hemopoiesis occur

outside the BM (mainly in liver and spleen) occurs in certain conditions
as in sever chronic hemolytic anemia and BM fibrosis.
 LO2
Erythropoiesis

It mean formation of RBC and require 7 days for complete new RBC
formation. This process required stem, progenitor and precursor cells for
complete formation of mature RBC.

Important cells in the BM for this process are precursor cells which
including:
• Proerythoblast.
• Early normoblasts.
• Intermediate normoblasts.
• Late normoblasts.
• Reticulocytes.

The cell gradually loss their nucleus until formation of reticulocyte as

last precursor cell without nucleus.
 LO2
• Reticulocytes: non nucleated red cells with diffusely basophilic
cytoplasm due to remaining ribosomal RNA, still able to synthesis
the Hb, slightly larger than mature RBC, it remains in BM about 2
days then release to circulation and remains 1-2 days to complete
their maturation in the spleen. Normal range in peripheral blood is
0.5-2.5 % from each 100 mature RBC.

• Mature RBC: non nucleated cells of 8µm in diameter, biconcave,

flexible, able to pass through microcirculation with minimal
diameter 3.5 µm. Life span 120 days, generate energy as ATP and
generate reducing power.

• Normoblast (precursor of RBC) normally present in the BM and not

present in peripheral blood and when appear called nucleated RBC
(NRBC).
Control of erythropoiesis: LO2

• Functional feedback: achieved by Erythropoietin (Epo).

• Certain hormones, like growth hormone and androgen enhance
erythropoiesis, while estrogen suppresses erythropoiesis.
• Nutritional factors like FA, B12, iron, B6, B2, vitamin C and E.

Epo is primarily expressed by hepatocytes during the fetal state. After birth,

Erythropoietin (Epo): peritubular fibroblasts in the renal cortex become the main production

It is a glycoprotein produced mainly by the kidney in the adult, stimulates

red cell progenitors and precursors cells for RBC formation from the BM.
Secretion of Epo is triggered by reduced oxygen carriage of blood:
• Reduced Hb (anemia).
• Hypoxia (cardiac and lung disease).
• Damage to renal circulation.

Epo of great clinical significant in many disorders using recombinant Epo

like end stage renal disease and anemia of chronic disease.
 LO2

Hemoglobin structure:

Hb consist of 4 polypeptide (globin) chains 2α and 2 non α, each one

attach to one haem group (iron and protoporphyrin).

According to type of globin chain, Hb present in different forms:

• In Adult: HbA 97 %
HbF 0.5 %
HbA2 2.5 %
• In Fetus (less than 6 months)
HbF 85 %
HbA 15 %

Major switching from fetal to adult Hb occurs 3-6 months of age.

 645 million molecule of Hb / RBC LO2

Alpha 1 Beta 1

Iron

Porphyrin

Globin

Beta 2 Alpha 2
 LO3
Initial hematological investigations in most
hematological disorders

Complete blood count; include Hb level, WBC count, platelets

count, RBC indices and WBC differential count.

Blood film stained usually with Leishman stain, toexamined red cells
morphology, leucocytes morphology, leucocyte differential count and
platelets morphology.

ESR (erythrocyte sedimentation rate): red cell sedimentation depends

mainly on plasma proteins as fibrinogen and other acute phase proteins
that increase the red cells rouleaux and extend of their sinking.

Reticulocyte count (retic count) is the estimation of number of

reticulocytes among mature peripheral RBC detected by a special stain,
normal range 0.5-2.5 %. Automated reticulocyte counts are performed similarly to automated RBCs. Before
counting, red blood cells are stained with a dye that stains for nucleic acid (such as acridine
orange) to differentiate reticulocytes from mature red blood cells.
 LO3

• Increase retic count occur in hemolytic anemias, hemolysis and

recovery state from anemia.
• Decrease retic count occur in bone marrow failure.

Bone marrow examination in certain conditions. There are two

types of marrow procedures:
1.Bone marrow aspirate: done from iliac crest or sternum, in which a
specimen is aspirated using a wide bore needle from the active marrow,
smeared, stained and then examined for any abnormalities.
2. Bone marrow biopsy: here a core of bone marrow tissue is taken,
processed and stained as in histopathological specimens.

Main indications of BM examination:

1. Marrow infiltration with leukemia, lymphoma, secondary carcinomas
and myelofibrosis.
2.Cytopenias of unexplained causes: neutropenia, thrombocytopenia,
anemia.
 LO3
Blood film
 LO3
Reticulocytes count (Retic count)

Reticulocyte: are young, immature non nucleated red

cells contain remnant RNA.

Retic count: mean calculate how many retic cell per 100
red cell under the microscope.
 LO3
Bone marrow examination

Bone marrow aspiration Bone marrow biopsy

 LO3
Definition of terms in RBC disorders

• Normocytic: normal size (normal MCV).

• Normochromic: normal Hb amount (normal MCH), RBC showing

central pallor less than 1/3 of cell diameter.

• Hypochromic: decrease in Hb amount (decrease in MCH), central

pallor more than 1/3 of cell diameter.

• Anisocytosis: change in RBC size as microcytic (decrease in MCV),

macrocytic (increase in MCV).

• Poikilocytosis: change in RBC shape as sherocytes, target, tear,

sickle, fragmented, oval, rod cells, etc..

• Polychromasia, rouleaux formation and agglutination of RBC.

 LO3

Red cell indices

• Hemoglobin (normal range for male 13.0– 17.0 g/dl, female 12.0-
15.0 g/dl).
• Packed cell volume (PCV) also called Hematocrit (Male 40-50 %,
Female 36-46 %).
• RBC count (Male 5.0 x 1012/L, Female 4.3 x 1012/L).

• MCV: mean cell volume (80-100 fl).

• MCH: mean cell Hb (27-32 pg).
• MCHC: mean cell Hb concentration (32-36 g/dl).
• RDW: red cells distribution width (12-15 %).
 Example of complete blood counts and blood film LO3
Red blood cells indices Platelets count: 332 ×109/L.
Hb: 14.1 gm/dl. Total WBC count: 9.7 × 109/L

PCV (Hematocrit): 43.2 % Differential count (%)

Neutrophils: 62
RBC: 4.8 × 1012/L Lymphocytes: 35
MCV: 88 fl Monocyte: 3
Eosinophils: 0
MCH: 28 pg Basophiles: 0
MCHC: 32 gm/dl.
RDW: 18 %

Retic count: % ESR: 8 mm/hr.

Blood film morphology

RBC: Normocytic normochromic red cells.
WBC: Look normal in total, differential count and morphology.
Platelets: Look normal in count and morphology on film.
 LO4
Red blood cells disorders
(Anemias and Polycythaemia)

Normal Hb is:
• Male: 13-17 gm/dl (PCV 40-50 %)
• Female: 12-15 gm/dl (PCV 36-46 %)

Anemia: decrease in Hb concentration below

normal range to age and sex.

In male Hb <13 g/dL or PCV < 40%

In female Hb <12 g/dL or PCV < 36 %
 LO4
Anemia
Definition: decrease in Hb concentration below normal range to age
and gender.
Classification:
Decrease in production (retic count decrease or normal)
1. Iron deficiency anemia (IDA).
2. Megaloblastic anemia (MBA).
3. Aplastic anemia (AA), pure RC aplasia (PRCA).
4. Anemia of chronic disease (ACD).
5. Myelophthesic anemia.
6. Sideroblastic anemia.
7. Many other less common causes.

Increase in distruction (retic count increase)

1. Bleeding (anemia of acute blood loss).
2. Hemolysis (HA) Intrinsic and extrinsic defects.
 LO4
Classification of anemia

( Retic count low or normal ) ( Retic count increase )

BM defect Peripheral blood loss

Like: Like:
1. Iron deficieny anemia 1. Bleeding
2. Megaloblastic anemia 2. Hemolysis (hemolytic anemia)
3. Aplastic anemia
4. Anemia of chronic dis.
5. Anemia associated
with BM infilteration.
 LO4
General clinical features of anemia:
• Symptoms; easy fatigability, palpitation, dyspnea, headache,
tinnitus, anorexia, nausea.
• Signs; pallor, tachycardia, jaundice and splenomegaly (in hemolytic
anemia), delay growth and sexual maturation in chronic anemia.

General initial laboratory investigations of anemia:

(1)CBC, blood film and retic count should be done for all cases
presented as a case of anemia.
(2) ESR in recommended cases.
(3) BM examination in certain indications, especially in cases of
decrease RBC production.
After that, special investigations done according to suspected cause of
anemia, like serum iron indices, Hb electrophoresis, coomb's test, etc.
 LO4

Anemia due to
BM causes

1. Iron deficieny anemia

2. Anemia of chronic disease
3. Megaloblastic anemia
4. Aplastic anemia
 LO5
Iron metabolism
Iron is essential for many metabolic processes and present in two forms
(Ferrous F+2 and Ferric F+3).
Total body iron 3-5 gm, more in male than female.
Majority of iron present in the hemoglobin.
Body iron present as physiological part (70%) or stored (30%).

Iron absorption in the duodenum and less so jejunum with mean

1mg/day and may increase in demand (not > 3-4 mg/day).

Dietary sources include meats especially liver and kidney, egg yolk, some
green vegetables. Milk has low iron content generally.
 LO5
Iron metabolism

Generally iron in the body present in main 3 pools are:

(1) Functional pool: (65-70%)

• Hemoglobin: New RBC formation required 30 mg iron/day mainly
derive from breakdown of old RBC. Each unit of blood (450ml) contains
200 mg iron.
• Myoglobin, mitochondria and iron containing enzymes.
(2)Storage pool: (20-25%) present in form of ferritin and hemosiderin
that present in RES (BM, liver and spleen) and in the liver parenchymal
cells.
(3)Transporting pool: (0.1%) plasma iron carried by iron transporting
protein (Transferrin).
 LO5

Destruction of RBC Absorption

after 120 days Stores
1 mg/day

Plasma transferrin

Other site
BM
RBC-Hb erythropoiesis
 LO5

• Hepcidin: is a small peptide, formed by liver and consider the

predominant negative regulator of iron absorption from small
intestine (decrease in iron absorption) and iron release from
macrophages (decrease in iron release from macrophage).

• Normal iron balance: mean the balance between daily requirement

and daily loss of the iron, usually iron requirement equal to iron loss.
Iron loss mainly in stool, urine, nail, hair, skin, and menses.

• Increase requirement occur in pregnancy, lactation, prematurely,

menses and periods of growth.
 LO5
Iron deficiency anemia
Iron deficiency anemia is the most common type of anemia and is more
common in developing countries.

Causes of iron deficiency:

1. Chronic blood loss: (at least 6-8 ml/day). Common cause in adult
and most likely from the gastrointestinal tract and in females
bleeding from genital tract is also quite common.

2. Increase in demand: prematurity and infancy (3-6 months),

pregnancy, lactation, menstruation and adolescence period.

3. Nutritional: rarely to be the sole cause of ID but quite common cause

of iron deficiency in developing and underdeveloped countries,
especially if inadequate intake is coupled with increased demand.

4. Inadequate absorption: from many causes of malabsorption e.g.

Celiac disease.
 LO5
Clinical features:

• Clinical features related to underlying pathology.

• General signs and symptoms of anemia.
• Mucosal changes in severe IDA as mouth soreness, painless glossitis,
angular stomatitis and nails changes as brittle, ridged, and spooning
(koilonychias) of nails.
• Pica (craving to eat unusual substances like clay and ice).
• In sever long standing IDA, patient may develop dysphagia
(Plummer Vinson syndrome).
• Mental development disturbance and premature labor may
associated.

• Plummer Vinson syndrome (Kelly Paterson syndrome) is a triad of

dysphagia (pharyngeal web), glossitis and IDA, it has risk of CA,
more in women, of unknown etiology.
 LO5
Pallor Pale conjunctiva

Nail changes Oral changes

 LO5

Stages of iron deficiency anemia:

Initially occur depletion in iron store then the BM will be affected and
finally the anemia become obvious.

1.Depletion of iron stores: no iron in store (low serum ferritin) and no

anemia yet.
2. Iron-deficient erythropoiesis: Low serum iron and high TIBC and
still no significant anemia yet.
3. Iron deficiency anemia: Low Hb, MCV and MCH.
Laboratory findings in IDA: LO5

1. Hematological findings:
• Reduce in Hb (6-8 gm/dl) usually moderate degree of anemia.
• Reduce PCV, MCV, MCH, and MCHC.
• Retic count is low.
• WBC usually normal, and platelets counts often increase.
• Blood film: hypochromic microcytic.
• Decrease or absence in marrow iron store which can detect by Perl's
stain/Prussian blue stain which is diagnostic, but the BM examination
is not an indication in suspected case of IDA.

2. Biochemical findings:
• Serum iron reduced.
• Total iron binding capacity increased.
• Transferrin saturation reduced <15%.
• Serum Ferritin reduced which reflects storage iron.

3. Investigations for suspected underlying causes.

 LO5
Normochromic Normocytic
(normal blood film)

Hypochromic microcytic
(blood film in IDA)
 LO5
Treatment:
• Treatment of primary cause.
• Oral iron (most effective) best with ferrous sulphate 200 mg (67 mg
elementary iron).
• Dose 100-200mg elementary iron/day, for 3-6 months (to correct
the storage state of iron).

• Response assessment by increase Hb (0.5-1gm/wk), retic count

increase (peak at 10 days).
• Failure to response may related to wrong diagnosis, failure to take
the drug, continuous hemorrhage, mixed anemias, another cause of
anemia and malabsorption.

• Parenteral iron: Indicated in sever intolerance of oral iron, require

rapid restoring, persistent hemorrhage, malabsorption. Iron sorbitol
(jectofer) IM, dextran (inferon) IV.
 LO6
Differential diagnosis of hypochromic microcytic anemias include
four main types of anemia are:

• Iron deficiency anemia.

• Anemia of chronic disease.
• Sideroblastic anemia, result from defect in protoporphyrin ring.
• Thalassemia, result from globin chain defect.
 LO6
Anemia of chronic disease

• Second most common cause of anemia that associated with certain

non-hematological diseaseschronic infections, chronic inflammations,
hematological and non-hematological malignancy and chronic renal
failure.
• Mild to moderate anemia (rarely Hb < 9 gm/dl), start 1-3 months after
the underlining disease and the severity related to illness severity.
• Normochromic red cell in most cases or may be hypochromic in
peripheral blood.
• Low serum iron despite adequate iron stores (due to defect in iron
mobilization from the storage sites by effect of hepcidin and
other inflammatory mediators).
• Low serum iron and low TIBC.
• High serum ferritin, high C-reactive protein and high ESR.
• High serum Hepcidin level (important acute phase protein with
significant role in regulation of body iron).
 LO7
Megaloblastic anemia

• Anemia due to impaired DNA synthesis, result mainly from B12 and
Folate deficiency.
• All haemopoietic cell lines (erythropiesis, granulopoiesis,
megakaryopoiesis) are affected result in severe anemia and even
pancytopenia.
• The hallmark enlargement of BM erythroid precursors (megaloblast)
give rise to abnormal large RBC in blood (macrocytes) in addition to
giant granulocytic precursors in BM yielding hypersegmented
neutrophils in peripheral blood.

• It important to recognition of MBA because main causes can completely

corrected with therapy and it is a serious disease that neurological and
psychiatric abnormalities of B12 deficiency may be preventable and
reversible with early stage of disease.
 LO7
B12 (cobalamin)
• Forms of B12:Methylcobalamin, Adenosylcobalamin, main form in
tissue, Cyanocobalamin, form use in investigations,
Hydroxycobalamin, form use in treatment.

• Human unable to synthesis B12 so required intake, it present only in

food of animal origin and less in dairy products. Small amount
synthesis by micro-organism in small intestine.
• Vegetables and fruits free of B12 and it is heat stable.
• Requirement of B12 increase in period of growth, pregnancy, infancy
and hyper-metabolic state.
 LO7
Absorption of B12 in the ileum pass through some steps:
• In stomach: B12 bind to R-factor which produce by saliva and gastric
juice.
• In duodenum: Digestion of this complex by pancreatic enzymes, then
the B12 bind to Intrinsic factor (IF) which secrete from stomach
parietal cells.
• In terminal ileum: IF bind to specific receptor (Cubilin) and B12
appear in portal circulation after 6 hrs bind to transcobalamin-II (TC
II).

Folic acid
• Human unable to synthesis FA so required intake, main source are
vegetable and fruits, but most foods contain FA and it destroyed by
cooking.
• Absorption take place in upper half of small intestine mainly jejunum
by saturation process.
• It act as a co-enzyme in purine and pyrimidine synthesis.
 LO7

Biochemical basis of MBA:

• MBA; is type of anemia characterized by impaired DNA synthesis.
• DNA synthesis required polymerization of 4 deoxyribonucleoside
triphosphates and FA deficiency impaired thymidylate of dUMP to
dTMP.
• B12 required to achieve the active form of folate inside the cells.
• So deficiency of any vitamin will lead to impair in DNA synthesis.
• Neurological manifestations occur only with B12 deficiency due to
defect in methylation of myelin.
 LO7
Causes of MBA:
Vitamin B12 and Folic acid deficiency or dysfunction (most important
causes).
In dependent on B12 or FA causes like some drugs and inborn errors of
metabolism.

Causes of vitamin B12 deficiency:

(1)Malabsorption (main cause) like:
o Gastric causes, as pernicious anemia.
o Intestinal causes, as ileal resection.
o Other causes like severe chronic pancreatitis.
(2) Dietary deficiency: as in vegans, pregnancy, poverty, infancy
(dietary cause unlikely related unless malabsorption association).
(3) B12 abnormal metabolism:
Acquired as nitrous oxide inhalation.
Inborn error: as TC II and IF deficiency.
 LO7
Causes of FA deficiency:

(1)Inadequate dietary intake (common cause due to low storage

state): old age, poverty, alcoholism, psychiatric disturbance.
(2) Malabsorption like celiac disease.
(3) Increase requirement or loss:
- Physiological as pregnancy.
- Pathological as hemolytic anemia.
(4) Antifolate drugs as anti-convulsants, alcohol and DHFR inhibitors.
 LO7
Clinical features of MBA (of both B12 & FA deficiencies):

• May be asymptomatic, usually insidious onset with signs and

symptoms of anemia.
• Mild jaundice (due to intramedullary destruction of red cell
precursors).
• Epithelial tissue changes as glossitis and angular stomatitis.
• NTD (neural tube defect ) in FA deficiency and may occur with B12
deficiency of uncleare mechanisms.
• Neurological manifestations only with B12 deficiency due to
accumulation of SAH and reduce level of SAM in nervous tissue with
defect in methylation of myelin.
• Psychatric abnormality.
 LO7

Pernicious anemia

• It is MBA due to B12 deficiency, characterized by gastric atrophy,

reduce or absent of intrinsic factor with achlorhydria.
• It more in female, mostly a disease of the elderly, more in patients
with autoimmune mediated disorders like autoimmune thyroid
disease.
• Not common in Iraq, common in north Europe.
• Mostly it is autoimmune in nature with presence of serum
antibodies like anti-IF Ab, anti-parietal cells Ab and anti-gasrtin
receptor Ab.
 LO7
Laboratory findings of MBA:

Hematological findings:
• Variable degree of anemia, usually severe anemia < 6 gm/dl.
• MCV increased >100 fl, may be up to 135 fl.
• Increase MCV, MCH, and normal MCHC.
• Increase RDW.
• Low retic count.
• Leucocytes may be reduced, platelets may be moderately reduced
(pancytopenia).
• Blood film: oval macrocytes, hypersegmented neutrophils,
leukoerythroblastic picture may found.
• BM findings: Hypercellular marrow with megaloblastic changes in
all cell lineages.
 LO7

Other investigations:
• low Serum B12, low serum FA.
• Therapeutic trials of both vitamins and assess the response by
increase Hb and retic count after 7 days.
• Search and exclude causes for B12 and FA e.g Schilling test.
• High S. LDH, indirect hyperbilirubinaemia due to intramedullary
destruction of red cell precursors.
• Serum Ab measuring and gastric biopsy in suspected cases of
pernicious anemia.

Blood film in MBA

 LO7

Management:
• Blood sample and BM examination done before any treatment.
• General measures may require as platelets and RBC concentrate.
• Treatment with specific vitamin if known, otherwise both vitamins
should be given.

• B12: lifelong B12 therapy using Hydroxocobalamin by injection. Six

injections of 1mg IM for body restore then monthly injection for life.
• Should never give folate on its own in cobalamin deficiency because
although response will be seen, aggravation or induction of
neurological complications may be induced.

• FA: Folic acid given orally 5-15 mg / day. Duration usually 4

months, but depend on the underlying pathology may be for life in
those with untreatable causes.
 LO7

Response to treatment:
• Initial correction of patient behavior and appetite within 1-2 days.
• Retic count increase with peak level at 7 days may reach 40-50%.
• Hb level increase 1 gm/dl /wk and corrected in 5-6 wks.
• Peripheral neuropathy may partially improve but spinal cord
damage is irreversible.
• Follow up the patient with Hb and retic not by BM examination.
 LO8
BM failure
BM failure may result from:
• Marrow infiltration or replacement by abnormal or malignant cells.
• Hypoplasia/aplasia (inherited or acquired) either single line or all
marrow lineage.

Inherited type:
Pancytopenia like Fanconi anemia.
Single line: Anemia; Diamond Blackfan anemia.
Neutropenia: Kostman’s syndrome.
Thrombocytopenia of congenital type.

Acquired type:
Pancytopenia: Acquired aplastic anemia.
Single line: Anemia; acquired pure red cell aplasia.
Neutropenia: induce by drugs and viral infection.
TCP: induce by drugs and viral infection.
 LO8
Pancytopenia

Definition: reduction in all cell line in peripheral blood (anemia,

neutropenia, thrombocytopenia).

Etiology of pancytopenia
Central (BM) causes:
• Aplastic anemia (congenital or acquired).
• Some cases of acute and chronic leukemias.
• Infiltration with abnormal or malignant cells.
• Megaloblastic anemia (MBA).
• Paroxysmal nocturnal hemoglobinurea (PNH).

Increase peripheral destruction: Hypersplenism, SLE and DIC.

 LO8
Aplastic anemia

Definition: Pancytopenia in the peripheral blood due to aplasia or

hypocellular marrow in which normal haemopoietic elements are
replaced by fat cells. Abnormal cells are not present in the peripheral
blood or bone marrow.

Causes of AA:
Inherited AA like Fanconi anemia.
Acquired AA:
1. Idiopathic in 50 -75% of cases, most common type and suggested to
be autoimmune T-cells mediated immune disorder.
2. Ionizing irradiation; Chemicals.
4. Drugs as: cytotoxic drugs, chloramphenicol, sulpha and gold.
5. Infective agents as hepatitis viruses, HIV, EBV, and other viruses.
 LO8
Clinical manifestations:
• Any age but peak at 30 yrs.
• Insidious or acute presentation.
• Bleeding tendency.
• Features of anemia.
• Infections.
• No jaundice except post-hepatitis cases.
• No organomegaly.

Laboratory Findings:
• Pancytopenia (anemia, neutropenia, TCP).
• Blood film: normochromic red cell and usually macrocytic.
• Reduced retic count.
• BMA: hypocellular, no abnormal cells. BMA may be dry (diagnosis
cannot made with BMA alone).
• BMB (required for diagnosis): hypocellular.
• Cytogenetic analysis for congenital types.
 LO8

Normal BM biopsy BMB in aplastic anemia

Good Luck