1

Clinical Haematology
Dr. Rashad Saleh M. Alkhwlany
MSc. Medical Microbiology
 Clinical Haematology Dr/ Rashad Saleh Alkhwlany

Leukemia
(British English: leukaemia) (Greek leukos λευκός, "white"; aima αίμα, "blood")
is a cancer of the blood
Introduction:

Note:
 Stem cells:
All cellular blood components are derived from haematopoietic stem cells. The
stem cells found within the bone marrow are the origin of all blood cells. The stem
cell has the capability of self-renewal. One stem cell is capable of producing about
106 mature blood cells after 20 cell divisions.
There are two types of stem cell:
1. Uncommitted stem cell:
.‫ازذ ِٓ اٌخالٌب‬ٚ ‫ع‬ٛٔ ‫ب غٍش ٍِزضِخ ثزسذٌذ‬ٕٙ‫ب ٌى‬ٙ‫َ ثّىبثشح ٔفس‬ٛ‫ رم‬:‫اٌخالٌب اٌدزػٍخ اٌغٍش ٍِزضِخ‬
2. Committed stem cell:
‫اع اٌخالٌب‬ٛٔ‫ع ِٓ أ‬ٛٔ ‫س إٌى إي‬ٛ‫اٌزس‬ٚ ‫ب اٌزّبٌض‬ٙ‫ثبسزطبػز‬ٚ ‫ب‬ٙ‫َ ثّىبثشح ٔفس‬ٛ‫ رم‬:‫اٌخالٌب اٌدزػٍخ اٌٍّزضِخ‬
.‫ٌخ‬ِٛ‫اٌذ‬

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 Clinical Haematology Dr/ Rashad Saleh Alkhwlany

ً‫ال ف‬ٚ Stem cell ً‫ ٌٍسذ ٔبردخ ػٓ االظطشاثبد ف‬Lukaemia ‫وٍٍّب‬ٌٍٛ‫ أْ ا‬ٛ٘ ‫ذف ِٓ ٘زٖ اٌّمذِخ‬ٌٙ‫ا‬
‫ِٕزدبد‬ٚ ‫ف ٌؤدي إٌى خًٍ فً خٍّغ ِخشخبد‬ٛ‫ (الْ رٌه س‬Myloid ً‫ال ف‬ٚ Pluripotential stem cell
‫فً زبٌخ‬ٚ Mono ٚ‫ أ‬Myelo ٚ‫ أ‬Lympho ‫ب ٔبردخ ػٓ خًٍ إِب فً اٌـ‬ٕٙ‫ٌى‬ٚ Bone marrow ‫اٌـ‬
.Erythrocyte ً‫ْ اٌخًٍ ف‬ٛ‫ ٌى‬Polycythemia ‫اٌـ‬
Lukaemia result from abnormal or defect in the region of leukopoiesis, result in:
o Abnormal in the number of WBCs.
o Appearance the immature WBCs in P.B.

M
yeloproliferation disorders:
yelo mean bone marrow
yeloproliferation disorders include:
 Abnormal proliferation in RBCs (Polycythemia).
WBCs (Leukaemia).
PLTs (Thrompocytosis).
So leukaemia is part of myeloproliferation disorder.
.ُ‫وٍٍّب خضء ِٓ اظطشاثبد ٔخبع اٌؼظ‬ٌٍٛ‫زا ا‬ٌٙٚ
:‫مالحظة‬
:‫وٍٍّب‬ٌٍٛ‫ٕ٘بن ِسبرٌش الثذ أْ رؤخز ثؼٍٓ االػزجبس ػٕذ رشخٍص ا‬
.ْ‫ ِؼشفخ اٌؼذد اٌطجٍؼً ٌخالٌب اٌذَ اٌجٍعبء فً خسُ اإلٔسب‬.1
.ْ‫ ِؼشفخ األِشاض اٌزً رشفغ اٌخالٌب اٌجٍعبء فً دَ اإلٔسب‬.2

Leukaemia
Leukaemia def.: Abnormal, uncontrolled proliferation of Leukocyte (WBCs).
‫اٌزً رزٍّض فً ٘زٖ اٌسبٌخ‬ٚ ,‫غٍش ِسٍطش ػٍٍخ ٌخالٌب اٌذَ اٌجٍعبء‬ٚ ً‫ غٍش غجٍؼ‬ّٛٔٚ ‫ً٘ ػجبسح ػٓ رىبثش سشٌغ‬
:ً‫س أِشاض ػذٌذح ِث‬ٛٙ‫ج ثشىً ػبَ ِّب ٌؤدي إٌى ظ‬ٛ‫ب ػٍى إٌع‬ٙ‫ثؼذَ لذسر‬
‫ِٓ ثُ ٔضٌف فً اٌٍثخ‬ٚ ‫رمشذ‬ٚ َ‫س‬ٛ‫ ر‬,‫ص‬ٌٍٛ‫رمشذ ا‬ٚ ُ‫ رعخ‬,‫ اٌطسبي‬ٚ ‫ رعخُ اٌىجذ‬,‫ٌخ‬ٚ‫ رعخُ اٌؼمذ اٌٍّفب‬.1
.‫ األخضاء اٌسبثك روش٘ب‬ٚ‫ وً رٌه ثسجت رغٍغً اٌخالٌب اٌسشغبٍٔخ فً األػعبء أ‬.....
.‫ٌخ إٌّبػٍخ اٌطجٍؼٍخ‬ِٛ‫فش اٌخالٌب اٌذ‬ٛ‫ٍِخ اٌمٍسٍخ ٌؼذَ ر‬ٛ‫بثبد اٌدشث‬ٙ‫ أزشبس االٌز‬.2
.‫رمشزبد خٍذٌخ ػٕذ اٌغذد‬ٚ ‫ غفر‬.3
.Anaemia َ‫ اإلصبثخ ثفمش اٌذ‬.4
.ًٌٍٍ ‫صذاع ِغ رؼشق‬ٚ ‫ زّى‬.5

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 Clinical Haematology Dr/ Rashad Saleh Alkhwlany

Classification of leukaemia
:‫س اٌّشض‬ٛ‫ رصٍٕف سشغبْ اٌذَ زست ِذح رط‬.1
:Acute leukaemia ‫ سشغبْ اٌذَ اٌسبد‬.a
‫ ثؼذ٘ب‬.‫ش‬ٙ‫ أش‬6 ‫دح إٌى‬ٚ‫ذ ِبثٍٓ أٌبَ ِؼذ‬ٚ‫فً ِذح لصٍشح رزشا‬ٚ ‫س اٌّشض ثشىً سشٌغ‬ٛ‫فٍخ ٌزُ رط‬ٚ
.‫د اٌّشٌط ِجبششح إرا ٌُ ٌؼبٌح‬ٌّٛ ْ‫لغ أ‬ٛ‫ٌز‬
:Subacute leukaemia ‫ سشغبْ اٌذَ اٌّؼزذي‬.b
.‫لذ اوزشبف اٌّشض‬ٚ ِٓ ‫اد‬ٕٛ‫ س‬3 ‫لغ أْ ٌؼٍش اٌّشٌط ِٓ سٕخ إٌى‬ٛ‫فٍخ ٌز‬ٚ
:Chronic leukaemia ِٓ‫ سشغبْ اٌذَ اٌّض‬.c
5-3 ٍٓ‫ذ ِبث‬ٚ‫ي رزشا‬ٛ‫لغ ٌٍّشٌط أْ ٌؼٍش فزشح أغ‬ٛ‫ٌز‬ٚ ً‫س اٌّشض ثشىً ثطئ‬ٛ‫فٍخ ٌزُ رط‬ٚ
.‫لذ اوزشبف اٌّشض‬ٚ ِٓ ‫اد فً ِؼظُ اٌسبالد‬ٕٛ‫س‬
Stages of development of WBCs:
Shift to right
Myeloblast Promyelocyte Myelocyte Metamyelocyte
Band form Neutrophil.
Eosinophil.
Basophil.
Shift to lift

 Leukaemia always Shift to lift it is Acute leukaemia.

 Leukaemia always Shift to right it is Chronic leukaemia.
 Increase in the No. of immature WBCs indicate Acute leukaemia
 Decrease in the No. of immature WBCs or Increase in the No. of mature WBCs
indicate Chronic leukaemia.

:‫ رصٍٕف سشغبْ اٌذَ زست ػذد وشٌبد اٌذَ اٌجٍعبء‬.2

a. Leukaemic leukaemia:
‫ٌخ غٍش اٌطجٍؼٍخ‬ِٛ‫خذ اٌخالٌب اٌذ‬ٛ‫ر‬ٚ )15000/mm3( ٓ‫ٌضٌذ ػذد اٌخالٌب اٌجٍعبء فً ٘زٖ اٌسبٌخ ػ‬
. َ‫ٌخ ػٓ غشٌك فسص ػٍٕخ اٌذ‬ٛٙ‫ثشىً ٌىفً ٌزشخٍص سشغبْ اٌذَ ثس‬
b. Subleukaemic leukaemia:
‫ٌخ غٍش اٌطجٍؼٍخ‬ِٛ‫د اٌخالٌب اٌذ‬ٛ‫خ‬ٚ ‫) ِغ‬15000/mm3( ٓ‫ٌمً ػذد اٌخالٌب اٌجٍعبء فً ٘زٖ اٌسبٌخ ػ‬
. َ‫ثشىً ٌسّر ثزشخٍص سشغبْ اٌذَ ػٓ غشٌك فسص ػٍٕخ اٌذ‬

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Clinical Haematology Dr/ Rashad Saleh Alkhwlany

c. Aleukaemic leukaemia:
‫ٌخ غٍش اٌطجٍؼٍخ‬ِٛ‫) ِغ لٍخ اٌخالٌب اٌذ‬15000/mm3( ٓ‫ٌمً ػذد اٌخالٌب اٌجٍعبء فً ٘زٖ اٌسبٌخ ػ‬
. َ‫ثشىً ال ٌسّر ثزشخٍص سشغبْ اٌذَ ػٓ غشٌك فسص ػٍٕخ اٌذ‬

:‫اع اٌخالٌب اٌّزأثشح‬ٛٔ‫ رصٍٕف سشغبْ اٌذَ ثٕبء ػٍى أ‬.3

a. Myeloid (Granuolocytic) leukaemia:
o Acute Myeloid leukaemia
o Chronic Myeloid leukaemia
b. Lymphoid (Lymphocytic) leukaemia:
o Acute Lymphoid leukaemia
o Chronic Lymphoid leukaemia
c. Monocytic leukaemia
o Acute Monoblstic leukaemia
o Chronic Monoblstic leukaemia
d. Plasma cell leukaemia.

:‫ رصٍٕف سشغبْ اٌذَ زست اٌشىً اٌظب٘شي ٌٍخالٌب اٌخالٌب‬.4

This classification of leukaemia are according to morphology (based on
morphology). This system of classification called FAB (French-American-British)
classification.

Causes and risk factors

Leukemia, like other cancers, results from somatic mutations in the DNA which
activate oncogenes or deactivate tumor suppressor genes, and disrupt the regulation
of cell death, differentiation or division. These mutations may occur spontaneously
or as a result of:
 Exposure to radiation or carcinogenic substances: ex. petrochemicals, (such
as benzene, and hair dyes). and ionizing radiation

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Clinical Haematology Dr/ Rashad Saleh Alkhwlany

 Viruses: For example, human immunodeficiency virus or human T-

lymphotropic virus (HTLV-1 and HTLV-2, causing adult T-cell leukemia
/lymphoma).
 Congenital factor.
 Genetics: such as chromosomal abnormalities.

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 Clinical Haematology Dr/ Rashad Saleh Alkhwlany

Chronic Myeloid Leukemia (CML)

Chronic Granulocytic Leukemia (CGL)

CML: condition characterized by considerable elevation of blood leukocyte count and

Mature granulocytes (90%)
accumulation of all form of
Immature granulocytes (10%)

Pathogenesis:
One arm of the chromosome in pair No. 22 is translocated to chromosome 9 in 90% of
cases of disease. This chromosome is called Philadelphia chromosome.

Clinical features:
1. Anaemia Normocytic normochromic anaemia.
2. Splenomegally.
3. Hepatomegally.
4. Fatigue.
5. Weight loss.
6. Night sweats.
7. Minor bruising.
8. Joint and bone pain.

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 Clinical Haematology Dr/ Rashad Saleh Alkhwlany

Note:
The severity of leukaemia associated with (or result from) anaemia and
thrompocytopenia.

Lab. Diagnosis:
 WBCs count is usually 100000 to 300000 cell/mm3.
 Less than 10% myeloblast are present in peripheral blood.
 There are complete spectrum of granulocytic cell from the myeloblast to the
mature neutrophil, eosinophil and basophil.
 There is predominance of neutrophil and myelocytes.
 PLTs count ↑ or normal.
 Basophil, eosinophl also monocyte ↑.
 Bone marrow: hypercellular with increased No. of myeloid cell.
 Neutrophil alkaline phosphatase is decreased or absent.
 Philadelphia chromosome on cytogenetic analysis of blood or bone marrow.

Leukaemoid reactions:
Increase No. of WBCs in response to severe infections eg: tuberculosis,
meningococcal meningitis, septicaemia, severe megaloblastic anaemia in pregnancy,
acute hepatic necrosis, amoebic liver abscess, burns and following severe
haemorrahage.

The main features which differentiate a leukaemoid reaction from CML

Total WBCs
Left shift
Eosinophils and basophils
Neutrophil alkaline phosphatase
Leukaemoid reaction CML
3
Rarely more than 60000 cell/mm 100000-300000 cell/mm3
Present, usually with toxic More prominent than in
granulation and neutrophil leukaemoid reaction. No toxic
vacuolation granulation
Reduced or normal Increased
Increased Reduced

Note:
 With recovery, a leukaemoid reaction resolves.
 CML is more often found in persons with 20 to 50 years.

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 Clinical Haematology Dr/ Rashad Saleh Alkhwlany

Treatment:
o Cytotoxic drug are most commonly used to treat CML which can keep patients
symptom-free for long periods but they don’t delay the onset of acute
transformation.
Examples:
 Busulophan (Myleran): choice to reduce the total granulocyte count.
 Hydroxyurea
 Alpha-interporn
 Allopurinol
o Bone marrow transplantation (BMT).

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 Clinical Haematology Dr/ Rashad Saleh Alkhwlany

Acute Myeloid Leukemia (AML)

Acute Granulocytic Leukemia (AGL)

AML: may be defined as a myeloproliferative disease in which there is preponderance

of primitive blast cell (immature WBCs) in bone marrow and in circulation.
 Failure of myeloid cell to differentiate beyond blast stage.
 Incidence increases with age (One at 15-20 years of age and other after 50 years of
age).
 Associated with exposure to:
 Benzene
 Radiation (ionizing radiation)
 Alkylating agents
 Congenital factors
 Viruses
 Chromosomal changes

Pathophysiology
o Uncontrolled growth of blasts in marrow leads to:
 Suppression of normal hematopoietic cells
 Appearance of blasts in peripheral blood
 Accumulation of blasts in other sites
o Chronic myeloproliferative disorders and myelodysplastic syndromes can
transform into AML

Clinical Features of AML

o Decrease in normal hematopoiesis
 Anemia
 Pallor, weakness, fatigue, dyspnea (difficulty in breathing) on exertion
 Thrombocytopenia
 Bleeding
 Purpura (rash of purple spots on the skin caused by internal bleeding from small
blood vessels)
 Associated with DIC
 Neutropenia infections
 Septicemia

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 Clinical Haematology Dr/ Rashad Saleh Alkhwlany

 Pneumonitis
 Skin and mucosal infections
o Accumulation of blast cells in marrow
 Skeletal pain
 Bony tenderness (softness), especially sternum
o Accumulation of blast cells at other sites
 Lymphadenopathy
 Hepatosplenomegaly
 Skin - leukemia cutis (skin in Latin)
 Gonads (sex gland an organ that produces gametes; a testis or ovary)
o Metabolic effects - aggravated by treatment
 Increase in uric acid ––> uric acid nephropathy
 Release of phosphates ––> decrease in Ca2+ and Mg2+
 Release of pro-coagulants ––> DIC

Diagnosis
 Peripheral blood film:
 Decreased RBCs and hemoglobin (usually normocytic, normochromic
anemia)
 Decreased platelets
 Variable leukocyte count
َ‫ْ ػٕذُ٘ وشٌبد اٌذ‬ٛ‫ سثغ اٌّشظى رى‬.‫ ِٕخفعخ‬ٚ‫ ِشرفؼخ أ‬ٚ‫ْ غجٍؼٍخ أ‬ٛ‫ً لذ رى‬ٙ‫ٕ٘بن اخزالفبد ف‬
‫ ٔصف‬. 3ُِ / ‫ خٍٍخ‬5000 ِٓ ‫ْ ػٕذُ٘ أوثش‬ٛ‫اٌشثغ األخش رى‬ٚ 3ُِ / ‫ خٍٍخ‬5000 ِٓ ً‫اٌجٍعبء أل‬
ً‫ٕ٘بن ثؼط اٌسبالد إٌبدسح اٌز‬ٚ . 3ُِ / ‫ خٍٍخ‬10000-20000 ٍٓ‫ْ ػٕذُ٘ ِبث‬ٛ‫اٌّشظى رى‬
.3ُِ / ‫ خٍٍخ‬100000 ‫ب ػذد وشٌبد اٌذَ اٌجٍعبء إٌى‬ٍٙ‫ٌصً ف‬
 Decrease in normal granulocytes
 Presence of blast cells (Auer Rods) –Auer rods are elliptical, spindle-like inclusions
composed of azurophilic granules within lysosomes.
 Bone marrow:
 Usually hypercellular
 Increased blast cells - > 30% leukemic blasts for definitive diagnosis
(normal < 5%)
 Decrease in normal erythropoiesis, myelopoiesis and megakaryocytes
 Cytogenetics and molecular analysis
 Increased uric acid, LDH and LFTs
 Decreased Ca2+

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 ‫‪Clinical Haematology‬‬ ‫‪Dr/ Rashad Saleh Alkhwlany‬‬

‫‪Treatment of AML‬‬
‫ر‪ٙ‬ذف ِؼبٌدخ ٘زا إٌ‪ٛ‬ع ِٓ اٌٍ‪ٛ‬وٍٍّب إٌى‪:‬‬
‫‪ ‬اسزئصبي اٌخالٌب اٌسشغبٍٔخ ثذ‪ ْٚ‬رسطٍُ اٌخالٌب اٌطجٍؼٍخ ٌٕخبع اٌؼظُ‪.‬‬
‫‪ ‬رمًٍٍ أ‪ ٚ‬اٌزخٍص ِٓ اٌزأثٍشاد اٌدبٔجٍخ ٌٍ‪ٛ‬وٍٍّب ِثً األٍٍّٔب ‪ٚ‬إٌضف‪.‬‬
‫‪ ‬األ‪ٚ‬ي ٌزُ ثبٌّؼبٌدخ اٌىٍٍّبئٍخ ‪ٚ Chemotherapy‬اٌثبًٔ ثبٌؼٕبٌخ اٌذاػّخ اٌضائذح‪.‬‬
‫‪o Supportive care:‬‬
‫ثبٌٕسجخ ٌألٍٍّٔب ٌزُ ِؼبٌدز‪ٙ‬ب ثٕمً اٌذَ ‪ٚ‬ثبٌٕسجخ ٌٍٕضف ٌزُ إػطبء اٌّشٌط ‪ Platelets‬ػٓ غشٌك اٌ‪ٛ‬سٌذ‪.‬‬
‫‪ٚ‬اإلصبثخ ػٓ غشٌك اسزخذاَ ِعبداد زٍ‪ٌٛ‬خ‪.‬‬
‫‪o Bone marrow transplantation.‬‬

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 Clinical Haematology Dr/ Rashad Saleh Alkhwlany

Chronic lymphocytic leukaemia (CLL)

Chronic lymphoid leukaemia (CLL)

Introduction:
Lymphocyte are mononuclear cells whose cytoplasm does not contain specifically
staining granules.
Lymphopoiesis:
o In the foetus: the yolk sac, liver and spleen are the primary lymphopoietic
organs.
o In the postnatal life: the bone marrow and thymus are the primary
lymphopoietic organs.
o The second lymphopoietic organs:
They are found in the thymus and lymph nodes.

 Types of lymphocyte: Large lymphocyte.

Small lymphocyte T-cell (70-80%)
B-cell (5-15%)
Non T or B (5%)
 By structure and function can be differentiate between the T and B lymphocyte.
 Immunity is the main function of T and B lymphocyte:
 B – lymphocyte are responsible for humoral immunity
i.e produce specific antibodies (B-cell is converted to plasma cell that produce
antibody)
 T – lymphocyte are responsible for cellular immunity such as:
 Against intracellular organisms:
o Bacteria
o Viruses
o Protozoa
o Fungi
 Against transplanted organs.
 T-cell produce: cytotoxic compound.
Helper T-cell.
Suppresser cell.
NK (natural killer T-cell).

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 Clinical Haematology Dr/ Rashad Saleh Alkhwlany

 Control helper T-cell …. Stimulate the cell during immunity (infection).

Suppresser cell …. Inhibit the cell after infection.

Lymphocyte marker:
Lymphocyte marker ….. found on the surface of T- lymphocyte and B- lymphocyte
called class differentiation or cluster of differentiation (CD) that used to distinguish
between T-cell and B-cell.

Antigen Markers of
Lymphocytes (CD)

 Pre-B (most mature)

o CD19, CD24, CD45, CD10
 B cell (mature)
o CD19, CD20, CD22, CD45
 T cell (most mature)
o CD2, CD3, CD4, CD5, CD7, CD8

Lymphoproliferative disorders
This group of lymphoproliferative disorders include:
1. Acute lymphocytic leukemia.
2. Chronic lymphocytic leukemia.
3. Plasma cell tumor (multiple myeloma)
4. Malignant lymphoma.

Chronic lymphocytic leukemia (CLL)

 CLL ….. the majority of cases of CLL is due to abnormal proliferation of B-

lymphocyte (The T- lymphocyte is less often involved) lead to:
 Accumulation of lymphocytes in blood, bone marrow, lymph nodes and spleen.
 CLL is more often found in older persons (over 60 y) with more men affected than
women.

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 Clinical Haematology Dr/ Rashad Saleh Alkhwlany

Clinical feature:
o Weight loss.
o Bone marrow failure
o Lymphadenopathy
o Hepatosplenomegally
o Thrombocytopenia
o Neutropenia.
o Hypogammaglobinemia
o Hyperuricemia with treatment
o Bacterial and fungal infection because immune deficiency.
o Patient die from:
 Immune deficiency
 Infection
 Bone marrow failure
Note:
CLL does not usually develop into acute lymphocytic leukaemia.

Lab. Diagnosis:
 ↑ WBCs count (lymphocytosis) 30000-100000 cell/mm3.
 Peripheral blood smear showing (60% to 95%) lymphocytes
o The cell are generally small type of mature lymphocytes.
o Lymphoblast is absent in peripheral blood (PB).
o Prolymphocyte is found in PB (rarely).
o Normocytic normochromic anaemia.
o Thrombocytopenia (↓ PLTs).
 Bone marrow …. Hypercellular with large No. of small lymphocyte (i.e: similar
to PB)
 Positive direct coombs test.
 Reduced concentration of serum immunoglobulins.

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 Clinical Haematology Dr/ Rashad Saleh Alkhwlany

Treatment:
 Chemotherapy:
o Alkylating agent such as chlorombucil are used to reduce the total lymphocyte
count.
o Corticosteroids and radiation of an enlarged spleen are employed.
 Immunoglobulin replacement is useful for patient who have
hypogammaglobulinaemia (↓IgG)

Acute lymphocytic leukemia (ALL)

Acute lymphoblastic leukaemia

 ALL is associated with large reduction of normal haematopoietic cells thus

always accompanied by anaemia, granulocytopenia and
thrompocytopenia.
 If not treated, all may be fatal due to combination of anemia, infection and
bleeding.
 ALL is the major disease of childhood.

Clinical features:
 Anaemia.
 Infection.
 Bleeding.
 Organ infiltration.

Lab. Diagnosis:
 WBCs:
‫ْ وثٍشح‬ٛ‫لذ رى‬ٚ ‫خٍٍخ‬111 ِٓ ً‫ْ لٍٍٍخ أل‬ٛ‫ فمذ رى‬,‫رخزٍف ٔسجخ ػذد خالٌب اٌذَ اٌجٍعبء ِٓ ِصبة ألخش‬
‫ْ ػٕذٖ اٌخالٌب اٌجٍعبء لٍٍٍخ ٌؼٍش فزشٖ أوثش‬ٛ‫ اٌشخص اٌّصبة اٌزي رى‬. 3ُِ/ ‫ خٍٍخ‬511111 ِٓ ‫أوثش‬
‫د إٌى أسذاد‬ٛ‫٘زا ٌم‬ٚ ‫خٍخ‬ٌٍٛٛ‫ْ إٌى ِعبػفبد فس‬ٛ‫ُ ٌسزبخ‬ٙٔ‫ِٓ اٌزٌٓ ػٕذُ٘ صٌبدح فً اٌخالٌب اٌجٍعبء أل‬
.‫ٌخ اٌصغٍشح خبصخ ي اٌذِبؽ‬ِٛ‫ػٍخ اٌذ‬ٚ‫األ‬

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 Clinical Haematology Dr/ Rashad Saleh Alkhwlany

 RBCs:
.‫ٌسذس أخفبض فً اٌخالٌب‬
 PLTs:
Thrombocytopenia is also observed in more than 90% of patients.
 Bone marrow:
Hypercellular with elevation of blast cell.

Treatment:
As the same with acute myeloid leukaemia as the following:
 Chemotherapy.
 Supportive therapy.
 Bone marrow transplantation.

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 Clinical Haematology Dr/ Rashad Saleh Alkhwlany

French American British Classification (FAB)

‫لغ ِسبس اٌّشض ِّب ٌسبػذ اٌطجٍت ػٍى اخزٍبس اٌؼالج‬ٛ‫ر‬ٚ ‫ٌخ ثبٌزٕجؤ‬ٚ‫ٌؼزّذ األغجبء ػٍى رصٍٕف اٌّشض ٌٍّسب‬
‫اٌجشٌطبٍٍٔٓ ثؼًّ رصٍٕف ٌٍّشض‬ٚ ٍٍٓ‫األٍِشو‬ٚ ٍٍٓ‫ لبَ ثؼط اٌؼٍّبء اٌفشٔس‬1791 َ‫ فً ػب‬.‫إٌّبست ٌٍّشض‬
‫ػشف ٘زا اٌزصٍٕف‬ٚ ,‫اد اٌىٍٍّبئٍخ‬ٌّٛ‫ب ِغ ثؼط ا‬ٍٙ‫زست رفبػ‬ٚ ‫٘ب‬ّٛٔ ‫دسخخ‬ٚ ‫رٌه زست شىً اٌخالٌب اٌّصبثخ‬ٚ
.‫ثٕبء ػٍٍٗ رُ رصٍٕف سشغبْ اٌذَ إٌخبػً اٌسبد إٌى ثّبٍٔخ أصٕبف‬ٚ FAB ‫ثزصٍٕف اٌـ‬

FAB Classification Acute Myeloid leukaemia:

FAB Other name Differential diagnosis

M0 Acute myeloid leukaemia with minimal
evidence of myeloid differentiation
 Blasts ≥30% of bone marrow nucleated cells
 Blasts ≥30% of bone marrow non-erythroid cells
 <3% of blasts positive for Sudan black B or for
myeloperoxidase by light microscopy
 Blasts demonstrated to be myeloblasts by immunological
markers or by ultrastructural cytochemistry
 Blasts ≥30% of bone marrow cells
 Blasts ≥90% of bone marrow non-erythroid cells
 ≥3% of blasts positive for peroxidase or Sudan black B

M1 Acute myeloid leukaemia without maturation

 Bone marrow maturing monocytic component
(promonocytes to monocytes) ≤10% of non-erythroid
cells
 Bone marrow maturing granulocytic component
(promyelocytes to polymorphonuclear leucocytes) ≤10%
of non-erythroid cells
 Blasts ≥30% of bone marrow cells
 Blasts 30–89% of bone marrow non-erythroid cells
 Bone marrow maturing granulocytic component
M2 Acute myeloid leukaemia with maturation (promyelocytes to polymorphonuclear leucocytes) >10%
of non-erythroid cells
 Bone marrow monocytic component (monoblasts to
monocytes) <20% of non-erythroid cells and other criteria
for M4 not met
M3 Acute Promyelocytic Leukemia
 Blasts ≥30% of bone marrow cells
 Blasts ≥30% of bone marrow non-erythroid cells
 Bone marrow granulocytic component (myeloblasts to
polymorphonuclear leucocytes) ≥20% of non-erythroid
cells
M4 Acute myelomonocytic leukaemia
 Significant monocytic component as shown by one of the
following:
o Bone marrow monocytic component (monoblasts to
monocytes) ≥20% of non-erythroid cells and
peripheral blood monocytic component ≥5 . 109/l, or
o Bone marrow monocytic component (monoblasts to
monocytes) ≥20% of non-erythroid cells and
confirmed by cytochemistry or increased serum or

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 Clinical Haematology Dr/ Rashad Saleh Alkhwlany

urinary lysozyme concentration, or

o Bone marrow resembling M2 but peripheral blood
monocyte component ≥5 . 109/l and confirmed by
cytochemistry or increased serum or urinary
lysozyme concentration
 Blasts ≥30% of bone marrow cells
 Blasts ≥30% of bone marrow non-erythroid cells
 Bone marrow monocytic component ≥80% of non-
M5 Acute monoblastic/monocytic leukaemia erythroid cells
Acute monoblastic leukaemia (M5a)
 Monoblasts ≥80% of bone marrow monocytic component
Acute monocytic leukaemia (M5b)
 Monoblasts <80% bone marrow monocytic component
M6 Acute erythroleukaemia
 Erythroblasts ≥50% of bone marrow nucleated cells
 Blasts ≥30% of bone marrow non-erythroid cells
 Blasts ≥30% of bone marrow nucleated cells
M7 Acute megakaryoblastic leukaemia  Blasts demonstrated to be megakaryoblasts by
immunological markers, ultrastructural examination or
ultrastructural cytochemistry

FAB classification of ALL

FAB category L1 ALL L2 ALL L3 ALL

Cell size Mainly small Large heterogeneous Large homogeneous
Fairly homogeneous,
Nuclear chromatin Finely stippled,
may be condensed in Heterogeneous
homogeneous
some cells

Mainly regular Irregular; clefting and

Nuclear shape Regular; oval or round
indentation common
Not visible or small
Nucleolus Usually visible, often large Usually prominent
and inconspicuous

Amount of cytoplasm Scanty Variable, often abundant Moderately abundant

Cytoplasmic basophilia Slight to moderate Variable Strong
Cytoplasmic vacuolation Variable Variable Often prominent

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 Clinical Haematology Dr/ Rashad Saleh Alkhwlany

FAB classification of certain chronic myeloid leukaemias

Atypical chronic Chronic

Chronic granulocytic
myeloid leukaemia myelomonocytic
leukaemia (CGL)
(aCML) leukaemia (CMML)
Basophils >2% <2% <2%
Monocytes <3% >3-10% (usually >10%) >3-10%
Granulocyte dysplasia (‫) َخٍَ ًُ اٌزََّٕسُّح‬ - ++ +
Immature granulocytes >20% 10–20% <10%
Blasts <2% >2% <2%
BM erythroid cells _ + +

Ultrastructural characteristics distinguishing blast cells and other immature leukaemic

cells from each other :

 Myeloblasts of neutrophil lineage

Small, medium or large granules; sometimes Auer rods, which may be
homogeneous or be composed of longitudinal tubules or dense material with a
periodic substructure.
 Promyelocytes of promyelocytic leukaemia
In hypergranular promyelocytic leukaemia the cytoplasm is packed with granules
ranging from 120 to 1000 nm in diameter; in the variant form of hypergranular
promyelocytic leukaemia the granules are much smaller, ranging from 100 to 400
nm, with some cells being packed with granules and other being agranular. Auer
rods in promyelocytic leukaemia differ from those in M1 and M2 AML; they are
composed of hexagonal structures and have a different periodicity from other Auer
rods; microfibrils and stellate configurations of rough endoplasmic reticulum are
also characteristic of M3 AML, particularly M3 variant
 Myeloblasts of eosinophil lineage
Granules tend to be larger than those of neutrophil series; homogeneous in early
cells, in later cells having a crystalline core set in a matrix; sometimes there is
asynchrony with granules lacking a central core, despite a mature nucleus; Auer
rods similar to those of the neutrophil lineage may be present
 Myeloblasts of basophil or mast cell lineage*
Basophil granules may be any of three types: (i) large electron-dense granules
composed of coarse particles; (ii) pale granules composed of fine particles; (iii) θ
(theta) granules, which are small granules containing pale flocculent material and
bisected by a membrane. Mast cell precursors sometimes have granules showing
the scrolled or whorled pattern that is characteristic of normal mast cells
 Monoblasts and promonocytes
Monoblasts are larger than myeloblasts and cytoplasm may be vacuolated.
Granules are smaller and less numerous

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 Clinical Haematology Dr/ Rashad Saleh Alkhwlany

 Megakaryoblasts
More mature megakaryoblasts show a granules, bull’s eye granules and platelet
demarcation membranes
 Early erythroid precursors
Immature cells can be identified as erythroid when they contain aggregates of
ferritin molecules or iron-laden mitochondria or when there is rhopheocytosis
(invagination of the surface membrane in association with extracellular ferritin
molecules)

Ultrastructural cytochemistry in the identification of blast cells and other immature

cells of different myeloid lineages.

 Myeloblasts of neutrophil lineage

Myeloperoxidase (MPO) activity in endoplasmic reticulum, perinuclear space,
Golgi zone, granules and Auer rods (if present); detected by standard technique for
MPO and by platelet peroxidase (PPO) techniques
 Myeloblasts of eosinophil lineage
MPO-positive granules and Auer rods (if present) detected by MPO and PPO
techniques
 Myeloblasts of basophil or mast cell lineage
Granules may be peroxidase positive or negative; endoplasmic reticulum,
perinuclear space and Golgi zone are rarely positive; more cases are positive by
PPO technique than MPO technique
 Promyelocytes of acute promyelocytic leukaemia
MPO-positivity is seen in granules, Auer rods, perinuclear space and some rough
endoplasmic reticulum profiles; strong lysozyme activity of granules and Auer rods
is seen in M3 AML whereas in M3 variant AML activity varies from weak to
moderately strong
 Monoblasts and promonocytes
The first granule to appear in a monoblast is a small, peripheral acid phosphatase-
positive granule. MPO activity appears initially in the perinuclear envelope, Golgi
apparatus and endoplasmic reticulum. Subsequently, mainly at the promonocyte
stage, there are small MPO-positive granules. A PPO technique is more sensitive in
the detection of peroxidase-positive granules than an MPO technique. Non-specific
esterase activity can also be demonstrated cytochemically
 Megakaryoblasts
PPO activity in endoplasmic reticulum and perinuclear space only
 Proerythroblasts
PPO-like activity may be present in the Golgi zone

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 Clinical Haematology Dr/ Rashad Saleh Alkhwlany

Benign disorder of WBCs

In an adult there are about 4.0-11.0 X 103 white cells (leukocytes) per mm3 of blood,
composed of:
 Absolute number
 Neutrophils 1.5-7.5 X 103/mm3
 Lymphocytes 1.2-4.0 X 103/ mm3
 Monocytes 0.2-1.0 X 103/ mm3
 Eosinophils 0.02-0.6 X 103/ mm3
 Basophils 0.01-0.1 X 103/ mm3
 Percentage
 Neutrophils 40–75%
 Lymphocytes 21–40%
 Monocytes 2–10%
 Eosinophils 1–6%
 Basophils 0–1%

Note
Lymphocytes: In an adult, lymphocytes are mainly of the small type whereas in a
child, large lymphocytes predominate.

Neutrophil
 Neutrophilia
o Increased in the No. of Neutrophil.
o Causes
 Acute infections:
 Bacterial, viral, fungal, mycobacterial and rickettsial
 Physical stimuli:
 Trauma, electric shock, anoxia, pregnancy
 Drugs and chemicals:
 Corticosteroids, adrenaline, lead, mercury poisoning, lithium
 Hematological causes:
 Acute haemorrhage, acute haemolysis, transfusion reactions, post-
splenectomy, leukaemia and myeloproliferative disorders.
 Malignant disease:
 Carcinoma, especially of gastro-intestinal tract, liver or bone marrow
 Miscellaneous conditions:
 Certain dermatoses (skin disease), hepatic necrosis.

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 Clinical Haematology Dr/ Rashad Saleh Alkhwlany

 Neutropenia
o Dcreased in the No. of Neutrophil.
o Causes
 Infections:
 Viral :– including hepatitis, influenza, rubella
 Bacterial :– typhoid fever, brucellosis, miliary tuberculosis
 Rickettsial and protozoal infections (Sometimes)
 Megaloblastic anaemia:
 Vitamin B12 or folate deficiency
 Congenital neutropenias
 Ionizing radiation and cytotoxic drugs
 Malignant disease:
 Acute leukaemia
 Multiple myeloma or lymphoma
 Micscellaneous conditions:
 Systemic lupus erythematosus, hypopituitrism, iron deficiency.

Lymphocyte
 Lymphocytosis
o Increased in the No. of Lymphocyte.
o Causes:
Non-Malignant causes
 Virus infections:
 Infectious mononucleosis
 Cytomegalovirus infection
 Occasionally mumps, varicella, hepatitis, rubella, influenza
 Bacterial Infections:
 Pertussis
 Occasionally tuberculosis, syphilis, brucellosis
 Protozoal infections:
 Toxoplasmosis
 Occasionally malaria
 Other rare causes:
 Hyperthyroidism, congenital adrenal hyperplasia (increase in the
reproduction rate of cells).

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 Clinical Haematology Dr/ Rashad Saleh Alkhwlany

 Lymphopenia
o Decreased in the No. of Lymphocyte.
o Causes
 Loss:
 Mostly from gut as in intestinal lymphangiectasia (widening of the
lymphatic vessels), Crohn’s disease (chronic inflammatory disease of the
intestines)
 Thoracic-duct fistula
 Vit B12 or folate deficiency
 Zinc deficiency
 Pharmacological pagents:
 Corticosteroids
 Cytotoxic drugs
 Infections:
 Severe septicaemias
 Influenza, occasionally other virus infections
 Colorado tick fever
 Miliary (resembling millet) tuberculosis
 Other miscellaneous conditions:
 Collagen vascular diseases, especially SLE
 Malignant disease
 Other conditions with lymhocytotoxins
 Radiotherapy
 Graft-versus-host disease

Monocytosis

o Increased in the No. of Monocyte.

o Causes
 Chronic bacterial infections:
 Tuberculosis, subacute bacterial endocarditis, brucellosis
 Other Specific Infections:
 Malaria, Kala-azar, trypanosomiasis, typhus, Rocky Mountain spotted
fever.
 Malignant diseases:
 Hodgkin’s disease, carcinoma
 Leukaemia:
 Acute myeloid leukaemia, chronic monocytic leukaemia

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 Clinical Haematology Dr/ Rashad Saleh Alkhwlany

 Neutropenias:
 Miscellaneous:
 Cirrhosis, systemic lupus erythematosus, rheumatoid arthritis

Eosinophilia

o Increased in the No. of Eosinophil.

o Causes
 Allergic reactions:
 Asthma, hay fever (allergy to pollen), urticaria (skin condition caused by an
allergic reaction)
 Parasitic Infestation:
 Tissue parasites :– trichinosis, filariasis, visceral larva migrans, etc..
 Intestinal parasites :– Ascaris, Taenia, etc. (less regularly)
 Skin disorders
 Drug hypersensitivity reactions
 Malignant diseases:
 Especially Hodgkin’s disease, carcinoma of ovary, lung and stomach
 lymphadenopathy.
 Following irradiation or splenectomy
 Eosinophilic leukaemia
 Miscellaneous Conditions:
 Ulcerative colitis, scarlet fever, pernicious anaemia, chronic active
hepatitis, eosinophilic granuloma

Basophilia
o Increased in the No. of Basophil.
o Causes
 Myeloproliferative disorders
 Some allergies
 Myxoedema (condition caused by hypothyroidism, characterize by swelling of
the skin and underlying tissues)

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 Clinical Haematology Dr/ Rashad Saleh Alkhwlany

Infectious mononucleosis
 Is a self-limited disease, characterized by fever, sore throat, lymphadenopathy
and presence of atypical lymphocyte in the blood.
 These are T. cells reacting against B- cells infected with Epstein-Barr virus
(EBV).
 The disease is associated with a high titer of heterophile (reacting with cells of
another species) antibody which reacts with sheep, horse or beef red cells.
 A similar clinical feature without heterophile antibodies may occur in adults with
toxoplasmosis, cytomegalovirus and other viral infection.

Epstein-Barr virus (EBV):

o The majority of patients are between the ages of 15-20 years (teens).
o The infection is transmitted orally (saliva)
o The following clinical features may be found:
 Lymphadenopathy.
 Splenomegally
 Nervous system disease: coma, convulsion.
 Sore throat, pharyngitis, follicular, tonsillitis and severe headache.

Cytomegalovirus (CMV):
o It occurs in young adults.
o It is transmitted by sexual contact (venereal).

Diagnosis:
o Leukocytosis with absolute lymphocytosis.
o Atypical lymphocyte:
 They are 2-3 times of mature cells (in size), with round or irregular cell
shape and 4:1 nucleus to cytoplasm ratio (> 9:1in mature cell).
 Shape of nucleus: either oval or kidney-shaped or lobulated (round in
mature cell).
o Detection of heterophile antibodies.

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 Clinical Haematology Dr/ Rashad Saleh Alkhwlany

Lymphoid tissue tumors

Malignant lymphoma
 In this disease, there is replacement of normal lymphoid structure by collection
of abnormal cells.
 Lymph node enlargement is the most prominent of lymphomas.
 Malignant lymphomas are classified into:
 Hodgkin’s disease
 Non-Hodgkin’s disease

Hodgkin’s disease

 Is characterized by the presence of Reed-Sternberg (RS) cells in the lymph node.

 Clinical features:

o Common:
 Superficial lymph nodes enlargement.
o Less common:
 Fever, night sweat, weight loss.
 Pyrexia of unknown origin (PUO).
 Abdominal pain, thrombocytopenia and leucopenia.
 Anaemia; haemolytic anaemia
o Occasional:
 Nasopharyngeal obstruction
 Intestinal obstruction
 Malabsorption
 Bone pain.

Non-Hodgkin’s disease
 Like Hodgkin’s disease these tumors may occur at age but show 2 peaks (1) at
childhood. (2) from 50 years.
 Is characterized by the presence of a collections of abnormal lymphocytes.
 Clinical features:
o Lymph node enlargement may causes obstruction.

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 Clinical Haematology Dr/ Rashad Saleh Alkhwlany

o Nasopharynx, tonsil and GIT involvement:

 Nasopharyngeal, tonsillar involvement causes:
 Soreness, pain the throat.
 Nasal obstruction or bleeding.
 GIT involvement causes:
 GI bleeding.
 Abdominal pain.
 Vomiting or weight loss.
 Intestinal obstruction.

Diagnosis:
o Lymph node biopsy.
o Liver biopsy.
Treatment:
o Radiation therapy.
o Chemotherapy.

Reed-Sternberg (RS) cells

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 Clinical Haematology Dr/ Rashad Saleh Alkhwlany

Hairy Cell Leukemia (HCL)

Epidemiology
o Adults
o Excellent prognosis: this is the “good news leukemia”

Signs/symptoms/manifestations
o Pancytopenia
o Splenomegaly
Diagnosis
o Hairy cells

Therapy
o Adenosine deaminase inhibitors (cladribine)

Hairy cells

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 Clinical Haematology Dr/ Rashad Saleh Alkhwlany

Haemostatic and platelets

Normal haemostatic:

o Haemostatic is the process where by flow of blood is stopping following vascular

injury. It include three stages:
1. Blood vessel wall.
2. Platelets.
3. Coagulation factors.

The blood vessel wall:

o The vessel wall has an important role in haemostasis. Endothelial cells produce:
 Prostacyclin: which causes vasodilatation (which decreases blood pressure) and
inhibits platelet aggregation.
 Antithrombin (AT) and protein C (PC) activator (thrombomodulin) which:
inhibit coagulation.
 Tissue plasminogen activator (TPA) which: activates fibrinolysis.

o Injury to the vessel wall:

(i) Activates membrane bound tissue factor (tissue factor) which initiates
coagulation.
(ii) Exposes subendothelial connective tissue (collagen) allowing binding of
platelets to von Willebrand factor (vWF), which mediates platelet
adhesion to endothelium and carries clotting factor VIII in plasma.

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Clinical Haematology Dr/ Rashad Saleh Alkhwlany

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 Clinical Haematology Dr/ Rashad Saleh Alkhwlany

Platelets

Platelets production:
o Platelets are produced in the bone marrow by fragmentation of the cytoplasm of
megakaryocytcs.
o Each megakaryocyte is responsible for the production of about 4000 platelets.
The time interval from differentiation of the stem cell to the production of
platelets is about 10 days.

Platelets production

Megakaryoblasts Promegakaryocyte Basophilic megakaryocyte

Megakaryocyte Platelets.

 Megakaryoblasts: are the most immature cell (10 to 15 μm) with a high
nuclear to cytoplasmic ratio and 2-6 nucleoli.
 Promegakaryocyte: is a large cell of 80 μm with dense alpha and lysosomal
granules.
 Basophilic megakaryocyte: shows evidence of cytoplasmic fragments
containing membranes, cytotubules, and several glycoprotein receptors.
 Megakaryocyte: is composed of cytoplasmic fragments that are released by a
process called the budding of platelets.

Regulation of the Platelets production:

o Thrombopoietin is the major regulator of platelet production.

o Thrombopoietin is produced by the liver and kidneys.
o Thrombopoietin increases the number and rate of maturation of megakaryocytes.
o Interleukin-l1 (IL 11) can also increase the circulating platelet count.
Platelets:
o Also called thrombocytes.
o Platelets were recognized in 1882 by Bizzozero.

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 Clinical Haematology Dr/ Rashad Saleh Alkhwlany

o PLTs are small colourless disc-shaped cell fragment without a nucleus with 3.6
µm in diameter and 0.9 µm in thickness, found in large numbers in blood and
involved in clotting.
o The normal platelet count is about 150-400 x l03/mm3 .
o The normal platelet lifespan is 7-10 days.
o Platelets secrete growth factors that stimulate mitosis in fibroblasts and smooth
muscle, and help maintain linings of blood vessels.
o They are destroyed by the reticuloendothelial system (RE).

Platelets structure:

o Platelets have no nucleus but do have granules: alpha granules, and dense
granules. These granules are secreted during the platelet release reaction and
contain many biochemically active components such as serotonin, ADP, and
ATP.
o The glycoproteins of the surface coat are particularly important in the platelet
reactions of adhesion and aggregation. Adhesion to collagen is facilitated by
glycoprotein la (GP Ia). Glycoproteins Ib and IIb/IIIa adhere with Van
willebrand factor.
o Open canalicular system: to facilitate absorption of plasma coagulation.
o Phospholipid (factor III): is important in the conversion of factor X to Xa and
prothrombin to thrombin.

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 Clinical Haematology Dr/ Rashad Saleh Alkhwlany

o The filaments and microtubules under the membrane composing the platelet
cytoskeleton.
o Electron dense granules and specific α- granules: is important in the adhesion and
aggregation of platelets.
o Dense tubular system: contains a substantial quantities of calcium and may be the
site of prostaglandins and thromboxan A2 synthesis for use in the platelet
function.

Platelet Function
o The main function of PLTs:
1. Formation of plug
2. Release and synthesis of coagulation factors.
o PLTs perform their function through several steps:
1. Adhesion.
2. Release.
3. Aggregation.
4. Fusion and procoagulant activity.

 Adhesion:
o Following vascular injury, PLTs adhere to subendothelial connective tissues by
Van willebrand factor (factor VIII) and GP Ib (see the figure).

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 Clinical Haematology Dr/ Rashad Saleh Alkhwlany

o Van willebrand factor (VWF): is referred to as factor VIII-related antigen

(VIII-Rag), the molecular weight (MW) 0.8-20 X 106. VWF is encoded by a
gene on chromosome 12 and is synthesized by endothelial cells and
megakaryocytes. It is stored in Weibel-Palade bodies in endothelial cells and in
specific α- granules in PLTs. Release of VWF occurs under the influence of
several hormones.

 Release:
o Exposure to collagen or thrombin action result in the release of PLTs granules
content which include: ADP, serotonin, fibrinogen, lysosomal enzymes, β-
thromboglobulin and heparin neutralizing factor (PLTs factor 4).
o Collagen or thrombin activate PLTs prostaglandins synthesis.
o The prostaglandins help in the formation of thromboxan A2 and prostacyclin.
o Thromboxan A2 activate PLTs aggregation and adhesion.
o Prostacyclin inhibits PLTs aggregation and deposition on normal vascular
endothelium.

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 Clinical Haematology Dr/ Rashad Saleh Alkhwlany

 PLTs aggregation:
o Release ADP and thromboxan A2 cause additional PLTs to aggregate.
o ADP causes PLTs to swell and encourages the PLTs membrane of adjacent PLTs
to adhere to each other.

 PLTs fusion and procoagulant activity:

o The adherent and aggregated platelets release factor V and expose platelet factor
3 to accelerate the coagulation cascade and promote activation of clotting factors
and ultimately stabilize the platelet plug with a fibrin clot.

 Growth factor:
PDGF (platelet derived growth factor) found in specific granules of platelets
stimulates vascular smooth muscle cells to multiply and this may healing of
vascular following injury.

Blood coagulation
 Blood coagulation factors:
 Blood coagulation factors (details in the table).
 The active form of factors: II, VII, IX, X, XI, XII and prekallikrin (Fletcher
factor) function as serine protease.
 The factors: II, VII, IX and X are vitamin K-dependent.
 Factor IV is calcium.
 Factor VI is not recognized.
 Most of these factors are synthesized in liver except VWF.
 There are three groups in which coagulation factors can be classified:
1. The fibrinogen group consists of factors I, V, VIII, and XIII. They are
consumed during coagulation. Factors V and VIII are labile and will
increase during pregnancy and inflammation.
2. The prothrombin group: Factors II, VII, IX, and X all are dependent on
vitamin K during their synthesis. This group is stable and remains preserved
in stored plasma.

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 Clinical Haematology Dr/ Rashad Saleh Alkhwlany

3. The contact group: Factor XI, factor XII, prekallikrein, and high-molecular-
weight kininogen (HMWK) are involved in the intrinsic pathway,
moderately stable, and not consumed during coagulation.

Half-life
Factor Source and function Clinical Picture If Deficient
(Hrs)
Fibrinogen* Bleed with trauma, stress, mucosal, umbilical
liver. Converted to fibrin. 64 to 96
I stump, intracranial, gastrointestinal
Prothrombin* liver with help of vitamin K.
Converted to thrombin. 48 Severe bleed, mucous membrane, spontaneous
II
Released from damaged tissue.
Tissue factor*
(thromboplastin)
III
Essential in activating in vivo coagulation
Calcium ions* Inorganic ions in plasma, derived from
(Ca2+) diet or bone.
IV Essential for the coagulation process
liver. Also released from platelets. Co-
V 12 Moderate-severe bleed, mucosal, large
factor involved in converting prothrombin
Labile factor ecchymoses
to thrombin.
Note: There is no factor VI
VII liver with the help of vitamin K. Intra-articular bleed, severe mucosal,
Proconvertin or 4 to 6 epistaxis, hemarthrosis, genitourinary,
Stable factor In vivo, activates factor IX.
gastrointestinal, and intrapulmonary
VIII Haemophilia A. Severity based on levels,
liver 15 to 20 hematuria, hemarthrosis, intra-articular,
Antihaemophilic
Co-factor, involved in activating factor X. intracranial
factor
Haemophilia B. Severe mucous membrane,
IX liver with the help of vitamin K 24 deep tissue,
Christmas factor Involved in activating factor X. intra-muscular
X liver with the help of vitamin K.
Stuart-Power Involved in converting prothrombin to 32 Mucous membrane, skin hemorrhages
factor thrombin.
XI
liver.
Plasma 60 to 80 Severity of bleeds vary, not proportional to
In vivo, activated by thrombin and factor
thromboplastin factor level
XII and important at major sites of trauma
antecedent
liver.
Involved in converting plasminogen to
XII
plasmin and activating factor XI in 50 to 70
Hageman (glass, Hemorrhage is rare, risk for thrombosis
fibrinolysis.
or contact) factor
In vitro (laboratory tests), it initiates the
clotting process
XIII liver and present in platelets.
40 to 50 Only homozygotes bleed, deep tissue muscle,
Fibrin stabilizing Converts fibrin polymer to stable
intracranial bleed
factor insoluble fibrin.
* Factor known by name, other factors are usually referred to by their Roman numeral.
Note: Vitamin K dependent factors are prothrombin, VII, IX, X.

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 Clinical Haematology Dr/ Rashad Saleh Alkhwlany

 Process of blood coagulation:

 The coagulation process is a complex series of enzymatic reactions involving
the coagulation factors (zymogens) and activity of co-factors (V, VIII), leading
to the production of thrombin which converts soluble plasma fibrinogen into
fibrin (as represented in Figure).
 Coagulation is initiated in vivo by tissue factor (found on the surface of
vascular tissue).
 The cascade has been divided on the basis of laboratory tests into:
1. Intrinsic pathway
2. Extrinsic pathway
3. Common pathway

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Clinical Haematology Dr/ Rashad Saleh Alkhwlany

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