Disorders of WBC

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OUT LINES
 Disorders of white blood cells
 Non malignant leucocytes disorder
 Malignant leucocytes disorders

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 OBJECTIVE
At the end of this session participants will be able to;
 Discus non malignant leukocyte disorder

 List examples of common conditions that can cause

leukocytosis or leukocytopenia?
 Describes characters of malignant leukocyte disorder

 Discuss myloproliferative disorder

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 DISORDERS OF WHITE BLOOD CELLS
 Leucocytes disorder may reflect underproduction or overproduction
of a cell line
 Leucocytes disorder may be reactive or malignant
 Non malignant disorder are most often reactive response there is a
stimulus eg, infection or inflammation
 They reaction disappears when the stimulus that provoked is gone
 Malignant leucocytes disorders have no knowen stimulus for the
abnormalities, cell proliferations are uncontrolled by normal
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regulatory mechanisms
 NONMALIGNANT WBC DISORDERS
 Nonmalignant disorders range from general increases or decreases in the total

leukocyte count to qualitative disorders, such as a defect in the killing ability of the

leukocytes

 Quantitative change

Change in number
 Cytosis/ philia

 Increase in number
 Cytopenia

 Decrease in number

Qualitative change


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
Morphologic changes

 Functional changes
 LEUKOCYTOSIS
Leukocytosis is an increase in the number of white blood cells
(>11x109/L)
 Leukocytosis is an increase in the concentration or percentage of
any of the leukocytes in the peripheral blood: neutrophils,
eosinophils, basophils, monocytes, or lymphocytes
 Although an increase in the total leukocyte count may be caused by
an increase in lymphocytes
 an increase in neutrophils is the most frequent cause of
nonmalignant increases in the total leukocyte count 6
 LEUKOCYTOSIS
Nonmalignant leukocytosis can be caused by various
conditions in several general categories
 These categories include
 Increased movement of immature cells out of the bone marrow’s
proliferative compartment
 Increased mobilization of cells from the maturation storage
compartment of the bone marrow to the peripheral blood
 Increased movement of mature cells from the marginating pool
to the circulating pool
 Decreased movement of mature cells from the circulation into
the tissues
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 LEUKOCYTOSIS

It is caused by:
Chronic infections
Inflammation

Leukemia

Allergy

Bone marrow stimulation

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 LEUCOPENIA

 Leucopenia is a decreased white blood cell count

(<3.5x109/L)

 TWBC lower than the reference range for the age is

defined as leucopenia

 Leucopenia may affect one or more lineages and it is

possible to be severely neutropenic or lymphopenic
without a reduction in total white cell count

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 LEUCOPENIA
It is caused by:
 Chemotherapy
 Radiation therapy
 Some types of cancer
 Malaria
 Tuberculosis
 Bone marrow failure
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 Destruction
 NEUTROPHILIA
Neutrophilia is defined as an absolute neutrophil count >7.5x109/L.
Causes :
Myeloproliferative disorders, like CML, PRV
Bacterial infection
Inflammation e.g Autoimmune disorders
Tissue destruction or necrosis: burns, surgical operations
Leukemoid reactions
Hemorrhage and hemolysis
Pregnancy, stress and exercise 11

Drugs e.g steroids, G-CSF

 NEUTROPENIA
 Neutropenia is an absolute reduction in the number of
circulating neutrophils.
 Mild (1-1.5 x 109/L)
 Moderate (0.5 -1 x 109/L)
 Severe (<0.5 x 109/L)
 Bacterial infections are the commonest
 Fungal, viral and parasitic infection are relatively
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uncommon
 CAUSES OF NEUTROPENIA

Decreased Production
General bone marrow failure
 aplastic anemia

 megaloblastic anemia

 myelodysplasia

 acute leukemia

 Chemotherapy

 Marrow infiltration ; replacement by tumor

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 CAUSES OF NEUTROPENIA
 Myeloid hypoplasia
 Drugs (chloramphenicol, phenylbutazone)
 Ionizing radiation
 Increased destruction; General. e.g Hypersplenism, Immune
disorder, autoimmune
 Acute infections
 Overwhelming sepsis due to various bacterial infections can lead to
severe Neutropenia
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 Eosinophilia
 Absolute eosinophil count greater than 0.5x10 9/L
 Most cases are secondary to an underlying
inflammatory, allergic, or atopic disorder
 Although eosinophilia is observed in patients with
parasitic infections as well as several malignant
disorders, including Hodgkin’s and non-Hodgkin
lymphoma
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 CAUSES OF EOSINOPHILIA
 Allergy
 bronchial asthma, seasonal rhinitis
 Atopic, drug sensitivity and pulmonary eosinophilia

 Infection
 Parasites (Intestinal parasitic infections: e.g. trichinosis,

taeniasis) and recovery from infections

 Malignancy
 Hodgkin’’s disease, NHL

 Myelproliferative disorders, like CML, PV

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 CAUSES OF EOSINOPHILIA
 Eosinophilic leukaemia
 AML with eosinophilia esp. M4Eo
 Drugs
 Skin disorders
 Gastrointestinal disorders
 Hypereosinophilic syndrome; a group of disorders of
unknown cause characterised by excessive production of
eosinophils associated with organ infiltration
 This syndrome results in end organ damage primarily
involving the heart, leading to eosinophilic endomyocardial
fibrosis and associated thromboembolic complications
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 Eosinopenia
 An eosinophil count below 0.04 x 109/L
 Occurs during:

 Acute stress due to secretion of adrenal glucocorticoid and

epinephrine
 This is a rare, stress-related condition that may be caused by
several factors.


Acute inflammatory states
 Eosinopenia is frequently related to the action of glucocorticosteroid
hormones or occurs as an aftermath of acute bacterial or viral 18

inflammation
Basophilia
 a basophil count above 0.2 x 109/L
 Basophilia can be associated with drugs, Allergic reactions,
tuberculosis and ulcerative colitis.
 The most common setting of basophilia is seen in
myeloproliferative disorders such as Chronic myelogenous
leukemia and Polycythemia vera

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 CAUSES OF BASOPHILIA
 Most commonly associated with hypersensitivity reactions to
drugs or food
 Inflammatory conditions
 e.g RA, ulcerative colitis

 Myeloproliferative disorders
 CML

 PRV

 Myelofibrosis

 Essential thrombocythaemia

 IgE-mediated hypersensitivity reactions

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Basopenia
Peripheral blood basophils <0.1x109/L
 As part of generalised leucocytopenia

e.g. infection, inflammation

 Haemorrhage

 Cushing’s syndrome
 Allergic reaction
 Drugs
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 Monocytosis
 A monocyte count above 1.0 x 109/l
 An absolute monocyte count greater than 1.0x109/L can occur as
a result of several chronic infectious or inflammatory disorders

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 CAUSES OF MONOCYTOSIS
 Infections
 Chronic infection (TB, typhoid fever, infective endocarditis)
 Malaria, trypanosomiasis, typhoid (commonest world-wide causes)
 Recovery from acute infection
 Malignant disease
 MDS, AML, HD, NHL, AML (M4 or M5).
 Connective tissue disorders
 Ulcerative colitis, Sarcoidosis, Crohn’’disease
 Post-splenectomy
 Post-chemotherapy or stem cell transplant esp. if GM-CSF used

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 Monocytopenia
 Peripheral blood monocytes <0.2 x109/L
Autoimmune disorders e.g. SLE
Hairy cell leukemia

Drugs e.g. glucocorticoids, chemotherapy

 Treatment with prednisone

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LYMPHOCYTOSIS
 Lymphocytosis is defined as absolute lymphocyte count above 4.0 x 10 9/L
in adults and above 8.0 x 10 9/L in children
 The blood contain only few percent of total body lymphocytes
 The most consistent variation is seen with age

 Alteration of lymphocyte counts can result from

 The redistribution of lymphocytes; Results in variation

in count in serial measurements
 Absolute increase of lymphocyte

 Loss of lymphocytes

 Combination of these

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 CAUSES OF LYMPHOCYTOSIS
 Infections
 Viral infections
 Infectious mononucleosis
 CMV
 Rubella, hepatitis, adenoviruses, chicken pox, dengue
 Bacterial infections
 Pertussis
 Healing TB, typhoid fever
 Protozoal infections
 Toxoplasmosis
 Allergic drug reactions
 Hyperthyroidism

 Splenectomy
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 LYMPHOCYTOPENIA
 a lymphocyte count below 1.0 x 109/l in adults and below 3.0 x
109/l in children
 Seen in
Immune deficiency disorders: HIV/AIDS
Drugs, radiation therapy
 MALIGNANT LEUCOCYTES DISORDERS

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Haematological malignancies are clonal diseases that derive from
a single cell in the marrow or peripheral lymphoid tissue which
has undergone a genetic alteration
 A combination of genetic and environmental factors determine
the risk of developing malignancy:
 Inherited factors – genetic diseases increase the incidence of
leukemia
 Down’s syndrome, Bloom’s syndrome, Fanconi’s anemia, ataxia telangiectasis
 Environmental influences
 Chemicals, drugs, radiation , infection
 THE GENETICS OF MALIGNANT TRANSFORMATION


29Malignant transformation - accumulation of genetic mutations in
cellular genes
 The genes involved in the development of cancer are divided broadly
into two groups:
 Oncogenes
 Arise because of gain-of-function mutations in normal cellular

genes called proto-oncogenes

 Oncogenic versions are generated when the activity of proto-

oncogenes is increased or they acquire a novel function through:

 Translocation

 Mutation

 Duplication

 Tumour suppressor genes

 May acquire loss-of-function point mutation or deletion leading to

malignant transformation
MALIGNANT (NEOPLASTIC ) LEUCOCYTES DISORDERS

 Leukemia, lymphomas, and myelomas are neoplastic

proliferative diseases of the WBC
 Leukemia is a disease, usually of leukocytes, in the blood
and bone marrow
 Lymphoma is a general term for malignancy that starts in the
lymph system, mainly the lymph nodes
 Myeloma is a form of cancer of the plasma cells. In myeloma, the
cells overgrow, forming a mass or tumor that is located in the bone
marrow
 LEUKAEMIA
 Leukemia is a malignant tumor of the hematopoietic system
with uncontrolled proliferation of atypical immature blood
cells in bone marrow and other organs (lymph nodes, spleen,
etc.)
 These abnormal cells may cause:
 Bone marrow failure
 A raised circulating cell count
 Infiltration of organs

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 MAIN FEATURES OF LEUKEMIA

 Proliferation of atypical clone of hematopoietic cells

 They originate from the precursors of granulocytes, lymphocytes
and monocytes, but are not able to differentiate into normal blood
cells
 Bone marrow is affected primarily

 Abnormal white cells in the peripheral blood

 A raised total white cell count
 Evidence of bone marrow failure (i.e., anemia, neutropenia,
thrombocytopenia) in the acute leukemias
 Involvement of other organs (e.g., liver, spleen, lymph nodes,
meninges, brain, skin or testes)
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 LEUKEMIA CONT’D
 Although viruses cause several forms of leukemia in animals, their
role in humans is uncertain
 Only two viral associations are identified

 Epstein-Barr virus, a DNA virus, associated with Burkitt's

lymphoma
 Human T-cell lymphotropic virus type I, called human T-cell
leukemia/lymphoma virus, an RNA retrovirus, associated with
some T-cell leukemias and lymphomas
 Exposure to ionizing radiation and certain chemicals (e.g.,
benzene, some anti-neoplastic drugs) is associated with an
increased risk of leukemia
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 FORM OF LEUKEMIA
 The clinical symptoms, maturity of the affected cells, and total
leukocyte count determine whether a leukemia is classified as
acute or chronic
 Acute leukemias are characterized by symptoms of short
duration, many immature cell forms in the bone marrow and/or
peripheral blood, and an elevated total leukocyte count
 Chronic leukemias have symptoms of long duration, mostly
mature cell forms in the bone marrow and/or peripheral blood,
and total leukocyte counts that range from extremely elevated to
lower than normal
 LEUKEMIA CONT’D
Classification of leukemia
 The main classification is into acute and chronic leukemia

 On the basis of morphology and cytochemistry, acute leukemia

is further subdivided into:
 Acute myeloid (myeloblastic/myelogenous) leukemia (AML)
 Acute lymphoblastic (lymphocytic) leukemia (ALL)
 AML is further subdivided into eight variants on a morphological
basis according to the French-American-British (FAB) scheme
(M0 – M7)

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FAB CLASSIFICATION OF AML
READING ASSIGNMENTS ??

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 CLASSIFICATION OF LEUKEMIA CONT’D
 ALL is subdivided on a morphological basis according to the
French-American-British (FAB) classification into L1, L2, and L3
 The chronic leukemias comprise two main types:
 Chronic myeloid leukemia (CML)
 Chronic lymphocytic (lymphatic) leukemia (CLL)
 Other chronic types include:

 Hairy cell leukemia

 Prolymphocytic leukemia
 Various leukemia/lymphoma syndromes

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 THE ACUTE LEUKEMIAS
 Acute leukemia is a proliferation of immature bone marrow-
derived cells (blasts) that may also involve peripheral blood or
solid organs
 The percentage of bone marrow blast cells required for a
diagnosis of acute leukemia has traditionally been set arbitrarily at
30% or more
 However, more recently proposed classification systems have
lowered the blast cell count to 20% for many leukemia types, and
do not require any minimum blast cell percentage when certain
morphologic and cytogenetic features are present

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 THE ACUTE LEUKEMIAS
 The leukemic cell population in ALL and AML probably result
from clonal proliferation by successive divisions form a single
abnormal stem or progenitor cell
 There are over 50% myeloblasts or lymphoblasts in the bone
marrow at clinical presentation, and these blast cells fail to
differentiate normally but are capable of further divisions
 Replacement of the normal hemopoietic precursor cells of the
bone marrow by myeloblasts or lymphoblasts and, ultimately
in bone marrow failure

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 THE ACUTE LEUKEMIAS CONT’D
 The clinical condition of the patient can be correlated with the total
number of leukemic cells in the body
 When the abnormal cell number approaches 1012 the patient is
usually gravely ill with severe bone marrow failure
 Peripheral blood involvement by the leukemic cells and infiltration
of organs such as the spleen, liver and lymph nodes may not occur
until the leukemic cell population comprised 60% or more of the
marrow cell total

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 THE ACUTE LEUKEMIAS CONT’D
 The disease may be recognized by conventional morphology only
when blast (leukemic) cells in the marrow exceed 5% of the cell
total (unless the blast cells have some particular abnormal feature,
e.g., Auer rods in myeloblasts)
 This corresponds to a total cell count in excess of 10 8
 The clinical presentation and mortality in acute leukemia arises
mainly from:
 Neutropenia

 Thrombocytopenia, and

 Anemia because of bone marrow failure

 Organ infiltration

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 THE ACUTE LEUKEMIAS CONT’D
 The acute leukemias comprise over half of the leukemias seen in
clinical practice
 ALL is the common form in children

 Its incidence is highest at 3-4 years

 Falls off by 10 years
 There is a lower frequency of ALL after 10 years of age with a
secondary rise after the age of 40
 AML occurs in all age groups

 It is the common form of acute leukemia in adults including the

elderly
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LABORATORY FEATURES IN ACUTE LEUKEMIAS
 A normochromic normocytic anemia
 The total white cell count may be decreased, normal or increased
up to 200x109/l or more
 Thrombocytopenia in most cases, often extreme in AML

 Blood film examination typically shows variable numbers of blast

cells
 In AML, the blasts my contain Auer rods and other abnormal
cells may be present, e.g., promyelocytes, myelocytes, agranular
neutrophils, pseudo-Pelger cells or myelomonocytic cells
 ALL must be differentiated from infectious mononucleosis and
other causes of lymphocytosis
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 LABORATORY FEATURES OF ACUTE
LEUKEMIAS CONT’D
 In AML M6 (erythroleukemia) many erythroblasts may be found
and these may also be seen in smaller numbers in other forms
 The bone marrow is hypercellular with a marked proliferation of
leukemic blast cells which amount to over 50% and typically over
75% of the marrow cell total
 In ALL the marrow may be difficult to aspirate because of
increased reticulin fiber
 In AML M7 the patient typically has an acute onset of

Pancytopenia with marrow fibrosis

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 THE CHRONIC LEUKEMIAS
Chronic Myeloid Leukemia (CML)
 Comprises <20% of all the leukemias and is seen most frequently
in middle age
 In over 95% of patients there is a replacement of normal bone
marrow by cells with an abnormal chromosome- the Philadelphia
or Ph chromosome
 This is an abnormal chromosome 22 due to the translocation of
part of a long (q) arm of chromosome 22 to another
chromosome, usually 9, with translocation of part of
chromosome 9 to chromosome 22

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 CHRONIC MYELOID LEUKEMIA (CML) CONT’D

Formation of the Philadelphia chromosome resulting in a BCR-

ABL fusion gene that generates a fusion protein (p210)
responsible for the chronic myeloid leukaemia phenotype 47
 CHRONIC MYELOID LEUKEMIA
(CML) CONT’D
 It is an acquired abnormality of hemopoietic stem cells that is
present in all dividing:
 Granulocytic cells
 Erythyroid cells
 Megakaryocytic cells in the marrow
 And also in some B and probably a minority of T lymphocytes
 A great increase in total body granulocyte mass is responsible for
most of the clinical features
 In at least 70% of patients there is a terminal metamorphosis to
acute leukemia (myeloblastic or lymphoblastic) with an increase of
blast cells n the marrow to 50% or more 48
CHRONIC MYELOID LEUKEMIA
(CML) CONT’D
 It occurs in most frequently between the ages of 40 and 60 years
 It may occur in children and neonates and in the very old

 In most cases there are no predisposing factors but the incidence

was increased in survivors of the atom bomb exposures in
Japan
Laboratory findings in CML
 Leucocytosis is usually >50x109/l and sometimes >500x109/l

 A complete spectrum of myeloid cells is seen in the peripheral

blood
 The levels of neutrophils and myelocytes exceed those of
blast cells and promyelocytes 49
 LABORATORY FINDINGS IN CML CONT’D

 Philadelphia (Ph) chromosome on cytogenetic analysis of blood

or bone marrow
 Hypercellular bone marrow with granulopoietic predominance

 Neutrophil alkaline phosphatase score is invariably low

 Increased circulating basophils

 Normochromic, normocytic anemia is usual

 Platelet count may be increased (most frequently), normal or

decreased

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 CHRONIC LYMPHOCYTIC LEUKEMIA(CLL)

 It accounts for 25% or more of the leukemias seen in clinical

practice.
 It occurs in older subjects and is rare before 40 years
 The accumulation of large numbers of lymphocytes to 50-100 times
the normal lymphoid mass in the blood, bone marrow, spleen, lymph
nodes and liver may be related to immunological non-reactivity
and excessive lifespan
 The cells are a monoclonal population of B lymphocytes
 With advanced CLL:
 Bone marrow failure
 A tumorous syndrome with generalized discrete
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lymphadenopathy
 Soft tissue lymphoid masses
CHRONIC LYMPHOCYTIC LEUKEMIA CONT’D
 Immunological failure results from reduced humoral and cellular
immune processes with a increased tendency to infection
Laboratory findings in CLL
 Lymphocytosis

 The absolute lymphocyte count is >5 x 109/l and may be up to

300x109/l or more
 Between 70% and 99% of white cells in the blood film appear
as small lymphocytes
 Smudge or smear cells are also present

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 LABORATORY FINDINGS IN CLL
 Normocytic normocytic anemia is present in later states due to
marrow infiltration or hypersplenism
 Autoimmune hemolysis may also occur
 Thrombocytopenia occurs in many patients

 Bone marrow aspiration shows lymphocytic replacement of normal

marrow elements
 Lymphocytes comprise 25-95% of all the cells
 Reduced concentrations of serum immunoglobulins

 More marked with advanced disease

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CLL

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MALIGNANT LYMPHOMAS

 Lymphoma is a malignant neoplasm of lymphocytes in lymph

nodes and organs that grows as nodular masses
 No malignant cells are detectable in blood

 This group of diseases is divided into:

 Hodgkin’s disease, and

 Non-Hodgkin’s lymphomas
 In both, there is replacement of normal lymphoid structure by
collections of abnormal cells
 Hodgkin’s disease is characterized by the presence of Reed-
Sternberg (RS) cells and
 The non-Hodgkin’s lymphomas are characterized by diffuse or
nodular collections of abnormal lymphocytes or, rarely,
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histiocytes
 HODGKIN’S DISEASE

 It is a type of lymphoma characterized by the presence of Reed-

Sternberg cells
 In many patients, the disease is localized initially to a single
peripheral lymph node region and its subsequent progression is by
contiguity within the lymphatic system
 RS cells and the associated abnormal and smaller mononuclear
cells are neoplastic and the associated inflammatory cells
represent a hypersensitivity response by the host
 After a variable period of containment within the lymph nodes, the
natural progression of the disease is to disseminate to involve non-
lymphatic tissue
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 HODGKIN’S DISEASE CONT’D
 The disease can present at any age but is rare in children
 It has bimodal age incidence

 First peak in young adults (age 20-30 years)

 A second after the age of 50

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58
59
 LABORATORY FINDINGS IN HODGKIN’S DISEASE
 Normochromic, normocytic anemias is most common
 One-third of patients have a leucocytosis due to a neutrophil
increase
 Eosinophilia is frequent

 Advanced disease is associated with lymphopenia

 The platelet count is normal or increased during early disease, and

reduced in later stages
 The ESR is usually raised and is useful in monitoring disease
progress

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LABORATORY FINDINGS IN HODGKIN’S DISEASE
CONT’D
 Bone marrow involvement is unusual in early disease
 It may be demonstrated by trephine biopsy, usually in patients
with disease at many sites
 There is progressive loss of immunologically competent T
lymphocytes with reduced cell-mediated immune reactions
 Infections are common, particularly:

 Herpes zoster
 Cytomegalovirus
 Fungal, e.g., Cryptococcus and Candida
 Tuberculosis may occur

61
LABORATORY FINDINGS IN HODGKIN’S DISEASE
CONT’D
 Patients with bone disease may show:
 Hypercalcaemia
 Hypophosphataemia
 Increased levels of serum alkaline phosphatase
 Serum lactate dehydrogenase (LDH) is raised initially in 30-
40% of cases an indicates a poor prognosis
 Elevated levels of serum transaminases may indicate liver
involvement
 Serum bilirubin may be raised due to biliary obstruction caused
by large lymph nodes at the portal hepatitis
 Hyperuricaemia may occur
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MULTIPLE MYELOMA

 It is a neoplastic monoclonal proliferation of bone marrow plasma

cells characterized by:
 Lytic bone lesions
 Plasma cell accumulation in the bone marrow, and
 The presence of monoclonal protein in the serum and urine
 98% of cases occur over the age of 40 with a peak incidence in
the seventh decade

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LABORATORY FINDING IN MULTIPLE MYELOMA

 In 98% of patients monoclonal protein occurs in the serum or urine

or both
 The serum paraprotein is IgG in two-thirds
 IgA in one-third
 Rare IgM or IgD or mixed cases
 Normal serum immunoglobulins (IgG, IgA and IgM) are
depressed
 The urine contains Bence-Jones protein in two-thirds of cases
 The bone marrow shows increased plasma cells often with
abnormal forms – ‘myeloma cells’
 Immunological testing shows these cells to be monoclonal B
cells
64
 Express the same immunoglobulin heavy and light chains as
the serum monoclonal protein
LABORATORY FINDING IN MULTIPLE MYELOMA
CONT’D

 There is usually a normochromic, normocytic or macrocytic

anemia
 Rouleaux formation is marked in most cases

 Neutropenia and thrombocytopenia occur in advanced disease

 Abnormal plasma cells appear in the blood film in 15% of

patients
 Leuco-erythroblastic changes are occasionally seen

 High ESR

 Serum calcium elevation occurs in 45% of patients

65
LABORATORY FINDING IN MULTIPLE MYELOMA
CONT’D
 The blood urea is raised above 14mmol/l and serum creatinine
raised in 20% of cases
 Proteinaceous deposits from heavy Bence-Jones proteinuria,
hypercalcaemia, uric acid, amyloid and pyelonephritis may all
contribute to renal failure
 A low serum album occurs with advance disease

 Serum β2-microglobulin (the light chain of the HLA class 1

antigens) is a useful indicator of prognosis

 It partly reflects renal function
 Levels less than 4mg/l imply a relatively good prognosis

66
MYELOPROLIFERATIVE DISORDERS
 A group of conditions characterized by clonal proliferation of one
or more hemopoietic components in the bone marrow and, in
many cases, the liver and spleen
 The MPNs are interrelated clonal hematopoietic stem cell
disorders characterized by excessive proliferation of one or more
mature myeloid cell lines, for example, granulocytes,
erythrocytes, megakaryocytes, or mast cells
 The discovery of mutations in crucial genes distinguishes MPNs
from other neoplasms
 Molecular analysis is now incorporated into the diagnosis workup
of MPNs.
 the JAK2, Janus kinase 2 (JAK2V617F mutation)

 This discovery allowed for refinement of the classification of 67

MPNs
MYELOPROLIFERATIVE DISORDERS

 MPNs are divided into

 CML
 Polycythemia vera (PV)
 Essential thrombocythemia
 Myelofibrosis
 MYELOPROLIFERATIVE DISORDERS

 All of the MPNs involve dysregulation at the multipotent

hematopoietic stem cell (CD34), with one or more of the following

shared features:

1. Cytogenetic abnormalities
2. Overproduction of one or more types of blood cells with dominance of a

transformed clone

3. Hypercellular marrow or marrow fibrosis

4. Thrombotic and/or hemorrhagic bleeding

5. Extramedullary hematopoiesis

6. Transformation to acute leukemia

 POLYCYTHEMIA VERA (PV)
 Also referred to as erythrocytosis
 Refers to a pattern of blood cell changes that includes:
 An increase in hemoglobin above 17.5g/dl in adult males and
15.5g/dl in females
 An accompanying rise in red cell count (above 6.0 x 1012/l in
males and 5.5x1012/l in females)
 Hematocrit (above 55% in males and 47% in females)
 The increase in red cell volume is caused by endogenous
myeloproliferation
 The stem cell origin of the defect is shown in many patients by
an over-production of granulocytes and platelets as well as of red
cells
 This is a disease of older subjects with an equal sex incidence 70
 LABORATORY FINDINGS IN PV

 The hemoglobin, hematocrit and red cell count are increased

 A neutrophil leucocytosis is seen in over half of the patients, and
some have increased circulating basophils
 A raised platelet count is present in about half of the patients

 The neutrophil alkaline phosphatase score is usually increased

above normal

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 LABORATORY FINDINGS IN PV CONT’D

 The bone marrow is hypercellular with prominent megakaryocytes

 Best assessed by a trephine biopsy
 Clonal cytogenetic abnormalities may occur, but there is no
single characteristic change
 Blood viscosity is increased

 Plasma urate is often increased

 Circulating erythroid progenitors are increased and grow in vitro

independently of added erythropoietin

72
 ESSENTIAL THROMBOCYTHEMIA
 Megakaryocyte proliferation and overproduction of platelets is the
dominant feature of this condition
 There is sustained increase in platelet count above normal
(400x109/l)
 Recurrent hemorrhage and thrombosis are the principal clinical
features
 Splenic enlargement is frequent in the early phase but splenic
atrophy due to platelets blocking the splenic mirocirculation is
seen in some patients
 There may be anemia due to:

 Iron deficiency from chronic gastrointestinal or uterine

hemorrhage
73
 The marrow disorder itself
LABORATORY FINDINGS IN ESSENTIAL THROMBOCYTHEMIA
 Abnormal large platelets and megakaryocyte fragments may be
seen in the blood film
 The bone marrow is similar to that in PV

 Platelet function tests are consistently abnormal

74
 MYELOFIBROSIS
 There is the gradual replacement of the bone marrow by
connective tissue
 A prime feature is extramedullary hematopoieis

 Patients will typically have an enlarged spleen and liver

 Typically affects patients more than 50 years old

Laboratory findings in myelofibrosis

 Anemia is usual but a normal or increased hemoglobin level may
be found in some patients
 The white cell and platelet counts are frequently high at the time
of presentation
 Later in the disease leucopenia and thrombocytopenia are 75
common
LABORATORY FINDINGS IN MYELOFIBROSIS CONT’D

 A leuco-erythroblastic blood film is found

 The red cells show characteristic ‘tear-drop’ poikilocytes
 Bone marrow is usually unobtainable by aspiration

 Trephine biopsy may show a hypercellular marrow with an

increase in reticulin-fibre pattern
 High serum urate, LDH and hydroxybutyrate dehydrogenase levels
reflect the increased but largely ineffective turnover of hemopoietic
cells
 Transformation to acute myeloid leukemia occurs in 10-20% of
patients

76
 OUT OF 15%
1. Describes heme synthesis steps?
2. Describes 3 Hemoglobin Measurement method with its
principles ?
3. Describes morphologic classifications of anemia with some
examples?
4. Discus composition, funcion, properties and formations of
blood?
5. Describes each stage of WBC, RBC, and platelet formations

77