MPDs divided into two groups : ACUTE and CHRONIC

ACUTE : Acute non lymphocytic leukemia (ANLL)

CHRONIC : Chronic myelocytic leukemia

Polycythemia vera
Idiopathic myelofibrosis
Essential thrombosis
 Characterized by a hyper cellular
bone marrow with increased
quantities of one or more cellular
lineages in the peripheral blood
 The Clinical Variants of The CMPDs
may share, to varying extents :
1. Affects middle – aged and older groups
2. Asymptomatic onset
3. Panhyperplasia of bone marrow
4. Extra medullary hematopoesis
5. Fibroblast proliferation and reticulin / collagen formation in
bone marrow
6. Frequent transitions between these disorders, with
overlapping manifestation
7. Terminating in acute leukemia
8. Elevation of platelet count ; Giant or bizzare platelets, or both
9. Hemorrhagic and thrombotic complications
 OTHERS :

1. CYTOGENETIC ABNORMALITIES
2. ABNORMAL P53 genes
Apoptosis induced by the P53 ,
in the presence of altered or absent p53
apoptosis does not occur, resulting in
continued proliferation.
 RELATIONSHIP BETWEEN
THE VARIOUS MPDS

PV 15 – 20%
1 – 2%
1 – 2%
10 – 15%
ET AML IMF
2 – 5%
ALL
60 – 70% 25%
1 – 2% 5%
CML
 CHRONIC MPD

1. Polycythemia Vera
2. Chronic Myelogenous Leukemia
3. Idiopathic Myelofibrosis
4. Essential Thrombocytosis
 POLYCYTHEMIA VERA

PV is a hematopoietic stem cell disorder

predominantly characterized by
accelerated erythropoiesis, proliferation
of myeloid and megakaryocytic
elements of the bone marrow.
 ELEVATED HEMATOCRIT
 50%

Absolute Erythrocytosis Relative Erythrocytosis

(Increased RC Volume) (Normal RC Volume)

POLYCYTHEMIA VERA DEHYDRATION

SECONDARY ERYTHROCYTOSIS STRESS POLYCYTEMIA
(Gaisbock syndr.)
 PATHOGENESIS

• Abnormal Pluripotent Cell

Erythroid colonies grow independently
from EPO

EPI DEMIOLOGY

2 Cases per 100,000 population

Median age 60 years
 CLINICAL PICTURES
• Insidious onset
• Symptoms related to increased red cell volume or hyperviscocity
• Cerebral circulatory disturbances : headache, dizzy, vertigo,
visual phenomena
• Hemorrhage
• Thrombosis
• Splenomegaly, modest hepatomegaly
• Reddish purple color or the face, nose, ears, lips (PLETHORA)
• Itching
• Fever
• Gout
 LABORATORY FEATURES
• Elevation of RBC, HB, HT are the most
important findings
• HT > 58% in men > 52% in women
• RBC >5.9x1012/L in women
>6.6X1012/L in men
• Elevation of WBC is moderate
(12 – 25. 109/L)
• Thrombocytosis (450 – 1000 x 109 /L)
• O2 saturation normal
 PV Sec Eryth Relative Eryth

Splenomegaly + 75% – –

Hepatomegaly + 35% – –
Heart or lung – + –
Dis
Cyanosis – + ±
Red Cell Mass   Normal
WBC  80% Normal Normal
Platelet  50% normal Normal
B12  75% Normal Normal
O2 saturation Normal  Normal
 PV STUDY GROUP CRITERIA
• MAYOR CRITERIA
1. Elevated Red Cell Mass
2. Normal Arterial O2 Saturation
3. Splenomegaly
• MINOR CRITERIA
1. Leukocytosis
2. Thrombocytosis
3. Elevated Leukocyte Alkaline Phosphatase
4. Increased serum Vit. B12
 ALL from mayor
or elevated red cell mass + two minor criteria
• SECONDARY ERYTHROCYTOSIS
 COPD
 Cyanotic congenital heart disease
 Cirrhosis
 Pickwickian Syndrome
 High Altitude
 Smoking
• RELATIVE ERYTHROCYTOSIS
 Dehydration
 GAISBOCK’S Syndrome (Hypertensive,
Obese, smoking)
 TREATMENT

PHLEBOTOMY
CHEMOTHERAPY : Hydroxyurea,
Busulphan, 32p

PROGNOSIS

Survival rate 8 – 15 years

Thrombohemorrhagic Events : 40% of deaths
10 – 15% : Malignant Transformation to AML
 ESSENTIAL
THROMBOCYTOSIS
MAYOR CAUSES OF THROMBOCYTOSIS

1. CLONAL
- Essential (Primary) Thrombocytosis
- Polycythemia Vera
- Chronic Myelogenous Leukemia
- Myelofibrosis (Myeloid Metaplasia)
2. FAMILIAL
Autosomal Dominant
Cont.
3. REACTIVE (SECONDARY) THROMBOCYTOSIS
A. Transient Reactive Processes
- Acute Blood Loss
- Rebound
- Acute Infection, Inflammation
- Response to Exercise
B. Sustained Processes
- Iron Deficiency
- Post Splenectomy
- Malignancy
- Chronic Inflammatory and Infection Diseases
- Hemolytic Anemia
- Response to Drug (Vincristine, Epinephrine,
ATRA, Growth Factors)
 PATHOGENESIS

• Clonal : Multipotensial Hematopoietic

Cell
• Chromosome Abnormality (17)
• JAK2 Gene : A Tyrosine kinase for
signaling from cell membrane receptor
• Splenomegaly in 40%
• Complications 
BLEEDING OR
THROMBOSIS
 DIAGNOSTIC CRITERIA
1. Platelet > 600.000/mm3
2. Normal Red Cell Mass
♂ < 36 ml/kg
♀ < 32 ml/kg
3. Stainable iron in marrow or failure of iron trial
4. No Philadelphia Chromosome
5. Collagen fibrosis of marrow :
Absent or < 1/3 biopsy area without
splenomegaly nor leukoerythroblastic reaction
6. No known cause for reactive thrombocytosis
7. Megakaryocytes in clumps
 CLINICAL RISK OF
THROMBOHEMORRHAGIC
THROMBOSIS BLEEDING
INCREASED • Previous History Aspirin or
RISK NSAID
of Thrombosis
• Cardiovascular > 1.500.000
Risk Factors
Especially Smoking
• Age > 60
• Inadequate Control
of Thrombocytosis
 CLINICAL FEATURES
CLONAL
REACTIVE
THROMBOCYTOSIS
Splenomegaly 40% 
Platelet morphology Giant platelet Normal
Platelet function Often abnormal Normal

Thrombotic – Digital, cerebral, large

complications vessel arterial or venous No
thrombosis
 THERAPY
 CYTOREDUCTION
• HYDROXYUREA
• NON ALKYLATING MYELOSUPPRESIVE
AGENT
• ANAGRELIDE
• RECOMBINANT  - INTERFERON
 ANTIPLATELET
• ASPIRIN
 PROGNOSIS
• Terminates by converting to acute
leukemia, myelodysplasia or
myelofibrosis
• Better overall prognosis than other
MPDs
• 5 years survival : 80%
 IDIOPATHIC MYELOFIBROSIS
History: First reported in 1879 by Heuck
Synonyms : Agnogenic myeloid metaplasia
Myelosclerosis
Osteosclerosis
Chronic Erythroblastosis
Myelofibrosis with Myeloid Metaplasia (MMM)

 CHARACTERIZED BY :
Fibrosis of the marrow
Extramedullary hematopoesis
Leukoerythroblastosis and teardrops
 INCIDENCE AND ETIOLOGY

• Annual incidence is 0.6 per 100,000

Male to female ratio = 2 : 1
Age distribution : 50 – 70

• Etiology : Mayority is unknown

Exposure to radiation,
toxins
 PATHOGENESIS

• STEM - CELL DEFECT

Mutation of multipotensial stem-cell
Bone marrow fibrosis occur
secondary, non neoplastic process
• MARROW FIBROSIS :
Platelet derived growth factor 
fibroblast  collagen production 
myelofibrosis
 CLINICAL PICTURES
• Insidious, symptoms free for many years
• Splenomegaly, hepatomegaly
• Anemia
• 10% bleeding secondary to thrombocytopenia or
thrombocytosis
• Bone pain
• Hypermetabolism
• Gout
 LABORATORY FINDINGS

• Leukoerythroblastic
• Teardrop formation
50% WBC increased, 35% WBC
normal, 15% WBC below normal
• Platelet : normal, elevated or decreased
• Bone marrow aspiration : Dry – Tap
• Histologic : Reticulin, Fibroblast and
collagen increased
 DIFFERENTIAL DIAGNOSIS
• Must be distinguished from other disease of the
CMPDs, as well as differentiated from fibrosis
secondary to infiltratif disorders
• CML considered most frequently
• 15 – 20% patients PV undergo a transition to terminal
myelofibrosis with marked anemia, bone marrow
fibrosis and splenomegaly
• Secondary myelofibrosis : Metastatic carcinoma,
leukemia, granulomatous disorders (TBC,
Histoplasmosis, Sarcoidosis)
 TREATMENT

• TO IMPROVE QUALITY OF
LIFE
• PALLIATIVE
• TRANSFUSION
• STEROID
• ANDROGEN
• SPLENECTOMY
• ALLOPURINOL
 PROGNOSIS

• Median survival 5 years

• Cause of death : Hemorrhage,
infection
 CASE STUDY
• 60 Y O MAN ADMITTED WITH PAIN AND
SWELLING OF LEFT LIMB,2 DAYS EARLIER HE
CAME TO EMG WITH HEADACHE,BLURRED
VISION,TINNITUS AND PRURITUS ESPECIALLY
AFTER BATHING. He had been treated for gout for the
past 2 months
• Physical examination : flushed face,engorged retinal
veins,ecchymosis on the legs,splenomegaly,no
hepatomegaly
Lab : Hb 18.8 gr% WBC 20.300
RBC 7.53x10¹²/L
Platelet 870.000 Hct 58% O2 saturation 94%
Bone marrow:panhyperplasia and large
megakaryocyte,reticulin content slightly
increased
 comment
History and physical findings : presumptive
diagnosis of PV
Headache and blurred vision: hyperviscosity
As well as thrombotic episode. Plethora , engorged
retinal veins : blood vessels congestion
Generalized pruritus occurs in 30%
Phlebotomy and cytoreduction therapy must be
initiated