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MYELOPROLIFERATIVE
DISORDERS
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CHRONIC MYELOPROLIFERATIVE
DISORDERS (MPD)
1. Polycythemia vera
2. Chronic myeloid leukaemia
3. Essential thrombocythemia
4. Idiopathic myelofibrosis
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CHRONIC MYELOPROLIFERATIVE
DISORDERS (MPD)
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ERYTHROCYTOSIS (Classification)
(1)
I. Absolute erythrocytosis (Polycythemia):
A. Secondary erythrocytosis (abnormal increase of serum erythropoietin level)
1. Erythrocytosis secondary to decreased tissue oxygenation:
a) chronic lung diseases
b) cyanotic congenital heart diseases
c) high-altitude erythrocytosis (Monge disease)
d) hypoventilation syndromes (Sleep apnoe)
e) hemoglobin-oxygen dissociation abnormalities
- hemoglobinopathies associated with high oxygen affinity
- carboxyhemoglobin in „smoker’s polycythemia”
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ERYTHROCYTOSIS (Classification)
(2)
I. Absolute erythrocytosis (Polycythemia):
A. Secondary erythrocytosis (abnormal increase of serum erythropoietin level)
2. Secondary to aberrant erythropoietin production or response:
a) Erythropoietin-producting tumors: hepatoma, uterine leiomyoma,
cerebellar hemangioblastoma, ovarian carcinoma, pheochromocytoma
b) Renal diseases: renal cell carcinoma, kidney cysts and
hydronephrosis, renal transplantation.
c) Androgen abuse: adrenal cortical hypersecretion, exogenous androgens
B. Primery erythrocytosis
1. Polycythemia vera
2. Familial erythrocytosis
II. Relative erythrocytosis (pseudopolycythemia):
1. Hemoconcentration
2. Spurious polycythemia (Gaisboek syndrome) 5
POLYCYTHEMIA VERA (PV)
Patogenesis
PV is a clonal disorder involving the hematopoietic stem cells; it leads to an
autonomous proliferation of the erythroid, myeloid, and megakaryocytic cell
lines. Increased erythroid proliferation is usually more prominent than that of
the other cell lines and occurs independently of erythropoietin levels (which are
usually very low in PV)
Epidemiology
The incidence rate of PV is approximately 2 per 100.000 population.
PV is slightly more prevalent in males with male/female ratio ranging from 1,2
to 2:1. Median age at diagnosis was 60 years in men and 62 years in women.
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POLYCYTHEMIA VERA
symptoms
1. Erythrocytosis and hyperviscosity, leading to impaired oxygen delivery:
• Poor CNS circulation: headaches, dizziness, vertigo, tinnitus and visual
disturbances
• Poor coronary circulation: angina pectoris
• Peripheral circulation intermittent claudication
2. Venous thrombosis or thromboembolism
3. Hemorrhage: epistaxis, gingival bleeding, ecchymoses, gastrointestinal
bleeding
4. Abdominal pain secondary to poptic ulcer
5. Early satiety due to splenomegaly
6. Pruritus is secondary to increased histamine release from the basophils and
mast cells
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POLYCYTHEMIA VERA
physical examination
1. Splenomegaly – is present in 75% of patients at the time of
diagnosis.
2. Hepatomegaly - is present in approximately 30% of patients at
the time of diagnosis.
3. Hypertension
4. On examination of the eye grounds, the vessels may be
engorged, tortuous, and irregular in diameter; the veins may be
dark purple.( fundus policythaemicus)
• Facial plethora
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DIAGNOSTIC CRITERIA FOR POLYCYTHEMIA
VERA
(Polycythemia Vera Study Group 75)
CATEGORY A
1. Total red cell mass
• male 36ml/kg
• female 32 ml/kg
2. Arterial oxygen saturation 92%
3. Splenomegaly
CATEGORY B
1. Thrombocytosis (platelet count > 400 G/l)
2. Leukocytosis (white cell count > 12 G/l, no fever or infection)
3. Increased leukocyte alkaline phosphatase (score> 100 )
4. Serum vitamin B12> 900 pg/ml or vitamin B12 binding capacity >2200 pg/ml
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POLYCYTHEMIA VERA -prognosis
• Untreated patients– the median survival ranges from 1-3 years
• Patients treated with phlebotomy or/and hydroxyurea
- median survival is 13,9 years
• Patients treated with 32P
- median survival is 11,8 years
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MYELOFIBROSIS
• The incidence of Myelofibrosis is about 0,5/100.000. The median
age at diagnosis was approximately 65 years.
• Common complaints: fatigue, weight loss, night sweats, bone pain,
abdominal pain, fever
• Physical findings: splenomegaly (often giant), hepatomegaly(in
about 50% of patients), symptoms of anaemia and
thrombocytopenia
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MYELOFIBROSIS
- laboratory findings (1)
• Anemia - Hb<10g/dL in 60% of patients
• Leukocytosis with counts generally below 50G/L(in about 50%), leukopenia
(in about 25% at the time of diagnosis)
• thrombocytosis in 50% at the time of diagnosis, with disease progression
thrombocytopenia becomes common
• eosinophilia and basophilia may be present
• retikulocytosis
• LAP score is usually elevaatedd
• Increased level of lactate dehydrogenase
• uric acid level is increased in most patients
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MYELOFIBROSIS
- laboratory findings(2)
• Peripheral blood smear:anisocytosis and poikilocytosis with the
presence of teardrop-shaped and nucleated red cells, immature
neutrophils but myeloblasts not always
• Aspiration of bone marrow is usually ansuccessful (dry tap).
Smears from successful aspirates usually show neutrophilic and
megakaryocytic hyperplasia
• Trephine biopsy often shows a hypercellular marrow with increased
reticulin fibers and variable collagen deposition . Increased numbers of
megakaryocytes are frequently seen.
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MYELOFIBROSIS
- diagnosis (Polycythemia Vera Study Group criteria)
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MYELOFIBROSIS - therapy 1
1. Androgens(oxymetholone 2-4mg/kg) in anemia from decreased red cell
production -overall response is about 40%
2. Cortykosteroids(prednisone 1mg/kg) in anemia with shortened red cell life-span-
response in 25-50% of patients
3. Hydroksyurea (15- 20mg/kg) for the control of leukocytosis, thrombocytosis, or
organomegaly
4. Allopurinol-to prevent hyperuricaemia
5. Vit. D3-analogues(1,25-dihydroxycholecalciferol-1ug/d (?)
6. Transfusions of packed red cells for anemia or platelets for thrombocytopenia
with bleeding
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MYELOFIBROSIS - therapy 2
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MYELOFIBROSIS
- prognosis
- a median survival of 3,5 to 5,5 years
- the principal causes of death are infections,
thrombohemorrhagic events, heart failure, and
leukemic transformation
- leukemic transformation occurs in
approximately 20% of patients during first 10
years
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ESSENTIAL THROMBOCYTHEMIA
(ET)
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clinical pictureESSENTIAL
THROMBOCYTHEMIA
1. Thrombotic complications (intermittent or permanent
occlusion of small blood vessels)
• transient cerebral and ocular ischemic episodes that may
progress to infarction
• peripheral arterial occlusive disease associated with
„erythromelalgia”(intermittent, painful errythema and
cyanosis of the fingers and toes
2. Hemorrhagic complications - bleeding after surgery and
spontaneus upper gastrointestinal bleeding (the hemorrhagic
tendency is worsened if nonsteroidal anti-inflammatory
agent are administered
3. Splenomegaly - 20-50% patients
4. Hepatomegaly - rarely 22
ESSENTIAL THROMBOCYTHEMIA
laboratory findings
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ESSENTIAL THROMBOCYTHEMIA
(UPDATED DIAGNOSTIC CRITERIA)
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ESSENTIAL THROMBOCYTHEMIA
-THERAPY
1. No treatment- asymptomatic( without thrombotic and bleeding
complications), young (< 60 r.ż.) patients with platelet count<1000G/L
2. Cytoreductive therapy – patients with platelet count>1000 G/L, especially
for these with previous thrombotic or bleeding problems
- hydroxyurea at doses 15-30mg/kg,, to maintein platelet count
between 400-600 G/l
3. Anti-aggregating therapy: Aspirin 75-150mg/d dipyridamol for older
patients and/or with a cardiovascular risk
4. Anagrelide (Agrylin)- drug that produces selective platelet cytoreduction,
and it also inhibits platelet activation doses from 0,5mg every 6 hours,
to max. 10 mg/d )
5. Interferon-: 3 million units/d s.c.
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