myeloproliferative disorders clonal haematopoeitic disorders proliferation of one of myeloid...
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Myeloproliferative disordersClonal haematopoeitic disordersProliferation of one of myeloid lineagesGranulocyticErythroidMegakaryocyticRelatively normal maturation
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Myeloproliferative disordersWHO ClassificationChronic Myeloid leukemia ( CML )Polycythemia Vera ( PV )Essential Thrombocythemia ( ET )Myelofibrosis ( agnogenic myeloid metaplasia )
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Bone marrow stem cellClonal abnormalityEssentialthrombocytosis(ET)Polycythaemia rubra vera(PRV)MyelofibrosisAMLChronic myeloid leukemia70%10%10%30%
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Polycythemia vera
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Causes of secondary polycythemiaERYTHROPOIETIN (EPO)-MEDIATEDHypoxia-DrivenChronic lung diseaseRight-to-left cardiopulmonary vascular shuntsHigh-altitude habitatChronic carbon monoxide exposure (e.g., smoking)Hypoventilation syndromes including sleep apneaRenal artery stenosis or an equivalent renal pathologyHypoxia-Independent (Pathologic EPO Production)Malignant tumorsHepatocellular carcinomaRenal cell cancerCerebellar hemangioblastomaNonmalignant conditionsUterine leiomyomasRenal cystsPostrenal transplantationAdrenal tumorsEPO RECEPTORMEDIATEDActivating mutation of the erythropoietin receptorDRUG-ASSOCIATEDEPO DopingTreatment with Androgen Preparations
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POLYCYTHEMIA VERAChronic, clonal myeloproliferative disorder characterized by an absolute increase in number of RBCs2-3 / 100000Median age at presentation: 55-60M/F: 0.8:1.2 50 % of pateints associated with concurrent leucocytosis and / thrombocytosis .
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POLYCYTHEMIA VERAJAK2 MutationJAK/STAT: cellular proliferation and cell survivaldeficiency in mice at embryonic stage is lethal due to the absence of definitive erythropoiesisAbnormal signaling in PV through JAK2 was first proposed in 2004 a single nucleotide JAK2 somatic mutation (JAK2V617F mutation) in the majority of PV patients
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Clinical featuresPlethoraPersistent leukocytosisPersistent thrombocytosisSplenomegalyGeneralized pruritus (after bathing)Unusual thrombosis (e.g., Budd-Chiari syndrome)Erythromelalgia (acral dysesthesia and erythema)
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Clinical featuresHypertentionGoutLeukaemic transformationMyelofibrosis
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Increased Hb female > 16.5 g / dL male > 18 g /dL
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Diagnostic CriteriaA1Raised red cell massA2Normal O2 sats and EPOA3Palpable spleenA4No BCR-ABL fusionB1Thrombocytosis >400 x 109/LB2Neutrophilia >10 x 109/LB3Radiological splenomegalyB4Endogenous erythroid colonies
A1+A2+either another A or two B establishes PV
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Treatment
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The mainstay of therapy in PV remains phlebotomy to keep the hematocrit below 45 percent in men and 42 percent in women
Additional hydroxyurea in high-risk pts for thrombosis (age over 70, prior thrombosis, platelet count >1,500,000/microL, presence of cardiovascular risk factors)
Aspirin (75-100 mg/d) if no CI
IFNa (3mu three times per week) in patients with refractory pruritus, pregnancy
Anagrelide (0.5 mg qds/d) is used mainly to manage thrombocytosis in patients refractory to other treatments.
Allopurinol
- Essential Thrombocythaemia (ET)Clonal MPDPersistent elevation of Plt >600 x109/lPoorly understoodLack of positive diagnostic criteria2.5 cases/100000M:F 2:1Median age at diagnosis: 60, however 20% cases
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Clinical FeaturesVasomotorHeadache Lightheadedness Syncope Erythromelalgia (burning pain of the hands or feet associated with erythema and warmth) Transient visual disturbances (eg, amaurosis fujax, ocular migraine) Thrombosis and HaemorrhageTransformation
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InvestigationsET is a diagnosis of exclusionRule out other causes of elevated platelet count
- Diagnostic criteria for ETPlatelet count >600 x 109/L for at least 2 months Megakaryocytic hyperplasia on bone marrow aspiration and biopsy No cause for reactive thrombocytosisAbsence of the Philadelphia chromosomeNormal red blood cell (RBC) mass or a HCT
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Treatment A symptomatic --- no therapy just aspirin .Interferon-alpha ,anagrelide can also reduce the platelets count .Hydroxyurea --- only if these agents are not effective or tolerable .Aminocaproic acid ---- if bleeding associated with thrombocytosis .
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