Myeloproliferative disorders Clonal haematopoeitic disorders Proliferation of one of myeloid...

Myeloproliferative disordersClonal haematopoeitic disordersProliferation of one of myeloid lineagesGranulocyticErythroidMegakaryocyticRelatively normal maturation

Myeloproliferative disordersWHO ClassificationChronic Myeloid leukemia ( CML )Polycythemia Vera ( PV )Essential Thrombocythemia ( ET )Myelofibrosis ( agnogenic myeloid metaplasia )

Bone marrow stem cellClonal abnormalityEssentialthrombocytosis(ET)Polycythaemia rubra vera(PRV)MyelofibrosisAMLChronic myeloid leukemia70%10%10%30%

Polycythemia vera

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

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 .

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

Clinical featuresPlethoraPersistent leukocytosisPersistent thrombocytosisSplenomegalyGeneralized pruritus (after bathing)Unusual thrombosis (e.g., Budd-Chiari syndrome)Erythromelalgia (acral dysesthesia and erythema)

Clinical featuresHypertentionGoutLeukaemic transformationMyelofibrosis

Increased Hb female > 16.5 g / dL male > 18 g /dL

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

Treatment

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

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

InvestigationsET is a diagnosis of exclusionRule out other causes of elevated platelet count

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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