Myeloproliferative Neoplasms

Polycythemia Vera: What is the core pathophysiology?

Clonal myeloproliferative neoplasm with erythrocytosis independent of erythropoietin, driven by constitutively active JAK2 signaling.

Polycythemia Vera: What mutation is present in ~95–100% of patients?

JAK2 V617F mutation causing constitutive tyrosine kinase activation. »Val to Phenylalanine which constantly activates JAK2»causes constant erthrocytosis (JAK-2 normally needs EPO to bind receptor to get activated)

Polycythemia Vera: What are typical lab findings?

↑Hgb/Hct, ~60% have platelets >400K, ~40% have WBC >12K, hypercellular marrow with ↓M:E ratio (erythroid predominance).

Polycythemia Vera: What symptoms result from blood “congestion”?

Headache, visual changes, dizziness, paresthesias, facial plethora(redness).

Polycythemia Vera: What are hallmark complications?

Aquagenic pruritus, bleeding, thrombosis (MI, DVT, PE, CVA, Budd‑Chiari), splenomegaly, erythromelalgia(painful red palms)

Polycythemia Vera: What are the WHO diagnostic criteria?

Persistent polycythemia, secondary causes excluded, JAK2 positive, low EPO, marrow with erythroid + megakaryocytic proliferation and fibrosis.

Polycythemia Vera: What is the natural history?

↑Thrombotic risk with age/WBC count. Risk of transformation to myelofibrosis»AML

Polycythemia Vera: What is first‑line treatment?

Phlebotomy (goal Hct <45% men, <42% women), hydroxyurea, aspirin 81 mg.

Essential Thrombocythemia: What is the core pathophysiology?

Clonal disorder(cancer) with platelet production independent of thrombopoietin

Essential Thrombocythemia: What mutation is present in ~50–65%?

JAK2 mutation.

Essential Thrombocythemia: Diagnostic criteria?

Sustained platelets ≥450K, rule out secondary causes + CML, JAK2 may be positive, marrow shows megakaryocytic hyperplasia.

Essential Thrombocythemia: Typical blood counts?

↑Platelets, normal or mildly ↑WBC, normal hemoglobin.

Essential Thrombocythemia: Natural history?

Bleeding (abnormal platelet function), thrombosis (CVA, TIA, MI, priapism), splenomegaly, erythromelalgia, risk of progression to myelofibrosis or AML.

Essential Thrombocythemia: Treatment?

Hydroxyurea (dec hematopoesis) and aspirin(clot prophalaxis)

Chronic Eosinophilic Leukemia: What is the core pathophysiology?

Clonal disorder with excess circulating eosinophils; some respond with imatinib

Primary Myelofibrosis: What causes marrow fibrosis?

Abnormal megakaryocytes secrete cytokines → fibroblasts produce excess collagen → reticulin/collagen fibrosis.

Primary Myelofibrosis: What happens to marrow cellularity?

Starts hypercellular, becomes hypocellular

Primary Myelofibrosis: Clinical presentation?

Massive splenomegaly, hepatomegaly, extramedullary hematopoiesis (pleural/pericardial effusions, ascites, CNS involvement).

Primary Myelofibrosis: Blood smear findings?

Leukoerythroblastic picture: pseudo‑Pelger‑Huet cells, immature neutrophils, nucleated RBCs, giant platelets

Primary Myelofibrosis: Mutation + transformation risk?

~50% have JAK2 mutation; risk of transformation to AML

Primary Myelofibrosis: Treatment?

Palliative: hydroxyurea, splenectomy, JAK2 inhibitors (limited benefit), AML therapy if transformed