myeloproliferative syndromes

what are myeloproliferative disorders?
clonal expansions of multipotent hematopoietic progenitor cells, leading to overproduction of 1+ elements of blood, and they may become acute leukemias
what are the myeloproliferative disorders?
polycythemia vera, chronic myelogenous leukemia (CML), essential thrombosis/essential thrombocythemia (samething), and agnogenic myeloid metaplasia/myelofibrosis (same thing)
what is polycythemia vera?
a rare accumulation of red cells, granulocytes and platelets due to damaged progenitor cells. it occurs across all age groups there is no consistent genetic abnormality, but JAK2 abnormalities (valine to phenylalanine @ codon 617, regulates JH1 kinase, hypersensitivity to EPO)
what happens clinically with polycythemia vera?
initially asymptomatic, some splenomegaly, high hgb/hct, vertigo/tinnitus/headache/HTN/visual disturbances/bruising/epistaxis/GI bleed, thrombosis (high viscosity can lead to budd chiari syndrome), and pruritis (increased histamine release from baso/mast cells)
polcythemia vera is a dx of excusion against what secondary causes? what is an easy way to determine if there is a secondary cause?
hypoxia (pulmonary/cardiac disease, hemoglobinopathy – all lead to less O2), renal disease (renal tumor or natural EPO overproduction), EPO receptor abnormal, and EPO therapy. *high EPO levels should indicate that a secondary cause is responsible
what are the main ways of diagnosing polycythemia vera?
EPO level (low is likely +), red cell mass (chromium markers on RBCs reinjected, then blood volume is calculated), microcytic erythrocytosis, JAK2, and bone marrow (to rule out other MPD)
what are complications associated with polycythemia vera?
hyperviscosity, erythromelalgia (erythema, pain, warmth and digital infarcts <- more common in lower extremity)
how is polycythemia vera treated?
keep hgb <14 for males, <12 for females. phlebotomy can help induce an iron deficiency to decrease RBC production), chemo can reduce RBCs (very uncommon), and management of symptoms: antihistamines for histamine release from mast cells/basophils, xanthine oxidase/ACE inhibitors for hyperuricemia, and NSAIDs for erythromelalgia
what is AMM/myelofibrosis? are there cytokines involved? how do the blood vessels look?
excessive marrow fibrosis as a result of myeloid *stem cells clones – the disease is a result of the polyclonal bone marrow fibroblasts and T cell response. there are higher than normal level of various cytokines: TGF-B, PDGF, IL-1, EGF, bFGF, the tissue/fibroblast growth factors could contribute to typical endothelial proliferation and growth of blood vessels. bone marrow microvessel density increases 70%, neoangiogenesis in both medullary and extramedullary (liver and spleen b/c of lack of space) hematopoiesis is seen, and increased serum vascular endothelial growth factor levels are seen
how does myelofibrotic tissue look?
very few cells, a lot of scarring, dry tap if aspirate is attempted
what are the hallmarks of myelofibrosis?
marrow fibrosis, myeloid metaplasia, extramedullary hematopoiesis (liver, spleen, even skin), no specific genetic abnormality, 20% will transform to acute leukemia w/in 10 yrs, and median survival is 3-5 years
who gets myelofibrosis more commonly?
white men, esp ashkenazi jews – generally after 50
what are clinical features of myelofibrosis?
initially asymptomatic -> become more anemic, leukopenic as time progresses leading to: massive splenomegaly, leukoerythroblastic smear (immature messed up cells), red bumpy skin, and osteosclerosis w/bone pain
why don’t you want to remove the spleen in myelofibrosis?
that may be one of the last places actually making RBCs in these pts
what is a leukoerythroblastic smear?
nucleated red cells that should not be out in the periphery, often tennis racket shaped (squeezed by fibrosis)
how is myelofibrosis diagnosed?
first r/o CML, myelophthesis (tumor), leukemia, other MPD. then do a bone marrow bx = dry tap (should be)
what is the therapy for myelofibrosis?
treat symptoms (anemic, need transfusions, infected, antibx – may need GSF), hydroxyurea, chemo, thalidomide (angiogenesis inhibitor), BMT,
who does essential thrombocythemia occur to? how lethal is it?
mostly female, any age, it is relatively benign
what are clinical features of essential thrombocythenia
mostly asymptomatic, rare bleeding and clotting problems (problems w/bleeding if platelets are ineffective or clotting if there are too many). possibly erythromelalgia, migrane, transient ischemic attack (TIA). 50% JAK2 +
how is essential thrombocythenia diagnosed?
r/o iron deficiency (b/c platelet count will rise), inflammation, CML (people with CML tend to have high WBC counts with low LAP scores), bone marrow bx,
how is essential thrombocythenia treated?
anagrelide (works well, headache) or hydroxyurea
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