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15 Cards in this Set
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Aplastic anemia overview
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Pleuripotent stem cell is damaged
Result is lack of ALL cell precursors – pancytopenia “Anemia” is misnomer |
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Aplastic anemia causes
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Congenital:
-Fanconi anemia (pancytopenia, congenital malformations) Acquired: (direct stem cell destruction) -Large doses of radiation -Large doses of chemotherapy -Medications! -Viral infections --Non-A, -B, -C hepatitis --HIV --EBV -Immune disorders --Systemic lupus erythematosis --Graft vs. host disease Idiopathic (most common cause): Think the mechanism is immune-mediated -(ie: autoimmune) -Immunosuppressive therapy improves counts -Graft vs. host disease can cause aplasia -Lymphocytes of AA patients can inhibit hematopoiesis of normal bone marrow Drug, virus, (unknown) antigen leads to lymphocyte activation which leads to inappropriate destruction of pleuripotent stem cell |
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Aplastic anemia CBC
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Pancytopenia
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Aplastic anemia treatment
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Withdraw potentially offending agents
Supportive care -Antibiotics, transfusions Immunosuppressive regimens Allogeneic bone marrow transplant |
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Paroxysmal nocturnal hemoglobinuria (PNH) misnomers
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It’s not paroxysmal
-Even in the absence of symptoms, destructive progression of hemolysis is ongoing It’s not nocturnal -Hemolysis in PNH is subtle and constant, 24 hours a day Hemoglobinuria is a less commonly seen complication -¾ patients present without hemoglobinuria |
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PNH overview
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Estimated 4,000 – 6,000 patients in U.S.
Diagnosed at all ages – Median age early 30’s 5 year mortality: 35% Progressive disease Quality of life diminished |
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PNH pathophysiology
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Normal red blood cells are protected from complement attack by a shield of terminal complement inhibitors
CD59 forms a defensive shield for RBCs protecting them from complement-mediated lysis PNH patients have a defect in the PIG A gene that encodes for the GPI-anchored proteins No anchor: no protection from complement-mediated lysis Without the gene to encode for the proteins that anchor the protective shield proteins, the RBCs get destroyed by the complement cascade: hemolysis |
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PNH effects
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PNH initially causes a hemolytic anemia
-Intracorpuscular, intravascular hemolysis Over time, patients develop pancytopenia -Progresses to aplastic anemia -Because all blood cells are GPI-deficient What do patients with PNH die of? -Infection -Hemorrhage (not enough platelets) -Thrombosis (platelets they do have are very activated) -Renal failure -Progression to myelodysplastic syndrome -Progression to acute myelogenous leukemia |
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PNH treatment
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Block complement
-Monoclonal antibody to C5 -Eculizumab (Soliris) |
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Myelodysplastic syndromes overview
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Ineffective hematopoiesis
Cells do not progress through the normal stages of maturation Bone marrow: hypercellular, with abnormal cells Peripheral blood: cytopenias |
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Myelodysplastic syndrome clinical presentation
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Recurrent infections
Fatigue, pallor Bleeding Usually don’t have splenomegaly (unlike myeloproliferative disorders) All of this is as a result of their cytopenias |
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Myelodysplastic syndrome diagnosis
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Bone marrow biopsy and aspirate
Look for dysplastic cells Look for an increased number of blasts -< 5% blasts: Normal ->20% blasts: Acute leukemia -6-19% blasts: MDS Also evaluate chromosomes (with cytogenetics and sometimes FISH) -Helps with prognosis |
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Myelodysplastic syndrome prognosis
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% Bonemarrow blasts
-as # increases, aggressiveness is greater # Mature blood cell lines impaired Cytogenetics Add up points Older and higher IPSS score correlate with lower median survival |
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MDS: 5q- syndrome
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Cytogenetics: 5q-
Clinical course tends to be relatively more benign Overall more responsive to certain treatments -Thalidomide -Lenalidomide |
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MDS: treatment
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Supportive care
-Antibiotics, transfusions -Growth factors: EPO, GCSF Iron chelators (Exjade [deferasirox]) -Binds iron which gets excreted in urine and bile Chemotherapy -Gentle, outpatient Monitor for transformation to AML -You will learn that outcomes are worse for patients with AML arising from MDS |