Bone Marrow Failure Flashcards
aplastic anemia - overview
*failure or destruction of pluripotent hematopoietic stem cell
*results in a lack of ALL cell precursors, aka a pancytopenia
*can be congenital, acquired, or idiopathic
*categorized into: moderate, severe, and very severe
causes of congenital aplastic anemia
*fanconi anemia (pancytopenia, congenital malformations)
causes of acquired aplastic anemia
*direct stem cell destruction:
-large doses of radiation or chemo
-meds!
-viral infections
-immune disorders
commonly - it is idiopathic (unknown cause)
idiopathic aplastic anemia
*unknown cause
*think the mechanism is immune-mediated
*drug, virus, or other unknown antigen leads to lymphocyte activation, leading to inappropriate destruction of the pluripotent stem cell
bone marrow appearance in aplastic anemia
*EMPTY!
CBC values in aplastic anemia
*PANCYTOPENIA (everything is low)
-leukopenia
-neutropenia
-anemia
-thrombocytopenia
aplastic anemia - treatment
*withdraw potentially offending agents
*supportive care (antibiotics, transfusions of pRBCs and platelets)
*immunosuppressive regimens
*allogeneic bone marrow transplant
paroxysmal nocturnal hemoglobinuria (PNH) - pathophysiology
*defect in the PIG A gene → increased complement-mediated intravascular hemolysis, especially at night
-normal RBCs are protected from complement attack by a shield of terminal complement inhibitors (CD55 and CD59)
-PNH patients have a defect in the PIG A gene that normally encodes for GPI-anchored proteins
-no anchor leads to 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
paroxysmal nocturnal hemoglobinuria (PNH) - pathophysiology [simplified]
*complement-mediated intravascular hemolysis occurs due to an acquired PIG A mutation
*PIG A mutation -> impaired GPI anchor synthesis for DAF/CD55 and MIRL/CD59, which normally protect RBC membrane from complement
paroxysmal nocturnal hemoglobinuria (PNH) - clinical course
*initially causes a hemolytic anemia (intracorpuscular, intravascular hemolysis)
*over time, patients develop pancytopenia
-progresses to aplastic anemia
-b/c ALL blood cells are GPI-deficient
paroxysmal nocturnal hemoglobinuria (PNH) - natural history
*patients die of: infection, hemorrhage, thrombosis, or renal failure
*progression to myelodysplastic syndrome
*progression to acute myelogenous leukemia (AML)
paroxysmal nocturnal hemoglobinuria (PNH) - treatment
*block complement with eculizumab: monoclonal antibody that targets the terminal complement protein C5
myelodysplastic syndromes (MDS) - bone marrow
*HYPERCELLULAR with abnormal cells
*bone marrow blasts < 20%
myelodysplastic syndromes (MDS) - overview
*stem cell disorders involving INEFFECTIVE HEMATOPOIESIS
*cells do not progress through the normal stages of maturation
myelodysplastic syndromes (MDS) - peripheral blood
cytopenias (b/c there are not enough mature blood cells)
myelodysplastic syndromes (MDS) - clinical presentation
*recurrent infections
*fatigue, pallor
*bleeding
*usually do NOT have splenomegaly [contrast to myeloproliferative disorders]
myelodysplastic syndromes (MDS) - diagnosis
2 ways to diagnose (patients only need to meet 1 of these criteria):
- hypercellular marrow & cytopenias with NORMAL number of myeloblasts (5% or less) and DYSPLASTIC cells
- hypercellular marrow & cytopenias with INCREASED number of myeloblasts (6-19% blasts) with or without dysplastic cells
2 biggest risk factors from developing AML from myelodysplastic syndromes (MDS)
- increasing age
- prognostic score (IPSS score - specifically, the % of blasts that the patient has in their bone marrow)
MDS 5q- syndrome
*cytogenetics: 5q- (part of the long arm of chromosome 5 is missing)
*clinical course tends to be relatively more benign
*overall more responsive to certain treatment
myelodysplastic syndromes (MDS) - treatment
*supportive care:
-antibiotics, transfusions
-growth factors: EPO, GCSF
-iron chelators (bind iron which gets excreted in urine and bile)
*chemo (gentle, outpatient)
*monitor for transformation to AML
