Bone Marrow Failure Flashcards
What two categories does bone marrow failure divide into?
Constitutional aplastic anemia, Acquired BM failure (Acquired aplastic anemia)
What is aplastic anemia?
A form of bone marrow failure, BM failed to produce enough hematopoietic cells in the absence of neoplasia or fribrosis, markedly hypocellular marrow, often used to imply ideopathic aplastic anemia - slide 4
What is the most common type of BM failure?
Aplastic anemia
What is the mechanims of idiopathic aplastic anemia?
Immune mediated, cytoxic T cells induce apoptosis of hematopoietic progenitors (reg Tcell are significantlly reduced), increased helper T cells)
What are the tests for idiopathic anemia?
Thrombocytopenia, Pancytopenia, Small PNH clone, high TPO
What is the clinical management for idiopathic anemia?
HSCT (transplant), Immunosuppresive Therapy (Horse ATG+cyclosporine)
What is the mechanims of Parovirus B19?
Selectively replicates in erythroid precursors in BM causing transient or permanent suppression of ertyropoiesis in immunocompromised patients
What happens to patients with Parovirus B19?
These patients develop chronic anemia, pure red cell aplasia, or less often neutropenia and thrombocytopenia
What is the mechanims of Paroxysmal nocturnal hemoglubinuria?
Due to acquired mutation in PIGA gene- missing of anchoring protein GPI leads to loss of proteins that attach to GPI including CD55 and CD59, which protect the cells from complement activation and MAC formation
What are the clinical features of PNH?
Associated with aplastic anemia, Triad - Coomb’s negative hemoltyic anemia, pancytopenia, venous thrombosis, patients may report red or pink urin
How is PNH diagnosed?
Flow cytometry
What is the treatment for PNH?
Eculizumab (inhibits terminal complement formation - targert complement protein C5)
What is the mechanism of Fanconi Anemia?
Increased chromosomal breakage, mutated gene products lost their function in DNA repair
What are the findings for Fanconi Anemia?
Impaired HSC pool, short stature, café-au-lait spots, thumb/radial defects, abnormal organ formation
What is the diagnostic test for Fanconi Anemia?
Chromosomal breakage study
What is the treatment for Fanconi Anemia?
HSCT, G-CSF, Androgens: oxymethalone, monitor for solid organ malignancy, gene therapy for TNF-aplpha inhibitors
What is the mechanism for Dyskeratosis Congenita?
shortened telomeres
What are the clinical findings for Dyskeratosis Congenita?
Leukoplakia, Lacy pigmentation, Nail Dystrophy (present early early in childhood),
How is Dyskeratosis diagnosed?
Mucocuatneous changes, family history, no single test, identify shortened telomere
How does Shwachaman-Diamond Syndrome present?
SBDS genes , chromosome 7 - Presents in infancy with exocrine pancreatic insufficiency and progressive bone marrow failure
What is the presentation of Shwachman-Diamond Syndrome?
Neutropenia is the most commone presentation
What is the pathogenesis of Shwachaman-Bodian-Diamond syndrome?
Unknown, mutations may affect RNA processing or ribosme
What is the treatment of Schwachman-Diamon Syndrome?
Not treated unless severe cytopenias or MDS/AML, transfusion
What is the pathogenesis of Diamond-Blackfan anemia (DBA)?
Mutations in ribosomal genes
