Lecture 22 Bone Marrow Failure Flashcards
Pancytopenia
- decrease of all 3 cell lines: RBC, WBC, Platelets
- can be fatal if untreated
- decr RBCs and Hgb causing anemia
- thrombocytopenia -> serious bleeding
- prolonged and severe neutropenia -> risk of life threatening bacterial and fungal infections
Mechanisms of BM Failure
- destruction of hematopoietic cells
- premature senescence and apoptosis due to stem cell mutations
- ineffective hematopoiesis
- disruption of BM microenvironment
- decreased produc’n of hematopoietic growth factors and hormones
- infiltration of marrow spaces by abnormal cells
Characteristic Features BM Failure
- peripheral blood pancytopenia
- decr’d retic count
- BM hypocellularity
- depletion of hematopoietic stem cells
Etiology BM Failure
Acquired aplastic anemia (80-85%) - idiopathic (70%): cause not known - secondary (10-15%): - dose dependent/predictable - idiosyncratic: not predictable, won't cause BM failure in some - viruses - miscellaneous conditions Inherited/congenital BM failure syndromes (15-20% of cases) - fanconi anemia - dyskeratosis congenita - Schwachman-Bodian-Diamond syndrome
BM Failure Pathophysiology
- quantitative and qualitative deficiency of hematopoietic stem cells
- EPO, TPO, CSF all elevated but not successful
- BM depletion may be due to:
- direct damage to stem cell DNA
- immune damage to stem cells from autoimmune T lymphs
- other unknown mechanisms
- drug, chemical, virus may alter self proteins
- telomeres abnormally short in 1/3 of aplastic anemias
Aplastic Anemias
Clinical Features:
- dry tap on BM aspirate
- symptoms from asymptomatic -> severe
- anemia, bleeding, fever from infections
Lab Findings:
- pancytopenia, initially one or two cell lines may be low
- peripheral blood:
i. neutrophils, monocytes and platelets decreased
ii. RBCs macrocytic or normocytic
iii. toxic granulation may be seen in infections
iv. RBC and platelet morphology normal
- serum iron and % transferrin saturation incr’d
- 1/3 develop paroxysmal nocturnal hemoglobinuria (PNH)
- BM severe hypocellularity
Toxic granulation
increased # and size of granules within the neutrophils
PNH
a leukemia like disease in which there is a stem cell defect causing RBCs to abnormally bind complement during sleep when the body’s pH falls
Treatment BM Failure
- remove causative agent
- transfusions:
- platelets < 10 x 10^9/L
- RBCs -> symptoms
- age of patient
- < 40 -> stem cell transplant (HLA matched sibling)
- > 40 or no siblings -> immunosuppressive therapy
- supportive therapies
- antibiotics/antifungals
Fanconi Aplastic Anemia (FA)
- autosomal recessive
- most common inherited aplastic anemia
- other congenital issues at birth:
- skeletal malformations
- abnormal skin pigmentations
- low birth rate
- developmental delay
- increased risk of solid tumor cancers and leukemias
FA Lab Findings
- apparent at 5-10 yrs
- pancytopenia, reitculocytopenia, hypocellular BM
- macrocytes
- thrombocytopenia
- Hgb F may be increased
- chromosomal studies is diagnostic
FA Treatment
- supportive (transfusions, cytokines)
- cure -> stem cell transplant from HLA-identical sibling
FA Prognosis
- death by age 20 common
- risk for acute myelogenous leukemia (AML), myelodysplastic syndrome (MDS), squamous cell cancers common
Dyskeratosis Congenita (DC)
- rare inherited BM failure
- mucocutaneous abnormalities BM failure, pancytopenia
- abnormal skin pigmentation dystrophic nails, oral leukoplakia (white patches)
- chromosomal abnormalities
- macrocytes, ^ HgbF
- treatment: BM transplant
Schwachman-Bodian-Diamond Syndrome (SBDS)
- inherited multisystem disorder
- pancreatic insufficiency and neutropenia are key differences from others
- pancreatic dysfunction causes malabsorption, ^ 72 hr fecal fat
- delayed bone maturation; 50% are short in stature
- chromosomal and cellular abnormalities
