What causes aplastic anemia?
Too few hematopoieic progenitor cells
What does Acquired Aplastic Anemia need to be differentiated from?
Inherited bone marrow failure syndrome
What causes the destruction of progenitors in bone marrow in SAA?
Assault by the T-cells
What symptoms are associated with AA?
· Epistaxis – Extended time
· Bacterial infections
What triggers are for acquired SAA?
· Usually not identified
· Check for CMV, EBV, HHV-6, Parvovirus, Hepatitis
· History of jaundice
· Medication history – Chloramphenicol
· Exposures (Radiation/Nuclear)
What is the Camitta Criteria?
Severe AA (SAA) “marked pancytopenia”
Peripheral Blood (2 of 3):
- < 500 PMN
- < 20,000 Platelets
- < 20,000
BM: 65% hypocellularity
How is AA treated?
Matched Sibling BM
Intensive Immune Suppression with ATG/CSA/Prednisone
Alternative, Alternative Donor BMT
- Halpo/Cord BMT; Double Cord BMT
Eltrombopag – TPO agonist, but also activates all erythroblasts
What are telomeres?
What is the significance of their length?
What do mutations of telomerase cause?
What happens without telomerase?
Repeat sequences at ends of chromosomes
Molecular mechanisms have evolved to maintain telomere
Mutations in telomerase can result in marrow failure, liver fibrosis, lung firbrosis
Without telomerase, somolescence
What is the classic disease of cancer biology?
What symptoms/findings are associated with Dyskeratosis Congenita?
What diagnostic parameters can be used to diagnose DC?
What is the treatment?
Leukoplakia, Lacy pigmentation, Abnormal finger and toe
Telomere length analysis is becoming a standard test
Genetic testing commercially available
Will need a transplant
What is Fanconi Anemia caused by?
What special test must be done for it and why?
How is it treated?
DNA repair defect in Fanconi Gene
40% without physical stigmata so must do diagnostic/functional DEB test to look for chromosome
If DEB test abnormal, genetic testing to classify
Will need a transplant
What is Schwachman-Diamond Syndrome?
What is it caused by?
What clinical findings are there?
What screening tests are there?
BM defect due to SBDS gene defect
Exocrine pancreatic deficiency and neutropenia
Isoamylase and trypsinogen are easily screening tests
What is Diamond-Blackfan Anemia?
What is severe congenital neutropenia?
Lack of PMNs congenitally