Aplastic Anemia - Margolis Flashcards
Broadly, what is aplastic anemia? What are the two major types?
A disease caused by too few hematopoietic progenitor cells, which can lead to cytopenias of all hematopoietic lineages. (Note: **SAA **= Severe Aplastic Anemia)
Two major types: Inherited and Acquired.
What leads to Acquired SAA? What are some specific triggers?
- An inciting event leads to autoimmune destruction of blood progenitor cells
- Triggers:
- Viral Infection: CMV, EBV, HHV-6, Parvovirus, Hepatitis viruses
- Possibly some medications? (Not sure if this would be autoimmune)
- Possibly radiation exposure? (Not sure if this would be autoimmune)
What is a common clinical symptom of aplastic anemia?
A history of jaundice
In detail, what are the Camitta Criteria for Severity of Aplastic Anemia?
- Marked Pancytopenia
- At least 2 of 3 of the following findings in peripheral blood:
- PMN < 500/ul
- Platelets < 20x103/ul
- Reticulocytes < 20x103/ul (corrected retic < 1%)
- Marrow findings:
- Marked hypocellularity
- Less than 65% of residual marrow cells being non-hematopoietic (I assume this is to rule out an invasive proliferation of other cells as the cause?)
- Marked hypocellularity
- At least 2 of 3 of the following findings in peripheral blood:
There are several well-recognized inherited marrow failure syndromes.
Can you name 8 specific diseases?
[Other than a few questions later in this deck - it is likely more important to just recognize these names instead of knowing them in detail.]
- Amegakaryocytic Thrombocytopenia
- Diamond-Blackfan Anemia
- Dyskeratosis Congenita
- Fanconi Anemia
- Pearson Syndrome
- Severe Congenital Neutropenia
- Schwachman-Diamond Syndrome
- Thrombocytopenia Absent Radii
- aka TAR, literally present with a lack of radius bone in forearm
Name three types of treatment for SAA.
- Bone Marrow Transplant
- Intensive Immunosuppression
- Thrombopoietin receptor agonists
- Eltrombopag
Name three types of bone marrow transplant options for SAA.
- Bone Marrow Transplant
- Matched Sibling
- Unrelated Donor, HLA-matched
- Double Cord BMT
- Two umbilical cords worth of HSCs is generally enough to sucessfully repopulate the bone marrow target
Name five immunosuppressive drugs useful in treating SAA.
Intensive Immunosuppression:
- Anti-thymocyte globulin (ATG)
- Cyclosporine A (CsA)
- Prednisone
- Alemtuzumab
- Cyclophosphamide
- Improper maintenence and protection of telomeres can result in marrow failure, as well as what other diseases?
- What is the classic bone marrow disease due to telomere dysfunction?
- Liver & Lung fibrosis (& cirrhosis) , due to aberrant tissue repair & regeneration
- Dyskeratosis Congenita
The average telomere length in normal blood leukocytes decreases with what physiological process?
Aging!
- Name two specific genes that lead to telomerase-related aplastic anemia when mutated.
- What is seen in the telomeres of pts with mutations in this gene?
- TERT - Telomerase Reverse Transcriptase
- TERC - Telomerase RNA Component (telomerase is a ribonucleoprotein!)
- Significantly shorter telomeres than a normal person
How does short vs. normal telomere length correspond with:
- Primary therapeutic response to ATG
- Risk of relapse
- Risk of clonal evolution (dysplasia-promoting mutations)
- Unrelated to ATG response
- Short telomeres = 2x risk of relapse
- Short telomeres = 5-6x risk of clonal evolution (e.g. MDS, AML)
- How are telomerase deficiencies screened for?
- How can telomerase deficiencies be treated?
- Telomere length of leukocytes
- Treatments:
- Avoidance of regenerative stress (smoke, EtOH, etc.)
- Chemotherapy (?)
- Sex hormones (they can modulate TERT)
Your patient presents with pancytopenia. Other than an inherited or acquired aplastic anemia, what else is on your differential?
- MDS
- Leukemia
- Autoimmune disease (that is not attacking the HSCs)
- Nutritional Deficiency
- HLH
Because it was discussed here again…
What is HLH and how is it caused?
HLH is due to uncontrolled T-cell and histiocyte activation. The condition is considered an emergency as **rapidly fatal cytokine storms **are possible. It can be inherited or acquired secondary to EBV, autoimmune disease, etc.
