Aplastic Anemia Flashcards
Define Aplastic Anemia
is a disease caused by too few hematopoietic progenitor cells
leading to too few red blood cells, white blood
cells, and platelets
***Acquired Aplastic Anemia needs to be
differentiated from an inherited bone marrow
failure syndrome.
Aplasic Anemia BM is hyper or hypocellular?
Hypocellular
What are common triggers for aquired aplastic anemia?
• Trigger is usually not identified
• Check for CMV, EBV, HHV-6, Parvovirus, Hepatitis
viruses
• History of jaundice
• Medication history
• Exposures
In aquired Severe AA, inciting event leads to an ______
destruction of blood progenitor cells
immune mediated
What is the Camita Criteria (broad definition) for SAA
Marked pancytopenia
MARROW: marked hypocellularity with less
than 65%of residual marrow cells beingnon
hematopoietic.
In Camita Criteria, we need to have 2 of the 3 following cytopenias, what are my cutoff numbers?
PMN
PLATELETS
RETICULOCYTES
PMN < 500/ul
PLATELETS < 20,000/ul
RETICULOCYTES < 20,000/ul (corrected retic< 1%)
what is a medication that historically caused aplastic anemia?
chlorophenocol
What 5 tx are available for aplastic anemia?
- Matched Sibling BMT
- Intensive Immune Suppression with ATG/CSA/Prednisone
- Unrelated donor BMT
- Alternative, Alternative Donor BMT
- Eltrombopag
What intenstive immune suprresion drug can we use in AA?
ATG/CSA/Prednisone
–along with alemtuxumab or cyclophosphamide
repeat sequences at the ends of chromosomes,
which are protective chromosomal material.
telomeres
Mutations in the genes that maintain and protect telomeres cause human disease including
marrow failure, liver fibrosis
and lung fibrosis.
classic disease of telomere biology.
• Dyskeratosis Congenita
What studies do we do to test telomere length?
FISh, Flow, southern blot, qPCR
What is a common mutation seen in aplastic anemia paients
TERT mutation ; for telelomere length
Telomeres and AA
- Telomere length____ to primary response to ATG!
- Short telomere length____ risk of relapse.
- Short telomeres increase risk of clonal evolution ___
fold.
unrelated
doubles
5-6
TELOMERE SHORTENING
2 explanations
TERT, TERC repair mutations== telomere erosion
Enviornment; immunity, toxins, infections == aberrant repair (pulmonary issues ) OR stem cell loss (BM fail)
What clues are in pt hisotry and clincial findings for telomere disease?
hematology-pulmonary-hepatic diseases linked in pedigrees subtle nail, skin, mucous membrane findings
What screening can we do for pt suspected of telomere defect?
What is our prognosis based on?
telomere length of leukocytes for diagnosis
stem cell transplant donors
Prognosis:
evolution of AA to MDS/AML
transplant outcomes
Tx for patient wth TERT mutation
Treatment
avoidance of regenerative stress (smoke, alcohol, etc.)
chemotherapy sensitivity
sex hormones for TERT modulation
Case w/ 4 yo w/ low blood counts for almost a year requiring intermittenet plats and RBC transfusions, BM shows moderate cellularity
ANC >500
HgB = 8-9
Plats = 15-30k
weird toenails
Dx:
• Acquired Severe Aplastic Anemia
• Inherited Marrow Failure Syndrome
– Fanconi Anemia
– Dyskeratosis Congenita
– Schwachman-Diamond Syndrome
• MDS
• Leukemia
• Autoimmune Disease
• Nutritional Deficiencies
What should we include in DDx in patient with pancytopenia?
HLH~ it’s very severe and key to catch early
How can we get HLH?
Primary or acquired pancytopenia
– Familial form due to uncontrolled T-cell and histiocyte activation, usually triggered by a stimulus
such as infection
– Acquired form due to infection (EBV, others), autoimmune disease, etc.
List of having “5+” of the following in HLH, but there is one really important consideration in that list, what is it?
Cytopenias in 2+ cell lines
– Leukoplakia, Lacy pigmentation, Abnormal finger
and toe nails,
– Telomere Length; Gene Sequence.
Dyskeratosis Congenita: inherited BM failure
Fanconi Anemia is inherited BM failure:
___ without physical stigmata
so must do diagnostic/functional___ test to look
for chromosome breakage.
40%
DEB
– If DEB test abnormal, genetic testing to classify defect
Inherited BM failure syndrome:
•Schwachman-Diamond Syndrome
-_____defect.
______pancreatic deficiency and neutropenia.
SBDS gene
Exocrine
Screening tests for Schwachman-Diamond Syndrome?
– Isoamylase and Trypsinogen are easy screening tests.
– Genetic Testing commercially available.
Inherited BM failure:
Congenital Amegakaryocytic Thrombocytopenia
____ defect.
Profound________ even at birth.
– Genetic testing commercially available.
MPL gene
thrombocytopenia
