Aplastic Anemia

Question 1

Define Aplastic Anemia

Answer 1

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.

Question 2

Aplasic Anemia BM is hyper or hypocellular?

Answer 2

Hypocellular

Question 3

What are common triggers for aquired aplastic anemia?

Answer 3

• Trigger is usually not identified
• Check for CMV, EBV, HHV-6, Parvovirus, Hepatitis
viruses
• History of jaundice
• Medication history
• Exposures

Question 4

In aquired Severe AA, inciting event leads to an ______
destruction of blood progenitor cells

Answer 4

immune mediated

Question 5

What is the Camita Criteria (broad definition) for SAA

Answer 5

Marked pancytopenia

MARROW: marked hypocellularity with less
than 65%of residual marrow cells beingnon
hematopoietic.

Question 6

In Camita Criteria, we need to have 2 of the 3 following cytopenias, what are my cutoff numbers?

 PMN
 PLATELETS
 RETICULOCYTES

Answer 6

 PMN < 500/ul
 PLATELETS < 20,000/ul
 RETICULOCYTES < 20,000/ul (corrected retic< 1%)

Question 7

what is a medication that historically caused aplastic anemia?

Answer 7

chlorophenocol

Question 8

What 5 tx are available for aplastic anemia?

Answer 8

• Matched Sibling BMT
• Intensive Immune Suppression with ATG/CSA/Prednisone
• Unrelated donor BMT
• Alternative, Alternative Donor BMT
• Eltrombopag

Question 9

What intenstive immune suprresion drug can we use in AA?

Answer 9

ATG/CSA/Prednisone

–along with alemtuxumab or cyclophosphamide

Question 10

repeat sequences at the ends of chromosomes,
which are protective chromosomal material.

Answer 10

telomeres

Question 11

Mutations in the genes that maintain and protect telomeres cause human disease including

Answer 11

marrow failure, liver fibrosis
and lung fibrosis.

Question 12

classic disease of telomere biology.

Answer 12

• Dyskeratosis Congenita

Question 13

What studies do we do to test telomere length?

Answer 13

FISh, Flow, southern blot, qPCR

Question 14

What is a common mutation seen in aplastic anemia paients

Answer 14

TERT mutation ; for telelomere length

Question 16

Telomeres and AA

• Telomere length____ to primary response to ATG!
• Short telomere length____ risk of relapse.
• Short telomeres increase risk of clonal evolution ___

fold.

Answer 16

unrelated

doubles

5-6

Question 17

TELOMERE SHORTENING

2 explanations

Answer 17

TERT, TERC repair mutations== telomere erosion

Enviornment; immunity, toxins, infections == aberrant repair (pulmonary issues ) OR stem cell loss (BM fail)

Question 18

What clues are in pt hisotry and clincial findings for telomere disease?

Answer 18

hematology-pulmonary-hepatic diseases linked in pedigrees subtle nail, skin, mucous membrane findings

Question 19

What screening can we do for pt suspected of telomere defect?

What is our prognosis based on?

Answer 19

telomere length of leukocytes for diagnosis
stem cell transplant donors

Prognosis:
evolution of AA to MDS/AML
transplant outcomes

Question 20

Tx for patient wth TERT mutation

Answer 20

Treatment
avoidance of regenerative stress (smoke, alcohol, etc.)
chemotherapy sensitivity
sex hormones for TERT modulation

Question 21

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:

Answer 21

• Acquired Severe Aplastic Anemia
• Inherited Marrow Failure Syndrome
– Fanconi Anemia
– Dyskeratosis Congenita
– Schwachman-Diamond Syndrome
• MDS
• Leukemia
• Autoimmune Disease
• Nutritional Deficiencies

Question 22

What should we include in DDx in patient with pancytopenia?

Answer 22

HLH~ it’s very severe and key to catch early

Question 23

How can we get HLH?

Answer 23

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.

Question 25

List of having “5+” of the following in HLH, but there is one really important consideration in that list, what is it?

Answer 25

Cytopenias in 2+ cell lines

Question 26

– Leukoplakia, Lacy pigmentation, Abnormal finger
and toe nails,
– Telomere Length; Gene Sequence.

Answer 26

Dyskeratosis Congenita: inherited BM failure

Question 27

Fanconi Anemia is inherited BM failure:

___ without physical stigmata
so must do diagnostic/functional___ test to look
for chromosome breakage.

Answer 27

40%

DEB

– If DEB test abnormal, genetic testing to classify defect

Question 28

Inherited BM failure syndrome:

•Schwachman-Diamond Syndrome

-_____defect.

______pancreatic deficiency and neutropenia.

Answer 28

SBDS gene

Exocrine

Question 29

Screening tests for Schwachman-Diamond Syndrome?

Answer 29

– Isoamylase and Trypsinogen are easy screening tests.
– Genetic Testing commercially available.

Question 30

Inherited BM failure:

Congenital Amegakaryocytic Thrombocytopenia

____ defect.

Profound________ even at birth.
– Genetic testing commercially available.

Answer 30

MPL gene

thrombocytopenia