aplastic anemia & bone marrow failure states

Question 1

aplastic anemia

Answer 1

stem cell failure

Question 2

cause of congenital aplastic anemia:

Fanconi anemia

1. inheritance
2. presents between _____ with _____
3. most common complementation group
4. defect in

Answer 2

1. autosomal recessive disorder (1/300)
2. between 5-9 yrs of age with congenital malformations, abn. thumbs and cytopenia
3. FANCA
4. defect in DNA repair

Question 3

cause of congenital aplastic anemia:

Shachman-Diamond syndrome

1. inheritance
2. presents at birth with
3. increased risk of developing
4. unlike Fanconi, all affected patients have homozygous mutations in the same gene _____
5. the gene plays a regulatory role in _________ at the nucleolus and also interacts with the ______ causing abnormal mitoses

Answer 3

1. autosomal recessive disorder
2. presents at birth with exocrine pancreatic deficiency, skeletal abnormalities and bone marrow failure
3. SBDS
4. appears to play a regulatory role in ribosomal RNA metabolism at the nucleolus, and also interact with the mitotic spindle causing abn. mitoses

Question 4

cause of congenital aplastic anemia:

dyskeratosis cogenita

1. inheritance
2. what do we see
3. mutations in several different genes that affect
4. ________ is the enzyme complex responsible for maintaining the integrity of linear ends of chromosomes during DNA replication
5. what is the only cure?

Answer 4

1. heterogeneous disorder either x-linked, AD or AR
2. Ectodermal dysplasia, BM failure, cancer predisposition
3. affects telomerase function
4. telomerase
5. stem cell transplantation is the only cure

Question 5

cause of congenital aplastic anemia:

congenital amegakaryocytic thrombocytopenia

1. inheritance
2. presents in infancy with _______ and _______ on bone marrow biopsy
3. often associated with mutations in ____ the gene for the thrombopoietin receptos

Answer 5

1. autosomal dominant
2. presents in infancy with isolated thrombocytopenia and absent megakaryocytes on bone marrow biopsy
3. mutations in MPL

Question 6

cause of acquired aplastic anemia:

Answer 6

1. radiation
2. drugs
3. autoimmune disorders
4. lymphoid malignancy
5. pregnancy

Question 7

paroxysmal nocturnal hemoglobinuria (PNH):

1. acquired syndrome of
2. cause
3. among these proteins are CD55 and CD59, two proteins that
4. PNH cells are unusually sensitive to complement lysis, leading to episodes of ____ and progressive damage to the ____
5. high frequency of

Answer 7

1. acquired syndrome of hemolysis and BM failure
2. somatic mutation in PIG-A gene in HSC leads to decreased expression of GPI-anchor needed for several proteins expressed on the sruface of RBC
3. they are proteins that limit the action of activated complement
4. epsiodes of hemolysis and progressive damage to the HSC compartment
5. high frequency of thrombosis

Question 8

clinical classification of aplastic anemia

has what hallmark in all three stages

Answer 8

hypoplastic BM

Question 9

clinical classification of aplastic anemia three stages

Answer 9

1. non-severe aplastic anemia
2. severe aplastic anemia
3. very severe aplastic anemia

Question 10

difference between very severe aplastic anemia and severe aplastic anemia

Answer 10

very severe aplastic anemia has <200 neutrophils

Question 11

2 principal causes of aplastic anemia

Answer 11

1. immune-mediated stem cell suppression

2. stem cell damage or loss

Question 12

2 main approaches to aplastic anemia

Answer 12

1. immune supression

2. stem cell replacement by transplantation

Question 13

treatment of aplastic anemia with immune supression

1. associated immune involvement
2. immunosuppressive regimens can increase blood counts including
3. what are the mainstays of therapy in older patient who are not transplant candidates
4. response rates

Answer 13

1. pure red cell aplasia and thymoma
2. corticosteroids, anti-thymocyte globlin and cyclosporin A
3. transfusion and immunosuppression
4. response rates are good 40-70% but long-term remission or cure is generally not possible

Question 14

treatment of aplastic anemia in stem cell replacement

1. cure
2. what could be a problem
3. what is still needed
4. why is the current recommendation is to avoid RBC transfusion prior to transplant

Answer 14

1. cure is allogenic hematopoietic stem cell transplantation
2. graft rejection is a problem
3. conditioning radiation and chemotherapy is still needed
4. we are worried of alloimmunization