Hematology Week 2: Failure of Bone Marrow Flashcards
(71 cards)
1
Q
Bone Marrow failure causes
A
Can be congenital or acquired
2
Q
Constitutional Aplastic Anemia examples
4 listed
A
- Fanconi Anemia
- Shwachman-Diamon Syndrome
- Dyskeratosis congenita
- Diamond-Blackfan Syndrome (red-cell aplasia)
3
Q
Acquired Bone Marrow Failure examples
2 listed
A
Idiopathic aplastic anemia
Paroxysmal nocturnal hemoglobinuria (PNH)
4
Q
BM failure vs Aplastic Anemia
A
not equal terms
aplastic anemia is a form of BM failure
5
Q
Criteria for Aplastic anemia
A
- Cytopenia
- Hypocellular Marrow
6
Q
Cellularity to age
A
age 80 = 20% cellularity
7
Q
Causes of Acquired Aplastic Anemia
6 listed
A
Idiopathic - majority of cases
8
Q
Idiopathic aplastic anemia Etiology
A
- Immune-mediated process underlying idiopathic aplastic anemia pathogenesis
- oligoclonally expanded cytotoxic T cells induce apoptosis of hematopoietic progenitors (Tregs significantly reduced, increased Thelp cells) indicative of antigen driven process
- Suggestive HLA class-I drive autoimmunity in Aplastic Anemia
9
Q
Idiopathic Aplastic Anemia clinical Features
4 listed
A
- Thrombocytopenia is a prominent feature
- Small PNH clone detected
- High TPO level
- Benefit from immunosuppressive therapy
10
Q
Pancytopenia
A
- very empty
- not enough RBCs
- Not enough Platelets
- Not enough Neutrophils
11
Q
Management of Aplastic Anemia
5 main
A
- need to rule out folate and B12 deficiency
- gastric bypass can resect where vitamins are absorbed
12
Q
Treatment of Idiopathic Aplastic Anemia
A
HSCT is curative
13
Q
Prognosis of Idiopathic Aplastic Anemia
A
50-80% 5 year survival
14
Q
If a sibling is not available for HSCT then Idiopathic Aplastic Anemia is treated with?
A
Immunosuppressive Therapy
- Horse ATG
15
Q
Horse ATG
A
in conjunction with prednisone and cyclosporine
16
Q
Idiopathic Aplastic Anemia Horse ATG or
A
17
Q
Idiopathic Aplastic Anemia can evolve into
A
MDS/AML
18
Q
Idiopathic Aplastic Anemia Supportive Care
A
very open to infections and fungal infections so prophylactic bacterial and fungal medications
19
Q
Drugs of Drug-induced Aplastic Anemia
A
20
Q
Infection-induced Aplastic Anemia
4 listed
A
21
Q
Parvovirus B19 is commonly associated with
A
- Megaloblastic anemia
- 5% will have aplastic anemia
22
Q
Case study
A
erythroblasts with nuclear inclusions of Parvovirus B19
23
Q
Parvovirus B19 stain
A
24
Q
Parvovirus B19 can cause?
A
25
PNH AKA
Paroxysmal Nocturnal Hemoglobinuria (PNH)
26
PNH Etiology
4 listed
* Acquired disorder of HSC
* a defect in the phosphatidylinositol glycan complementation class A (PIGA) gene which leads to a defect in GPI synthesis
* GPI are membrane anchors for other proteins such as enzymes, receptors, complement regulators CD55 and CD59 and adhesion molecules
* When CD55 and CD59 are missing, complement activation will lead to MAC formation, thus intravascular hemolysis
27
GPI AKA
Glycophosphatidylinositol
28
PNH Treated with?
* Eculizumab
* the MAC will be blocked however C3 will accumulate and the RBCs will be preyed on by macrophages because of complement deposition
* before treatment Coombs test is negative but after treatment Coombs test is positive
29
PNH Progressivity
30
PNH Clinical Presentation
4 listed
31
Diagnosis of PNH
32
Ham Test
No longer used
33
PNH diagnosis test of choice
cells that dont have CD157 and FLAER are PNH clones because they dont not have the anchor proteins
34
RBC PNH Test
35
% of patients with PNH will progress to?
30% to Aplastic Anemia
36
PNH Unique Relationship to Aplastic Anemia
37
Only _________ Aplastic Anemia can develop a PNH clone
Acquired
38
Management of PNH
2 listed
eculizumab (targe on complement protein C5)
39
Constitutional BM failure Syndromes
Fanconi Anemia
Shwachman-Diamond Syndrome
Dyskeratosis Congenita
Diamond-Blackfan Syndrome (red cell aplasia)
More types
40
Fanconi Anemia
5 main
41
Fanconi Anemia common manifestation
Failure of BM production
42
Fanconi Anemia Age of onset
can be young but some patients remain undiagnosed until adulthood
43
Fanconi Anemia Test
Increased Chromosomal Breakage when induced with chemicals
44
Fanconi Anemia Genetics
* at least 16 FA gene mutations have been discovered
* loss of function in DNA repair
45
FA HSC
* Impaired HSC pool
* progressive Attrition of HSCs
46
FA Diagnostic Test
Chromosomal breakage study
47
FA physical Manifestations
* short stature
* abnormal internal organ formation (kidney, urinary, heart, eyes, ears, etc..)
* malformed thumbs and or forearms
48
Dyskeratosis Congenita Etiology
shortened telomeres
49
Dyskeratosis Congenita Hereditary patterns
very diverse can be
* X-linked
* autosomal recessive
* autosomal dominant
50
Dyskeratosis Congenita Clinical Features
51
Dyskeratosis Congenita % developing malignancies
52
Dyskeratosis Congenita BM failure
occurs by 20 years in 80% of patients
53
Dyskeratosis Congenita mucocutaneous abnormalities
often present in early childhood before 10 years
54
Diagnosis of Dyskeratosis Congenita
* very difficult to diagnose
* no single test can definitively diagnose
Mucocutaneous changes and family history become very important
55
Shwachman-Diamond Syndrome
56
Shwachman-Diamond Syndrome Age of onset
Infancy with exocrine pancreatic insufficiency and progressive bone marrow failure
57
Shwachman-Diamond Syndrome Clinical presentations
* Exocrine pancreatic insufficiency
* progressive bone marrow failure
* Neutropenia is the most common presentation
* BM failure progresses to complete in 25% of patients and to MDS/AML in 5%-33% of patients
58
Shwachman-Diamond Syndrome Genetics
Shwachman-Bodian-Diamond Syndrome gene (SBDS) on chromosome 7
59
Shwachman-Diamond Syndrome Pathogenesis
* unknown
* mutations may affect RNA processing or ribosomes
60
Diamond-Blackfan Anemia Genetics
* Mutations of Ribosomal genes (RPS19, RPL5, RPL11, RPL35A, and others)
61
Diamond-Blackfan Anemia Clinical Presentations
* Thumb malformation
* craniofacial abnormalities
* Macrocytic anemia
* Paucity of erythroid precursors in the BM (pure red cell aplasia)
62
Diamond-Blackfan Anemia Increased risks of
Developing acute leukemia
63
Diamond-Blackfan Anemia pictures
erythroid lineage is missing
64
Next Generation Sequencing
65
Fanconi Anemia Clinical Management
5 listed
* HSCT - curative option
* Colony stimulating factors for support
* androgens - mechanism is unclear
* monitor for solid organ malignancies
* Gene therapy TNF-Alpha inhibitors are currently being investigated
66
Dyskeratosis Congenita Clinical Management
* HSCT Curative option
* Androgen therapy - modulates TERT gene expression and slows telomerase attrition
67
Shwachman-Diamond Syndrome Clinical Management
* Hematologic abnormalities no treated unless severe
* Transfusion as necessary
* G-CSF/prophylactic antibiotics for severe neutropenia
* HSCT for severe pancytopenia or progression to MDS/AML
* Monitor CBC q3-6 months and BM 1-3 years
* pancreatic enzyme replacement
68
Diamond-Blackfan Anemia Clinical Management
* Corticosteroids
* Transfusion/iron chelation
* HSCT
* Remission is possible (reason is unknown)
69
BM Failure Summary
70
BM Failure Summary
71
BM Failure Summary
