Flashcards in Chapter 20: Aplastic Anemia and Bone Marrow Failure Deck (29):
What is pancytopenia?
A reduction in the blood cell count of all major cell lines.
What is aplastic anemia?
Anemia caused by aplasia of the bone marrow. Classified as primary (congenital or acquired) and secondary.
What is the pathogenesis of aplastic anemia?
(1) a reduction in the number of hematopoietic pluripotential stem cells.
(2) A fault of the remaining stem cells
(3) An immune reaction against stem cells.
What are the congenital aplastic anemias?
(1) Fanconi's anemia (AR)
(2) Dyskeratosis congenita (XL)
What causes Fanconi's anemia?
Fanconi's anemia is caused by a mutation in the FAND1 gene which operates in DNA repair much like BRCA1. Cells in FA show abnormal chromosome breakages.
What diagnostic test can be used for FA?
Genetic analysis and Diepoxybutane test (DEB).
What is dyskeratosis congenita?
A mutation in the DKC1 or TERC genes both involved in maintenance of telomere length. causes nail/skin atrophy,
What is the usual age or presentation for Fanconi's anemia?
5-10 years old.
What secondary disease condition sometimes develops from Fanconi's anemia?
AML in 10% of cases.
What is the most common type of aplastic anemia?
Idiopathic acquired aplastic anemia
What is idiopathic acquired aplastic anemia?
An immune reaction targeted at hematopoietic stem cells destroys the bone marrow. Oligoclonal CTL populations secreteing INF-gamma and TNF are often involved.
How is idiopathic aplastic anemia treated?
(1) antilymphocyte globulin (ALG)
What are causes of secondary aplastic anemia?
(2) Antimetabolites and mitotic inhibitors (temporary)(methotrexate, daunorubicin)
(3) Alkylating agents (busulfan)(chronic aplasia)
Aplastic anemia may be the presenting symptom of which other diseases?
What are the clinical features of Aplastic anemia?
(2) Neutropenia (recurrent infections)
(3) Thrombocytopenia (bruising and bleeding)
What are the laboratory findings of aplastic anemia?
(1) Normocytic/chromic anemia
(2) low retic count for degree of anemia
(3) WBC below 1.5/L
(5) Bone marrow 75% fat with mostly lymphocytes and plasma cells.
How is aplastic anemia differentiated from other causes of pancytopenia?
Cytogenetic analysis is used to diagnose aplastic anemia.
What general measures are used to treat aplastic anemia?
(1) The cause is removed if possible
(2) Supportive care with blood transfusions (Blood must be irradiated to prevent GVHD)
(3) Antifibrinolytic agents (tranexamic acid) may be used to counter thrombocytopenia.
What specific treatments are used for Aplastic anemia?
(1) ATG or ALG (effective in 50-60% of patients)(given with corticosteroids)
(2) Ciclosporin (effective in 80% with ALG)
(3) Androgens (oxymetholone)(marked side effects)
(5) G-CSF provides only minimal improvement.
What disorders might aplastic anemia transform into?
(2) acute leukemia
What is Diamond-Blackfan syndrome?
Congenital (AR) red cell aplasia. Ribosomal protein mutation is thought to be the cause. Associated with other somatic disorders (face and heart)
What is the cause of acquired red cell aplasia?
(3) Thymoma, lymphoma, CML
(4) Anti-erythropoietin antibodies
What are the treatments for Red cell aplasia?
(2) MABs (rituximab, Campath)
What infectious agent is linked with red cell aplasia?
Parvovirus B19 can cause transient RBC aplasia in disorders in patients with reduced red cell survival.
What is Schwachman-Diamond syndrome?
Autosomal recessive syndrome with variable cytopenia. Exocrine pancreatic dysfunction, skeletal abnormalities, hepatic impairment, short stature.
What are Congenital dyserythropoietic anemias?
A group of anemias characterized by ineffective erythropoiesis and multi-nucleated erythroblasts.
What are the findings of CDAs?
(1) low retic count
(3) possible iron overload
(4) first noted in infancy or childhood
What is the differential diagnosis for pancytopenia?
(1) increased destruction
(3) Decreased production