1.5 Red cell disorders 2: aplastic anaemia, myelodysplastic syndrome Flashcards
Define aplasia
No tissue
Define Dysplasia
Bad tissue
Define hyperplasia
More tissue than normal
Define hypoplastic
Less tissue than normal
define pancytopenia
reduction in all cell types (red, white and platelets)
What are the possible causes of bone marrow aplasia?
Genetic: Fanconi anaemia, dyskeratosis congenita
Drugs: antibiotics, anti-inflammatory, anti-convulsants, anti-thyroid, anti-cancer, anti-diabetics, antidepressants
Chemicals: benzene, nitrogen mustard
Radiation
Infection: non-A, non-B, non-C viral hepatitis
Immune in 70-80% cases
define aplastic anaemia
Pancytopenia resulting from aplasia of the bone marrow
What antigen is over represented in aplastic anaemia?
HLA-DR2
What are the clinical features of aplastic anaemia?
Anaemia: tiredness, lethargy, dyspnoea, reduced exercise tolerance, cardiac failure
Thrombocytopenia: bleeding or bruising
Neutropenia: cutaneous and deep-seated infections, opportunistic infections
What are the clinical features of aplastic anaemia?
Anaemia: tiredness, lethargy, dyspnoea, reduced exercise tolerance, cardiac failure
Thrombocytopenia: bleeding or bruising
Neutropenia: cutaneous and deep-seated infections, opportunistic infections
What tests do you need to do for suspected aplastic anaemia?
- FBC and reticulocyte count
- Blood film examination
- HbF% in children
- Bone marrow aspirate, cytogenetics
- Peripheral blood chromosomal breakage to exclude Fanconi anaemia
- Flow cytometry for GPI-anchored proteins
- Vitamin B12 and folate
- LFT (hepatits)
- Viral: hepatitis, EBV, HIV
- ANti-nuclear antibody and anti-dnDNA
- Chest x-ray (infections and pneumonia)
- Abdominal US and echo
- Peripheral blood gene mutation analysis for dyskeratosis congenital
What tests do you need to do for suspected aplastic anaemia?
- FBC and reticulocyte count
- Blood film examination
- HbF% in children
- Bone marrow aspirate, cytogenetics
- Peripheral blood chromosomal breakage to exclude Fanconi anaemia
- Flow cytometry for GPI-anchored proteins
- Vitamin B12 and folate
- LFT (hepatits)
- Viral: hepatitis, EBV, HIV
- ANti-nuclear antibody and anti-dnDNA
- Chest x-ray (infections and pneumonia)
- Abdominal US and echo
- Peripheral blood gene mutation analysis for dyskeratosis congenital
What is the initial treatment for aplastic anaemia?
Transfusion of red cells and platelets
Treatment of neutropenic sepsis and shock
Prevent infections
Long term IV line if needed
What are the non transplant options for aplastic anaemia?
Immunosuppressive therapy with rabbit-ATG, cyclosporin and steroids to knock out T cells
Oxymethalone
What are the complications of allografts?
Graft vs. host disease graft failure/rejection Immunosuppression Opportunistic infection second malignancies Infertility
Define myelodysplastic syndrome
A heterogenous group of clonal disorders of haemopoietic stem cells leading to ineffective haematopoiesis
What are the causes of myelodysplastic syndrome?
Prior chemotherapy
Complication of IAA
Any cause of leukaemia
What is the pathophysiology of myelodysplastic syndrome?
Acduired gene mutations in multi potent stem cells which leads to the blockage of maturation, development and/or differentiation
What are the clinical features of myelodysplastic syndrome?
Those of bone marrow failure (same as AA)
- Anaemia, thrombocytopenia, neutropenia
What are the laboratory findings of myelodysplastic syndrome?
Cytopenia
Macrocytosis
RC: basophilic stippling, dimorphism, Nucleated RBC, Shape abnormalities
Myeloid morphology: pseudo-Pelger-Huet anomaly, hypergranulaton, blasts
Platelets: giant and agranular
Raised reticulocyte and LDH
What is the pathophysiology of myelodysplastic syndrome?
Acquired gene mutations in multi potent stem cells which leads to the blockage of maturation, development and/or differentiation
What are the laboratory findings of myelodysplastic syndrome?
Cytopenia
Macrocytosis
RC: basophilic stippling, dimorphism, Nucleated RBC, Shape abnormalities
Myeloid morphology: pseudo-Pelger-Huet anomaly, hypergranulaton, blasts
Platelets: giant and agranular
Raised reticulocyte and LDH
Marrow: ring spiderblasts, iron granules
What will flow cytometry show in myelodysplastic syndrome?
CD34+ blast count (blasts will be an indication of leukaemia)
what are the cytogenetics of myelodysplastic syndrome
5q-, 7q- mutated SF3B1
