Pancytopenia Flashcards
What is pancytopenia?
Pancytopenia is a deficiency of blood cells of all lineages
This is not a diagnosis, but reflects a diagnosis
What are the 2 main mechanisms of pancytopenia?
Reduced cell production
Increased cell destruction
What is the main cause of reduced cell production?
Bone marrow failure
What are the main forms of bone marrow failure?
Primary acquired bone marrow failure
Secondary acquired bone marrow failure
Inherited bone marrow failure
What are some causes of primary acquired bone marrow failure?
- Idiopathic aplastic anaemia
- Myelodysplastic syndromes
- Acute leukaemia
What is idiopathic aplastic anaemia?
Idiopathic aplastic anaemia is a condition in which auto-reactive T-cells produce IFN-y and TNF-a against haemopoietic stem cells and common myeloid progenitors
This prevents production of erythrocytes, platelets and granulocytes
What are myelodysplastic syndromes?
Myelodysplastic syndromes are clonal haemopoietic stem cell disorders characterised by dysplasia (Disordered development) or unique genetic abnormalities of the bone marrow
This involves increased apoptosis of progenitor and mature cells (Ineffective haemopoiesis)
What is a possible risk of myelodysplastic syndromes?
Evolution into AML
How can acute leukaemia cause pancytopenia?
Leukaemic stem cells can cause proliferation of abnormal cells (Blasts), which fail to differentiate or mature into normal cells
This also prevents normal haemopoietic stem cell/progenitor development by hijacking or altering the haemopoietic niche and marrow microenvironment (Pushes aside normal cells)
What are some causes of secondary acquired bone marrow failure?
- Drug induced
- B12/Folate deficiency (Nuclear maturation can affect all lineages)
- Infiltrative (Non-haemopoietic malignant infiltration, lymphoma)
- Viral (e.g. HIV)
- Storage diseases
What are some drugs that can cause secondary acquired bone marrow failure?
Chemotherapy
Alcohol
Azathioprine
Methotrexate
Chloramphenicol
What are inherited bone marrow failures?
These are disorders characterised by impaired haemopoiesis, congenital abnormalities and cancer predisposition
How do inherited bone marrow failures occur?
They arise due to defects in DNA repair, ribosomes and telomeres
What is an example of an inherited bone marrow failure?
Fanconi’s anaemia
What is Fanconi’s anaemia?
Fanconi’s anaemia is a rare inherited condition affecting the bone marrow, in which there is an inability to correct inter-strand cross-links in DNA (DNA damage)
What are some features of Fanconi’s anaemia?
- Short stature
- Skin pigmentation abnormalities
- Radial ray abnormalities
- Hypogenitilia
- Endocrinopathies
- GI defects
- Cardiovascular defects
- Renal defects
- Haematological defects
- Skeletal abnormalities
- Cafe au lait spots
What is the main cause of increased cell destruction in pancytopenia?
Hypersplenism
What are the 3 main cell defects in pancytopenia?
- Anaemia (RBCs)
- Neutropenia (Neutrophils)
- Thrombocytopenia (Platelets)
What is the main risk of neutropenia?
Neutropenic patients can contract both gram +ve and -ve bacteria, however, gram -ve bacteria can lead to life-threatening neutropenic sepsis within hours
Risk of cutaneous and invasive fungal infection
What are some investigations required in pancytopenia?
- History including family
- Clinical findings
- FBC and film
- B12/folate
- LFTs
- Virology
- Autoantibody tests
- Bone marrow examination
- Cytogenetics
What will be shown on bone marrow examination in pancytopenia?
- Hypocellular in aplastic anaemia
- Hypercellular in myelodysplastic syndromes, B12/folate deficiency, hypersplenism
What are some supportive treatment options used in pancytopenia?
- Red cell transfusions
- Platelet transfusions
- Neutrophil transfusions (not routine)
- Antibiotics prophylaxis and treatment (Antibacterial and anti-fungal)
How will pancytopenia caused by malignancy be managed?
Chemotherapy
How will pancytopenia caused by congenital disorders be managed?
Allogenic stem cell transplantation
How will pancytopenia caused by idiopathic aplastic anaemia be managed?
Immunosuppression
How will pancytopenia caused by myelodysplastic syndromes be managed?
Depends on risk of leukaemic transformation, EPO stimulating agents in low risk, demethylating agents or chemo in high risk
How will pancytopenia caused by drug reaction be managed?
STOP drug
How will pancytopenia caused by viral infection be managed?
Treatment e.g. HIV
How will pancytopenia caused by B12 or folate deficiency be managed?
B12 and folate supplementation
