Pancytopenia Flashcards
Define pancytopenia
A deficiency of blood cells of all lineages
Name the two key causes of pancytopenia
Reduced production
Increased destruction
What are the causes of reduced production?
Bone marrow failure - inherited or acquired
What are the features of inherited bone marrow failure?
Impaired haemopoiesis
Congenital anomalies
Cancer pre-disposition
Why do inherited conditions cause marrow failure?
Defects in DNA repair/ribososmes/telomeres
Name an example of an inherited bone marrow failure disease
Faconi’s Anaemia
What are the clinical features of Faconi’s?
Short stature, skin pigment abnormalities (cafe au lait) radial ray abnormality, hypogenitalia, endocrinopathies, GI, cardio, renal defects
Describe Faconi’s haematological problems
Onset 7 years old
Unable to correct cross links in strands of DNA
Macrocytosis and thrombocytopenia
What does Faconi’s anaemia increase your risk of?
Marrow failure - 84% by 20 years old
Leukaemia - 52% by 40 years old
State the causes of primary acquired bone marrow failure
Idiopathic aplastic anaemia
Myelodysplastic syndrome
Acute leukaemia
Describe idiopathic aplastic anaemia
Auto-reaction T cells against stem cells and progenitors
INF gamma and TNF alpha produced
What will trephine biopsy of idiopathic aplastic anaemia show?
Loss of all haemopoietic cells and excess of fat spaces
What is myelodysplastic syndrome?
Disordered development and increased apoptosis of progenitor and mature cells leads to hyper cellular bone marrow
What can myelodysplastic syndrome progress to?
AML
What can help predict risk of AML in myelodysplastic syndrome?
Cytogenetic/chromosome abnormalities
How does acute leukaemia cause pancytopenia?
Proliferation of leukaemia stem cells that fail to mature/differentiate prevents normal haemopoietic development by altering the niche
State the causes of secondary acquired marrow failure
Drug induced - hypo cellular B12/folate deficiency - hyper cellular Infiltrative Viral Storage disease
What drugs can cause marrow failure?
Chemotherapy Azathioprine Chloramphenicol Alcohol Methotrexate
What causes increased marrow destruction?
Hypersplenism
What are the features of hypersplenism?
Splenomegaly, reduced circulation of blood cells and compensatory increase in cellularity of bone marrow
What causes hypersplenism?
Congestion - portal hypertension
Systemic - rheumatoid arthritis
Haematological - splenic lymphoma
What is meant by splenic pooling?
Spleen red cell mass increases
Red cells transit is much slower
Platelet pool increases
What are the clinical features of pancytopenia?
Anaemia
Neutropenia
Thrombocytopenia
How is pancytopenia investigated?
FBC, blood film
Additional - B12/folate, LFT, virology, autoantibodies
Bone marrow examination
Specialised - cytogenetics
How is pancytopenia treated?
Supportive - transfusions/antibiotics
Specific to cause
How is primary pancytopenia treated?
Malignancy - chemo
Congenital - bone marrow transplant
Aplastic anaemia - immunosuppression or transplant
How is secondary pancytopenia treated?
Drugs - stop and consider antidote
Treat infection
Replace B12/folate
What is the antidote to methotrexate?
Folic acid
How is hypersplenism treated?
Treat cause
Consider splenectomy
