Pancytopaenia Flashcards
Define pancytopaenia?
Deficiency of blood cells of ALL lineages (but generally excluding lymphocytes)
Patient has anaemia + neutropaenia + thrombocytopaenia
It is not a diagnosis and does not always mean bone marrow failure
Lifespan of rbcs?
~120 days (longest life span of any blood cell)
Lifespan of neutrophils?
~7-8 hours
Cell turnover is very high, which is why the myeloid : erythroid ratio favours the myeloid compartment
2 broad causes of pancytopaenia?
Reduced production
OR
Increased destruction
Causes of reduced production in pancytopaenia?
Bone marrow failure:
• Inherited syndromes - arise due to defects in DNA repair / ribosomes; very rare
• Acquired (primary or secondary) - more common
Occurrence of Fanconi’s anaemia?
Very rare; median age of onset if 7 years of age
Short stature, skin pigment abnormalities (cafe au lait spots), radial ray abnormalities, hypogenitalia, endocrinopathies
GI, CV, renal, haematological defects
Cause of haematological abnormalities in Fanconi’s anaemia?
Unable to correct inter-strand cross-links (DNA damage)
Patients has a macrocytosis followed by a thrombocytopenia and then a neutropenia
Risk of bone marrow failure (aplasia) in Fanconi’s anaemia?
84% by the age of 20 years old (very high risk)
Risk of leukaemia in Fanconi’s anaemia?
52% by 40 years old (very high risk)
Evolution of Fanconi’s anaemia?
Patient starts with bone marrow failure, with no mutations
They sustain mutations, due to an inability to repair DNA, and eventually develop cancer
Reasons for acquired primary bone marrow failure (reduced production)?
No obvious cause; although there is usually a stem cell defect
There is an intrinsic marrow issue, i.e: problem with the cells in the bone marrow
Causes of an intrinsic marrow problem, i.e: acquired primary bone marrow failure?
Idiopathic aplastic anaemia - autoimmune attack against haemopoietic stem cell(s)
Myelodysplastic syndrome (MDS)
Acute leukaemia (WCC can be variable)
Pathogenesis of aplastic anaemia?
Auto-reactive T cells produce IFN-ᵞ and TNF-α, which result in death of the HSC, so there are no progenitors or mature cells
Bone marrow biopsy appearance of aplastic anaemia?
Normal cells are absent and replaced with fat
What is myelodysplastic syndrome?
Dysplastic cells create a HYPERCELLULAR marrow
There is increased apoptosis of progenitor and mature cells (ineffective haemopoiesis)
Risks assoc. with myelodysplastic syndrome?
Propensity for evolution into AML
Occurrence of myelodysplastic syndrome?
Relatively common >60 years old
Why can acute leukaemia cause pancytopaenia?
- Proliferation of ABNORMAL cells (blasts) from leukaemic stem cells (LSC)
- Failure to differentiate or mature into normal cells
- Prevent normal HSC development by altering the haemopoietic niche and marrow micro-environment
Causes of acquired secondary bone marrow failure?
EXAMS
Drug-induced, e.g: chemotherapy, CHLORAMPHENICOL (antibiotic), alcohol - cause aplasia
B12 / folate deficiency (NUCLEAR MATURATION CAN AFFECT ALL LINEAGES) - causes HYPERCELLULAR MARROW
Infiltrative, e.g: non-haemopoietic malignancy infiltration, lymphoma
Others:
• Viral, e.g: HIV
• Storage disease
Why does B12 / folate deficiency cause hypercellular marrow?
Hypoxia, due to the anaemia, triggers increased Epo production and the more primitive compartment of the bone marrow begins to expand
Causes of increased destruction resulting in pancytopaenia?
Hypersplenism:
• Increased splenic pool
• Increased destruction that exceeds bone marrow capacity, usually assoc. with significantly enlarged spleen
Any cause of splenomegaly can potentially cause hypersplenism
NOTE - splenic size alone may not always correlate with hypersplenism
Compare features of the normal spleen vs hypersplenism?
Normal spleen:
• Splenic red cell mass - 5%
• Red cell transit - fast
• Splenic platelet pool - 20-40%
Hypersplenism:
• Splenic red cell mass - 40%
• Red cell transit - slow
• Splenic platelet pool - 90%
Causes of hypersplenism?
Splenic congestion:
• Portal hypertension
• CCF
Systemic disease:
• RA (Felty’s)
Haematological disease:
• Spenic lymphoma
Summarise the causes of pancytopaenia?
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