Pancytopenia Flashcards
What is pancytopeenia?
A deficiency of blood cells of all lineages (generally excludes lymphocytes)
For steady state haemostasis, what must occur?
Cell production= cell destruction
What are the fundamental causes behind pancytopenia?
Reduced production or increased destruction
What are the causes of reduced production?
Bone marrow failure- Inherited syndromes, acquired: primary/secondary
What are the characteristics of inherited marrow failure syndromes?
Cancer pre-disposition
Impaired haemopoiesis
Congenital anomalies
Due to what do inherited marrow failure syndromes arise?
Defects in DNA repair/ribosomes
What are the clinical features of inherited marrow failure syndromes (very rare, e.g. Fanconi’s anaemia)?
Short stature Skin pigment abnormalities Radial ray abnormalities Hypogenitilia Endocrinopathies GI defects Cardiovascular Renal Haematological
What skeletal and skin abnormalities occur in inherited marrow failure syndromes?
Oligodactyly
Café au lait spots
What haematological abnormalities occur in inherited marrow failure syndromes?
Median age onset:7yo
Unable to correct inter-strand cross-links (DNA damage)
Macrocytosis followed by thrombocytopenia, then neutropenia
Bone marrow failure (aplasia) risk: 84% by 20 years
Leukaemia risk: 52% by 40 years
What are the causes of acquired primary bone marrow failure?
Aplastic anaemia: AI attack against haemopoietic stem cell
Myelodysplastic syndrome (MDS)
Acute leukaemia
What cytokines are involved in aplastic anaemia?
IFN gamma
TNF alpha
What occurs in myelodysplastic syndrome?
Dysplasia
Hypercellular marrow
Increased apopotosis of progenitor and mature cells (inefffective haemopoiesis)
Propensity for evolution into AML
Why can acute leukaemia cause pancytopenia?
Proliferation of ABNORMAL cells (blasts) from leukaemic stem cells (LSC)
Failure to differentiate or mature into normal cells
Prevent normal haemopoietic stem/progenitor (HSC) development by ‘hijacking’/altering the haemopoietic niche and marrow microenvironment
What can cause secondary bone marrow failure?
Drug induced [eg chemotherapy, chloramphenicol, alcohol] – causes aplasia
B12/folate deficiency (nuclear maturation can affect all lineages) (remember hypercellular)
Infiltrative- non-haemopoietic malignant infiltration, lymphoma
Misc.: Viral (eg HIV)/storage diseases
What does hypersplenism cause?
Increased splenic pool
Increased destruction that exceeds bone marrow capacity, usually associated with significantly enlarged spleen
What changes occur with the splenic pool in hypersplenism?
Increased splenic red cell mass (from 5% to 40%)
Red cell transit slowed
Splenic platelet pool increased (20-40% to 90%)
What are the causes of hypersplenism?
Splenic Congestion- Portal Hypertension, Congestive cardiac failure
Systemic diseases- Rheumatoid Arthritis (Felty’s)
Haematological diseases- Splenic lymphoma
What is the triad of features in pancytopenia?
Anaemia
Neutropenia
Thrombocytopenia
Signs and symptoms of pancytopenia can reflect what?
Lack of circulating blood cells
Cause of pancytopenia
What are the signs and symptoms of anaemia?
Fatigue
SOB
CV compromise
How is the cause of pancytopenia established?
History, including family history
Clinical findings
FBC, Blood film
Additional routine tests guided by above (B12/folate, LFT’s, virology, autoantibody tests)
Bone marrow examination (trephine biopsy)
Specialised tests guided by above (cytogenetics, eg chromosome fragility testing in Fanconi’s syndrome)
How is a core marrow biopsy obtained?
Jamshidi needle
What is the marrow cellularity in pancytopenia?
Variable
Hypocellular in aplastic anaemia
Hypercellular in MDS, B12/Folate deficiency, hypersplenism
What is the treatment of pancytopenia?
Supportive
Specific- dependent on cause
What is supportive treatment in pancytopenia?
Red cell transfusions
Platelet transfusions
Antibiotics and prophylaxis
Treat neutropenic fever promptly based on local policy without waiting for results
What is the specific treatment for pancytopenia caused by primary bone marrow disorder?
Malignancy – consider chemotherapy
Congenital – consider bone marrow transplantation
Idiopathic Aplastic Anaemia – Immunosuppression
What is the specific treatment for pancytopenia caused by secondary bone marrow disorder?
Drug reaction – STOP
Viral – eg treat HIV
Replace B12/folate
What is the specific treatment for pancytopenia caused by hypersplenism?
Treat cause if possible Consider splenectomy (not appropriate in all cases)
