Pancytopaenia Flashcards
what is pancytopenia?
deficiency of blood cells of all lineages (bute generally excludes lymphocytes)
is pancytopenia a diagnosis?
no
just reflects another diagnosis
(but does not always mean bone marrow failure)
steady state?
cell production = cell destruction
cell intermediates in erythropoiesis?
pronormoblast > basophilic/early normoblast > polychromatophilic/intermediate normoblast > orthochromatic/late normoblast > reticulocyte > mature RBC/erythrocyte
how many RBCs made per second?
2.5 million
how many neutrophils mad per second?
1-2 million
how many platelets made per second?
1 million
broad causes of pancytopenia?
reduced production
increased destruction
what can cause reduced production resulting in pancytopenia?
inherited syndromes acquired causes (primary/secondary)
characteristics of inherited marrow failure?
pre-disposition to cancer
impaired haemopoiesis
congenital anomalies
(all arise due to defects in DNA repair/ribosomes)
give an examples of an inherited marrow failure syndrome
Fanconi’s anaemia
- short stature
- skin pigment anomalies
- radial ray abnormalities
- hypogenitalia
- endocrinopathies
- GI defects
- cardio problems
- renal
- haematological
what skeletal and skin changes occur in marrow failure?
café au lait spots
skeletal abnormalities
what causes the problem in inherited bone marrow failure?
unable to correct inter-strand cross-links (DNA damage)
what haematological problems are associated with inherited bone marrow failure syndromes?
microcytosis followed by thrombocytopenia then neutropenia
risk of bone marrow failure and leukaemia in inherited bone marrow failure syndromes?
84% risk of bone marrow failure by age 20
52% risk of leukaemia by age 40
examples of primary acquired causes of reduced production resulting in pancytopenia?
idiopathic aplastic anaemia (autoimmune attack against haemopoietic stem cells) myelodysplastic syndromes (MDS) acute leukaemia
pathogenesis of aplastic anaemia pathogenesis?
auto-reactive T cells attack haematopoietic stem cells and myeloid lineage precursors
what happens in myelodysplastic syndromes?
dysplasia (disordered cell development)
hypercellular marrow
increased apoptosis of progenitor and mature cells (ineffective haemopoiesis)
has a propensity for evolution into AML
how can acute leukaemia cause pancytopenia?
proliferation of abnormal cells (…blasts) from leukaemic stem cells
failure to differentiate or mature into normal cells
prevents normal haematopoietic stem cell/progenitor cell development by hijacking/altering the haematopoietic niche and marrow microenvironment
secondary acquired causes of reduced production resulting in pancytopenia?
drugs (chemo, chloramphenicol, alcohol) can cause aplasia
B12/folate deficiency (causes problems with nuclear maturation and cell division in all lineages - causes hypercellular marrow)
infiltrative (non-haematopoietic malignant infiltration, lymphoma)
viral (HIV etc)
storage disease
causes of increased destruction of cells resulting in pancytopenia?
hypersplenism
what is found within parenchyma of spleen?
red pulp
- sinusoids and cords
white pulp
features of sinusoids?
fenestrated
lined with endothelial cells
supported by hoops of reticulin
features of cords?
contain macrophages, some fibroblasts, cells in transit (RBCs, WBCs) platelets and some CD8 T cells
functions of spleen?
detect, retain and eliminate unwanted foreign/damaged material (including cells)
facilitates immune responses to blood borne antigens
how does hypersplenism cause increased destruction of cells?
increased splenic pool
increased destruction that exceeds bone marrow capacity, usually associated with significantly enlarged spleen
splenic red cell mass in normal/enlarged spleen?
normal = 5% enlarged = 40%
red cell transit in normal/enlarged spleen?
normal = fast enlarged = slow
splenic platelet pool in normal/enlarged spleen?
normal = 20-40% enlarged = 90%
causes of hypersplenism?
splenic congestion (portal hypertension, congestive cardiac failure) systemic diseases (RA) haematological diseases (splenic lymphoma)
primary acquired reduced production?
idiopathic aplastic anaemia
myelodysplastic syndromes
acute leukaemias (bone marrow malignancy)
secondary acquired reduced production?
drug induced aplasia B12/folate deficiency infections metastatic cancer storage disorders
clinical features of pancytopenia can reflect what?
lack of circulating blood cells
the cause of the pancytopenia
pancytopenia is a lack of what cells?
RBCs anaemia
neutrophils (neutrophils)
platelets (thrombocytopenia)
investigations in establishing cause of pancytopenia?
history (including FH) clinical findings FBC and blood film additional tests guided by above (B12, folate, LFT, virology, autoantibodies etc) bone marrow examination specialised tests
types of bone marrow examination?
aspirate from posterior iliac crest trephine biopsy (bone sample)
how is bone marrow affected in pancytopenia?
aplastic anaemia = hypocellular
myelodysplastic syndromes = proliferation, apoptosis and hypercellular
B12/folate deficiency = late cell maturation failure, early proliferation, apoptosis and hypercellular)
treatment of pancytopenia?
supportive
specific depending on cause
types of supportive treatment in pancytopenia?
red cell transfusion
platelet transfusion
neutrophil transfusion (not routine)
antibiotic prophylaxis
do you wait for microbiology results before antibiotics in neutropenic fever?
no
specific treatment of primary bone marrow disorder?
malignancy = consider chemo
congenital = consider bone marrow transplant
idiopathic aplastic anaemia = immunosuppression
specific treatment of secondary bone marrow disorder?
drug reaction = Stop the drug
viral = treat infection (eg HIV)
replace B12/folate
specific treatment of hypersplenism?
treat cause if possible
consider splenomegaly
