Pancytopenia Flashcards
what is pancytopenia
generalised deficiency of blood cells of all lineages (generally excludes lymphcocytes)
what cells are affected most in pancytopneia
erythrocytes
platelets
granulocytes
is pancytopenia a diagnosis
no
does pancytopenia always mean marrow failure
no
how long is a RBCs lifespan
~120 days
how long is a neutrophils lifespan
~7-8 hours
how long is a platelets lifespan
7-10 days
what are the two mechanisms behind pancytopenia
reduced production (marrow failure) or increased destruction (hypersplensim)
what are the categories of marrow failure
inherited syndromes
acquired: primary and secondary
what causes inherited marrow failure syndromes
defects in DNA repair/ ribosomes creates triad of cancer pre-disposition, impaired haemopoeisis and congenital anomalies
what is fanconis anaemia
inherited marrow failure syndrome:
- short stature and skeletal abnormalities
- skin pigment (cafe au lait spots) abnormalities
- hypogenitalia
- GI defects
- endocrineopathies
- cardio/ renal/ haem problems
what haem abnormalities occur in inherited marrow failure syndrome
usually occur by ~7
UNABLE TO CORRECT INTER-STRAND CROSS LINKS (DNA damage)
get macrocytosis -> thrombocytopenia -> neutropenia
84% bone marrow failure (aplasia) by 20
52% leukaemia by 40
what causes a primary acquired bone marrow failure
an intrinsic marrow problem (usually stem cell defect)
- idiopathic aplastic anaemia (AI attack against stem cells)
- myelodysplastic syndromes
- acute leukaemia
what cells are reduced in aplastic anaemia
erythrocytes
platelets
granulocytes
what are the features of myelodysplastic syndromes
dysplasia
hypercellular marrow
increases apoptosis of progenitor and mature cells (ineffective haemopoiesis)
PROPENSITY FOR EVOLUTION INTO AML
how can acute leukaemia cause pancytopenia
proliferation of abnormal ‘blast’ cells
failure to differentiate/ mature into normal cells
what can cause secondary bone marrow failure
drug induced: chemotherapy, chloramphenicol, alcohol (all cause aplasia)
B12/folate deficiency (nuclear maturation can affect all lineages- will be hypercellular)
infiltrative: non haemopoietic malignant infiltration, lymphoma
viral (e.g. HIV)
storage diseases
what type of lymphoid tissue is the spleen
secondary lymphoid organ
what is the blood supply to the spleen
splenic artery (branch on coeliac) drained by splenic vein (with SMV forms portal vein)
hows does hyperplenism cause pancytopenia
increased splenic pool (trapping of platelets in spleen)
increased transit time through spleen for cells
increased destruction exceeds bone marrow capacity
what can cause hypersplenism
splenic congestion (portal hypertension, congestive cardiac failure) systemic diseases (RA)
haematological diseases (splenic lymphoma)
what clinical problems make up pancytopenia
anaemia
neutropenia
thrombocytopenia
what are the clinical features of pancytopenia
anaemia: fatigue, SOB, cardiovascular compromise
neutropenia: infections
thrombocytopenia: bleeding (purpura, petechiae, ‘wet bleeds’ e.g. visceral bleeds)
features of the cause of the pancytopenia
how can you find the cause of pancytopenia
Hx FHx clinical findings FBC, blood film B12/ folate, LFTs, virology, autoantibody bone marrow examination cytogenetics (e.g. fanconis syndrome)
what is marrow cellularity like in aplastic anaemia IMPORTANT
hypocellular
what causes marrow hypercellularity in pancytopenia IMPORTANT
myelodysplastic syndromes (porliferation and apoptosis) B12/folate deficiency late maturation failure, early proliferation + apoptosis) hypersplenism
what is the treatment for pancytopenia
supportive : red cell and platelet transfusions (platelets transfusions not routine), antibiotic and antifungal prophylaxis (treat neutropenic fever ASAP)
specific- dependent on cause (e.g. B12/ folate deficiency)
what are the treatments for primary bone marrow disorders
malignancy- chemo
congenital- bone marrow transplantation
idiopathic aplastic anaemia- immunosuppression
what are the treatments for secondary bone marrow disorders
drug reactions- STOP
viral- treat
replace B12/folate
what is the treatment for hypersplenism
treat cause if possible
consider splenectomy
