Pancytopenia Flashcards
What is pancytopenia?
A deficiency of blood cell of ALL lineages (but generally excludes lymphocytes)
Commonly see reduced Hb, platelets and neutrophil count
Is pancytopenia a diagnosis?
No
Does pancytopenia always mean bone marrow failure?
No
What is the life span of a red cell?
120 days
What is the life span of a neutrophil?
7-8 hours
What is the lifespan of a platelet?
7-10 days
Generally, what can cause pancytopenia?
Reduced production
Increased destruction
What are the causes of reduced production in pancytopenia?
Bone marrow failure; inherited or acquired (primary or secondary)
What are the characteristics of inherited marrow failure syndromes?
Cancer predisposition
Impaired hematopoiesis
Congenital anomalies
Arises due to defects in DNA repair/ ribosomes
What is an example of an inherited bone marrow failure syndrome?
Fanconi's Anaemia: Short stature Skin pigment abnormalities Radial ray abnormalities Hypogenitalia Endocrinopathies GI defects CV Renal Haem
What are the haematological abnormalities seen in fanconi’s anaemia?
Macrocytosis followed by thrombocytopenia then neutropenia
Bone marrow failure (aplasia): 84% by 20 years
Leukaemia risk: 52% by 40 years
What is the pathogenic basis of the haematological abnormalities seen in fanconi’s anaemia?
Unable to correct inter-strand cross-links (DNA damage)
What are examples of acquired primary bone marrow failure (an intrinsic marrow problem)
Idiopathic aplastic anaemia (autoimmune attack against haemopoietic stem cells) Myelodysplastic syndromes (MDS) Acute leukaemia
What cytokines are involved in aplastic anaemia?
IFN-gamma
TNF- alpha
Describe myelodysplastic syndromes?
Dysplasia (disordered development)
Hypercellular marrow
Increased apoptosis of progenitor and mature cells (ineffective haemopoiesis)
What cancer is linked with myelodysplastic syndromes?
Can progress into AML
How is aplastic anaemia diagnosed?
Bone marrow biopsy
What are the causes for aplastic anaemia?
Fanconi's anaemia Autoimmune Drugs Virus; parvovirus B19, hepatitis Irradiation
Why can acute leukaemia cause pancytopenia?
Proliferation of blasts from leukemic stem cell
Failure to differentiate or mature into normal cells
Prevents normal haemopoietic stems from developing by hijacking the haemopoietic niche and marrow microenvironment
What can cause secondary bone marrow failure?
Drug induced (chemo, chloramphenicol, alcohol)
B12 / folate deficiency (nuclear maturation can affect all lineages)
Infiltrative; non-haemopoietic malignant infiltration, lymphoma
Misc; viral; HIB, parvovirus B19
Storage diseases
How will the bone marrow look in B12/ folate deficiency?
Hypercellular
What can result in pancytopenia via increased destruction?
Hypersplenism
What does the red pulp of the spleen contain?
Sinusoids and cords
What does the cord of red pulp contain?
Macrophages
Fibroblasts
Cells in transit (RBC, WBC, platelets, CD8 T cells)
What is the function of the spleen?
Detects, retains and eliminates unwanted foreign or damaged material
Facilitates immune responses to blood borne antigens
Why does hypersplenism result in increased destruction of cells?
Increased splenic pool
Increased destruction that exceeds bone marrow capacity, usually assoc with significant splenomegaly
Does splenic size correlate with hypersplenism?
No; any cause of splenomegaly could result in hypersplenism but splenic size alone is not predictive of the degree of hypersplenism
What can cause hypersplenism?
Splenic congestion; portal hypertx, CCF
Systemic; RA (felty’s)
Haemo: splenic lymphoma
What can the clinical features of pancytopenia reflect?
Lack of circulating blood cells
Cause of pancytopenia
What are the consequences of lack of circulating cells in pancytopenia?
Anaemia
Neutropenia
Thrombocytopenia
What are the features of anaemia?
Fatigue
SOB
CV compromise; dizziness, palpitations
What are the features of neutropenia?
Infections; determine severity and duration
What are the features of thrombocytopenia?
Bleeding; purpura, petechiae, wet bleeding including visceral bleeds
How is the cause of pancytopenia established?
Hx including FMHx
Clinical findings
FBC, blood film
Additional tests; B12/folate, LFTs, virology, autoantibody tests
Bone marrow aspirate
Specialised tests; chromosome fragility testing for fanconi’s syndrome
What will cause hypocellular marrow cellularity in pancytopenia?
Aplasitc anaemia
What will cause hypercellularity in marrow cellularity in pancytopenia?
Myelodysplastic syndromes (proliferation and apoptosis) B12/ folate deficiency (late maturation failure, early proliferation and apoptosis) Hypersplenism
What is the treatment for pancytopenia?
Supportive
Specific; dependent on cause (pancytopenia due to B12/folate deficiency)
What is the supportive treatment for pancytopenia?
Red cell transfusions
Platelet transfusions
Antibiotic prophylaxis; antibacterials, antifungals
Should you wait for microbial results before antibiotic treatment in neutropenic fever?
NO; give broad spectrum antibiotics that specifically cover gram negs
What is the specific treatment for pancytopenia caused by a primary bone marrow disorder?
Malignancy; chemo
Congenital; bone marrow transplantation
Idiopathic aplastic anaemia; immunosuppression
What is the specific treatment for pancytopenia caused by a secondary bone marrow disorder?
Drug reaction; STOP
Viral; treat HIV
Replace B12/ folate
What is the specific treatment for pancytopenia caused by hypersplenism?
Treat cause if poss
Consider splenectomy
