Week 2- pancytopenia Flashcards
What is pancytopenia?
A deficiency of blood cells of all lineages (however generally excludes lymphocytes). This means low RBC, low platelets, low neutrophils.
For steady state in blood cells, what does it need to be?
Cell production needs to equal cell destruction.
what is the lifespan of RBCs?
120 days
What is the lifespan of platelets?
7-10 days
What is the lifespan of neutrophils?
7-8 hours.
Using general principles, what are the causes of pancytopenia?
Decreased production or increased destruction.
What are causes of reduced production in pancytopenia?
Bone marrow failure- could be inherited or acquired.
Acquired can be further divided into primary and secondary.
Are inherited marrow syndromes common?
No they are very rare.
What is the presentation of Fanconi’s syndrome?
Short stature Skin pigment abnormalities- cafe au lait Radial ray abnormalities Hypogenitalia Endocrinopathies GI defects Cardiovascular Renal Haematological
What are the haematological abnormalities seen in Falconi’s syndrome?
These arise around the age of 7, the patient is unable to correct inter strand cross links (DNA damage)
You get macrocytosis followed by thrombocytopenia followed by neutropenia.
Bone marrow failure (aplasia)
What are the primary causes of acquired reduced production in pancytopenia?
Usually a stem cell defect- however no obvious cause.
What are the primary causes of acquired bone marrow failure?
Usually a stem cell defect causing an intrinsic marrow problem however no obvious cause. Idiopathic aplastic anaemia- autoimmune attack against haemopoetic stem cells Myelodysplastic syndromes Acute leukaemia (white cell count can be variable)
Describe the pathogenesis of aplastic anaemia?
Auto-reactive T cells attack haemopoetic stem cells of myeloid lineage leading to no maturation and therefore no neutrophils, RBC’s and platelets.
What will the bone marrow of aplastic anaemia show?
Severely hypocellular.
What is myelodysplastic syndrome?
Blast cells in the blood/bone marrow due to them not being able to mature. You get increased apoptosis of progenitor and mature cells.
Propensity for evolution into AML.
Why can acute leukaemia cause pancytopenia?
In acute leukaemia you get proliferation of abnormal immature cells. These fail to mature into normal cells and prevent normal haemopoetic stem cells from developing by hijacking the haemopoetic niche and marrow microenvironment.
What can cause secondary bone marrow failure?
Drug induced e.g. chemotherapy, chloramphenicol
B12/folate deficiency
Viral e.g. HIV
Infiltrative non-haemopoetic malignant infiltration
What can cause increased destruction of blood cells leading to pancytopenia?
Hypersplenism- increased splenic pool or increased destruction exceeding bone marrow capacity, usually associated with a significantly enlarged spleen.
What can cause hypersplenism?
Splenic congestion- portal hypertension, congestive cardiac failure
Systemic disease e.g. RA
Haematological diseases e.g. splenic lymphoma.
What clinical features are associated with pancytopenia?
Signs and symptoms can reflect the lack of circulating blood cells and the cause of the pancytopenia.
What are the three things making up pancytopenia?
Anaemia
Neutropenia
Thrombocytopenia
What signs and symptoms are seen with anaemia?
Fatigue
Shortness of breath
Cardiovascular compromise
What signs and symptoms are associated with neutropenia?
Infections
What signs and symptoms are associated with thrombocytopenia?
Bleeding
Purpura
Petechiae
‘Wet’ bleeds including visceral bleeds.
How can you establish the cause of pancytopenia?
Hx- inc family Hx Clinical findings FBC, blood film B12/folate, LFTS, virology, autoantibody testing Bone marrow examination
What will the marrow cellularity be like in aplastic anaemia?
Hypocellular.
What will the marrow cellularity be like in myelodysplastic disorders?
Hypercellular- lots of immature cells.
What will the marrow cellularity be like in B12/folate deficiency?
Hypercellular- lots of immature cells. Issue is that they don’t have the means to mature.
How do you treat pancytopenia?
Dependent on the cause.
Also supportive treatment.
What supportive measures would you use for pancytopenia?
Red cell transfusions
Platelet transfusions
Antibiotics prophylactically
What specific therapy would you use for primary bone marrow failures?
If malignancy- consider chemotherapy
If congenital- consider bone marrow transplantation
Idiopathic aplastic anaemia- immunosuppression
How would you treat secondary bone marrow disorders?
If its a drug- stop it
If its viral- supportive
Replace B12/folate
How do you treat hypersplenism?
Treat cause
Consider splenectomy
