Bone Marrow Failure Flashcards
What causes cytopenia?
- Reduced cell production
- B12, folate, iron deficiency
- EPO deficiency in CKD
- Excess loss of cells, or destruction
- Single cell line affected
- Pancytopenia - all 3 cell lines - Failure of appropriate utilisation
Anaemia of chronic disease.
What are the symptoms and signs of bone marrow failure?
Red cells - causing Lethargy, poor concentration, loss of appetite, pale skin, shortness of breath, tachycardia, reduced exercise tolerance
White cells - causing Fevers and infections - especially urine, chest, sinus and skin, sore mouth.
Platelets - causing Easy bruising and bleeding, menorrhagia, epistaxis, petechiae, gum bleeding
What does pancytopenia mean?
deficiency of all three cellular components of the blood (red cells, white cells, and platelets).
What are the classifications of bone marrow failure?
Acquired/Inherited and then within this there is Single lineage and Pancytopenia.
What are the different types of inherited single lineage bone marrow failure disorders?
• Anaemia [Diamond - Blackfan]
• Neutropenia [congenital]
Thrombocytopenia [congenital amegakaryocytic & thrombocytopenia with absent radii-TAR]
What are the different types of inherited pancytopenia bone marrow failure disorders?
• Fanconi anaemia
• Dyskeratosis congenita
* Shwachman-Diamond Pearson
What are the different types of acquired single lineage bone marrow failure disorders?
Pure red cell aplasia [viral, immune, drug]
What are the different types of acquired pancytopenia bone marrow failure disorders?
• Aplastic anaemia [drugs, viral, immune]
• Bone marrow infiltration [leukaemia, MDS]
Paroxysmal nocturnal haemoglobinuria
Diamond-Blackfan Anaemia
Inherited PRCA. Skeletal abnormalities [craniofacial, thumb & upper limb, cardiac and urogential malformation, cleft palate, increased risk of leukaemia
Thrombocytopenia with absent radii
Low platelet count with no radius bone. Associated with lactose intolerance, cardiac and kidney problems
Fanconi anaemia
Pancytopenia, short stature, endocrine problems, skin pigmentation, abnormalities of arms, eyes, kidneys, ears. Increased risk of cancer, especially AML
Dyskeratosis congenita
Skin pigmentation, nail dystrophy and oral leukoplakia, with progressive BMF
Shwachman-Diamond Pearson
Predominantly a neutropenia, but all 3 cell lines affected, exocrine pancreatic dysfunction, growth retardation
Myelodysplastic syndrome
Abnormal cells in the BM which do not mature properly
Paroxysmal nocturnal haemoglobinuria
Defective blood cells, especially RBCs very susceptible to destruction by the complement system; haemolysis, haemoglobinuria. A degree of bone marrow dysfunction and risk of life threatening blood clots
What is aplastic anaemia?
• Hypocellular bone marrow
• No abnormal cells
• No fibrosis
• At least 2 of the following:
- Hb < 100 g/L
- Plt <50 x 109/L
- Neut <1.5 x 109/LWhat are the causes of aplastic anaemia?
- Predictable - Radiation, high dose chemotherapy - dose dependant. Predictable recover course
- Idiosyncratic - drug induced, not dose relates.
- Viral - Hepatits (5-10% of cases) ?EBV/CMV/HIV
- Idiopathic - Majority of cases (60-70%)
What is the pathogenesis of aplastic anaemia?
• Unclear, probably autoimmune component
• BM environment and stromal cells may have a role
* Demonstrated increased progressive shortening of the terminal restriction fragments of chromosomes - telomere shortening
How is aplastic anaemia diagnosed?
FBC, blood film, retics, BM, viral studies, LFTs
Exclude paroxysmal nocturnal haemoglobinuria (PNH):
• PIG-A gene mutation causing absence of GPI anchored proteins
• Disregulated complement leads to intravascular haemolysis (thromboses)
• NO depletion leads to smooth muscle contraction & vasoconstriction - pain
Exclude malignant hypocellular disease:
• Immunophenotyping, cytogenetics
Exclude late presentation of congenital forms:
• Chromosomal breakage analysis for fanconi anaemia
• X-rays, autoimmune studies.
What are the complications of aplastic anaemia?
Severe disease: • Risk of infection - life threatening • Blood transfusion support • Antibodies, reactions • Iron overload Reduced quality of life
What are the treatment options of aplastic anaemia?
- Supportive treatment
- Blood product support, antibiotics, general advice - Immunosuppression
- Ciclosporin
- ATG (rabbit or horse) - Growth factors
- E.g. GCSF in combination with the above - Haemopoietic stem cell transplant
Sibling donor first line treatment now if pt <40 yrs
What is falcon anaemia?
AR disorder with progressive pancytopenia
High frequency of chromosome breakages
Can isolate breakage points
What is the clinical presentation of falconi anaemia?
Increased predisposition to malignancies
Most (60%) patients have somatic abnormalities
Skin - café au lait
Skeletal - e.g. absent thumbs
GU - horseshoe kidneys
Cardiac
Neurological
What is the presentation and progression of fanconi anaemia?
Very rare and varied presentations Difficult diagnosis Normal FBC at birth Usually presents between 5 and 10 years Progresses with age BM failure in 90% by 40yrs
Acute leukaemia: 33% cumulative incidence by 40 years
Solid tumours: 28% cumulative incidence by 40 years
What is the treatment of falcon anaemia?
Risk of disease is from BM failure
BMT if possible: Definitive treatment
Prior to BMT - supportive treatment, steroids and androgens but life expectancy mid-20s
What is Dyskeratosis congenita?
- Abnormal skin pigmentation, nail dystrophy, mucosal leucoplakia
- BM failure cause of early mortality
- Pulmonary complications, risk of malignancy
X-linked, dyskerin gene
How do you diagnose parvovirus-induced aplasia?
Diagnosis:
• Parvo B19 serology testing
• (IgM positive shows acute infection) and PCR
How do you treat parvovirus-induced aplasia?
Treatment:
• Supportive (isolation - saliva, respiratory spread)
• RBC transfusion if necessary
Keep away from pregnant women: crosses placenta
How do you diagnose bone marrow failure?
- Low blood counts (pancytopenia)
- Refer for urgent evaluation
- Repeat FBC and blood film
What is neutropenic sepsis?
A medical emergency - ABC approach needs to be taken.
It is a life threatening complication of chemotherapy. Suspect it in someone who is hypotensive and tachycardic. There may not have a fever.
Neutrophil count <1.0 x 10^9/L
Give broad spectrum Abx without delay.
What is thrombocytopenia?
Characterised by purpura, easy bruising and overt bleeding - such as menorrhagia, epistaxis and gastrointestinal bleeds.
What are the treatment options in ITP?
Usually self-limiting in children - can have spontaneous remissions
If actively bleeding:
• Intravenous immunoglobulin & steroids +/- TXA
• In very severe cases e.g. intracranial haemorrhage give platelets
• May require red cell transfusion & correction of clotting abnormalities
In chronic cases:
• Immunosuppressants & steroid sparing agents
• E.g. azathroprine, MMF, Rituximav, TPO receptor agonists: Romiplostm/eltrombopag, splenectomy
