IOD Bone Marrow Failure Flashcards
What are all cells made from?
stem cells
Which cells are made?
Erythrocyte, platelets, macrophages, neutrophils, eosinophils, basophils, B cells, T cells
What does BM need?
cytokines
EPO, TPO, GCSF and many others
Haematinics: B12, folate, iron
do WCC need iron?
no
What should be in peripheral blood?
Should be mature red cells, white cells and platelets
In abnormal cases, often reflects problems of BM
Reasons for cytopenias and examples?
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
signs of red cell cytopenia?
Lethargy, poor concentration, loss of appetite, pale skin, shortness of breath, tachycardia, reduced exercise tolerance
signs of white cells cytopenia?
Fevers and infections – esp urine, chest, sinus and skin, sore mouth
signs of platelets cytopenia?
Easy bruising and bleeding, menorrhagia, epistaxis, petechiae, gum bleeding
Inherited single lineage
Anaemia [Diamond-Blackfan]
Neutropenia [Congenital]
Thrombocytopenia [Congenital amegakaryocytic & thrombocytopenia with absent radii-TAR]
inherited pancytopenia?
Fanconi Anaemia
Dyskeratosis Congenita
Shwachman-Diamond Pearson
acquired single lineage?
Pure red cell aplasia [viral, immune, drugs]
acquired pancytopenia?
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
Scwachman-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
Signs of aplastic anaemia?
Hypocellular bone marrow
No abnormal cells
No fibrosis
At least 2 of the following:
Hb <100 g/L
Plt <50x109/L
Neut <1.5x109/L
Severity of AA?
RBCs less than 20 , platelets less than 20, neutrophils less than 0.5 -severe
very severe-neutrophils less than 0.2
Appearance of AA?
fat, no cancer cells , no BM cells
Info AA?
Rare (2-3 cases per million per year)
Wide age range (peak ~25 yrs, >65 yrs) Oriental+
Diagnosed by absence of cells
no characteristic presence or diagnostic test
Thorough history of viruses, travel, occupation, vaccinations, childhood history, skeletal abnormalities, medications – including over the counter
Marked neutropenia leads to risk of overwhelming infection; may be life threatening. Signs and symptoms related to cytopenias
Causes of AA?
PREDICTABLE
Radiation, high dose chemotherapy - dose dependent
Predictable recovery course
IDIOSYNCRATIC
Drug induced – not dose related
Many small case reports – evidence unclear
Chloramphenicol
VIRAL
Hepatitis ( 5-10% of cases) ? EBV/CMV/ HIV
IDIOPATHIC
Majority of cases (60-70%)
Pathogenesis AA?
Unclear, probably autoimmune component-T cell reaction
BM environment and stromal cells may have a role
Demonstrated increased progressive shortening of the terminal
restriction fragments of chromosomes – telomere shortening
Diagnosis AA?
FBC, blood film, retics, BM, Viral studies, LFTs
how to exclude 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
how to exclude malignant hypocellular disease?
Immunophenotyping, cytogenetics
how to exclude late presentation of congenital forms
Chromosomal breakage analysis for Fanconi anaemia
X-rays, Autoimmune studies
Complications?
Risk of infection – life threatening Blood transfusion support Antibodies, reactions Iron overload Reduced quality of life
Evolution to PNH ~7%
Transformation to acute leukaemia ~10%
Treatment AA?
Supportive treatment: Blood product support, antibiotics, general advice Immunosuppression: Ciclosporin ATG (rabbit or horse) Growth factors: Eg GCSF in combination with the above Haemopoietic Stem Cell Transplant: Sibling donor first line treatment now if pt <40yrs
Fanconi anaemia?
AR disorder with progressive pancytopenia High frequency of chromosome breakages Can isolate breakage points Increased predisposition to malignancies Most (60%) patients have somatic abnormalities Skin – cafe au lait Skeletal – eg absent thumbs GU – horseshoe kidneys Cardiac Neurological
Porgression?
Very rare and varied presentations Difficult diagnosis Normal FBC at birth Usually presents between 5 and 10 yrs Progresses with age BM failure in 90% by 40 yrs
Acute Leukaemia: 33% cumulative incidence by 40yrs
Solid tumours: 28% cumulative incidence by 40 yrs
Treatment FA?
Risk of death from disease is from BM failure
BMT if possible: Definitive treatment
Prior to BMT – supportive treatment, steroids and androgens but life expectancy mid-20s-growth factors
Dyskeratosis congenita?
Abnormal skin pigmentation, nail dystrophy,
mucosal leucoplakia
BM failure cause of early mortality
Pulmonary complications, risk of malignancy
X linked, dyskerin gene
Transient red cell aplasia?
Infection with Parvovirus B19
‘Slapped cheek’ syndrome
Specifically infects & destroys erythroid precursor cells
Erythropoiesis ceases for 5-10 days
Unconcerning in normal people (RBCs live for 120 days)
Can be life-threatening in those with an underlying
chronic anaemia
Diagnosis of tca?
Parvo B19 serology testing
(IgM positive shows acute infection) and PCR
treatment of TCA?
Supportive (isolation – saliva, respiratory spread)
RBC transfusion if necessary
Keep away from pregnant women: crosses placenta
Diagnosis of BMF?
Low blood counts (pancytopenia)
Refer for urgent evaluation
Repeat FBC and blood film
other tests?
LFT’s, RBCs, B12, folate, ferritin,
Coag screen
Viral serology
Autoimmune profile
history and exam?
sepsis, bleeding, splenomegaly, jaundice, lymphadenopathy
Approach to neutropenic sepsis?
This is a medical emergency!!
(ABC approach to a sick patient)
A life threatening complication of chemotherapy
Suspect in anyone who is hypotensive and tachycardic
They may not have a fever
Neutrophil count <1.0 x109/L
Give broad spectrum IV antibiotics without delay
Classification of thrombocytopenia?
Characterised by purpura, easy bruising and overt bleeding - such as menorrhagia, epistaxis and gastrointestinal bleeds.
Reduced production
Congenital
Acquired – marrow infiltration eg myelofibrosis, aplastic anaemia, drugs eg omeprazole
Increased destruction
Immune – idiopathic, viral, drugs
Microangiopathic disease – TTP, DIC, HUS
Septicaemia – usually secondary to Gram-negative organisms
Thrombocytopenia therapy?
If actively bleeding:
Intravenous immunoglobulin & steroids +/- TXA
In very severe cases eg intracranial haemorrhage give platelets
May require red cell transfusion & correction of clotting abnormalities.
In chronic cases:
Immunosuppressants & steroid sparing agents
eg azathioprine, MMF, Rituximab, TPO receptor agonists: romiplostim/ eltrombopag, splenectomy
Always look for the underlying cause, and treat it!
