Bone marrow failure syndromes

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Mind Map by , created over 6 years ago

Blood Science Mind Map on Bone marrow failure syndromes, created by maisie_oj on 05/01/2013.

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Created by maisie_oj over 6 years ago
Haemostasis (part 1: primary haemostasis)
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Haematopoietic System Malignancies 2
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Blood transfusion and haematopoietic stem cell transplantation
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Haemopoietic System Malignancies
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Bone marrow failure syndromes
1 Definition
1.1 Failure of the bone marrow to provide sufficient cells to support a normal blood count
1.1.1 May be due to inefficient production or inadequate production
1.1.2 Usually all cell lines affected (but may be limited to one)
2 Clinical features of bone marrow failure
2.1 Red cell effects
2.1.1 Anaemia
2.1.1.1 Pallor
2.1.1.2 Lethargy
2.1.1.3 Dypnoea
2.1.1.3.1 = difficulty breathing
2.2 White cell effects
2.2.1 Infections
2.2.1.1 Fever
2.2.1.2 Malaise
2.2.1.3 Local infections: often of skin, perianal, chest, throat and mouth ulcers
2.2.1.4 Septicaemia
2.3 Platelet effects
2.3.1 Spontaneous bruising
2.3.2 Purpura
2.3.3 Bleeding gums
2.3.4 Rarely a severe haemorrhage
2.4 Supportive management
2.4.1 Anaemia
2.4.1.1 Transfuse red cells
2.4.1.2 Iron chelation
2.4.2 Bleeding
2.4.2.1 Prophylactic with platelet transfusions
2.4.2.2 Treatment of bleeding episodes
2.4.2.2.1 Packing, cautery, make sure not on 'blood thinners' (aspirin and NSAIDs)
2.4.3 Infection
2.4.3.1 Prophylactic antibiotics/antifungals/antivirals/PCP (protozoan)
2.4.3.2 Protective isolation
2.4.3.3 Life threatening events usually G-ve sepsis
2.4.3.4 Promt treatment of infections
2.4.3.4.1 Emergency antibiotics
2.4.3.4.1.1 Rapid admission to hospital
2.4.4 Other issues
2.4.4.1 Venous access
2.4.4.2 Growth factors
2.4.4.2.1 Granulocyte colony stimulating factor (G-CSF)
2.4.4.2.2 Erythropoietin (EPO)
3 Causes
3.1 Ineffective production
3.1.1 Myelodysplasia (MDS)
3.1.1.1 What is it?
3.1.1.1.1 Group of disorders
3.1.1.1.1.1 Characteristic morphological abnormalities
3.1.1.1.1.2 Impaired BM function
3.1.1.1.1.3 Peripheral cytopenias
3.1.1.1.1.3.1 Cytopenia = reduction in blood cells
3.1.1.1.1.4 Tendency to evolve into acute leukaemia
3.1.1.1.2 Usually occurs in the elderly (80-85yrs, with >75% >70yrs)
3.1.1.2 Aetiology (cause)
3.1.1.2.1 Primary
3.1.1.2.1.1 Most common
3.1.1.2.1.2 Unknown cause
3.1.1.2.1.2.1 Low dose radiation?
3.1.1.2.1.2.2 Organic chemicals?
3.1.1.2.2 Secondary
3.1.1.2.2.1 Following previous chemotherapy
3.1.1.2.2.1.1 Usually 4-10 years after treatment
3.1.1.2.2.1.2 Most common with alkylating agents (nitrogen mustards - e.g. cyclophosphamide)
3.1.1.2.2.2 Other drugs include; azathrioprine (immunosuppressant)
3.1.1.3 Presentation
3.1.1.3.1 Bone marrow failure
3.1.1.3.1.1 Obvious symptoms (see AA)
3.1.1.3.2 Splenomegaly (in 10%)
3.1.1.3.3 Incidental asymptomatic finding
3.1.1.3.3.1 Macrocytosis (large RBCs)
3.1.1.3.3.2 Cyopenias
3.1.1.3.3.3 Monocytosis
3.1.1.3.3.3.1 Increase in peripheral monocytes
3.1.1.4 Diagnosis
3.1.1.4.1 Full blood count
3.1.1.4.2 Morphology
3.1.1.4.2.1 Often tri-lineage abnormalities
3.1.1.4.2.1.1 In peripheral blood...
3.1.1.4.2.1.1.1 Oval macrocytes
3.1.1.4.2.1.1.2 Basophilic stippling
3.1.1.4.2.1.1.3 Hypogranulated/lobulated neutrophils
3.1.1.4.2.1.1.4 Agranular/giant platelets
3.1.1.4.3 Bone marrow
3.1.1.4.3.1 Hypercellular
3.1.1.4.3.2 Erythroid
3.1.1.4.3.2.1 Nuclear/cytoplasmic abnormalities
3.1.1.4.3.2.2 Ring sideroblasts
3.1.1.4.3.3 Small megakaryocytes (micromegakaryocytes) with abnormal nuclei
3.1.1.4.3.4 Myeloid
3.1.1.4.3.4.1 Hypogranular
3.1.1.4.3.4.2 Increased immature cells
3.1.1.4.4 Cytogenetics
3.1.1.4.4.1 30-50% primary MDS
3.1.1.4.4.2 80% is therpay related
3.1.1.4.4.3 Prognostic significance
3.1.1.4.4.4 Common genetic abnormalities
3.1.1.4.4.4.1 5q-
3.1.1.4.4.4.1.1 Primary (10-20%)
3.1.1.4.4.4.1.2 Secondary (20%)
3.1.1.4.4.4.2 Monosomy 7
3.1.1.4.4.4.2.1 Primary (10-15%)
3.1.1.4.4.4.2.2 Secondary (30-50%)
3.1.1.4.4.4.3 Trisomy 8
3.1.1.4.4.4.4 17p-
3.1.1.4.4.4.4.1 Secondary (10%)>primary(3%)
3.1.1.5 Prognosis
3.1.1.5.1 Apporx. 66% die from bone marrow failure
3.1.1.5.2 50% progress to acute leukaemia
3.1.1.5.2.1 Depends on number of blast cells in BM
3.1.1.5.3 International prognostic scoring system
3.1.1.5.3.1 Based on: % BM blasts, karyotype and number of cytopenias
3.1.1.5.3.1.1 Survival
3.1.1.5.3.1.1.1 Low risk = 36 months
3.1.1.5.3.1.1.2 Medium risk = 18 months
3.1.1.5.3.1.1.3 High risk = 8 months
3.1.1.5.3.1.2 Other prognostic factors
3.1.1.5.3.1.2.1 Age
3.1.1.5.3.1.2.2 Subtypes
3.1.1.6 Treatment
3.1.1.6.1 Observation
3.1.1.6.2 Supportive care
3.1.1.6.3 Chemotherapy
3.1.1.6.3.1 Reduction in abnormal cells and hypomethylating agents
3.1.1.6.4 Anti-lymphocyte globulin
3.1.1.6.5 Bone marrow transplantation
3.1.1.6.5.1 Especially in younger patients
3.2 Insufficient production
3.2.1 Aplastic anaemia (AA)
3.2.1.1 What is it?
3.2.1.1.1 Pancytopaenia (reduction in all red, white and platelet blood cells)
3.2.1.1.1.1 Results from an aplasia (reduction/destruction of the tissue) of the bone marrow
3.2.1.1.1.1.1 Cause is probably autoimmune
3.2.1.1.1.1.2 Microscopically appears as hypocellular bone marrow
3.2.1.1.2 No evidence of marrow fibrosis or malignancy
3.2.1.2 Classification
3.2.1.2.1 Constitutional / inherited
3.2.1.2.1.1 Causes 25% of childhood AA
3.2.1.2.1.2 Rarely adult AA
3.2.1.2.1.3 Inherited?
3.2.1.2.1.3.1 Family history
3.2.1.2.1.3.2 Somatic abnormailities
3.2.1.2.1.3.3 Forms
3.2.1.2.1.3.3.1 Fanconi anaemia
3.2.1.2.1.3.3.2 Dykeratosis congenita
3.2.1.2.1.3.3.3 Schwachmann-diamond syndrome
3.2.1.2.1.3.3.4 Reticular dysgenesis
3.2.1.2.2 Acquired
3.2.1.2.2.1 In most cases, no cause is identified (= idiopathic)
3.2.1.2.2.1.1 Causes can include
3.2.1.2.2.1.1.1 Direct bone marrow toxicity
3.2.1.2.2.1.1.2 Ionising radiation
3.2.1.2.2.1.1.3 Chemicals (e.g. benzene; organic solvents; insecticides)
3.2.1.2.2.1.1.4 Drugs
3.2.1.2.2.1.1.4.1 Anti-rheumatics
3.2.1.2.2.1.1.4.2 Anti-inflammatory
3.2.1.2.2.1.1.4.3 Anti-convulsants
3.2.1.2.2.1.1.4.4 Anti-thyroids
3.2.1.2.2.1.1.4.5 Anti-depressants
3.2.1.2.2.1.1.4.6 Anti-diabetics
3.2.1.2.2.1.1.4.7 Anti-malarials
3.2.1.2.2.1.1.5 Immune-mediated
3.2.1.2.2.1.1.5.1 Pregnancy
3.2.1.2.2.1.1.5.2 Idiosyncratic drug reaction (individual's react to drugs differerntly)
3.2.1.2.2.1.1.5.3 Viruses (EBV, parvovirus (causes fifth's disease in children), HIV)
3.2.1.2.2.1.1.5.4 Transfusion-associated Graft versus host disease (TA-GVHD)
3.2.1.2.2.1.1.5.4.1 T-lymphocytes in donor blood start an immune reaction against the recipient
3.2.1.2.2.1.1.5.5 Eosinophilic fasciitis
3.2.1.2.2.1.1.5.5.1 Eosinophil-mediated inflammation of the fascias (connective tissue around; muscles, nerves, blood vessels)
3.2.1.3 Diagnosis
3.2.1.3.1 Full blood count (FBC)
3.2.1.3.1.1 Hb <10g/dL
3.2.1.3.1.2 Platelets <50
3.2.1.3.1.3 Neutrophils <1.5
3.2.1.3.1.4 Everything is LOW
3.2.1.3.2 Reticulocyte count (= low)
3.2.1.3.3 Blood film
3.2.1.3.3.1 Normal looking cells, but reduced in number / absent
3.2.1.3.4 Bone marrow aspirate and trephine (and cytogenetics)
3.2.1.3.4.1 Trephine = cyclindrical core biopsy of bone+marrow
3.2.1.3.5 Exclude other causes of pancytopaenia
3.2.1.3.5.1 Vit. B12 and folate levels
3.2.1.3.5.2 Liver function tests
3.2.1.3.5.3 BM and cytogenetics - exclude myelodysplasia (MDS)
3.2.1.3.5.4 Exclude drug causes
3.2.1.3.5.5 Liver function and virology
3.2.1.3.5.6 Test for paroxysmal nocturnal haemoglobinuria
3.2.1.4 Treatment
3.2.1.4.1 Supportive care
3.2.1.4.1.1 Blood product replacement
3.2.1.4.1.1.1 Bone marrow transplant
3.2.1.4.1.1.1.1 Avoid HLA sensitisation and cytomegalo virus (CMV) exposure
3.2.1.4.1.2 Antimicrobials
3.2.1.4.1.3 Growth factors
3.2.1.4.2 Specific therapy for AA
3.2.1.4.2.1 Aimed at functional peripheral blood count recovery
3.2.1.4.2.1.1 Depends on: type of AA, age and donor availability
3.2.1.4.2.1.2 Immunosupression
3.2.1.4.2.1.3 Bone marrow transplant
3.2.1.4.2.1.3.1 Up to 80% patients are cured
3.2.1.4.2.1.3.1.1 Typically reserved with sibling matches (HLA matching)
3.2.1.4.2.1.4 G-CSF
3.2.1.4.2.1.4.1 May cause monosomy 7 in children
3.2.1.4.2.1.5 Oxymethalone
3.2.1.4.2.1.5.1 Androgenic steroid hormone -> increases erythropoiesis and BM recovery
3.2.1.4.2.1.6 Splenectomy
3.2.1.4.2.1.6.1 Reduces transfusion requirements, increases thrombocyte count and progressive haemopoiesis
3.2.2 Bone marrow infiltration with malignancy (lymphoma, leukaemia, carcinoma etc.)

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