Bone marrow failure syndromes

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.

Created by maisie_oj over 6 years ago
Haemostasis (part 1: primary haemostasis)
Haemostasis (part 2: secondary haemostasis)
Haematopoietic System Malignancies 2
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Cell adaptations
Acute Inflammation
Rheumatoid Arthritis
Blood transfusion and haematopoietic stem cell transplantation
Haemopoietic System Malignancies
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 Pallor Lethargy Dypnoea = difficulty breathing
2.2 White cell effects
2.2.1 Infections Fever Malaise Local infections: often of skin, perianal, chest, throat and mouth ulcers 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 Transfuse red cells Iron chelation
2.4.2 Bleeding Prophylactic with platelet transfusions Treatment of bleeding episodes Packing, cautery, make sure not on 'blood thinners' (aspirin and NSAIDs)
2.4.3 Infection Prophylactic antibiotics/antifungals/antivirals/PCP (protozoan) Protective isolation Life threatening events usually G-ve sepsis Promt treatment of infections Emergency antibiotics Rapid admission to hospital
2.4.4 Other issues Venous access Growth factors Granulocyte colony stimulating factor (G-CSF) Erythropoietin (EPO)
3 Causes
3.1 Ineffective production
3.1.1 Myelodysplasia (MDS) What is it? Group of disorders Characteristic morphological abnormalities Impaired BM function Peripheral cytopenias Cytopenia = reduction in blood cells Tendency to evolve into acute leukaemia Usually occurs in the elderly (80-85yrs, with >75% >70yrs) Aetiology (cause) Primary Most common Unknown cause Low dose radiation? Organic chemicals? Secondary Following previous chemotherapy Usually 4-10 years after treatment Most common with alkylating agents (nitrogen mustards - e.g. cyclophosphamide) Other drugs include; azathrioprine (immunosuppressant) Presentation Bone marrow failure Obvious symptoms (see AA) Splenomegaly (in 10%) Incidental asymptomatic finding Macrocytosis (large RBCs) Cyopenias Monocytosis Increase in peripheral monocytes Diagnosis Full blood count Morphology Often tri-lineage abnormalities In peripheral blood... Oval macrocytes Basophilic stippling Hypogranulated/lobulated neutrophils Agranular/giant platelets Bone marrow Hypercellular Erythroid Nuclear/cytoplasmic abnormalities Ring sideroblasts Small megakaryocytes (micromegakaryocytes) with abnormal nuclei Myeloid Hypogranular Increased immature cells Cytogenetics 30-50% primary MDS 80% is therpay related Prognostic significance Common genetic abnormalities 5q- Primary (10-20%) Secondary (20%) Monosomy 7 Primary (10-15%) Secondary (30-50%) Trisomy 8 17p- Secondary (10%)>primary(3%) Prognosis Apporx. 66% die from bone marrow failure 50% progress to acute leukaemia Depends on number of blast cells in BM International prognostic scoring system Based on: % BM blasts, karyotype and number of cytopenias Survival Low risk = 36 months Medium risk = 18 months High risk = 8 months Other prognostic factors Age Subtypes Treatment Observation Supportive care Chemotherapy Reduction in abnormal cells and hypomethylating agents Anti-lymphocyte globulin Bone marrow transplantation Especially in younger patients
3.2 Insufficient production
3.2.1 Aplastic anaemia (AA) What is it? Pancytopaenia (reduction in all red, white and platelet blood cells) Results from an aplasia (reduction/destruction of the tissue) of the bone marrow Cause is probably autoimmune Microscopically appears as hypocellular bone marrow No evidence of marrow fibrosis or malignancy Classification Constitutional / inherited Causes 25% of childhood AA Rarely adult AA Inherited? Family history Somatic abnormailities Forms Fanconi anaemia Dykeratosis congenita Schwachmann-diamond syndrome Reticular dysgenesis Acquired In most cases, no cause is identified (= idiopathic) Causes can include Direct bone marrow toxicity Ionising radiation Chemicals (e.g. benzene; organic solvents; insecticides) Drugs Anti-rheumatics Anti-inflammatory Anti-convulsants Anti-thyroids Anti-depressants Anti-diabetics Anti-malarials Immune-mediated Pregnancy Idiosyncratic drug reaction (individual's react to drugs differerntly) Viruses (EBV, parvovirus (causes fifth's disease in children), HIV) Transfusion-associated Graft versus host disease (TA-GVHD) T-lymphocytes in donor blood start an immune reaction against the recipient Eosinophilic fasciitis Eosinophil-mediated inflammation of the fascias (connective tissue around; muscles, nerves, blood vessels) Diagnosis Full blood count (FBC) Hb <10g/dL Platelets <50 Neutrophils <1.5 Everything is LOW Reticulocyte count (= low) Blood film Normal looking cells, but reduced in number / absent Bone marrow aspirate and trephine (and cytogenetics) Trephine = cyclindrical core biopsy of bone+marrow Exclude other causes of pancytopaenia Vit. B12 and folate levels Liver function tests BM and cytogenetics - exclude myelodysplasia (MDS) Exclude drug causes Liver function and virology Test for paroxysmal nocturnal haemoglobinuria Treatment Supportive care Blood product replacement Bone marrow transplant Avoid HLA sensitisation and cytomegalo virus (CMV) exposure Antimicrobials Growth factors Specific therapy for AA Aimed at functional peripheral blood count recovery Depends on: type of AA, age and donor availability Immunosupression Bone marrow transplant Up to 80% patients are cured Typically reserved with sibling matches (HLA matching) G-CSF May cause monosomy 7 in children Oxymethalone Androgenic steroid hormone -> increases erythropoiesis and BM recovery Splenectomy 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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