My Haematology

  1. What are the requirements for erythropoiesis?
    • Erythropoietin
    • Correct gene sequence
    • Components - iron, b12, folate, minerals
    • Functioning bone marrow
    • No increased loss/destruction (for haemoglobin)
  2. B12 (Cobalamin)
    - Digestion
    - Metabolism
    - Sources
    - Deficiency features
    • B12 released by stomach. Parietal cells produce intrinsic factor = binds. Complex binds with cubulin (in ileum) then transported by transcobalamin
    • Used in homocysteine methylation to methionine
    • Found in meat, dairy. Microorganism synthesis.
    • Stores last 3-4 yrs. 1-2µg lost daily. Periphery neuropathy, pyramidal tract demyelination
  3. Folate
    - Digestion
    - Metabolism
    - Sources
    - Deficiency
    - Investigations
    • Absorbed in small bowel with no carrier molecules
    • Used in end product of DNA
    • Green vegetables, destroyed by cooking
    • Stores last days. Dysfunction of rapidly dividing tissues = reduced nuclear vs cytoplasm synthesis. Fetal tissue and bone marrow
    • Blood markers are raised bilirubin an LDH.
  4. Haemoglobinopathies
    - Define thalassaemia
    - Define Sickle cell disease
    • Inherited condition, with mutation affecting a globin protein. Presentation and severity depends on protein affected.
    • Polymerisation of haemoglobin creating Hb S. This de and repolymerises frequently causing RBC morphology to change.
  5. What are the clinical findings of haemolytic anaemia?
    • Reduced Haemoglobin
    • Increased reticulocytes
    • Increased bilirubin
    • Splenomegaly
    • Polychromatic, spherocytic cells if congenital.
  6. Define haemolytic anaemia and outline the causes and treatment
    • Anaemia related to a reduced RBC lifespan, with no blood loss or haematinic deficiency
    • Congenital:
    • Haemoglobinopathies
    • Abnormal RBC enzymes, e.g. pyruvate kinase or G6P
    • Acquired:
    • Autoimmunity (warm IgG or cold IgM)
    • Isoimmune (haemolytic disease of infant)
    • Non immune (fragmentation, e.g. mechanical valve)
  7. What are the clinical features and findings of iron deficiency anaemia?
    • Clinical features:
    • Gradual onset
    • Koilonychia
    • Fatigue
    • Clinical findings:
    • Reduced haemoglobin
    • Hypochromic and microcytic cells in blood smear
    • Increased transferrin concentration, reduced saturation
    • Low serum ferritin (acute phase protein = variable)
  8. What are the findings in the anaemia of chronic disease?
    • Mean corpuscular volume reduction - microcytic
    • Mean corpuscular haemoglobin reduction - hypochromic
    • ESR and ferritin raised
    • Iron and transferrin (TIBC) lowered
    • Rouleax seen in blood smear - 'stack' of RBCs
  9. What are the causes of B12 and folate deficiency
    • B12:
    • Pernicious anaemia
    • Gastrectomy/achlorhydria
    • Ileal disorders e.g. Crohns
    • Folate:
    • Dietary, e.g. extensive small bowel disease
    • Increased cell turnover, e.g. haemolysis or skin disorders
  10. Describe the approach to investigating anaemic patients
    • IDA in males/post menopausal females is due to GI blood loss unless proven otherwise
    • In young women, IDA caused by menstruation/pregnancy. GI investigated only if symptoms or FOB
  11. Outline the pathogenesis of a stem cell clonal disorder
    • A healthy haemopoietic stem cell is affected by a mutagen, becoming leukaemogenic.
    • Pluriporten stem cell either becomes abnormal, or a primitive progenitor gains self renewing ability = clonal haemopoietic disorder
    • Causes a raised number of abnormal blast cells in blood, either myeloid or lymphoid
    • Leukemia is a clonal disorder of WBCs
  12. Outline the pathogenesis of myeloproliferative disorders
    • An over production of a single myeloid ancestral cell = one or more mature, functional blood progeny
    • Associated with JAK receptor mutations, causing continuous activation and reduced apoptosis
    • May transform into an acute leukemia
    • Examples include polycythemia rubra vera, essential thrombocytosis and myelofibrosis
  13. Define aplastic anaemia
    When the bone marrow does not produce sufficient new cells to replenish destroyed cells. I.e. Bone marrow failure.
  14. Fanconi's anaemia
    - Inheritance
    - Clinical features
    - Pathophysiology
    • Autosomal recessive inheritance, onset till adulthood
    • Short stature, limb abnormalities, skin hypo/hyperpigmentation, mental retardation, hearing loss, GU/GI/CNS abnormalities
    • Loss of telomere maintenance + increased TNF + oxidative stress = chromosomal instability = BM failure and malignancy
  15. Outline the treatment of Fanconi's anaemia
    • Screening
    • Allogeneic stem cell transplant
    • Coricosteroids
    • Androgens
    • Lifetime surveillance for secondary tumours
  16. Define a myelodysplastic syndrome
    • Disease characterised by dysplasia and ineffective haemopoiesis in more than one myeloid series
    • Can be spontaneous or secondary to radio/chemo
    • Aggressiveness = increased myeloblasts
  17. Describe the pathophysiology of myelodysplastic syndromes
    • Often associated with acquired cytogenetic abnormalities, e.g. monosomy 5 or 7, trisomy 8
    • Characterised by progressive bone marrow failure: reduced haemopoiesis and haematocrit
    • Some progress to more aggressive conditions e.g. AML
    • The incidence increases with age, but usually an incidental finding investigating fatigue and anaemia
  18. Outline the prognosis and treatment of myelodysplastic syndromes
    • Prognosis: depends on the % of bone marrow which is blasts, karyotype and cytopenias
    • Treatment: Iron chelation, growth factors or immunosuppresion if very aggressive
  19. Describe methods for taking a bone marrow biopsy
    • Aspirate: 'Liquid blood' showing a mixture of cells
    • Trephine: 'A solid core of bone, with bone and fat spaces. Allows architecture to be investigated
  20. What are the indications for a bone marrow transplant?
    • In malignancy, to utilise graft vs leukemia effect
    • Acute and chronic leukemias
    • Relapsed lymphoma
    • Aplastic anaemia
    • Hereditary disorders
  21. How is an apheresis bone marrow transplant taken?
    • Patient given G-CSF and chemotherapy to mobilise cells
    • Cells removed by a needle
    • Blood spun in the machine
    • Stem cells removed and frozen
    • Chemotherapy and radiotherapy given to recipient and stemm cells reperfused
  22. What is the difference between a 'mini' and a 'myeloblative' bone marrow transplant
    • Mini: Patient given immunosuppressive treatment and transplant given. Used for older, weaker patients
    • Myeloblative: chemotherapy or total body irradiation given and immune system destroyed. Marrow transplant given and system replaced.
  23. Define lymphoma
    A cancer of lymphoid cells, commonly found in lymph nodes, with a wide bariation in clinical behaviour and prognosis depending on sub-type
  24. Outline the difference between Hodgkins and non-Hodgkins
    • Hodgkins: Characteristic spread to adjacent nodes, with no hepatosplenomegaly. Usually presents in teens-middle age.
    • Non-hodgkins: A wide variety of lymphomas, either localised or general. Only usually presents in 60+
  25. Describe the pathology of Hodgkins
    • Malignant cell is the 'reed-sternberg' cell: giant cells
    • Majority of cells are reactive in a Hodgkins lymphoma node
    • Painless lymphadenopathy spreading to adjacent nodes
    • In later stages, haemogenous spread to liver, lungs and marrow.
  26. What are the clinical features of Hodgkins lymphoma
    • Fever, with no infection
    • Night sweats
    • Weight loss; more than 10% of body in 6 months
    • Generalised pruritis
    • Alcohol induced lymph node pain; rare but very specific
  27. Outline the investigations for Hodgkins lymphoma
    • Bloods: anaemia, WBC [raised or low] and platelets [high]. ESR
    • Biochemistry: LFTs + renal, LDH
    • Imaging: CT and PET for lymphadenopathy
    • Biopsy: Aspirate/trephine for staging + infiltration
  28. What is the Ann Arbor staging system?
    • Stage 1: Single lymph node region
    • Stage 2: 2 or more nodes on same side of diaphragm
    • Stage 3: Nodes on both side of diaphragm
    • Stage 4: Disseminated disease, in marrow, liver etc.
    • A/B: Presence or absence of B symptoms: fever, night sweats, weight loss.
  29. How are different stages of lymphoma treated?
    • Early (1a-2a): 3 courses ABVD and radiotherapy of involved node/field
    • Advanced (>2b): 6 courses ABVD and/or radiotherapy
    • Follow ups important due to effects of radio/chemo, e.g. cardiac, pulmonary, endocrine and malignancy
  30. High grade lymphoma
    - Definition
    - Clinical features
    - Treatment
    • Aggressive non-hodkins lymphoma type, e.g. diffuse large b cell
    • Localised with rapid growth and earlier presentation.
    • If 1a - 3 courses combined mod. If >1a - 6 courses
  31. Low grade lymphoma
    - Definition
    - Clinical features
    - Treatment
    • Non-hodgkins, indolent lymphoma
    • Usually between 60-65yoa male. Asymptomatic, diffuse lymphadenopathy, B symptoms. Late presentation
    • Conservative. If progressing, rituximab and chemo.
  32. How is a non-hodgkins lymphoma diagnosed?
    • Clinical features
    • Fine needle aspirate
    • Trephine biopsy
    • Immunohistochemistry
    • Flow cytometry: cell markers (e.g. CD20)
    • Cytogenetics/molecular studies
  33. Multiple myeloma
    - Definition
    - Clinical features
    - Treatment
    • Neoplastic proliferation of plasma cells in bone marrow
    • Lytic lesions in bones. Anaemia. Renal failure. Hypercalcaemia. Infection (low Ig and neutropenia)
    • Thalidomide, but usually incurable.
  34. What investigations are performed for multiple myeloma? What can be expected?
    • FBC: Anaemia
    • Biochemistry: Increased Ig or hypercalcaemia
    • Ig electrophoresis: Monoclonal band
    • BM aspirate: basophilic cytoplasm, monomorphic infiltration, eccentric nuclei
    • Imaging: Bone lesions
  35. Outline the pathogenesis of acute leukemias
    • An acquired clonal disorder; cells descended from a mutated bone marrow cell
    • Mutations = no maturation and increased proliferation
    • Blastic proliferation in bone marrow = failure
  36. How do acute leukemias commonly present?
    - Age groups
    - Signs
    - Symptoms
    • ALL most common in children (80-90% of cases), AML most common in adults
    • Rapid onset. Infection (pancytopenia). Mucosal swelling. Bleeding/bruising. Liver/lymph swelling. Retinal haemorrhage.
    • Bone pain. Lethargy (anaemia)
  37. What blood abnormalities are normally found in acute leukemias?
    • Blood count: Anaemia, neutropenia, thrombocytopenia
    • Blood smear: Monoblasts and myeloblasts
    • Flow cytometry: Cell markers = subtype + chronicity
    • Immunohisto: Cell marker predominance
  38. What chromosomal abnormalities can be found in acute leukemias?
    • AML: 15-17 or 8-21 translocation.
    • Philadelphia chromosome (95% of CML but also ALL)
  39. Outline supportive care for acute leukemias
    • BM removal with replacement transfusions
    • Palliative transfusions; platelet, granulocyte, RBC
    • Antibiotics; prophylaxis and treatments
  40. Outline different treatments for acute leukemias, and their problems
    • BM transplant: Selectively used due to toxicity. Higher mortality but reduced relapse
    • Chemotherapy: Steroids, monoclonal Ig. High morbidity; sterility, mucositis, bleeding, infection.
  41. Outline the clinical presentation of chronic leukemias
    • Usually asymptomatic, with 50% of cases incidental
    • Classic B symptoms and increased infection risk
    • Genetics the main factor affecting aggression and presentation
    • In CLL, presentation usually when BM fails = anaemia
    • In CML, presentation can include abdominal pain from splenomegaly
  42. What are the typical investigative abnormalities found in chronic lymphoid leukemia?
    • LN biopsy: Lymphocytosis - clonal b cells
    • Flow cytometry: T cell antigen overexpression
    • Blood smear: small lymphoid cells, with condense chromatin (mature cells)
    • BM biopsy: Nodular/diffuse infiltration
    • Ctyogenetics: Chromosomal abnormalities
  43. What are the typical investigative abnormalities found in chronic myeloid leukemia?
    • Neutrophilia, with sometimes other lineages proliferating
    • Shift towards immature cells - may become acute "blast crisis"
    • Philadelphia gene the ONLY cause of CML
  44. Outline management of the chronic leukemias
    • CLL: Watch for infection, autoimmune haemolytic anaemia, pure red cell aplasia and treat if present
    • CML: Imatinib most commonly used - tyrosine kinase blocks proliferation. Correct cytogenetics and normalise blood count main goals.
Card Set
My Haematology
Erythropoiesis, leukemia, anaemia