My Haematology

• Erythropoietin
• Correct gene sequence
• Components - iron, b12, folate, minerals
• Functioning bone marrow
• No increased loss/destruction (for haemoglobin)

• 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

• 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.

• 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.

• Reduced Haemoglobin
• Increased reticulocytes
• Increased bilirubin
• Splenomegaly
• Polychromatic, spherocytic cells if congenital.

• 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)

• 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)

• 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

• 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

• 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

• 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

• 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

When the bone marrow does not produce sufficient new cells to replenish destroyed cells. I.e. Bone marrow failure.

• 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

• Screening
• Allogeneic stem cell transplant
• Coricosteroids
• Androgens
• Lifetime surveillance for secondary tumours

• Disease characterised by dysplasia and ineffective haemopoiesis in more than one myeloid series
• Can be spontaneous or secondary to radio/chemo
• Aggressiveness = increased myeloblasts

• 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

• Prognosis: depends on the % of bone marrow which is blasts, karyotype and cytopenias
• Treatment: Iron chelation, growth factors or immunosuppresion if very aggressive

• Aspirate: 'Liquid blood' showing a mixture of cells
• Trephine: 'A solid core of bone, with bone and fat spaces. Allows architecture to be investigated

• In malignancy, to utilise graft vs leukemia effect
• Acute and chronic leukemias
• Relapsed lymphoma
• Aplastic anaemia
• Hereditary disorders

• 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

• 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.

A cancer of lymphoid cells, commonly found in lymph nodes, with a wide bariation in clinical behaviour and prognosis depending on sub-type

• 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+

• 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.

• 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

• 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

• 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.

• 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

• 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

• Non-hodgkins, indolent lymphoma
• Usually between 60-65yoa male. Asymptomatic, diffuse lymphadenopathy, B symptoms. Late presentation
• Conservative. If progressing, rituximab and chemo.

• Clinical features
• Fine needle aspirate
• Trephine biopsy
• Immunohistochemistry
• Flow cytometry: cell markers (e.g. CD20)
• Cytogenetics/molecular studies

• 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.

• FBC: Anaemia
• Biochemistry: Increased Ig or hypercalcaemia
• Ig electrophoresis: Monoclonal band
• BM aspirate: basophilic cytoplasm, monomorphic infiltration, eccentric nuclei
• Imaging: Bone lesions

• An acquired clonal disorder; cells descended from a mutated bone marrow cell
• Mutations = no maturation and increased proliferation
• Blastic proliferation in bone marrow = failure

• 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)

• Blood count: Anaemia, neutropenia, thrombocytopenia
• Blood smear: Monoblasts and myeloblasts
• Flow cytometry: Cell markers = subtype + chronicity
• Immunohisto: Cell marker predominance

• AML: 15-17 or 8-21 translocation.
• Philadelphia chromosome (95% of CML but also ALL)

• BM removal with replacement transfusions
• Palliative transfusions; platelet, granulocyte, RBC
• Antibiotics; prophylaxis and treatments

• BM transplant: Selectively used due to toxicity. Higher mortality but reduced relapse
• Chemotherapy: Steroids, monoclonal Ig. High morbidity; sterility, mucositis, bleeding, infection.

• 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

• 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

• Neutrophilia, with sometimes other lineages proliferating
• Shift towards immature cells - may become acute "blast crisis"
• Philadelphia gene the ONLY cause of CML

• 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.