Card Set Information
Haematology week leukemia
Erythropoiesis, leukemia, anaemia
What are the requirements for erythropoiesis?
Correct gene sequence
Components - iron, b12, folate, minerals
Functioning bone marrow
No increased loss/destruction (for haemoglobin)
- 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
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.
- 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.
What are the clinical findings of haemolytic anaemia?
Polychromatic, spherocytic cells if congenital.
Define haemolytic anaemia and outline the causes and treatment
Anaemia related to a reduced RBC lifespan, with no blood loss or haematinic deficiency
Abnormal RBC enzymes, e.g. pyruvate kinase or G6P
Autoimmunity (warm IgG or cold IgM)
Isoimmune (haemolytic disease of infant)
Non immune (fragmentation, e.g. mechanical valve)
What are the clinical features and findings of iron deficiency anaemia?
Hypochromic and microcytic cells in blood smear
Increased transferrin concentration, reduced saturation
Low serum ferritin (acute phase protein = variable)
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
What are the causes of B12 and folate deficiency
Ileal disorders e.g. Crohns
Dietary, e.g. extensive small bowel disease
Increased cell turnover, e.g. haemolysis or skin disorders
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
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
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
Define aplastic anaemia
When the bone marrow does not produce sufficient new cells to replenish destroyed cells. I.e. Bone marrow failure.
- Clinical features
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
Outline the treatment of Fanconi's anaemia
Allogeneic stem cell transplant
Lifetime surveillance for secondary tumours
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
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
Outline the prognosis and treatment of myelodysplastic syndromes
depends on the % of bone marrow which is blasts, karyotype and cytopenias
Iron chelation, growth factors or immunosuppresion if very aggressive
Describe methods for taking a bone marrow biopsy
: 'Liquid blood' showing a mixture of cells
'A solid core of bone, with bone and fat spaces. Allows architecture to be investigated
What are the indications for a bone marrow transplant?
In malignancy, to utilise graft vs leukemia effect
Acute and chronic leukemias
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
What is the difference between a 'mini' and a 'myeloblative' bone marrow transplant
: Patient given immunosuppressive treatment and transplant given. Used for older, weaker patients
: 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
Outline the difference between Hodgkins and non-Hodgkins
: Characteristic spread to adjacent nodes, with no hepatosplenomegaly. Usually presents in teens-middle age.
: A wide variety of lymphomas, either localised or general. Only usually presents in 60+
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.
What are the clinical features of Hodgkins lymphoma
Fever, with no infection
Weight loss; more than 10% of body in 6 months
Alcohol induced lymph node pain; rare but very specific
Outline the investigations for Hodgkins lymphoma
anaemia, WBC [raised or low] and platelets [high]. ESR
LFTs + renal, LDH
CT and PET for lymphadenopathy
Aspirate/trephine for staging + infiltration
What is the Ann Arbor staging system?
: Single lymph node region
: 2 or more nodes on same side of diaphragm
: Nodes on both side of diaphragm
: Disseminated disease, in marrow, liver etc.
: Presence or absence of B symptoms: fever, night sweats, weight loss.
How are different stages of lymphoma treated?
: 3 courses ABVD and radiotherapy of involved node/field
: 6 courses ABVD and/or radiotherapy
Follow ups important due to effects of radio/chemo, e.g. cardiac, pulmonary, endocrine and malignancy
High grade lymphoma
- Clinical features
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
Low grade lymphoma
- Clinical features
Non-hodgkins, indolent lymphoma
Usually between 60-65yoa male. Asymptomatic, diffuse lymphadenopathy, B symptoms. Late presentation
Conservative. If progressing, rituximab and chemo.
How is a non-hodgkins lymphoma diagnosed?
Fine needle aspirate
: cell markers (e.g. CD20)
- Clinical features
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.
What investigations are performed for multiple myeloma? What can be expected?
: Increased Ig or hypercalcaemia
: Monoclonal band
: basophilic cytoplasm, monomorphic infiltration, eccentric nuclei
: Bone lesions
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
How do acute leukemias commonly present?
- Age groups
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)
What blood abnormalities are normally found in acute leukemias?
: Anaemia, neutropenia, thrombocytopenia
: Monoblasts and myeloblasts
: Cell markers = subtype + chronicity
: Cell marker predominance
What chromosomal abnormalities can be found in acute leukemias?
: 15-17 or 8-21 translocation.
Philadelphia chromosome (95% of CML but also ALL)
Outline supportive care for acute leukemias
BM removal with replacement transfusions
Palliative transfusions; platelet, granulocyte, RBC
Antibiotics; prophylaxis and treatments
Outline different treatments for acute leukemias, and their problems
: Selectively used due to toxicity. Higher mortality but reduced relapse
: Steroids, monoclonal Ig. High morbidity; sterility, mucositis, bleeding, infection.
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
What are the typical investigative abnormalities found in chronic lymphoid leukemia?
: Lymphocytosis - clonal b cells
: T cell antigen overexpression
: small lymphoid cells, with condense chromatin (mature cells)
: Nodular/diffuse infiltration
: Chromosomal abnormalities
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
Outline management of the chronic leukemias
: Watch for infection, autoimmune haemolytic anaemia, pure red cell aplasia and treat if present
: Imatinib most commonly used - tyrosine kinase blocks proliferation. Correct cytogenetics and normalise blood count main goals.