Haematology Flashcards
What is myeloma?
Malignancy of plasma cells leading to progressive bone marrow failure. It is associated with production of characteristic paraprotein, bone disease and renal failure.
In order to make a diagnosis of myeloma, there must be evidence of mono-clonality. What is mono-clonality?
Abnormal proliferation of a single clone of plasma cell leading to immunoglobulin secretion and causing organ dysfunction especially to the kidney.
What disease often precedes myeloma?
Monoclonal gammopathy of undetermined significance (MGUS).
What is MGUS?
A common disease with paraprotein present in the serum but no myeloma. Often asymptomatic. <10% plasma cells in the bone marrow.
In approximately 2/3 of people with myeloma, what might their urine contain?
Immunoglobulin light chains with kappa or lamda lineage.
Give 3 symptoms of myeloma.
- Tiredness.
- Bone/back pain.
- Infections.
Give 4 signs of myeloma.
CRAB!
1. Calcium is elevated.
2. Renal failure.
3. Anaemia.
4. Bone lesions.
Why is calcium elevated in myeloma?
There is increased bone resorption and decreased formation meaning there is more calcium in the blood.
Why might someone with myeloma have anaemia?
The bone marrow is infiltrated with plasma cells. Consequences of this are anaemia, infections and bleeding.
Why might someone with myeloma have renal failure?
Due to light chain deposition.
What investigations might you do in someone who you suspect has myeloma?
- Blood film.
- Bone marrow aspirate and trephine biopsy.
- Electrophoresis.
- X-ray.
- CT scan.
- MRI scan.
- Chromosomal abnormalities.
What would you expect to see on the blood film taken from someone with myeloma?
Rouleaux formation (aggregations of RBC’s).
What are you looking for on a bone marrow biopsy taken from someone with myeloma?
Increased plasma cells.
What are you looking for on electrophoresis in a patient with myeloma?
Monoclonal protein band.
What are you looking for on an X-ray taken from someone with myeloma?
Bone lesions.
What is the treatment for MGUS and asymptomatic myeloma?
Watch and wait.
Describe the treatment for symptomatic myeloma.
Chemotherapy, analgesia and bisphosphonates.
Radiotherapy and bone marrow transplant can also be done.
What is lymphoma?
A malignant growth of WBC’s predominantly in the lymph nodes.
Although predominantly in the lymph nodes, lymphoma is systemic. What other organs might it effect?
- Blood.
- Liver.
- Spleen.
- Bone marrow.
Give 4 risk factors for lymphoma.
- Primary immunodeficiency.
- Secondary immunodeficiency e.g. HIV.
- Infection e.g. EBV, HTLV-1.
- Autoimmune disorders e.g. RA.
Describe the pathophysiology of lymphoma.
There is impaired immunosurveillance and infected B cells escape regulation and proliferate. (This is just a theory).
Give 4 symptoms of lymphoma.
- Enlarged lymph nodes in arm/neck.
- Symptoms of compression syndromes.
- General systemic ‘B’ symptoms e.g. weight loss, night sweats, malaise.
- Liver and spleen enlargement.
What investigations might you do in someone who you suspect has lymphoma?
- Blood film.
- Bone marrow biopsy.
- Lymph node biopsy.
- Immunophenotyping.
- Cytogenetics.
What are the two sub-types of lymphoma?
- Hodgkins lymphoma.
- Non-hodgkins lymphoma.
What are the symptoms of Hodgkins lymphoma?
- Painless lymphadenopathy.
- Presence of ‘B’ symptoms e.g. night sweats, weight loss.
What is needed for diagnosis of Hodgkins lymphoma?
Presence of Reed-sternberg cells.
Describe the staging of Hodgkins lymphoma.
- Stage 1: confined to a single lymph node region.
- Stage 2: Involvement of two or more nodal areas on the same side of the diaphragm.
- Stage 3: involvement of nodes on both sides of the diaphragm.
- Stage 4: Spread beyond the lymph nodes e.g. liver.
Each stage is either ‘A’ - absence of ‘B’ symptoms or ‘B’ - presence of ‘B’ symptoms.
What is the treatment for stage 1 - 2A Hodgkins lymphoma?
Short course combination chemotherapy followed by radiotherapy.
What is the treatment for stage 2B - 4 Hodgkins lymphoma?
Combination chemotherapy.
What are the possible complications of treatment for Hodgkins lymphoma?
- Secondary malignancies.
- IHD.
- Infertility.
- Nausea.
- Alopecia.
Describe low grade non-hodgkins lymphoma.
Slow growing, advanced at presentation, often incurable. Median survival is 10 years.
What is the treatment for low grade non-hodgkins lymphoma?
If symptomless - do nothing.
Radiotherapy, combination chemotherapy and mAb may be used if symptomatic.
Describe high grade non-hodgkins lymphoma.
Aggressive. Nodal presentation, patient unwell. Often curable.
Describe the treatment for high grade non-hodgkins lymphoma.
- Early: short course chemotherapy and radiotherapy.
- Advanced: combination chemotherapy and mAb.
What is leukaemia?
A malignant proliferation of haemopoietic stem cells.
Name 4 sub-types of leukaemia.
- AML - acute myeloid leukaemia.
- CML - chronic myeloid leukaemia.
- ALL - acute lymphoblastic leukaemia.
- CLL - chronic lymphoblastic leukaemia.
What is acute myeloid leukaemia?
Neoplastic proliferation of blast cells.
What can increase the risk of developing AML?
- Preceding haematological disorders.
- Prior chemotherapy.
- Exposure to ionising radiation.
Give 5 symptoms of leukaemia.
- Anaemia.
- Infection.
- Bleeding.
- Hepatomegaly.
- Splenomegaly.
Why are anaemia, infection and bleeding symptoms of leukaemia?
Because of bone marrow failure.
Why are hepatomegaly and splenomoegaly symptoms of leukaemia?
Because of tissue infiltration.
What investigations might you do on someone who you suspect has leukaemia?
- Blood film.
- Bone marrow biopsy.
- Lymph node biopsy.
- Immunophenotyping.
- Cytogenetics.
Describe the treatment for AML.
- Supportive care.
- Chemotherapy: curative v palliative.
- Bone marrow transplant.
What is CML?
Chronic myeloid leukaemia, there is uncontrolled clonal proliferation of basophils, eosinophils and neutrophils.
What would the FBC from someone with CML look like?
High WBC’s.
What chromosome is present in >80% of people with CML?
Philadelphia chromosome.
What is the treatment for CML?
Tyrasine kinase inhibitors.
What is ALL?
Acute lymphoid leukaemia. There is uncontroleld proliferation of immature lymphoblast cells.
What is the treatment for ALL?
CNS directed therapy and stem cell transplant.
What is CLL?
Chronic lymphoid leukaemia. Proliferation of B lymphocytes leads to the accumulation of mature B cells that have escaped apoptosis.
What is the treatment for CLL?
- Do nothing.
- Chemotherapy.
- mAb.
- Bone marrow transplant.
Name the 3 broad categories of red cell disorders.
- Haemoglobinopathies.
- Membranopathies.
- Enzymopathies.
What is normal adult haemoglobin made of?
2 alpha and 2 beta chains.
What is foetal haemoglobin made of?
2 alpha and 2 gamma chains.
What is haemoglobin S?
Haemoglobin S is a variant of Hb arising from a point mutation in the beta globin gene. The mutation leads to a single amino acid change, valine -> glutamine.
What is sickle cell disease?
A haemoglobin disorder of quality. HbS polymerises -> sickle shaped RBC.
What is the advantage of being a carrier of sickle cell disease?
Carriage offers protection against falciparum malaria.
Describe the inheritance pattern of sickle cell disease.
Autosomal recessive. Sickle cell disease is homozygous SS.
If both parents are carriers of the sickle trait. What is the chance that their first child will have sickle cell disease?
Their offspring have a 1/4 chance of being affected with a sickle cell disease. (50% chance of being a carrier).
How long do sickle cells last for?
5-10 days - this explains why sickle cell disease is described as haemolytic.
Give 4 acute complications of sickle cell disease.
- Very painful crisis.
- Stroke in children.
- Cognitive impairment.
- Infections.
Give 3 chronic complications of sickle cell disease.
- Renal impairment.
- Pulmonary hypertension.
- Joint damage.
Describe the treatment for sickle cell disease.
- Transfusion.
- Hydroxycarbamide.
- Stem cell transplant.
What is thalassaemia?
A haemoglobin disorder of quantity. There is reduced synthesis of one or more globin chains with leading to a reduction in Hb -> anaemia.
If someone has beta thalassaemia do they have more alpha or beta globin chains?
They have very few beta chains, alpha chains are in excess.
What is the clinical classification of beta thalassaemia?
- Thalassaemia major.
- Thalassaemia intermedia.
- Thalassaemia carrier/heterozygote.
Which clinical classification of thalassaemia relies on regular transfusions?
Thalassaemia major.
Which clinical classification of thalassaemia is often asymptormatic?
Thalassaemia carrier/heterozygote.
When do people with beta thalassaemia major usually present and why?
These patients usually present very young due to having severe anaemia and so a failure to feed/thrive.
Why is it important to monitor iron levels in someone with beta thalassaemia major?
There is a risk of iron overload from the regular trasnfusions. Excess iron will be deposited in various organs e.g. the liver and spleen and cause fibrosis.
What is the significance of parvovirus for someone with sickle cell disease?
Parvovirus is a common infection in children. It leads to decreased RBC production and can cause a dramatic drop in Hb in patients who already have a reduced RBC lifespan. This can be dangerous for someone with sickle cell.
Describe the inheritance pattern for membranopathies.
Autosomal dominant.
Name 2 common membranopathies.
- Spherocytosis.
- Elliptocytosis.
Briefly describe the physiology of membranopathies.
Deficiency of red cell membrane proteins caused by genetic lesions
What are enzymopathies?
Enzyme deficiencies lead to shortened RBC lifespan.
Name a common enzymopathy.
G6PD deficiency.
Give 3 signs of G6PD deficiency.
Crises characterised by:
1. Haemolysis.
2. Jaundice.
3. Anaemia.
What is anaemia?
A decrease in the amount of Hb in the blood below the reference range.
What is the function of Hb?
It carries and delivers oxygen to tissues.