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!
- Calcium is elevated.
- Renal failure.
- Anaemia.
- 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.
2. Non-hodgkins lymphoma.
What are the symptoms of Hodgkins lymphoma?
- Painless lymphadenopathy.
2. 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.
2. 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:
- Haemolysis.
- Jaundice.
- 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.
What organs are responsible for removal of RBC’s?
- Spleen.
- Liver.
- Bone marrow.
- Blood loss.
Give 3 causes of microcytic anaemia.
- Iron deficiency.
- Anaemia of chronic disease.
- Thalassaemia.
Give 3 causes of normocytic anaemia.
- Acute blood loss.
- Anaemia of chronic disease.
- Combined hematinic deficiency.
Give 3 causes of macrocytic anaemia.
- B12/folate deficiency.
- Alcohol excess/liver disease.
- Hypothyroid.
Where is B12 absorbed?
The terminal ileum.
Explain how pernicious anaemia leads to B12 deficiency.
Pernicious anaemia leads to a loss of parietal cells -> reduced intrinsic factor production -> vitamin B12 malabsorption.
Give 5 causes of iron deficiency.
- Blood loss.
- Poor absorption.
- Decreased intake in diet.
- Hook worm!
- Breastfeeding, low iron in breast milk.
Give 3 symptoms of anaemia.
- Fatigue.
- Faintness.
- Breathlessness.
- Reduced exercise tolerance.
What investigations might you do in someone with anaemia?
- Blood tests: FBC and blood film.
- Biopsies.
- Reticulocyte count.
- B12 levels.
- Serum ferritin.
What is the treatment for anaemia?
Treat the underlying cause e.g. if iron deficient give ferrous sulphate.
What is polycythaemia?
Too many RBC’s, an increase in Hb.
What hormone is responsible for regulating RBC production?
Erythropoietin.
What stimulates EPO?
Tissue hypoxia.
Name a primary cause of polycythaemia.
Polycythaemia rubra vera - over reactive bone marrow.
Give 3 secondary causes of polycythaemia.
- Heavy smoking.
- Lung disease.
- Cyanotic heart disease.
- High altitude.
What is the treatment for polycythaemia?
- If a secondary cause treat the underlying cause.
2. If a primary cause, treatment aims to maintain a normal blood count and prevent complications e.g. aspirin.
What is neutrophilia?
Too many neutrophils.
Give 3 causes of neutrophilia.
- Infection.
- Inflammation.
- CML.
- Cancer.
What is lymphocytosis?
Too many lymphocytes.
Give 3 causes of lymphocytosis.
- Viral infections.
- Inflammation.
- Malignancy.
- CLL.
What is thrombocytopenia?
Not enough platelets.
Give 2 causes of thrombocytopenia.
- Production failure e.g. marrow suppression, marrow failure.
- Increased removal e.g. immune response (ITP), consumption (DIC), splenomegaly.
What is thrombocytosis?
Too many platelets.
What is neutropenia?
Not enough neutrophils.
What is the major risk associated with being neutropenic?
Susceptible to infection.
Give 3 causes of neutropenia.
- Marrow failure.
- Marrow infiltration.
- Marrow toxicity.
Where are platelets produced?
In the bone marrow. They are fragments of megakaryocytes.
What hormone regulates platelet production?
Thrombopoietin - produced mainly in the liver.
What is the lifespan of a a platelet?
7 - 10 days.
What organ is responsible for platelet removal?
The spleen.
What can cause platelet dysfunction.
- Reduced platelet number (thrombocyotpenia).
2. Reduced platelet function.
Platelet dysfunction: what can cause decreased platelet production?
- Congenital causes e.g. malfunctioning megakaryocytes.
- Infiltration of bone marrow e.g. leukaemia.
- Alcohol.
- Infection e.g. HIV/TB.
Platelet dysfunction: what can cause increased platelet destruction?
- Autoimmune e.g. ITP.
- Hypersplenism.
- Drug related e.g. heparin induced.
- DIC and TTP -> increased consumption.
Platelet dysfunction: what can cause reduced platelet function?
- Congenital abnormality.
- Medication e.g. aspirin.
- VWF disease.
- Uraemia.
Give 3 symptoms of platelet dysfunction.
- Mucosal bleeding.
- Easy bruising.
- Petechiae/purpura.
Give 4 causes of bleeding.
- Trauma.
- Platelet deficiency e.g. thrombocytopenia.
- Platelet dysfunction e.g. aspirin induced.
- Vascular disorders.
What is the definition of febrile neutropenia.
Temperature >38°C in a patient with neutrophil count <1x10^9/L.
Give 4 risk factors for febrile neutropenia.
- If the patient had chemotherapy <6 weeks ago.
- Any patient who has had a stem cell transplant <1 year ago.
- Any haematological condition causing neutropenia.
- Bone marrow infiltration.
What is the presentation of febrile neutropenia?
- Pyrexia, 38°C.
- Generally unwell.
- Confusion.
- Hypotensive.
- Tachycardic.
Describe the management of febrile neutropenia.
- Thorough history and examination.
- Bloods.
- Antibiotics within 1 hour!
Give a risk factor for spinal cord compression.
Any malignancy that can cause compression e.g. bone metastasis.
Describe the presentation of spinal cord compression.
- Back pain.
- Weakness in legs.
- Inability to control bladder.
- Spastic paresis.
- Sensory level.
Describe the management of spinal cord compression.
- Bed rest.
- High dose steroids.
- Analgesia.
- Urgent MRI of the whole spine.
What is tumour lysis syndrome?
Break down of malignant cells -> content release -> metabolic disturbances; can cause hyperuricaemia, hyperkalaemia, hypocalcaemia.
Give 3 risk factors for tumour lysis syndrome.
- High tumour burden.
- Pre-existing renal failure.
- Increasing age.
Describe the treatment of tumour lysis syndrome.
- Aggressive hydration.
- Monitor electrolytes.
- Drugs to reduce uric acid production e.g. allopurinol.
What is hyperviscosity syndrome?
Increase in blood viscosity usually due to high levels of immunoglobulins.
Give 2 consequences of hyperviscosity syndrome.
- Vascular stasis.
2. Hypoperfusion.
Describe the presentation of hyperviscosity syndrome.
- Mucosal bleeding.
- Visual change.
- Neurological disturbances.
- Breathlessness.
- Fatigue.
What investigations might you do in someone who you suspect has hyperviscosity syndrome?
- FBC and blood film; look for rouleaux formation.
- U&E.
- Immunoglobulins.
What is the treatment for hyperviscosity syndrome?
- Keep hydrated!
- Avoid blood transfusion.
- Treat the underlying cause.
Give 5 signs/symptoms of hypercalcaemia.
- Confusion.
- Bone pain.
- Constipation.
- Nausea.
- Abdominal pain.
What might you see in the ECG taken from someone with hypercalcaemia.
Shortened QT interval.
Hypercalcaemia = risk of MI.
What is the treatment for hypercalcaemia?
IV hydration and bisphosphonates.
What does rituximab target?
Targets CD20 on the surface of B.
What is the characteristic genetic abnormality in chronic myeloid leukaemia?
t(9; 22) - philadelphia chromosome.
How is myeloma bone disease usually assessed?
X-ray.
What is the commonest cause of microcytic anaemia?
Iron deficiency.
What is the affect of sickle cell anaemia on reticulocyte count?
Reticulocyte count is raised.
Why is reticulocyte count raised in sickle cell anaemia?
Sickle cell disease is haemolytic, there is increased degradation of RBC’s. Production therefore increases in order to keep up with degradation and so reticulocyte count is raised.
What clotting factors depend on vitamin K?
2, 7, 9 and 10.
Haemophilia A is due to deficiency of what clotting factor?
Factor 8 deficiency.
Haemophilia B is due to deficiency of what clotting factor?
Factor 9 deficiency.
Give 4 symptoms of ALL.
- Bone pain.
- Recurrent infections (neutropenia).
- Pale and tired (anaemia).
- Bruising (low platelets).
Is ALL more common in adults or children?
ALL is mainly a childhood disease.
What kind of anaemia could methotrexate cause?
Macrocytic due to folate deficiency.
Give 4 causes of folate deficiency.
- Dietary.
- Malabsorption.
- Increased requirement e.g. in pregnancy.
- Folate antagonists e.g. methotrexate.
Give 3 signs of haemolytic anaemia.
- Pallor.
- Jaundice.
- Splenomegaly.
Give 4 causes of haemolytic anaemia.
- GP6D deficiency.
- Sickle cell anaemia.
- Spherocytosis/elliptocytosis (membranopathies).
- Autoimmune haemolytic anaemia.
Give 3 things that can cause coagulation disorders.
- Vitamin K deficiency.
- Liver disease.
- Congenital e.g. haemophilia.
How does warfarin work?
It antagonises vitamin K and so you get a reduction in clotting factors 2, 7, 9 and 10.
How does heparin work?
It activates antithrombin which then inhibits thrombin and factor Xa.
What is disseminated intravascular coagulation (DIC)?
Pathological activation of the coagulation cascade -> fibrin in vessel walls. There is platelet (thrombocytopenia) and coagulation factor consumption.
Give 3 causes of disseminated intravascular coagulation (DIC).
- Sepsis.
- Major trauma.
- Malignancy.
What is the affect on TT, PTT and APTT in someone with disseminated intravascular coagulation (DIC)?
All increased.
What is the affect on fibrinogen in someone with disseminated intravascular coagulation (DIC)?
Decreased.
Give 5 risk factors for DVT.
- Increasing age.
- Obesity.
- Pregnancy.
- OCP (hyper-coagulability).
- Major surgery.
- Immobility.
- Past DVT.
Give 3 symptoms of DVT.
Unilateral warm, tender, painful, swollen leg.
What forms the differential diagnosis for a DVT?
Cellulitis.
What investigations might you do in someone to see if they have a DVT?
- D-dimer in those patients with a low clinical probability.
- US compression.
What is the name of the score used to determine someones probability of having a DVT?
The Wells score.
The Wells score determines someones clinical probability of having a DVT. Give 3 factors the score takes into account.
- Active cancer.
- Recently bedridden or major surgery.
- Tenderness along deep venous system.
- Swollen leg/calf.
- Unilateral pitting oedema.
Describe the management for a DVT.
Aim of management is to prevent a PE!
- Anticoagulants e.g. warfarin/heparin.
Explain why philadelphia chromosome causes CML.
Philadelphia chromosome leads to a fusion gene that has tyrosine kinase activity and enhanced phosphorylating activity -> altered cell growth.
Where would you normally take a bone marrow biopsy from?
Posterior iliac crest.
What is the most important medical treatment for DVT prophylaxis?
LMWH.
What is the affect of iron deficiency anaemia on iron binding capacity?
Iron binding capacity will be raised.
Why might measuring serum ferritin be inaccurate for looking at iron levels?
Ferritin is an acute phase protein and so its concentration will increase in response to inflammation.
Describe the treatment for iron deficiency anaemia.
Ferrous sulphate tablets.
What is aplastic anaemia?
When bone marrow stem cells are damaged -> pancytopenia.
Give 3 symptoms of iron-deficiency anaemia.
- Koilonychia.
- Brittle hair and nails.
- Atrophic glossitis.
- Tiredness, reduced exercise tolerance.
- SOB.
What is the difference between Raynaud’s disease and Raynaud’s phenomenon?
Raynaud’s disease is idiopathic.
Raynaud’s phenomenon can be due to SLE, scleroderma, RA, drugs e.g. beta blockers.
Describe the pathophysiological mechanism behind Raynaud’s disease.
Peripheral digital ischaemia due to intermittent spasm in arteries that supply the fingers/toes. Precipitated by cold/stress.
Describe the colour changes that are seen in Raynaud’s.
- Pale - due to vasoconstriction.
- Cyanotic - due to deoxygenation.
- Red - due to hyperaemia.
Describe the treatment for Raynaud’s disease.
- Physical protection.
- Vasodilators.
- Nifedipine (CCB).
- Stop smoking.
State two features with regards to red blood cell appearance that would make you think a patient had anaemia due to iron deficiency.
- Hypochromia (pale).
2. Microcytosis.
Suggest 3 ways in which multiple myeloma can lead to AKI.
- Deposition of light chain.
- Hypercalcaemia.
- Hyperuricaemia.
In extreme cases, patients with myeloma can present with blurred vision, gangrene and bleeding. What is the pathology behind this?
Paraproteins form aggregates in the blood and change the viscosity.
Why are patients with myeloma susceptible to recurrent infections?
There is a reduction in polyclonal immunoglobulin levels.
What kind of anaemia is seen in patients with multiple myeloma?
Normochromic normocytic.
What chemotherapy regime is used in patients with myeloma?
VAD or CTD.
What combination chemotherapy regime is commonly used in patients with non hodgkin’s lymphoma?
RCHOP.
Give 3 environmental causes of leukaemia.
- Radiation exposure.
- Chemicals e.g. benzene compounds.
- Drugs.
Give 3 signs of anaemia.
- Pale skin and mucous membranes.
- Tachycardia.
- Bounding pulse.
Describe the appearance of RBC’s seen in iron deficiency anaemia.
Hypochromic microcytic.
What might you see on a blood count taken from someone with beta thalassaemia major?
- Raised reticulocyte count.
2. Microcytic anaemia.
What can precipitate sickling in sickle cell anaemia?
Trauma, cold, stress, exercise.
Why does sickle cell anaemia not present until after 6 months of age?
HbF is not affected by sickle cell anaemia as it is made up of 2 alpha and 2 gamma chains.
What drug can be used to prevent painful crises in people with sickle cell anaemia?
Hydroxycarbamide.
Give 3 clinical features of a patient with a membranopathy.
- Jaundice.
- Anaemia.
- Splenomegaly.
Why does a deficiency in glucose-6-phosphate dehydrogenase lead to shortened red cell lifespan?
G6PD protects cells against oxidative damage.
What 3 blood test values would be increased in someone with polycythaemia?
- Hb.
- RCC.
- PCV.
Give 3 symptoms of polycythaemia.
- Itching.
- Headache.
- Dizziness.
- Visual disturbance.
What can cause ITP?
- Viral infection.
2. Malignancy.
What antibodies are often found in ITP?
IgG.
Are PTT and APTT increased or decreased in DIC?
Increased.
Are fibrinogen and platelets increased or decreased in DIC?
Decreased.
Name 2 things that are increased and 2 that are decreased in DIC.
Increased: PTT and APTT.
Decreased: fibrinogen and platelets.
How would you treat haemophilia A?
IV infusion of factor 8.
