Haematology Flashcards
What is myeloma?
Cancer of differentiated B lymphocytes (plasma cells)
Describe the pathophysiology of myeloma
Accumulation of malignant plasma cells in bone –> progressive bone marrow failure
Production of one excess immunoglobulin (monoclonal paraprotein)
What monoclonal paraprotein is usually produced in myeloma?
IgG = 55% IgA = 20%
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
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?
Increased bone resorption and decreased bone formation so more calcium in the blood
Why might someone with myeloma have anaemia?
BM infiltrated with plasma cells = anaemia, neutropenia (infections) and thrombocytopenia (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?
- Bloods and blood film
- Blood marrow aspirate and trephine biopsy
- Electrophoresis
- X-ray
- Urinalysis
What would you expect to see on the blood film taken from someone with myeloma?
Rouleaux formation (aggregation of RBCs)
What are you looking for on a bone marrow biopsy taken from someone with myeloma?
Increase plasma cells
What are you looking for on electrophoresis in a patient with myeloma?
Monoclonal protein band
What would you expect to see on the x-ray taken from someone with myeloma?
Lytic ‘punched out’ lesions –> pepper pot skull, vertebral collapse
Fractures
Osteoporosis
What might the urine of someone with myeloma contain?
Bence-jones protein - immunoglobulin light chains with kappa or lamda lineage
What does a diagnosis of myeloma require?
- Monoclonal protein band in serum or urine
- Increased plasma cells on bone marrow biopsy
- Hypercalcaemia/renal failure/anaemia
- Bone lesion on skeletal survey
Describe the treatment for symptomatic myeloma
Bone pain = analgesia Bisphosphonates (zolendronate) Blood transfusion - for anaemia Fluids and dialysis - renal failure Chemotherapy Stem cell transplant
How is myeloma bone disease usually assessed?
X-ray
Suggest 3 ways in which multiple myeloma can lead to AKI
- Deposition of light chain
- Hypercalcaemia
- Hyperuricaemia
What kind of anaemia is seen in patients with multiple myeloma?
Normochromic normocytic
What chemotherapy regime is used in patients with myeloma?
VAD (fitter people) or CTD (less fit people)
What is leukaemia?
A malignant proliferation of haemopoietic stem cells (immature blood 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 (AML)?
Neoplastic proliferation of blast cells (immature blood cells)
Acute malignant transformation of myeloid progenitor cells
What can increase the risk of developing AML?
- Preceding haematological disorders
- Prior chemotherapy
- Exposure to ionising radiation
- Down’s syndrome
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 splenomegaly symptoms of leukaemia?
Because of tissue infiltration
What investigations do you do on someone who you suspect has leukaemia?
- Blood film
- Bone marrow biopsy
- Lymph node biopsy
- Immunophyenotyping
- Cytogenetics
What would you expect to see on a blood film and bone marrow biopsy in someone you suspect to have AML?
Blood film = anaemia and thrombocytopenia
BM biopsy = leukaemic blast cells
Describe the treatment for AML
- Supportive therapy (blood transfusions, infections prophylaxis etc)
- Chemotherapy - curative vs palliative
- Bone marrow transplant
What is chronic myeloid leukaemia (CML)?
Uncontrolled clonal proliferation of myeloid cells (basophils, eosinophils and neutrophils)
What chromosome is present in >80% of people with CML?
Philadelphia chromosome
Give 4 symptoms of CML
Insidious onset
- Symptomatic anaemia
- Abdominal pain - splenomegaly
- Weight loss
- Tiredness
- Gout
- Bleeding
What would the FBC from someone with CML look like?
High WCC
Anaemia - normochromic and normocytic
What is the treatment for CML?
Imatinib = tyrosine kinase inhibitor
Stem cell transplant
Why does the Philadelphia chromosome cause CML?
Froms fusion gene BCR/ABL on chromosome 22 –> tyrosine kinase activity –> stimulates cell division
What is acute lymphoblastic leukaemia (ALL)?
Uncontrolled proliferation of immature lymphoblast cells (lymphoid progenitor cells)
Acute malignant transformation of lymphoid progenitor cells
Give 4 signs of ALL
- BM failure
- Heaptosplenomelgay
- Lymphadenopathy
- Headache and CN palsies
- Mediastinal masses with SVC obstruction
Due to organ infiltration
What is the treatment for ALL?
Chemotherapy
Supportive therapy - Blood and platelet transfusion, Allopurinal (prevents tumour lysis syndrome)
Bone marrow transplant
What is Chronic lymphoblastic leukaemia (CLL)?
Proliferation of mature B lymphocytes leads to accumulation of mature B cells that have escaped apoptosis
Chronic malignant transformation of mature lymphoid cells
What may be seen on the blood film of someone with CLL?
Smudge cells on histology
What is the treatment for CLL?
- Do nothing
- Chemotherapy
- Monoclonal antibodies
- Bone marrow transplant
Is ALL more common in adults or children?
Mainly a childhood disease
Give 4 symptoms of ALL
- Bone pain
- Recurrent infections (neutropenia)
- Pale and tired (anaemia)
- Bruising (low platelets)
Give 3 environmental causes of leukaemia
- Radiation exposure
- Chemicals (benzene compounds)
- Drugs
What is lymphoma?
Malignant proliferation of lymphocytes, normally in the lymph nodes
Although predominantly in the lymph nodes, what other organs can lymphoma effect?
- Blood
- Bone marrow
- Liver
- Spleen
Give 4 risk factors for lymphoma
- Primary immunodeficiency
- Secondary immunodeficiency - HIV, transplant recipients
- Infections - EBV, H. pylori, HTLV-1
- Autoimmune disorders - SLE, RA
Describe the pathophysiology of lymphoma
Impaired immunosurveillance and infected B cells escape regulation and proliferate
Give 4 symptoms of lymphoma
- Enlarged lymph nodes in arm/neck
- Symptoms of compression syndromes
3, General systemic ‘B’ symtoms - weight loss, night sweats, malaise - Hepatosplenomeglay
What investigations might you do in someone who you suspect has lymphoma?
- Blood fim
- Bone marrow biopsy
- Lymph node biopsy
- Immunophenotyping
- Cytogenetics (karyotyping/FISH)
What staging investigations might you do in someone with lymphoma?
- Blood tests
- CT scan chest, abdomen, pelvis
- Bone marrow biopsy
- PET scan
What are the 2 sub-types of lymphoma
- Hodgkins lymphoma
2. Non-hodgkins lymphoma
What are symptoms of Hodgkins lymphoma?
- Painless lymphadenopathy
2. Presence of ‘B’ symptoms - fever, weight loss, night sweats, lethargy
What is needed for the diagnosis of Hodgkins lymphoma?
Presence of Reed-Sternberg cells (in lymph node biopsy)
What blood results may you seen in someone with Hodgkins lymphoma?
High ESR
Low Hb
High serum lactase dehydrogenase
Describe the staging go 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 treatment for stage 1 - 2A Hodgkins lymphoma?
Short course chemotherapy followed by radiotherapy
What is the treatment for stage 2B - 4 Hodgkins lymphoma?
Cyclic chemotherapy and radiotherapy
What chemotherapy regime is used for the treatment of Hodgkins lymphoma?
ABVD regime: Adriamycin Bleomycin Vinblastine Dacarbazine
What treatment is used for a relapse of Hodgkins lymphoma?
Stem cell transplant
What are the possible complications of treatment for Hodgkins lymphoma?
- Secondary malignancies
- IHD
- Infertility
- Nausea
- Alopecia
What is non-hodgkins lymphoma?
Any lymphoma not involving Reed-Sternberg cells
Describe low-grade non-hodgkins lymphoma
E.g. Follicular lymphoma
Slow growing
Often advanced at presentation
Often incurable (mens survival 10 years)
Describe high grade non-hodgkins lymphoma
E.g. Diffuse Large B cell Lymphoma
Agressive
Nodal presentation
Often curable
Give an example of a very high grade Non-Hodgkin’s lymphoma
Burkitt’s lymphoma
Give 4 features of non-hodgkins lymphoma
- Lymphadenopathy - painless
- Extranodal involvement - skins, CNS
- Systemic symptoms - fever, weight loss, night sweats
- Pancytopenia - anaemia, thrombocytopenia and leukopenia due to BM involvement
What is the treatment for low grade non-hodgkins lymphoma?
If symptomless - do nothing
Radiotherapy, combination chemotherapy and monoclonal antibodies may be used if symptomatic
What is the treatment for high grade non-hodgkins lymphoma?
Early = short course chemotherapy and radiotherapy Advanced = combination chemotherapy and monoclonal antibody (Rituximab)
What is anaemia?
A reduced RBC mass +/- reduced Hb concentration
What is the functions of Hb?
It carries and delivers oxygen to tissues
What are the normal Hb concentrations for:
a) Males
b) Females
a) Males = 131-166 g/L
b) Females = 110-147 g/L
What organs are responsible for the removal of RBCs?
- Spleen
- Liver
- Bone marrow
- Blood loss
What are the normal MCV values for:
a) Males
b) Females
a) Males = 81.8-96.3 fl
b) Females = 80.0-98.1 fl
Give 3 causes of microcytic anaemia
- Iron deficiency
- Chronic disease
- Thalassaemia
Give 3 causes of normocytic anaemia
- Acute blood loss
- Chronic disease
- Combined haematinic deficiency (iron and B12 deficiency)
Give 3 causes of macrocytic anaemia
- B12/folate deficiency
- Alcohol excess –> liver disease
- Haemolytic anaemia
- Hypothyroid
Briefly describe the pathophysiology of anaemia
Reduced O2 transport –> tissue hypoxia –> compensatory mechanism = increased tissue perfusion, increased O2 transfer to tissue, increase RBC production
What pathological changes occur due to anaemia?
- Heart/liver fat change
- Ischaemia
- Skin/nail atrophy
- CNS death
- Aggravate angina and claudication
What do reticulocytes show you?
Marker of balance between formation and removal of RBCs
Give 4 symptoms of anaemia
Non-specific
- Fatigue
- Dyspnoea
- Headache
- Faintness
- Palpitations
- Anorexia
Give 3 signs of anaemia
- Conjunctival pallor
- Hyper-dynamic circulation
- Tachycardia
- Systolic flow murmur
What investigations might you do in someone with anaemia?
- FBC and Blood film
- Reticulocyte count
- B12, folate and ferritin levels
- U+E’s, LFT’s, TSH levels
What is the treatment for anaemia?
Treat the underlying cause
Give 3 causes of iron deficiency anaemia
- Blood loss
- Poor absorption
- Decreased intake in diet
- Increased demand - growth/pregnancy
- Hookworm
Describe the pathophysiology of iron deficiency anaemia
Lack of iron –> no haem production –> lack of effective RBCs
What would the results of investigations be for someone with iron deficiency anaemia?
MICROCYTIC HYPOCHROMIC ANAEMIA
Low ferritin, low reticulocyte
How do you treat iron deficiency anaemia?
Improve diet and treat cause Ferrous sulphate (iron supplement) - SE = black stool and constipation
Describe the pathophysiology of B12 deficiency/pernicious anaemia
Lack of B12/intrinsic factor –> B12 not absorbed in terminal ileum –> big facile RBCs
Give 2 causes of B12 deficiency/pernicious anaemia
- Autoimmune parietal cell destruction (pernicious)
- Poor diet
- Ileectomy
What are 2 specific signs of B12 deficiency/pernicious anaemia?
Inflamed tongue
Neurological - paraesthesia, psychological problems
What would the results of the investigations be for someone with B12 deficiency/pernicious anaemia?
MACROCYTIC NORMOCHROMIC ANAEMIA with polysegmented neutrophils
Autoantibodies = intrinsic factor and coeliac antibodies
How would you treat B12 deficiency/pernicious anaemia ?
Treat cause
B12 replacement - hydroxocobalamin
Describe the pathophysiology of folate deficiency
Lack of folate –> can’t be absorbed in upper intestine –> large fragile RBC
Macrocytic anaemia with low erythrocyte folate levels
How do you treat folate deficiency?
Folic acid supplement
Describe the pathophysiology of haemolytic anaemia
RBC destroyed before 120 day lifespan –> compensatory reticulocytes from BM –> RBC destruction
- Extravascular
- Intravascular
Give 3 inherited causes of haemolytic anaemia
- RBC membrane defect
- Abnormal Hb - thalassaemia’s, sickle cell
- Enzyme defects - Glucose-6-phosphate dehydrogenase deficiency
Give 3 acquired causes of haemolytic anaemia
- Autoimmune
- Drug induced
- Secondary to systemic disease
- Malaria
What is the management for haemolytic anaemia
Dietary = folate and iron supplementation
AI cause = immunosuppression
Surgical = splenectomy
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?
Variant haemoglobin arising because of a point mutation in the beta globin gene
Mutation leads to a single AA change, Glutamate –> Valine
What two categories can haemoglobinopathies be divided in to?
- Disorders of quality - abnormal molecule or variant haemoglobin (sickle cell)
- Disorders of quantity - reduced production (thalassaemia’s)
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?
Offers protection against falciparum malaria
They are symptom free
Describe the inheritance pattern of sickle cell disease
Autosomal recessive
Homozygous SS
If both parents are carries of the sickle trait, what is the chance of their first child having sickle cell disease?
25% chance of having sickle cell
50% chance of being a carrier
How long do sickle cells last for?
5-10 days
Give 3 acute complications of sick cell disease
- Painful crisis
- Sickle cell syndrome - blockage of blood vessels within bone leading to pain
- Strokes in children
- Infections
Give 3 chronic complications of sickle cell disease
- Renal impairment
- Pulmonary hypertension
- Joint damage
What investigations are done to confirm a diagnosis of sickle cell disease?
Neonatal screening = sickle cells on blood film
Hb electrophoresis confirms diagnosis
Describe the treatment for sickle cell disease
- Transfusion
- Hydroxycarbamide
- Stem cell transplant
What is thalassaemia?
A haemoglobin disorder of quantity
Reduced synthesis of one or more globin chain leading to a reduction in Hb –> anaemia
If someone has beta thalassaemia, do they have more alpha or beta globing chains
Beta thalassaemia = reduced Beta chain synthesis
Very few beta chains, excess alpha chains
What is the clinical classification of beta thalassaemia?
- Thalassaemia major
- Thalassaemia intermedia
- Thalassaemia carrier/heterozygote
What clinical classification of Thalassaemia relies on regular transfusions?
Thalassaemia major
What clinical classification of Thalassaemia relies is often asymptomatic?
Thalassaemia carrier/heterozygote
When do people with beta Thalassaemia major usually present and why?
Present very young due to having severe anaemia and so a failure to feed and thrive
What results would you see from investigations of someone with beta Thalassaemia major?
Hb 40-70 g/L
Blood film = large and small (irregular) very pale red cells
Hb F > 90% (neonatal sample)
What is the treatment for beta Thalassaemia major?
Regular transfusions
Iron chelation
Endocrine supplementation
Fertility help
Why is it important to monitor iron levels in someone with beta Thalassaemia major?
Risk of iron overload from the regular transfusion
Excess iron will be deposited in various organs (e.g. liver and spleen) and cause fibrosis
What is the significance of parvovirus in someone with sickle cell disease?
Parvovirus is common infection in children
Leads to decreased RBC production and an cause a dramatic drop in Hb in patients who already have a reduced RBC lifespan
Describe the inheritance pattern for membranoapthies
Autosomal dominant
Name 2 common membrnaopathies
- Spherocytosis
2. Elliptocytosis
Briefly describe the physiology of membranopathies
Deficiency in red cell membrane protein 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
Name 3 things that can precipitate G6PD deficiency
- Broad beans
- Infection
- Drugs - Primaquine, sulphonamide, quinolones
What is polycythaemia?
Too many RBC’s, increased Hb
Due to a JACK2 mutation
What hormone is responsible for regulating RBC production?
Erythropoietin (EPO)
What stimulates EPO?
Tissue hypoxia
Name a primary cause of polycythaemia
Polycythaemia rubra vera - overactive bone marrow
Give 3 secondary causes of polycythaemia
- Smoking
- Lung disease
- Cyanotic heart disease
- High altitude
- Excess EPO
Give 3 signs of polycythaemia
- Hyper-viscosity - headaches, dizziness, visual disturbances
- Red face
- Splenomegaly
What is the treatment for polycythaemia?
- Secondary cause = treat underlying causes
- Primary cause = aims to maintain a normal blood count and prevent complications
- Aspirin
- Venesection (in young)
- Hydroxycarbamide (in old)
Where are platelets produced?
In the bone marrow
They are fragments fo megakaryocytes
What hormone regulated platelet production?
Thrombopoietin - produced mainly in the liver
What is the lifespan of a platelet?
7-10 days
What organ is responsible for platelet removal?
Spleen
What can cause platelet dysfunction?
Reduced platelet number (thrombocytopenia)
Reduced platelet function
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)
- Reduced TPO
- Aplastic anaemia
What can cause increased platelet destruction?
- Autoimmune (e.g. ITP)
- Hypersplenism
- Drug related (e.g. heparin induced)
- DIC and TTP –> increased consumption
What can cause reduced platelet function?
- Congenital abnormality
- Medications - aspirin
- VWF disease
- Uraemia
Give 3 symptoms of platelet dysfunction
- Mucosal bleeding - epistaxis, gum bleeding, menorrhagia
- Easy bruising
- Petechiae/purpura
- Traumatic haematomas
Give 4 causes of bleeding
- Trauma
- Platelet deficiency - thrombocytopenia
- Platelet dysfunction - aspirin induced
- Vascular disorders
Give 3 things that can cause coagulation disorders
- Vitamin K deficiency
- Liver disease
- Congenital - haemophilia
What is disseminated intravascular coagulation (DIC)?
Pathological activation of coagulation cascade –> fibrin in vessel walls
Platelet (thrombocytopenia) and coagulation factor consumption
Thrombin activated inappropriately –> excess diffuse clotting –> uncontrolled bleeding
Give 3 causes of DIC
- Sepsis
- Malignancy
- Trauma
What is the affect on thrombin time, prothrombin time and APTT in someone with DIC?
All increased
What the effect on fibrinogen in someone with DIC?
Decreased
How do you treat DIC?
- Treat underlying condition
- Platelet transfusions
- FFP - contain clotting factors
- Cryoprecipitate - contains fibrinogen and some clotting factors
What is thrombotic thrombocytopenia?
ADAMTS13 deficiency –> no vWF degradation –> widespread aggregation of platelets –> thrombosis in microvasculature or heart/lungs/brain
Give 3 symptoms of thrombotic thrombocytopenia
- Renal/CNS/cardiac impairment
- Fever
- Haemolytic anaemia
What is the treatment for thrombotic thrombocytopenia?
Plasma exchange (removed ADAMTS13 autoantibodies) Splenectomy
What is immune thrombocytopenia?
Antibodies formed against platelet –> autoimmune platelet destruction via reticuloendothelial system
Give 3 causes of immune thrombocytopenia
Primary = viral infection (children) Secondary (chronic, adults) - Autoimmune condition - SLE - Malignancies - CLL - Infections - HIV/Hep C
Give 3 symptoms of immune thrombocytopenia
- Rapid purpura
- Epistaxis
- Easy bruising
What is the management for immune thrombocytopenia?
Corticosteroid (prednisolone)
Splenectomy
Give 4 casues of folate deficiency
- Dietary
- Malabsorption
- Increased requirement - pregnancy
- Folate antagonists - methotrexate
Give 3 signs of haemolytic anaemia
- Pallor
- Jaundice
- Splenomegaly
Give 2 specific symptoms of iron deficiency anaemia
- Koilonychia
- Brittle har and nails
- Atrophic glossitis
What is neutrophilia?
Too many neutrophils
Give 3 causes of neutrophilia
- Infection
- Inflammation
- Cancer
- CML = primary cause
What is lymphocytosis?
Too many lymphocytes
Give 3 causes of lymphocytosis
- Viral infection
- Inflammation
- Cancer
- CLL = primary cause
What is thrombocytopenia?
Not enough platelets
What is thrombocytosis?
Too many platelets
Give 3 causes of thrombocytosis
- Infection
- Inflammation
- Cancer
- Essential thrombocythaemia = primary cause
What is neutropenia?
Not enough neutrophils
What is the major risk associated with being neutropenic?
Susceptible to infection
Give 3 causes of neutropenia
- Underproduction = marrow failure, marrow infiltration, marrow toxicity (e.g. drugs)
- Increased removal = autoimmune, Felty’s syndrome, cyclical
Give 2 causes of thrombocytopenia
- Production failure - marrow suppression, marrow failure
2. Increased removal - immune response (ITP), consumption (DIC), splenomegaly
What is the definition of febrile neutropenia?
Temperature >38 degrees 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
Give a risk for spinal cord compression
Any malignancy that can cause compression - bone metastasis
What is tumour lysis syndrome?
Breakdown of malignancy 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
What is hyper viscosity syndrome?
Increase in blood viscosity usually due to high levels of immunoglobulins
Give 2 consequences of hyperviscosity syndrome
- Vascular stasis
2. Hypoperfusion
What does rituximab target?
Targets CD20 on the surface of B cells
What is the affect of sickle cell anaemia on reticulocyte count?
Raised
What clotting factors depend on vitamin K?
2, 7, 9, 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
How does warfarin work?
Antagonises vitamin K so reduction in clotting factors 2, 7, 9 and 10
How does heparin work?
It activates antithrombin which then inhibits thrombin and factor Xa
What 3 blood test values would be increased in someone with polycythaemia?
- Hb
- RCC
- PCV