Haematology Flashcards
1
Q
In the UK what cancer screening programmes are in place?
A
Cervical, colon, breast
2
Q
What are serum tumour markers and what are they used for?
A
Intracellular proteins or cell surface glycoproteins that may be released into the circulation, and are in higher than usual concentrations in patients with cancer
Used for monitoring treatment effectiveness
3
Q
What is the difference between adjuvant and neoadjuvant therapy?
A
Adjuvant = chemo,radio, hormone given after surgery to lower risk of micrometastasis
Neoadjuvant = chemo, radio, hormone given before surgery to shrink tumour
4
Q
How does chemotherapy work and what other cells does it affect and why?
A
Chemo damages DNA and RNA, promotes apoptosis
Damages all rapidly dividing cells, e.g. bone marrow, gastrointestinal tract and germinal epithelium
5
Q
Side effects of chemotherapy?
A
- Bone marrow supression –> anaemia, thrombocytopenia, neutropenia
- Mucositis
- Alopecia
- Sterility
- Nausea and vomiting
6
Q
Examples of antiemetics?
A
- Metaclopramide and domperidone
or for severe
5-HT3 antagonists (ondansetron and granisetron) with dexamethosone
7
Q
How does radiotherapy work?
A
Causes strand breaks in DNA and apoptosis
8
Q
Side effects of radiotherapy?
A
- Damage to the skin (erythema and desquamation)
- Damage to the gut (ulceration, nausea and diarrhoea)
- Damage to testis
- Damage to bone marrow (anaemia, leucopenia)
- General lethargy
9
Q
What cancers are endocrine therapies used in?
A
Breast and prostate
10
Q
Agonist and antagonist of oestrogen used in breast cancer as an adjuvant therapy?
A
Tamoxifen
11
Q
What drug type is rituximab and what conditions could it be used in?
A
Monoclonal antibody - destroys cells with CD20 on their surface (B cells), could be used in rheumatoid arthritis, leukaemia, lymphoma
12
Q
What is myeloablative therapy?
A
High dose chemotherapy or chemo plus radiation with the aim to clear the bone marrow completely of both benign and malignant cells
13
Q
What are the 2 main methods of bone marrow transplantation post myeloablative therapy?
A
- Allogeneic - bone marrow or peripheral blood stem cells from another individual - usually HLA-identical sibling.
- Autologous - patient acts as his or her own source of stem cells. Collected from bone marrow or peripheral blood before myeloablative therapy
14
Q
What are the main symptoms of graft-versus host disease and how are they caused?
A
T cells infiltrate the skin, gut, and liver - causing maculopapular rash, diarrhoea and liver necrosis.
15
Q
What are the normal ranges for haemoglobin levels in both males and females?
A
Males 13.5-17.5g/dL
Females 11.5-16g/dL
16
Q
What are the normal ranges for WBC count in both males and females?
A
4-11 x 10^9 /L
17
Q
What is the normal platelet count?
A
150-400 x 10^9 /L
18
Q
What is the normal range for MCV (mean corpuscular volume)?
A
80-96fL
19
Q
What is anaemia?
A
Reduced red cell mass, and therefore reduced haemoglobin.
20
Q
In anaemia what values decrease?
A
RCC, PCV, haemoglobin
21
Q
What is dilutional anaemia and give an example
A
If the plasma volume increases, but the RCC/PCV remain the same then they appear smaller per volume plasma, e.g. in pregnancy or in massive splenomegaly
22
Q
How does anaemia often present?
A
If acute - fatigue, faintness, breathlessness. Will also often see pale mucous membranes, and tachycardia
23
Q
What are reticulocytes and what 3 things will cause their levels to be increased?
A
Young red cells, still contain RNA. Are larger than mature cells.
Will be increased in haemorrage, haemolysis, treatment with specific haemanitics (iron, B12, folate) in deficiency states
24
Q
What are the main 3 causes of microcytic anaemia?
A
- Iron deficiency
- Chronic disease
- Thalassemia
25
Why can a diagnosis of anaemia not always be based around ferritin levels?
Ferritin can be falsely elevated in inflammation
26
What are the main causes of iron deficiency in anaemia?
In most men and post menopausal women = GI bleeding
In most pre-menopausal women = menorrhagia
Other potential causes: Hookworm, cancer, breast feeding, pregnancy, decreased absorption (small bowel disease/ post gastrectomy) or poor intake (but this is rare)
27
Most common cause of anaemia world wide?
Iron deficiency
28
Factors that promote intestinal absorption of iron?
Gastric acid, iron deficiency, increased erythropoietic activity
29
What are the signs and symptoms of iron deficiency (not including normal signs of anaemia)?
1. Brittle hair and nails
2. Atrophic glossitis
3. Angular stomatitis
30
What tests would be done to confirm and try to work out the cause of suspected iron deficiency anaemia?
Confirm - blood count and film - microcytic and hypochromic RBC's. Serum ferritin low.
To work out cause would do colonoscopy
31
What chronic diseases can cause microcytic anaemia?
1. Inflammatory diseases - Crohn's, RA
2. Chronic infections - TB, malignancy, CKD
In kidney problem= decrease EPO
32
What are the 3 main causes of normocytic anaemia?
1. Acute blood loss
2. Anaemia of chronic disease
3. Combined haematinic deficiency
33
What are the 4 main causes of macrocytic anaemia?
1. B12/folate deficiency
2. Alcohol excess/liver disease
3. Hypothyroid
4. HAEMATOLOGICAL (chemo drugs, haemolysis (more reticulocytes) bone marrow failure, bone marrow infiltration)
34
What would be the initial investigation done to determine the cause of macrocytic anaemia?
Serum B12 and red cell folate measurement (B12 is necessary to convert serum folate to active intracellular form)
35
Where do we get our B12/ folate?
B12- animal products (meat and dairy)
| Folate - green vegetables and offal
36
What is megaloblastic anaemia and what is the main cause?
Developing red blood cells in the bone marrow with delayed nuclear maturation in comparison to cytoplasm (macrocytic). Main cause is due to defective DNA synthesis due to deficiency of vitamin B12 or folate
37
How is vitamin B12 absorbed?
Parietal cells in the stomach secrete both instrinsic factor and H+. Instrinsic factor bind to B12 and it is absorbed in the terminal ileum. Stored in the liver
38
What is pernicious anaemia, and what is it a cause of ?
Autoimmune condition in which there is atrophic gastritis (infiltration of fundus with plasma cells and lymphoid cells) causing loss of parietal cells, and so lack of B12 absorption
39
What are the main causes of B12 deficiency?
1. Low dietary intake (vegan)
2. Impaired absorption- pernicious anaemia, gastrectomy, ileal disease (e.g. Crohns), coeliac disease
3. Abnormal utilization - nitrous oxide inactivates B12
40
What clinical features are seen in B12 deficiency?
1. Symptoms of anaemia - glossitis, angular, stomatitis, and mild jaundice
2. Neurological features - polyneuropathy, subacute combined degeneration of the cord (posterior and lateral columns) which leads to progressive weakness, ataxia and paralplegia
41
Prophylactic folic acid is given to who?
1. Individuals with chronic haemolysis
| 2. Pregnant women
42
How is alcohol excess thought to cause macrocytic anaemia?
Altered or excess lipid deposition on red cell membranes
43
Why does vitamin B12/folate deficiency cause macrocytic anaemia?
Not enough B12 to divide between all cells so do 1 fewer divisions
44
How does Haemoglobin S occur in sickle cell anaemia?
Point mutation in B globin gene (chromosome 11)
45
What type of inheritance does sickle cell disease have?
Autosomal recessive
46
What are the two types of haemoglobinopathy and give examples of both
1. Disorders of quality (abnormal chain structure) e.g. sickle cell anaemia
2. Disorders of quantity (abnormal chain production) e.g. Thalassaemia
47
Where is sickle B gene abundant in the population?
Africa, India, Middle East, Mediterranean countries
48
What 4 factors precipitate sickling?
1. Hypoxia
2. Dehydration
3. Infection
4. Cold
49
At what age does sickle cell anaemia usually manifest?
6 months (HbF decreases to adult levels)
50
Name 3 acute complications of sickle cell disease?
1. Painful crisis- avascular necrosis of bone marrow
2. Sickle chest syndrome (medical emergency) - fever,cough,dyspnoea caused by infection, fat embolism from necrotic bone marrow or pulmonary infarction due to sequestration of cells
3. Stroke in children, and neurocognitive issues (due to vaso-occlusion)
51
Name 3 chronic complications of sickle cell disease?
1. Renal impairment
2. Pulmonary hypertension
3. Joint damage
52
What treatments can be used in patients with sever sickle cell anaemia to control symptoms?
1. Stem cell transplant
2. Hydroxycarbamide - raises concentration of fetal Hb in patients with recurrent painful crisis
3. Blood transfusion
53
How is sickle cell anaemia diagnosed?
Neonate: cord blood or heel prick test
- Hb 6-8g/dL
- High reticulocyte count
- Blood film showing sickle erythrocytes
- Diagnosis by electrophoresis *80-95% HbSS and no HbA
54
What is thalassaemia?
Reduced rate of production of one or more globin chains, and consequent reduction of haemoglobin
55
What is the difference between B thalassaemia intermedia and major in terms of treatment
Major relies on transfusions regularly
56
When looking at a blood count and blood film from an individual with homozygous thalessaemia what is seen?
Hypochromic, microcytic anaemia
Raised reticulocyte count
Nucleated red cells in the peripheral circulation
57
What is the management for an individual with major thalessaemia?
- Blood transfusion
- Iron overload can damage endocrine glands, liver, pancreas, heart so iron chelating agents used
- Ascorbic acid given as it increases urinary excretion of iron
58
How many alpha-thalessaemia genes are there per cell and how does this affect the manifestation of the disease?
4
| More affected = more severe disease. If all four are affected then child will be still born (hydrops fetalis)
59
What are the most common types of membranopathies?
Spherocytosis and elliptocytosis
60
What pattern of inheritance do spherocytosis and elliptocytosis show?
Autosomal dominant
61
Pathophysiology of membranopathies?
1. Defect in red cell membrane leads to increased permeability to sodium (spectrin)
2. Red cells become either spherical or elliptical in shape as well as being more rigid and less deformable
3. Destroyed prematurely in the spleen
62
In severe cases of spherocytosis what are the clinical features?
Haemolytic anaemia with jaundice and splenomegaly. Occasionally can lead to pigment gallstones
63
Which membranopathy is normally the most severe?
Spherocytosis
64
What is the normal management on spherocytosis?
Splenectomy in all but mildest cases
65
How does parvovirus present and what is its significance in haematology?
'Slapped cheek' syndrome. Causes decreased RBC production, so massive Hb drop in those who already have reduced red cell lifespan
66
What is the most common enzymopathy that causes haemolytic anaemia?
Glucose-6-phosphate dehydrogenase deficinecy
67
Which haematolytic anaemias can lead to an increased risk of neonatal jaundice?
1. G6PD deficiency
2. Spherocytosis
3. ABO haemolytic disease
68
What precipitates acute haemolysis in G6PD deficiency?
Broad beans, infection, common drugs
69
What is myeloma a cancer of?
Plasma cells- clonal proliferation and accumulation in the bone marrow leading to secretion of monoclonal antibodies (paraproteins) - normally IgG
70
What are the symptoms of a patient with myeloma?
1. Tiredness/malaise
2. Back pain
3. Infections
4. CRAB (hyperCalcaemia, Renal failure, Anaemia, lytic Bone lesions)
71
What monoclonal antibody is produced in excess in multiple myeloma?
IgG
72
Why does multiple myeloma cause renal failure?
1. There is excretion of light chains in the urine (either kappa or lambda) - so they deposit themselves in tubules
2. Hypercalcaemia
3. Hyperuricaemia
4. Amyloid deposition in kidneys
73
Why are patients with multiple myeloma at an increased risk of infection?
Because there is a reduction in the normal polyclonal antibody levels (immune paresis)
74
What is the mean age for diagnosis of multiple myeloma?
70 yrs - 15% of patients are less than 60 and 2% less than 40
75
What does CRAB stand for in MM?
Calcium increased
Renal failure
Anaemia (normochromic normocytic)
Bone lesions
76
What tests would be done in suspected multiple myeloma?
1. FBC (normocytic normochromic anaemia)
2. ESR - high (or PV)
3. Serum and urine electrophoresis
4. Xray/CT/MRI
5. Bone marrow aspirate / trephine biopsy
77
What is the screening test for multiple myeloma? And what patients should it be done on?
1. Serum and urine electrophoresis
2. ESR
All patients over 50 with back pain
78
What is the general prognosis for a patient with multiple myeloma?
Generally can have long term control of neoplasia and symptoms. Should be thought of as a chronic disease. Long period of good quality life is expected for patients on treatment.
79
What is the treatment for a patient with multiple myeloma
1. Bisphosphonate - inhibits osteoclastic activity so reduces fracture rates and bone pain
2. Local radiotherapy in focal disease
3. Chemotherapy - in fit patients VAD (vincristine, adriamycin, dexamethosone). In less fit patients less intense - melphan and prednisolone
4. Stem cell transplant - to replace those damaged by chemotherapy
80
What drugs are used in patients that have relapsed multiple myeloma?
Thalidomide/ bortezomib
81
What drugs are used in patients that have relapsed multiple myeloma?
Thalidomide/ bortezomib
3rd line = lenalidomide
82
Why should bone pain in multiple myeloma patients not be treated with NSAIDs?
Cause renal failure which may already be occurring due to light chain deposition
83
What is the difference between an autologous and an allogeneic stem cell transplant?
Autologous - Patient's own stem cells. Is not curative
| Allogeneic - from a donor. Can be curative in younger patients but is risky.
84
What is MGUS?
Monoclonal gammopathy of undetermined significance - raised level of paraprotein (usually IgA) found in the blood but without other features of myeloma. Normally in older patients.
85
What percentage of people with MGUS will go on to develop multiple myeloma over a 25 year period?
20-30%
86
Hodgkins lymphoma is primarily a disease of...?
Young people
87
What factor is thought to be involved in the pathogenesis of Hodgkins lymphoma?
Previous infection with EBV
88
What is Burkitt's lymphoma?
Occurs mainly in African children and is associated with EBV virus. Very high grade NHL
Jaw tumours are common, often with gastrointestinal involvement.
89
What is lymphoma?
Malignant growth of white cells predominantly found in lymph nodes
90
Give 4 underlying causes of lymphoma?
1. Immunodefiency syndromes (primary and secondary)
2. Infection (EBV, helicobacter pylori)
3. Autoimmune disorders
And infected cells eg. EBV infected B cells escape regulation and proliferate autonomously, but most cases it is unknown
91
Presenting symptoms of lymphoma?
1. Painless lymphadenopathy
2. Extranodal disease
3. Compression syndromes
4. Systemic 'B' symptoms - e.g. fever, drenching night sweats, weight loss
92
What tools and investigations are done to diagnose lymphoma?
1. Blood film/ bone marrow biopsy
2. Lymph node biopsy
3. Immunophenotyping
4. Cytogenetics e.g. FISH
5. Molecular techniques eg. PCR
All wrapped together by HODS (haematooncology diagnostic service)
93
What tests would be done to stage lymphoma?
Blood tests, CT scan, bone marrow biopsy, PET scan
94
Give one example of both a very high grade and low grade NHL?
Low grade- Follicular
| Very high grade - Burkitt's lymphoma
95
Characteristic histological feature of Hodgkins lymphoma?
Reed Sternberg cell (multinucleated giant cell)
96
Hodgkins lymphoma is primarily a disease of whom?
Young adults
97
What is one of the biggest risk factors for Hodgkins lymphoma?
Previous infection with EBV (around 50% of cases) and therefore previous infectious mononucleosis.
HIV and cigarette smoking also
98
How does Hodgkins lymphoma typically present?
- Enlarged but asymptomatic lymph node typically in lower neck / supraclavicular region
- Systemic symptoms (B symptoms): Drenching night sweats, fever, weight loss
- Alcohol induced pain at sites of nodal disease
On examination: Hepatosplenomegaly, lymphadenopathy and SVCS
99
Hodgkins lymphoma can be staged 1-4 (A & B) Outline these stages briefly and what is the treatment for these stages?
Stage 1- 1 lymph node region
Stage 2- Two or more lymph node regions on same side of diaphragm
Stage 3 - lymph nodes on both sides of diaphragm
Stage 4- Involvement of extranodal sites
Stage 1-2A = Short course combination chemo (ABVD) followed by radio
Stage 2B-4 = Combination chemo (ABVD)
100
How is relapse of Hodgkins lymphoma treated?
Autologous bone marrow Tx
101
What combination chemotherapy is used in Hodgkins lymphoma?
ABVD (adriamycin, bleomycin, vinblastine, dacarbazine)
102
What is the staging system for Hodgkins and NH lymphoma called?
Ann Arbor
103
Some of the chemotherapy used to treat Hodgkins lymphoma have side effects. What are the side effects and what drugs cause them?
1. Bleomycin - lung damage
2. Vinca alkaloids - peripheral neuropathy
3. Anthracyclines -cardiomyopathy
104
What are some of the long term side effects of chemotherapy? (ABVD)
Cardiomyopathy, peripheral neuropathy, lung damage, infertility, psychological issues
105
Is extranodal involvement more common in Hodgkins or non hodgkins lymphoma?
Non-Hodgkins
106
What age range is generally affected by NHL?
Over 40
107
Which lymphoma is most common?
NHL x 5
108
How does NHL often present?
1. Lymphadenopathy - painless
2. Extranodal involvement (almost any organ in body)
3. Systemic symptoms - weight loss, fever, night sweats
4. Bone marrow infiltration - leading to anaemia, infection and bleeding
5. Skin involvement - mycosis fungoides and Sezary syndrome
109
How is NHL managed?
Very ranged depending on classification and stage
Watchful waiting, single or multi agent chemotherapy, regional or extended radiotherapy.
Monoclonal antibodies can be used in combination with chemotherapy in advanced high grade lymphoma e.g. R-CHOP
110
How is NHL classified?
WHO classification:
| B cell or T cell lymphoma - further divided into high grade or low grade
111
What is the most common form of NHL? and is this a high or low grade lymphoma?
Diffuse large B cell lymphoma
| High grade
112
What disease is R-CHOP used in and what is it?
Chemotherapy + rituximab (monoclonal antibody)
Used in NHL
113
How does rituximab work in NHL?
Is a monoclonal antibody so targets CD-20 which is only on B cells. Chimeric mouse/human protein with minimal side effects
114
Prognostic indicatiors in NHL?
Serum lactate dehydrogenase and B2- microglobulin
115
Acute lymphoblastic leukaemia is predominantly a disease of?
Childhood
