Haematology Flashcards
1
Q
What is lymphoproliferative disease?
A
neoplastic, clonal proliferation of lymphoid cells
basically cancer of white blood cells
2
Q
What are the 2 classes go lymphoma?
A
Hodgkin lymphoma
Non-hodgkin lymphoma (2 classes: aggressive and indolent)
3
Q
What are the classes of non-hodgkin lymphoma other than aggressive and indolent?
A
B cells - 90%
T cells - 10%
NK cells - <1%
4
Q
At what rate does indolent lymphoma progress?
A
slow growing and advanced at presentation
5
Q
Is indolent lymphoma curable?
A
no.
6
Q
What are the subtypes of indolent lymphoma?
A
follicular
marginal zone
mantle cell
CLL
7
Q
What is the survival of indolent lymphoma?
A
median survival of 9-12 years but variable across sub-groups
8
Q
What are the risk factors of indolent lymphoma?
A
most cases cause is unknown
primary immunodeficiency (e.g. wiscott-aldrich syndrome, common variable immunodeficiency)
secondary immunodeficiency (e.g. HIV, transplant recipients)
infection (e.g. EBV, HTLV-1, Helicobacter pylori)
autoimmune disorders
9
Q
How do most indolent lymphomas present?
A
painless lymphadenopathy
10
Q
What investigations can confirm a diagnosis of indolent lymphoma?
A
lymph node biopsy- core needle biopsy/ excision node biopsy (not FNA)
bone marrow biopsy
11
Q
Why is existent of a breast lump relevant to diagnosing lymphoma?
A
If a patient has breast cancer the tumour may spread to axilla, so it wouldn’t actually be lymphoma but a spread of the breast cancer
12
Q
How do we stage indolent lymphoma?
A
Lugano staging classification typical for most indolent lymphomas, requires imaging (CT neck, thorax, abdomen, pelvis, PET-CT)
bloods
bone marrow
13
Q
What are B symptoms?
A
fever
night sweats
weight loss
14
Q
What is the treatment for indolent lymphoma?
A
incurable
watch and wait/ active surveillance for asymptomatic patients, follow up regularly, does compromise overall survival
radiotherapy for symptomatic patients for palliative reasons
15
Q
What are the types of chemoimmunotherapy?
A
alkylating agents (e.g. chlorambucil, bendamustine, cyclophosphamide)
anthracyclines (e.g. doxorubicin)
vina alkaloids (e.g. vincristine)
corticosteroids
mostly use combinations of these
16
Q
What are myelodysplastic syndromes?
A
abnormal bone marrow syndromes
17
Q
What does ‘myelo’ mean?
A
marrow
18
Q
What is acute myeloid leukaemia?
A
AML is a heterogenous clonal malignancy characterised by:
- immature myeloid cell proliferation
- bone marrow failure
19
Q
What is the main risk of myelodysplastic syndromes?
A
they can progress to acute myeloid leukaemia
20
Q
How do myelodysplastic syndromes cause harm?
A
- bone marrow cells fail to make enough healthy blood cells (quantity and quality of cells are effected)
- abnormal cells crowd out remaining normal cells
- risk of progression to acute myeloid leukaemia
21
Q
What are cytopenias?
A
low blood cell counts
can be red cells, white cells or platelets
22
Q
How does low red cell count present?
A
fatigue
shortness of breath
lightheadedness
23
Q
How does low white cell count present?
A
increased risk of frequent and/ or severe infections
24
Q
How does low platelet count present?
A
bleeding/ bruising
25
How do you diagnose AML?
full blood count/ blood film
white cells can be low, normal or high but red cells and platelets will be low
bone marrow aspirate and trephine biopsy
26
What is the morphology of myelodysplastic syndrome?
- requirement of 10% dysplasia in any cell line(s)
- blast % can be anywhere from 0-19%
27
What do you do if there are blasts on a FBC?
refer straight to haematology- there shouldn't be any blasts on the FBC
28
What is the morphology of myeloid leukaemia?
minimum 20% blasts
29
What is paraprotein?
abnormal immunoglobulins produced by clonal plasma cells
30
What are the signs and symptoms of multiple myeloma?
CRAB
C- hyperCalcaemia
R- renal impairment, oedema, decreased urine output
A- anemia, neutropenia, thrombocytopenia
B- osteolytic bone lesions: pepper pot skull
31
What other rare syndromes might a patient present with in multiple myeloma?
paraethesia
fever (<1%)
splenomegaly (1%)
hepatomegaly (4%)
lymphadenopathy (1%)
neurological syndromes: hyperviscocity syndrome, spinal cord compression
32
What % of patients with multiple myeloma will experience spinal cord compression?
5%
33
What investigations can confirm a diagnosis of multiple myeloma?
bloods
protein electrophoresis and immunofixation
urine protein electrophoresis
serum light free chains
bone marrow aspirate/ biopsy
skeletal survey (x-ray)
CT/MRI
beta-2 microglobulin
34
How does multiple myeloma show on a blood test?
FBC- marrow failure
ESR- raised
blood film- rouleaux formation
U&Es- raised urea and creatinine
Hypercalcemia
35
How does multiple myeloma show on protein electrophoresis and immunofixation tests?
increased number of antibodies
monoclonal protein band
36
How does multiple myeloma show on protein electrophoresis and immunofixation tests?
increased number of antibodies
monoclonal protein band
37
How does multiple myeloma show on urine protein electrophoresis?
Bence Jones' protein- monoclonal light chains
38
How does multiple myeloma show on serum free light chains test?
ratio of light chains kappa and lambda
39
How does multiple myeloma show on a bone marrow biopsy?
increased plasma cell
40
How does multiple myeloma show on an x-ray/ skeletal survey?
lytic lesions
pepper pot skull
vertebral collapse
lytic punched out lesions
fracture risk
41
How does multiple myeloma show on a CT/MRI?
lesions that may not have been identified on x-ray
42
What is the principle behind treatment of multiple myeloma?
it is incurable, so treatment aims to increase periods of disease remission
43
What is induction therapy in multiple myeloma?
initial treatment option
combination of 3 drugs
this treatment is dependent on high-risk features and co-morbidities
44
Give an example of induction therapy for multiple myeloma.
VELCADE (bortezomib)- protease inhibitor
REVLIMIN (lenalidomide)- immunomodulatory imide drug
inhibits tumour angiogenesis, tumour-secreted cytokines and tumour proliferation
induces apoptosis
DEXAMETHASONE- steroid
45
What is ASCT in multiple myeloma?
autologous stem cell transplant
best treatment option for long periods of remission
is combined with high dose chemo (e.g. melphalan)
46
What drugs are used to maintain remission for multiple myeloma?
bortezomin/ lenalidomide
47
Which molecule is a prognostic tool for multiple myeloma?
beta2 micro-globulin
48
How is multiple myeloma staged?
Uses international staging system (ISS) for myeloma which grades based on levels of serum beta-2 micro globulin and albumin levels
stage 1: median survival 62 months
stage 2: median survival 44 months
stage 3: median survival 29 months
49
What are the three categories of red cell disorders?
haemoglobinopathies
membranopathies
enzymopathies
50
What is a haemoglobinopathy?
deficiency related to low quality or quantity of haemoglobin production
51
What is membranopathy?
deficiency related to red blood cell membrane protein
52
What is enzymopathy?
deficiency related to RBC enzyme synthesis, leads to shortened lifespan due to oxidative stress
53
What is the normal range for haemoglobin?
120-180g/L
54
What is the difference between adult and foetal haemoglobin?
adult (HbA): 2 alpha and 2 beta chains
foetal (HbF): 2 alpha and 2 gamma chains
55
What is haemoglobin S?
variant of Hb arising from a point mutation in the beta globin gene, leading to a single amino acid change (valine to glutamine)
56
What is sickle cell disease?
a haemoglobin disorder of quality- polymerisation of HbS results in characteristic sickle shaped RBCs
57
What is the lifespan of a sickle cell?
5-10 days- described as haemolytic
58
What factors can precipitate sickling in sickle cell anaemia?
trauma
cold
stress
exercise
59
Why does sickle cell anaemia not present until after 6 months old?
HbF is not affected by sickle cell anaemia as it is made up of 2 alpha and 2 gamma chains
60
How does sickle cell anaemia affect reticulocyte count?
raised- 2-3% (normally 0.45-1.8%)
61
Why is reticulocyte count raised in sickle cell anaemia?
sickle cell disease is haemolytic- increased degradation of RBcs
production is inceased
reticulocyte count is raised
61
Why is reticulocyte count raised in sickle cell anaemia?
sickle cell disease is haemolytic- increased degradation of RBcs
production is inceased
reticulocyte count is raised
62
What drug is used to prevent painful crises in people with sickle cell anaemia?
hydroxycarbamide
63
What are the acute complications of sickle cell disease?
painful vast-occlusive crisis (sickle chest syndrome)
stroke in children
cognitive impairment
infections
64
What are the chronic complications of sickle cell disease?
renal impairment
pulmonary hypertension
joint damage
65
What is the treatment for sickle cell disease?
blood transfusion
hydroxycarbamide
stem cell transplant
gene therapy and gene editing
66
How is parvovirus related to sickle cell disease?
Common URTI in children, leading to decreased RBC production. In individuals with sickle cell disease it can cause a dramatic drop in Hb due to inherently reduced RBC lifespan
67
What is thalassaemia?
A Hb disorder of quantity
globing chain disorder resulting in diminished synthesis of one or more globing chains, leading to a reduction in Hb and inherent anaemia
68
What are the 2 main types of thalassaemia?
alpha and beta thalassaemia
69
How is beta thalassaemia classified?
THALASSAEMIA MAJOR- transfusion dependent
THALASSAEMIA INTERMEDIA- less severe and individual can survive without regular transfusions
THALASSAEMIA CARRIER/ HETEROZYGOUS- asymptomatic
70
What is the major difference between alpha and beta thalassaemia?
alpha thalassaemia is categorised by a deficiency in the alpha chains whereas beta thalassaemia is deficiency of beta chains
71
When does beta thalassaemia tend to present?
6-12 months
72
What is the clinical presentations of beta thalassaemia?
severe microcytic anaemia resulting in failure to feed/ thrive, pallor, crying
73
What are the blood characteristics of an individual with beta thalassaemia?
Hb: 40-70g/L
Very low MCV (RBC size) and MCH (RBC Hb content)
HbF > 90%
blood film- irregularly sized very pale nucleated RBCs
74
What is the risk of regular transfusions in an individual with beta thalassaemia major?
risk of iron overload
excess iron is deposited in various organs (liver, spleen, etc) and cause fibrosis
75
What is the treatment for beta thalassaemia major?
regular transfusion
iron chelation
endocrine supplementation (fertility)
76
Describe the essential monitoring in individuals with beta thalassaemia major
ferritin (monitoring tool for iron overload)
cardiac and liver MRI
endocrine testing (gonadal function, diabetes screening, growth and puberty, vitamin D, calcium, PTH, thyroid)
DEXA scanning for bone health
77
What is the inheritance pattern of membranopathies?
autosomal dominant
78
What are the two most common membranopathies?
spherocytosis (horizontal)- more severe, presents as neonatal jaundice and haemolysis
elliptocytosis (vertical)
79
What are the two most common membranopathies?
spherocytosis (horizontal)- more severe, presents as neonatal jaundice and haemolysis
elliptocytosis (vertical)
80
What is polycythaemia vera?
AKA erthyrocytosis, having a high concentration of RBCs
blood neoplasms
81
What is a normal haematocrit?
45%
82
What is the synthesis of blood cells called?
haematopoiesis
83
Where does haematopoesis happen?
bone marrow
84
Where does haematopoesis happen?
bone marrow
85
How is haematopoeisis regulated?
through action of cytokines
86
Define myeloproliferative neoplasms
haematological malignancies
chronic conditions- they present and evolve over many years
87
How do myeloproliferative neoplasms manifest?
accumulation of mature blood cells in circulation
88
Where do myeloproliferative neoplasms arise from?
haematopoietic stem cells
89
What causes myeloproliferative neoplasms?
genetic mutations in haematopoietic stem cells
cells inappropriately and permanently switched on by signalling cytokines that control haemoatopoiesis
90
What causes myeloproliferative neoplasms?
genetic mutations in haematopoietic stem cells
cells inappropriately and permanently switched on by signalling cytokines that control haemoatopoiesis
91
What is the prognosis of Polycythaemia vera?
13 years
92
How common is Polycythaemia vera?
2 cases per 100,000 people per year
92
How common is Polycythaemia vera?
2 cases per 100,000 people per year
93
What are the symptoms of Polycythaemia vera?
itching
fatigue
94
What are the differential diagnoses for Polycythaemia vera?
ELIMINATE SECONDARY CAUSES:
lung disease
alcohol
apparent erythrocytosis
erythropoietin (EPO) secreting tumours
95
What is the management of Polycythaemia vera?
venesection (removing blood)
aspirin
hydroxycarbamide
management of cardiovascular risk factors
96
What are the complications of Polycythaemia vera?
arterial thrombosis - stroke/ MI
venous thrombosis- DVT, portal vein thrombosis, splanchnic vein thrombosis
97
What is the possible progression of Polycythaemia vera?
transform to acute leukaemia and myelofibrosis
98
What is essential thrombocytosis?
elevated platelet count
99
What is the prognosis of essential thrombocytosis?
normal life expectancy
100
How common is essential thrombocytosis?
2 cases per 100,00 per year
RARE
101
What causes essential thrombocytosis?
mostly JAK mutation- thrombopoetin (TPO) always switched on
102
What is the differential diagnosis of essential thrombocytosis?
ELIMINATE SECONDARY CAUSES:
infection
inflammation (including post-surgical)
solid tumours
102
What is the differential diagnosis of essential thrombocytosis?
ELIMINATE SECONDARY CAUSES:
infection
inflammation (including post-surgical)
solid tumours
103
How is essential thrombocytosis managed?
assess and manage cardiovascular risk
aspirin
hydroxycarbamide
104
What are the complications of essential thrombocytosis?
arterial thrombosis
venous thrombosis
bleeding
105
What is the possible progression of essential thrombocytosis?
acute leukaemia
myelofibrosis
106
What is myelofibrosis?
bone marrow cancer
107
What is the prognosis of myelofibrosis?
5 years
108
How common is myelofibrosis?
very rare
1 case per 100,000 per year
109
What are the causes of myelofibrosis?
predominantly JAK2 mutation
110
What are the symptoms of myelofibrosis?
weight loss
fatigue
features of cytopaenias
111
How is myelofibrosis managed?
supportive management:
blood transfusions, EPO, treat infection
hydroxycarbamide
allogenic stem cell transplant (ASCT)
ruxolitinab (JAK1/2 inhibitor)
112
What are the complications of myelofibrosis?
bone marrow failure
cytopaenias (low Hb, platelets, neutrophils)
bone marrow filled with reticulin fibrosis
elevated white cell count
blasts in circulation
splenomegaly
113
What is the possible progression of myelofibrosis?
acute leukaemia
114
What is chronic myeloid leukaemia?
elevated white cell count (granulocytes- neutrophils, basophils)
elevated platelets
splenomegaly
115
How rare is chronic myeloid leukaemia?
7 cases per year in UK
116
What causes chronic myeloid leukaemia?
almost all patients have a translocation between chromosome 9 and chromosome 22 ('Philadelphia chromosome') that creases a 'fusion gene' from BCR and ABL kinase
116
What causes chronic myeloid leukaemia?
almost all patients have a translocation between chromosome 9 and chromosome 22 ('Philadelphia chromosome') that creases a 'fusion gene' from BCR and ABL kinase
117
How is chronic myeloid leukaemia managed?
inhibitors of ABL kinase, i.e. imatinib
118
What can chronic myeloid leukaemia progress to?
'blast phase' - acute leukaemia
118
What can chronic myeloid leukaemia progress to?
'blast phase' - acute leukaemia
119
What is the common clinical presentation of alpha thalassaemia?
anaemia
splenomagaly
gallstones
delayed growth
120
What is the treatment for alpha thalassaemia major?
blood transfusions
splenectomy
stem cell transplant
121
Describe the pathophysiology of membranopathies
deficiency of red cell membrane proteins caused by genetic lesions, haemolytic anaemia
122
What are the common clinical features of membranopathies?
jaundice
anaemia
splenomegaly
123
Name a common enzymopathy
G6PD deficiency
mostly asymptomatic but can lead to haemolytic anaemia
124
Name a common enzymopathy
G6PD deficiency
mostly asymptomatic but can lead to haemolytic anaemia
125
Describe the inheritance pattern for G6PD deficiency
X-linked
126
Describe the inheritance pattern for G6PD deficiency
X-linked
127
What are the common clinical features of G6PD deficiency?
haemolysis
jaundice
anaemia
128
Which drugs can not be given to patients with G6PD deficiency?
primaquine
sulphonamides
nitrofurantoin
quinolones
dapsone
129
Describe bilirubin metabolism
- Haem > Biliverdin > Bilirubin
- Bilirubin binds with albumin = unconjugated bilirubin
- Unconjugated bilirubin combines with glucuronic acid = conjugated bilirubin (Excretable, example of phase 2 metabolism)
- Conjugated bilirubin forms bile, which gets pushed into the duodenum
- Bacteria in the gut breaks down conjugated bilirubin into urobilinogen (AKA faecal stercobilinogen)
- Urobilinogen can be reabsorbed and excreted via the urine as urobilin (makes urine yellow)
- Urobilinogen can become stercobilin and excreted in the faeces (makes poo brown)
129
Describe bilirubin metabolism
- Haem > Biliverdin > Bilirubin
- Bilirubin binds with albumin = unconjugated bilirubin
- Unconjugated bilirubin combines with glucuronic acid = conjugated bilirubin (Excretable, example of phase 2 metabolism)
- Conjugated bilirubin forms bile, which gets pushed into the duodenum
- Bacteria in the gut breaks down conjugated bilirubin into urobilinogen (AKA faecal stercobilinogen)
- Urobilinogen can be reabsorbed and excreted via the urine as urobilin (makes urine yellow)
- Urobilinogen can become stercobilin and excreted in the faeces (makes poo brown)
130
What is anaemia?
low level of Hb in blood
results of an underlying disease, not a disease itself
131
What Hb level is considered anaemic for men and women at sea level?
men: <135 g/L
women: <115 g/L
131
What Hb level is considered anaemic for men and women at sea level?
men: <135 g/L
women: <115 g/L
132
What are the 3 main categories of anaemia?
- microcytic anaemia (low MCV indicating small RBCs)
- normocytic anaemia (normal MCV indicating normal sized RBCs)
- macrocytic anaemia (large MCV indicating large RBCs)
133
What are the main causes of microcytic anaemia?
TAILS
T- thalassaemia
A- anaemia of chronic disease
I- iron deficiency anaemic
L- lead poisoning
S- sideroblastic anaemia (unable to put iron in Hb)
134
What is haemoptysis?
coughing up blood
135
What are the main causes of normocytic anaemia?
AHAHA!
Acute blood loss
Haemolytic anaemia
Anaemia of chronic disease
Hypothyroidism
Aplastic anaemia
135
What are the main causes of normocytic anaemia?
AHAHA!
Acute blood loss
Haemolytic anaemia
Anaemia of chronic disease
Hypothyroidism
Aplastic anaemia
136
What are the main causes of macrocytic anaemia?
B12 deficiency
folate deficiency
alcohol
reticulocytosis
hypothyroidism
liver disease
iatrogenic
137
What are the main causes of macrocytic anaemia?
B12 deficiency
folate deficiency
alcohol
reticulocytosis
hypothyroidism
liver disease
iatrogenic
138
What are the general signs and symptoms of anaemia?
tiredness
shortness of breath
headaches
dizziness
palpitations
pale skin
conjunctival pallor
tachycardia
raised respiratory rate
139
What is anaemia of chronic disease?
most common form of anaemia amongst hospital patients and 2nd commonest worldwide
results from poor use of iron during erythropoiesis, cytokine shortening of RBC lifespan, and decreased production or response to EPO
140
What is an autologous stem cell transplant?
stem cells are obtained from the patient
the cells are frozen before patient undergoes chemotherapy
used for myeloma and lymphoma
141
What is an allogenic stem cell transplant?
stem cells from a suitable donor
used for blood cancers like AML, ALL, MDS that cannot be cured with chemotherapy
142
What is anaemia?
lower than normal concentration of Hb or RBCs
143
What is the general presentation of anaemia?
symptoms: fatigue, headache, dizziness, dyspnoea (especially on exertion)
signs: tachycardia, skin pallor, conjuctiva pallor, intermittent claudation
144
What is intermittent claudation?
muscle pain that happens when you're active and stops when you rest
145
What are the rarer signs of anaemia and what causes them?
- Koilonychia (spoon-shaped nails)- iron deficiency
- Angular stomatitis- iron deficiency, B12 deficiency
- Lemon-yellow skin- B12 deficiency
- Jaundice/dark urine- haemolytic anaemia
146
What are the main types of anaemia?
Microcytic- reduced MCV
Normocytic- normal MCV
Macrocytic- normal MCV
Haemolytic- increased breakdown of RBCs
Aplastic- decreased production of new blood cells incl. RBCs, WBCs and platelets
147
What is sideroblastic anaemia?
the body produces enough iron but can't put it into Hb
148
What is a healthy MCV for men and women?
80-100 femtolitres
149
Why might the MCV be in a normal range for microcytic/ macrocytic anaemia?
It is a mean volume, so if some cells are too big and some are too small, the mean will be normal
150
What are the main causes of microcytic anaemia?
TAILS
Thalassaemia
Anaemia of chronic disease
Iron deficiency
Lead poisoning
Sideroblastic anaemia
151
What is Thalassaemia?
Inherited condition where body doesn't produce enough haemoglobin
