Haematology Flashcards
1
Q
what are the three components of blood?
A
red blood cells
plasma
clotting agents
2
Q
what are the three principal functions of blood?
A
transport
fighting infection
promoting vascular integrity
3
Q
what are the three general pathogenic mechanisms of haematological abnormalities?
A
- too many cells
- not enough cells
- abnormal function of cells
4
Q
what aremain components of bone marrow?
A
haemopoietic stem cells
adipose tissue
5
Q
which types of blood cells are classed as myeloid cells?
A
erythrocytes platelets neutrophils basophils eosinophils monocytes
6
Q
which types of blood cells are classed as lymphoid cells?
A
B cells
T cells
NK cells
7
Q
what are the three subtypes of T cells, and what is their function?
A
- cytotoxic T cells - kill pathogen
- helper T cells - help cytotoxic T cells kill pathogens and help antibody production
- regulatory T cells - dampen down immune response
8
Q
what can reticulocytes be useful for?
A
useful for measuring bone marrow function (ie red cell production)
9
Q
what is erythropoietin, where is it produced and why?
A
hormone that is produced by the kidneys in response to hypoxia, stimulates red blood cell production by bone marrow
10
Q
what is the function of erythropoietin?
A
it stimulates haematopoietic stem cells in bone marrow to differentiate into erythrocytes
11
Q
what are the stages of red blood cell differentiation?
A
haematopoietic stem cell –> myeloid progenitor cell -> erythroblast -> reticulocyte -> erythrocyte
12
Q
how long does it take for reticulocytes to differentiate into erythrocytes?
A
~24 hours
13
Q
what is the lifespan of an erythrocyte?
A
~120 days
14
Q
what hormone regulates platelet production?
A
thrombopoietin
15
Q
what is the lifespan of a platelet?
A
7 days
16
Q
where is thrombopoietin produced?
A
in the liver
17
Q
what is the lifespan of a neutrophil?
A
1-2 days
18
Q
what stimulates neutrophil production?
A
granulocyte-colony stimulating factors
interleukins
macrophages
19
Q
what are the stages of platelet differentiation?
A
haematopoietic stem cell -> myeloid progenitor cell -> megakaryocyte -> platelet
20
Q
what are the stages of neutrophil differentiation?
A
haematopoietic stem cell -> myeloid progenitor cell -> neutrophil
21
Q
what are monocytes?
A
macrophages that stay in the blood
22
Q
what name is given to monocytes that have migrated to 1. liver, 2. kidneys, 3. skin, 4. brain?
A
- kuppfer cells
- mesangial cells
- langerhans cells
- microglia
23
Q
what is main function of eosinophils?
A
fighting off parasite infections and mediating allergies
24
Q
where do B and T cells mature?
A
B cells - bone marrow
T cells - thymus
25
what is the main role of B cells?
antibody production
| immune memory
26
main action of antibodies?
opsonisation of pathogen
27
what is the role of IgG?
immune surveillance in circulation long after infection
28
what is the role of IgA?
immune surveillance of mucosa (gut, trachea)
29
what is the role of IgE?
mediation of allergies
30
what is the role of IgM?
first antibody to respond during an infection
31
what is positive and negative selection in terms of lymphocyte maturation?
positive selection - if cell doesn't react to self-antigens it survives and is taken to periphery
negative selection - if cell reacts to self-antigens it is killed
32
what is the difference between Class I and Class II HLA?
Class I HLA - displays self-antigens on all own cells
| Class II HLA - displays foreign antigens eaten by APC's
33
what are paraproteins?
monoclonal antibodies in the blood which only arise from abnormal proliferation of mature B cells or plasma cells
34
what is the normal value range for Haemoglobin for men an women?
men: 135-170
women: 120-160
35
what is the normal value range for platelets in the blood?
150-400
36
what is the normal value range for WBC in the blood?
4-10
37
name the main diagnostic tools that are done in haematology
- FBC
- clotting factors/platelet clotting times
- chemical assays (haematinics)
- biopsies (bone marrow, lymph node)
- imaging (Xray, CT, MRI)
38
what are the three most common haematinics?
iron
folate
vitamin B12
39
what does a blood group depend on?
it depends on the antigens its red blood cells have on their surface
40
what antibodies does blood group A produce?
anti-B antibodies
41
what antibodies does blood group B produce?
anti-A antibodies
42
what antibodies does blood group O produce?
anti-A and anti-B antibodies
43
why can blood group O give blood to everyone but can only receive from other O?
because group O has no antigens, therefore group A and group B won't trigger an immune response against it. however, group O produces anti-A and anti-B antibodies, therefore it can only receive from blood group O
44
what kind of antibody do blood groups present?
IgM
45
which antibodies can fix complement?
IgM
46
what are the most common blood groups?
A and O
47
who can blood group O donate to?
A, B, AB and O
48
what is the difference between giving someone red blood cells (RBC) and FFP (fresh frozen plasma)?
RBC is literally only a donation of red cells
| FFP contains proteins, antibodies and clotting factors but no red cells
49
name a few indications of RBC transfusion
severe acute anaemia
bone marrow failure
prior to major surgery
to replace damaged RBC eg sickle cell
50
what is the storage temperature for blood?
4 degrees
51
what is the storage temperature for platelets?
22 degrees
52
what is the average transfusion time for blood?
2-4 hours
53
what is the average transfusion time for platelets?
20-30mins
54
what antibodies does AB produce?
no antibodies
55
who can an AB fresh frozen plasma donor give blood to, and why?
AB FFP donor can give to A, AB, B and O because their plasma contains no antibodies at all
56
why is RhD blood group important?
because if someone is RhD negative, they can get a transfusion reaction if they are transfused with RhD positive blood
57
what is apheresis?
the process of separating blood into individual components for transfusion
58
what is contained in the plasma once whole blood is separated?
clotting factors
albumin
antibodies
59
what is contained in the buffy coat layer once whole blood is separated?
white blood cells
| platelets
60
name a few indications for platelet transfusion
massive haemorrhage
bone marrow failure
prior to surgery
cardiopulmonary bypass
61
what is the main aim of fresh frozen plasma transfusions?
to promote coagulation
62
what is the main aim of red cell transfusions?
to increase hemoglobin and oxygen levels
63
what is the main aim of platelet transfusions?
to correct low platelet levels
64
what are the processes in place when taking blood to the blood bank?
- EDTA tubes (x2)
- group and screen (blood type, antibodies)
- Coombs test
65
what is the process of the Coombs test in haematology?
it involves adding anti-human antibodies to a blood sample; if there are autoantibodies or complement stuck to the RBC, the anti-human antibodies will attach to these, causing the RBC to crosslink and agglutinate
66
what is the aim of the Coombs test?
it is used in haemolytic anaemia to identify whether the cause of the haemolysis is auto-immune or not
67
what is the difference between direct and indirect Coombs test?
Direct - identifies antibodies stuck to RBCs
| Indirect - identifies free floating antibodies in plasma
68
when is a Coombs test positive for antibodies?
when the RBC agglutinate on the blood film
69
what is haemolytic disease of the newborn (HDN) and what causes it?
it is the destruction of baby's red cells by mum's antibodies, when baby has RhD positive blood and mum has RhD negative blood
70
for which pregnancy is haemolytic disease of the newborn normally a problem?
any pregnancy after the first one with a baby who has RhD positive blood
71
when is prophylactic anti-D given to pregnant women?
as routine during week 28
72
what is the aim of giving prophylactic anti-D to pregnant women?
it neutralises any RhD positive antigens that get into the circulation, so that mum doesn't form any antibodies against them
73
in which areas of red blood cells can congenital anaemias occur?
- cell membrane
- enzymes
- haemoglobin
74
what happens to red blood cells in congenital anaemias like spherocytosis and elliptocytosis?
structural proteins that maintain the biconcave shape are mutated, causing the red cells to change shape
75
what are the structural proteins in red cell membranes that, when mutated, can cause congenital anaemias?
ankyrin
Band 3
spectrin (alpha and beta)
76
why are red cells normally biconcave?
because this allows them to squeeze through tight capillaries
77
what is the consequence of congenital anaemias affecting the cell membrane?
early haemolysis by the reticuloendothelial system
78
what system in the body is responsible for getting rid of old or faulty red blood cells?
the reticuloendothelial system
79
what are the main cellular processes which occur in red blood cells? what is the role of each?
glycolysis - energy
| pentose phosphate pathway - protection against reactive oxygen species
80
mutation in which red blood cell enzymes can cause congenital anaemias?
- glucose 6 phosphate dehydrogenase (G6PD) deficiency
| - pyruvate kinase deficiency
81
why is G6PD important in red cell metabolism?
it forms a link between glycolysis and the pentose phosphate pathway, and protects red cells from oxidation
82
what is the genetic inheritance of G6PD deficiency?
X linked
83
what triggers haemolytic anaemia in G6PD deficiency?
drugs
fava beans
infections
severe disease eg DKA
84
where does haemolysis occur in anaemia caused by G6PD deficiency?
intravascular haemolysis
85
name a few symptoms/signs of intravascular haemolysis
- anaemia
- pigment gallstones
- dark urine
- jaundice
- splenomegaly
- hepatomegaly
86
what is the pathology behind the signs of intravascular haemolysis?
red cells bursting in the circulation, causing haemoglobin to spill into the circulation and bilirubin levels in the blood increasing
87
what is the general treatment of haemolysis?
folic acid and iron replacement
| blood transfusion
88
why is B12 not routinely given as replacement of anaemia, unless there is a specific B12 deficiency?
because normally B12 stores in the liver last for about 3 years
89
what are the main congenital haemoglobinopathies?
thalassaemia
| sickle cell disease
90
what is thalassaemia?
loss or mutation of certain globin genes, causing a reduction in globin chains and lower haemoglobin levels
91
what is sickle cell disease?
structural abnormality in beta chains of haemoglobin, which cause the chains to crystallise and change the shape of the red cell
92
what is HbF, and what is it made up of?
HbF is fetal haemoglobin
| 2 alpha chains + 2 gamma chains
93
what is HbA2 and what is it made up of?
HbA2 is a type of haemoglobin that makes up 2% of our total haemoglobin
2 alpha chains + 2 delta chains
94
what is 97% of our haemoglobin made up of?
2 alpha chains + 2 beta chains
95
what is alpha thalassaemia?
it's a congenital anaemia caused by absence in one or more alpha genes, causing a reduced number of alpha chains and therefore less haemoglobin
96
why is a lack of alpha globin chains incompatible with life?
because formation of haemoglobin depends on 2 alpha chains bound to two beta, delta or gamma chains
97
what is beta thalassaemia major?
it's a congenital anaemia caused by absence of beta globin genes, resulting in loss of beta chains and therefore very low levels of haemoglobin
98
what does beta thalassaemia minor look like on a blood film?
microcytic and hypochromic red cells
99
what is sickle cell disease?
it's a congenital anaemia caused by abnormal beta globin chains, which crystallise in low oxygen tension areas and cause the red cell to become sickle shaped
100
what are the main complications of sickle cell disease, as a result of the abnormal red cell shape?
early haemolysis
| vaso-occlusion
101
why is sickle cell disease a risk factor for CVA?
because the sickle cell shaped red cells can cause vaso-occlusion
102
how does sickle cell disease cause anaemia?
because of the red cells are haemolysed due to their abnormal shape
103
why do people with sickle cell anaemia not have any problems with hypoxia?
because sickle red cells have slightly lower affinity for oxygen so give it up more readily
104
what is the appearance of G6PD deficient red blood cells?
bite cells
| blister cells
105
how many alpha and beta genes do you get from mother and father?
alpha genes - two from mum, two from dad
| beta genes - one from mum, one from dad
106
what is the genetic inheritance of thalassaemia?
autosomal recessive
107
what is the genetic inheritance of sickle cell anaemia?
autosomal recessive
108
what is the appearance of red blood cells in thalassaemia minor?
hypochronic microcytic
109
how is a sickle cell crisis managed?
supportive: analgesia, oxygen, fluids, antibiotics if needed
110
how does sickle cell anaemia affect the spleen?
it causes hyposplenism
111
as a result of vaso-occlusion in sickle cell anaemia, name a few clinical presentations that may occur
vaso-occlusion (CVA, bone pain, chest crisis, pain crisis)
sequestration (liver, spleen)
hyposplenism (increased infections)
chronic haemolytic anaemia (gallstones, dark urine, jaundice)
112
what is the long-term treatment for sickle cell disease?
vaccinations and prophylactic antibiotics
folic acid replacement
blood transfusions
hydroxycarbamide
113
what is the acute treatment for sickle cell disease presentations?
```
oxygen
analgesia
fluids
antibiotics
blood transfusion if severe
```
114
what's an important complication in beta thalassaemia treatment, and how is it prevented?
iron overload
| iron chelation therapy is started alongside transfusions to prevent iron overload
115
how does hydroxycarbamide reduce the amount of sickle cell acute attacks?
by increasing the production of fetal haemoglobin, which doesn't sickle, and therefore reducing the number of sickle cells
116
in anaemia, what investigation is done to confirm the presence of haemolysis?
bilirubin and LDH levels
117
in anaemia, what investigation is done to assess bone marrow function?
reticulocyte count
118
in anaemia, what investigation is done to assess iron levels?
ferritin levels
119
in anaemia, what investigation is done to test for megaloblastic anaemia?
B12/folate levels
120
what haematinic replacement should anyone with haemolytic anaemia receive?
folic acid replacement
121
what is the presentation of beta thalassaemia major?
```
severe anaemia from 3 months of age
bone deformities
bone marrow expansion
splenomegaly
growth retardation
```
122
why does beta thalassaemia major cause bone deformities?
because the lack of haemoglobin causes bone marrow to expand in an effort to create red cells
123
what is the treatment for beta thalassaemia?
blood transfusion every 4-6 weeks
124
what are the hereditary anaemias caused by abnormalities in haem synthesis steps? name the steps affected
mitochondrial step abnormalities - sideroblastic anaemias
| cytoplasmic step abnormalities - porphyrias
125
what is the genetic inheritance of G6PD deficiency?
X-linked
126
what type of haemolysis is caused by a trigger in G6PD deficiency anaemia?
intravascular haemolysis
127
what are the generic features of anaemia?
```
pallor
tiredness
swollen ankles
breathlessness/dizzyness
gallstones
chest pain
```
128
why do men have higher haemoglobin levels than women?
because hormones affect Hb production, and testosterone in men causes an increase in Hb production
129
how does age affect Hb levels?
babies are polycythaemic, whereas old people tend to have low Hb
130
why is acute anaemia more likely to cause hypoxic symptoms than chronic anaemia?
because chronic anaemia allow the body to adapt to lower levels of Hb
131
what are the morphological features of red blood cells that can help identify the type of acquired anaemia?
MCV - mean cell volume (size)
| MCH - mean cell haemoglobin (colour)
132
what are the 3 possible morphological features of acquired anaemia?
- hypochromic microcytic
- normochromic normocytic
- macrocytic
133
what is the commonest cause of anaemia?
iron deficiency
134
what diagnostic test should be done if a blood film shows hypochromic microcytic anaemia?
serum ferritin levels
135
in hypochromic microcytic anaemia, what diagnosis do high/normal levels vs low levels of serum ferritin indicate?
low levels - iron deficiency
| high/normal levels: thalassaemia trait, secondary anaemia
136
what is the pathology behind secondary anaemia?
increased hepcidin levels - ferroportin blocked, not allowing iron to be transported into cells and therefore reducing ability to make red blood cells
137
in iron metabolism, define the role of ferritin, transferrin, ferroportin and hepcidin
ferritin - molecule used to store iron
transferrin - protein used to carry iron in the circulation
ferroportin - endothelial channel that allows iron to enter and exit cells
hepcidin - molecule that regulates iron absorption by opening/blocking ferroportin according to iron levels
138
which blood cancer is characterised by proliferation of undifferentiated myeloid progenitor cells?
acute myeloid leukaemia
139
in AML, are the proliferating cells differentiated?
no
140
how does AML affect the bone marrow?
it causes bone marrow failure, due to the overwhelming amount of undifferentiated blasts taking over the bone marrow
141
what percentage of cells on the blood film have to be undifferentiated blasts, for it to be classed as AML?
>20% of cells on blood film have to be undifferentiated blasts
142
what are the three classic features of bone marrow failure? think about the cells involved
anaemia (due to low red cells)
thrombocytopaenia (due to low platelets)
neutropaenia (due to low neutrophils)
143
what symptoms can occur in bone marrow failure, as a result of the pancytopaenia?
anaemia - pale, tiredness, fatigue, SoB
thrombocytopaenia - purpura, mucosal bleeding, ecchymosis
neutropaenia - increased risk of infections
144
what is pancytopaenia?
reduction in all blood cell numbers
145
what investigations are essential in diagnosing myeloid malignancies?
- full blood count
- blood film
- bone marrow aspirate
- cytogenetics/immunohistochemistry
146
what is the treatment of AML?
- chemotherapy
- supportive treatment (prophylaxis for infections)
- stem cell transplantation
147
why is AML more severe than CML?
- AML develops more rapidly
- AML causes bone marrow failure as a result of blast proliferation
- blasts in AML do not function at all, whereas the proliferating myeloid cells in CML still function to a degree
148
which population is more at risk of developing AML?
older population
149
in which type of myeloid malignancy is there proliferation of differentiated myeloid cells?
chronic myeloid leukaemia
150
what is the pathophysiology of CML?
uncontrolled proliferation caused by abnormal tyrosine kinase protein (BCR-ABL) as a result of a translocation between chromosomes 9 and 22 forming the Philadelphia Chromosome
151
what is the treatment of CML?
- tyrosine kinase inhibitors (imatinib = Glivec)
| - stem cell transplantation (if TKI fail)
152
what is an important complication in AML chemotherapy treatment?
severe bleeding in brain and lungs
153
why is there need for supportive treatment during AML chemotherapy treatment?
because chemotherapy completely stops bone marrow function for several weeks, leaving patients severely immunocompromised
154
in which malignancy is the Philadelphia Chromosome found, and what is it formed by?
CML
| formed by translocation between chromosomes 9 and 22
155
name some features of CML
high WBC and platelet count
anaemia
significant splenomegaly
gout
156
why is stem cell transplantation essential after chemotherapy in AML?
because it maintains remission of disease
157
what is the myeloproliferative disease which affects red cells?
polycytaemia vera
158
what is the pathophysiology of myeloproliferative diseases?
constant activation of JAK receptors causing proliferation of certain myeloid cells
159
which myeloid cells are increased in polycytaemia vera?
mainly red cells, but also white cells and platelets
160
which myeloid cells are increased in essential thrombocytaemia?
mainly platelets
161
what is the treatment of polycytaemia vera, and what is its aim?
venesection, aspirin, hydroxycarbamide, JAK inhibitors
| aim to reduce haematocrit to <45% and reduce risk of CVA resulting from thrombosis
162
what are some symptoms of polycytaemia vera?
itching
headaches
thrombosis - MI, stroke etc
163
what is the treatment of essential thrombocytaemia, and what is its aim?
aspirin, hydroxycarbamide, JAK inhibitors
| aim to block platelet action and reduce risk of CVA/thrombosis
164
what is a significant risk when a patient develops a myeloproliferative disease?
it can develop into AML further down the line
165
blood cancers make up what percentage of total cancers?
about 10%
166
which type of leukaemia are children more likely to develop?
acute lymphoblastic leukaemia
167
which blood cancers involve proliferation of undifferentiated cells?
acute myeloid leukaemia
| acute lymphoblastic leukaemia
168
which blood cancers involve proliferation of differentiated myeloid cells?
chronic myeloid leukaemia
polycytaemia vera
essential thrombocytaemia
169
which blood cancers are also called myeloproliferative neoplasms?
polycytaemia vera
| essential thrombocytaemia
170
which blood cancers involve proliferation of differentiated lymphoid cells?
chronic lymphocytic leukaemia
Hodgkin's lymphoma
Non-Hodgkin's lymphoma
171
what differentiates Hodgkin's from Non-Hodgkin's lymphoma?
- Hodgkin's Lymphoma mainly affects lymph nodes around the head and respiratory tract, without much extra-nodal involvement
- Non-Hodgkin's Lymphoma affects symmetrical lymph nodes all over the body and has more frequent extra-nodal involvement
172
where do lymphomas normally arise?
in the germinal center of a lymph node
173
which lymphoid cell type is most commonly affected in lymphomas? why is that?
B cell most commonly affected, because they proliferate at very high rates to make memory and plasma cells, increasing the risk of an accidental mutation in the process
174
during which process in B cell maturation do lymphomas commonly arise?
during somatic hypermutation (extensive proliferation to make plasma and memory cells)
175
when is a swollen, localised lymph node more likely to be an infection or a tumour?
if localised and painful - more commonly an infection
| if localised and painless - more commonly cancer metastasis
176
when do swollen, painless lymph nodes point towards lymphoma rather than metastatic cancer? explain why
when the swollen lymph nodes are generalised - lymphomas spread through lymphatic system, whereas metastases spread through circulation so are unlikely to present in multiple lymph nodes
177
what causes secondary anaemia to develop?
increased levels of hepcidin (eg due to inflammation/infection) cause a decrease in iron passing through ferroportin and into cells
178
name a few common causes of iron deficiency anaemia
```
lack of iron in diet
malabsorption
GI bleed
menorrhagia
increased requirement (pregnancy)
```
179
what do red cells look like in iron deficiency anaemia?
hypochromic and microcytic
180
what feature of anaemia can be seen in nails?
koilonychia
181
what features of anaemia can be present in the mouth?
atrophic, painful tongue
| angular stomatitis
182
what is the first line treatment of iron deficiency?
oral iron replacement tablets
183
what investigation is done when a blood film shows normochromic, normocytic anaemia?
reticulocyte count
184
what does a low reticulocyte count mean in normochromic, normocytic anaemia?
it means bone marrow can't produce new reticulocytes because there is a lack of available iron ie secondary anaemia
185
what does a high reticulocyte count mean in normochromic, normocytic anaemia?
it means the bone marrow is working hard to replace red cells ie haemorrhage or acute haemolysis
186
in secondary anaemia, is serum ferritin high or low? explain why
high, because underlying condition is causing an increase in hepcidin which stops ferritin from being absorbed, but it also increases ferritin levels
187
ferritin is an acute phase reactant. what does that mean?
it means that during infection or inflammation the ferritin levels in the circulation go up
188
what is haemolytic anaemia?
it's premature destruction/removal of red blood cells from the circulation
189
what are the two possible mechanisms haemolytic anaemia can be acquired? where does each one occur in relation to the circulation?
- autoimmune - occurs extravascularly
| - non-autoimmune - occurs intravascularly
190
what red cell abnormalities might cause congenital haemolytic anaemia?
- abnormal red cell shape (spherocytosis)
- abnormal haemoglobin (sickle cell anaemia, thalassaemia)
- abnormal enzymes (G6PD deficiency)
191
what organ can be noticeably affected in autoimmune haemolytic anaemia? how and why?
the spleen can become very enlarged, because it is working harder than usual to remove the red blood cells it sees as foreign
192
what investigation is done to identify whether haemolytic anaemia is autoimmune or not?
Coombs test (ie antiglobulin testing)
193
if a Coombs test result shows agglutinated red blood cells, what does that mean?
it means the haemolytic anaemia is autoimmune
194
if a Coombs test result shows non-agglutinated red blood cells, what does that mean?
it means the haemolytic anaemia is not caused by an autoimmune response
195
what is an important consideration when interpreting the results of a Coombs test in haematology?
some antibodies only activate in warm conditions, and some only in cold conditions. this can point to different causes for immune haemolytic anaemia
196
what blood tests are done to identify whether a patient with anaemia is haemolysing?
- FBC
- reticulocyte count
- bilirubin/LDH
- haptoglobin
- Coombs test
197
what are the management options of haemolytic anaemia?
- folic acid replacement
- treating underlying cause
- immunosuppression
- transfusion
- splenectomy
198
what is macrocytic anaemia also called?
megaloblastic anaemia
199
what is macrocytic/megaloblastic anaemia caused by?
mainly vitamin B12 or folic acid deficiency
| also: myelodysplasia, drugs, liver disease, alcohol, hypothyroidism
200
how is vitamin B12 deficiency managed?
intramuscular B12 injections (every 3 months)
201
what causes vitamin B12 deficiency?
- pernicious anaemia
| - gastrectomy
202
what causes folate deficiency?
- diet
- increased requirement
- malabsorption
203
what are the main features of B12/folate deficiency?
```
anaemia symptoms (pale, fatigue, SoB, jaundice)
neurological symptoms (peripheral neuropathy)
```
204
what does megaloblastic anaemia look like on a blood film?
- red cells look large and flabby, more friable and prone to haemolysis
- neutrophils look hypersegmented
205
in anaemia, what specific blood tests help point towards the presence of haemolysis?
bilirubin levels
lactate dehydrogenase levels
haptoglobin levels
206
how is folate deficiency managed?
oral folate replacement
207
other than anaemia, what can vitamin B12/folate deficiency present with?
peripheral neuropathy
208
what are B symptoms in lymphoma?
```
weight loss
night sweats
fever
pruritis
fatigue
```
209
what is the commonest physical presentation of lymphoma?
lymphadenopathy
210
what is the first line investigation for lymphoma?
biopsy of lymph node/bone marrow
211
which type of leukaemia is the commonest in children?
Acute lymphoblastic leukaemia
212
what is the commonest type of lymphoma? how aggressive is it?
diffuse large B cell lymphoma - high grade
213
what is the commonest low-grade lymphoma?
follicular lymphoma
214
which blood cancer involves proliferation of undifferentiated lymphoid cells?
acute lymphoblastic leukaemia
215
how can children with ALL present?
bone marrow failure
bone pain
limp
216
which lymphoid progenitors are often involved in ALL?
- B cell progenitors
217
how is the type of lymphocyte progenitor identified in ALL?
through immunophenotyping - if it expresses CD19 it's a B-lymphoblast
218
what is the management of ALL?
chemotherapy
CNS therapy
stem cell transplant
immunotherapy - RiTe, CAR
219
why is there need for CNS specific therapy in ALL, and how is it administered?
- because chemotherapy drugs normally don't penetrate BBB, and lymphoblasts often hide in the brain
- intrathecal methotrexate injection
220
what is the commonest type of leukaemia?
chronic lymphocytic leukaemia
221
what is the gender distribution of CLL?
2:1 males to females
222
exposure to what virus has been associated with CLL development?
EBV virus
223
how does CLL often present?
often asymptomatic presentation
224
what is immune paresis?
loss of immunoglobulin production
225
what type of blood cancer is immune paresis associated with?
CLL
226
what is the staging score used for CLL?
Binet staging
227
what are the three stages of CLL according to the Binet score?
A - less than 3 lymph nodes involved
B - more than 3 lymph nodes involved
C - 3 or more lymph nodes + cytopaenia
228
name a few indications to treat CLL
```
bone marrow failure
lymphadenopathy
splenomegaly
systemic symptoms
rapid lymphocyte proliferation
```
229
if there are no severe symptoms, what is the management of CLL?
watch and wait
| frequent monitoring
230
what is the management of CLL?
chemotherapy
| monoclonal antibodies
231
what are some possible signs/symptoms of lymphoma?
lymphadenopathy
B symptoms
hepatosplenomegaly
232
what are the main diagnostic investigations for lymphoma?
lymph node biopsy
bone marrow biopsy
CT scan
233
what lymphocytic lineage is normally presented by non-Hodgkin lymphoma?
B cell lineage
234
why are low grade lymphomas incurable?
because they are very slow growing, so it is difficult to target actively proliferating cells
235
what is the management of low grade lymphoma?
watch and wait
236
what is the therapeutic management of non-Hodgkin lymphoma?
chemotherapy + monoclonal antibody (anti-CD20)
237
what are the commonest age groups to get Hodgkin lymphoma?
20-30s
| over 60
238
which subgroup of Hodgkin lymphoma patients are more likely to have had EBV exposure?
those patients who get Hodgkin lymphoma later in life
239
what is the presentation of lymphadenopathy in Hodgkin's lymphoma?
symmetrical lymphadenopathy in upper respiratory tract and head, with little extranodal involvement
240
what is the presentation of lymphadenopathy in non-Hodgkin lymphoma?
lymphadenopathy not symmetrical, can present anywhere, 60% with extranodal involvement
241
what is he treatment of Hodgkin's lymphoma?
chemotherapy
radiotherapy
monoclonal antibodies (anti-CD30)
242
with regards to monoclonal antibody treatment, which cell marker is targeted in non-Hodgkin lymphoma and Hodgkin lymphoma respectively?
non-Hodgkin - CD20
| Hodgkin - CD30
243
what is the scoring system for lymphoma called, and what are the four stages?
Ann Arbor staging score:
1 - one lymph node
2 - two lymph nodes on same side of diaphragm
3 - disseminated lymph nodes on both sides of diaphragm
4 - extranodal disease
+ A (no systemic symptoms) or B (B symptoms)
244
what pattern of bleeding is found in platelet disorders?
mucosal bleeding:
| ecchymosis, epistaxis, purpura, petechiae, menorrhagia
245
what pattern of bleeding is found in coagulation factor disorders?
muscle hematoma
haemarthrosis
CNS bleeding
246
what is haemophilia type A?
loss of coagulation factor VIII
247
what is haemophilia type B?
loss of coagulation factor IX
248
what is the mode of inheritance of haemophilia A and B?
X-linked
249
how can haemophilia affect the joints in the long run, if uncontrolled?
it can increase risk of osteoarthritis and haemophilic arthropathy
250
what is the management of haemophilia?
- recombinant factor 8/9 replacement
- desmopressin
- tranexamic acid
- prophylaxis in severe cases
- gene therapy
251
which bleeding disorders is desmopressin useful in?
Type 1 von Willebrand disease
| Haemophilia A
252
what are the three subtypes of von Willebrand disease?
Type 1 - quantitative, not enough vWF
Type 2 - abnormal function of vWF
Type 3 - complete lack of vWF
253
what is the genetic inheritance of von Willebrand disease?
autosomal dominant
254
is von Willebrand disease inherited or acquired?
inherited
255
how does desmopressin work in bleeding disorders?
- it releases vWF from the endothelial cells
| - it stabilises factor 8
256
which coagulation factors are only involved in the extrinsic pathway?
tissue factor
factor VII
factor V
257
which coagulation factors are only involved in the extrinsic pathway?
factor XII
factor XI
factor IX
factor VIII
258
does von Willebrand disease cause platelet deficiency type bleeding or coagulation factor deficiency type bleeding?
platelet deficiency type bleeding - mucosal, ecchymosis, epistaxis, menorrhagia
259
how common is von Willebrand disease?
common - 1 in 200
260
which type of haemophilia is more common?
Haemophilia A
261
what investigations are done to diagnose haemophilia, and what might they show?
platelet count - normal
prothrombin time (PT) - normal
partial thromboplastic time (APTT) - high
clotting factors - factor 8 or 9 low
262
what do PT and APTT test respectively in haematology?
PT - tests extrinsic and common coagulation pathway
| APTT - tests intrinsic and common coagulation pathway
263
which clotting factors are vitamin K dependent?
factors 2, 7, 9 and 10
264
name a few causes of acquired bleeding disorders
- liver failure
- renal failure
- autoimmunity to clotting agents
- vitamin K deficiency
- diffuse intravascular coagulation
- drugs (warfarin, DOACs, aspirin)
265
what are the management options for von Willebrand disease?
- vWF concentrate
- desmopressin
- tranexamic acid
- menorrhagia management
266
what is the mechanism of action of tranexamic acid?
tranexamic acid blocks the conversion from plasminogen to plasmin, therefore stopping fibrin degradation
267
why does liver failure lead to bleeding disorders?
liver failure affects the liver's production of clotting factors
268
why does disseminated intravascular failure lead to bleeding disorders?
because extensive coagulation uses up all available clotting factors, eventually leading to uncontrolled bleeding
269
what is autoimmune thrombocytopaenic purpura?
thrombocytopaenia (low platelet count) as a result of autoimmune reaction against own platelets
270
how is immune thrombocytopaenia treated?
steroids
IV immunoglobulin
splenectomy if hypersplenism
thrombopoietin analogues
271
define primary haemostasis and secondary haemostasis
primary haemostasis - initial platelet activity and start of fibrin plug formation
secondary haemostasis - coagulation cascade and stabilisation of solid fibrin plug
272
which molecules drive the degradation of fibrin in haemostasis?
t-PA: it converts plasminogen into plasmin, and plasmin breaks down fibrin plug
273
where is t-PA released from in haemostasis?
t-PA is released from endothelial cells
274
what is t-PA?
tissue plasminogen activator - converts plasminogen into plasmin, which breaks down fibrin plug
275
what diagnostic molecule is found in the circulation as a result of fibrin degradation?
d-dimer
276
what other conditions is immune thrombocytopaenic purpura associated with?
infections (EBV, HIV)
lymphoma
drug related
277
why is Vitamin K injected in babies right after birth?
to give their coagulation system a boost and prevent Haemorrhagic Disease of the Newborn
278
when is a diagnosis of haemophilia first made?
in children between 6months and 2 years of age
279
what defines haemophilia as mild, moderate or severe?
residual coagulation activity:
mild is 5-30%
moderate is 1-5%
severe is <1%
280
what is the monoclonal antibody that can now be used for haemophilia A treatment, and what is its mechanism of action?
Emicizubab (Hemlibra)
it replaces factor VIII and binds factor X to factor IXa in order to activate factor X and trigger common coagulation cascade
281
name a few complications of haemophilia treatment
- viral infections (HIV, HBV, HCV)
- inhibitors (anti-factor 8 antibodies)
- MI (desmopressin promotes platelet adherence)
282
why does liver failure show prolonged PT and aPTT time on coagulation tests?
because the liver produces all coagulation factors, so a lack in production causes deficiency in both extrinsic and intrinsic coagulation pathway
283
which coagulation factors are only involved in the common pathway?
```
factor X
factor II (prothrombin)
factor I (fibrinogen)
```
284
vitamin K dependent coagulation factor deficiency is associated with which GI condition and why?
cholestasis/biliary tree disease, because it leads to an inability to absorb fat from diet which is essential for factor II, VII, IX and X production
285
what's the purpose of heparans, thrombomodulin and TFPI in a healthy blood vessel?
they inhibit the adhesion of platelets to the endothelial wall
286
what is the physiological activator that triggers platelet adhesion in a damaged blood vessel?
tissue factor
287
which platelet surface glycoprotein binds fibrinogen?
GP 2b/3a
288
which platelet surface glycoprotein binds to collagen exposed by blood vessel damage?
GP Ia/2a
289
what are the most important cell surface receptors on a platelet?
ADP receptor
epinephrine receptor
thrombin receptor
290
what are the two granules inside a platelet called, and what does each release?
alpha granule - vWF, thrombin
| dense granule - calcium, serotonin, ADP/ATP
291
what is von Willebrand Factor released by?
platelets and endothelial cells
292
which platelet surface glycoprotein binds to von Willebrand Factor?
GP 1b
293
what are the three main actions of platelets?
adhere
activate
aggregate
294
how do platelets adhere to damaged blood vessels?
they adhere to collagen through GP Ia and to von Willebrand Factor through GP 1b
295
how do platelets activate?
they activate through ADP and epinephrine attaching to their receptors, causing arachidonic acid to be converted into thromboxane A2 through COX-1
296
how do platelets aggregate?
they aggregate through the action of thromboxane A2, which allows them to shrink and stick together
297
how do platelets facilitate coagulation?
platelets help the coagulation process by flipping their phospholipid membrane over
298
what enzyme helps the phospholipid membrane of platelets flip inside out to help coagulation?
scramblase
299
what are the three main natural anticoagulants?
- tissue factor pathway inhibitor (TFPI)
- activated protein S and protein C
- antithrombin
300
which coagulation factors are switched off by TFPI?
factor VIIa and factor Xa
301
which coagulation factors are switched off by activated protein S and C?
factor Va and factor VIIIa
302
which coagulation factors are switched off by antithrombin?
mainly factor Xa and thrombin, but also factor XIa, IXa and VIIIa
303
what is the purpose of natural anticoagulants in haemostasis?
they ensure the fibrin clot is confined to the area of damage
304
how does aspirin inhibit platelet action?
it inhibits platelet aggregation by blocking COX-1 pathway, preventing the conversion of arachidonic acid to thromboxane A2
305
how do clopidogrel and ticagrelor inhibit platelet action?
they inhibit platelet activation by blocking the ADP/epinephrine receptors and stopping the P2Y12 pathway
306
how do abciximab and tirofiban inhibit platelet action?
it they stop fibrinogen binding to GP 2b/3a
307
how does warfarin stop coagulation?
it blocks factors 2, 7, 9 and 10
308
how can the effects of warfarin be reversed?
by injecting vitamin K
309
how does heparin stop coagulation? which natural anticoagulant does it mimic?
it blocks factor Xa and thrombin, mimicking antithrombin
310
how do NOACs like apixaban and rivaroxaban stop coagulation?
they stop factor X from being activated, by sitting on the serine site where the inactive zymogen is normally cleaved to activate it
311
what is the serine site on coagulation factors?
it's the area on the protein that is cleaved in order to activate the factor
312
how does dabigatran stop coagulation?
it acts as a direct thrombin inhibitor, by binding to its active site
313
what are arterial thrombi mainly made of, and what colour are they?
white thrombi containing mostly platelets (and some fibrin)
314
what are venous thrombi mainly made of, and what colour are they?
red thrombi containing mostly fibrin (and some red cells)
315
which elements of Virchow's triad are most likely to lead to venous thrombosis?
hypercoagulability ie cancer, pregnancy, OCP
| stasis ie long haul flights, immobility
316
which element of Virchow's triad is most likely to lead to arterial thrombosis?
vessel damage - ie atherosclerosis
317
what are the two commonly used pre-test probability scores for DVT?
Wells score
| Geneva score
318
when is a D-dimer test done for DVT?
when the pre-test probability score is low
319
what is the main aim of a D-dimer test for DVT?
to rule out the diagnosis of DVT
320
when testing compressibility of a vein, when is it more or less likely to be a DVT?
if vein compressible - probably not DVT
| if vein non-compressible - probably DVT
321
what imaging tests are carried out for DVT and PE?
DVT - doppler USS
| PE - V/Q scan
322
which types of long-term conditions can predispose to DVT?
cancer
myeloproliferative neoplasms
autoimmune conditions
323
which class of drug is given to patients following a DVT/PE?
anticoagulants
324
what is Factor V Leiden?
it's a mutation in factor 5, which makes it resistant to being switched off by activated protein S and C
325
what is the genetic inheritance of Factor V Leiden?
autosomal dominant
326
what are microvascular thrombi seen in DIC made up of?
can be either platelets, fibrin or both
327
name some risk factors for arterial thrombosis
```
hypertension
smoking
obesity
diet
sedentary lifestyle
diabetes
high cholesterol
age
```
328
name some risk factors for venous thrombosis
```
immobility
pregnancy
long haul flights
older age
obesity
HRT/OCP
surgery
systemic disease (eg cancer, autoimmune disease)
family history
inherited conditions (factor V leiden, antithrombin deficiency)
```
329
what is the iron level in the blood in polycythaemia vera?
almost always low
330
what is the pathogenesis of myelofibrosis?
proliferation of abnormal megakaryocytes, leading to fibrosis in bone marrow
331
what is a characteristic sign of myelofibrosis on a blood film?
tear-drop shaped red cells
nucleated red cells
large platelets
blast cells
332
name a few signs that point to a diagnosis of myelofibrosis
very enlarged spleen
tear-drop shaped red cells on blood film
fibrosis in bone marrow biopsy
333
how can chronic leukaemia and myeloma affect red blood cell count?
they can cause anaemia due to autoimmune haemolysis
334
which monoclonal antibody is used to target CD20 B cells in lymphoma?
rituximab
335
what chemotherapy drug is used for low grade lymphomas?
bendamustine
336
what treatment regimen is used for high grade lymphoma?
R-CHOP
- rituximab
- cyclophosphamide
- hydroxydoxorubicin
- vincristine
- prednisolone
337
what is the difference between CD19 and CD20 B cells?
CD19 is found on all B cells, regardless of their maturity
| CD20 is only found on mature B cells
338
what cell marker is expressed on T cells in CLL?
CD5
339
which portion of an antibody defines the class of antibody?
the heavy chain - Fc portion
340
which immunoglobulin has the highest molecular weight and why?
IgM - because it's a pentamer
341
what are the two possible structures of a light chain in antibody production?
kappa
| lambda
342
what is the most prevalent class of immunoglobulin?
IgG
343
what is the first line investigation for the diagnosis of myeloma? what does it identify?
serum protein electrophoresis - identifies presence of paraproteins in the blood
344
name a few examples of lab tests that can be done to help diagnose myeloma
- total immunoglobulin levels
- serum protein electrophoresis
- immunofixation
- light chains levels (kappa vs lambda)
345
proliferation of B lymphocytes leads to which type of blood cancer?
lymphoma
346
proliferation of plasma cells leads to which type of blood cancer?
myeloma
347
which immunoglobulin is released in lymphoma?
IgM
348
which immunoglobulin is released in myeloma?
IgG, IgA
349
do plasma cells release IgM?
no
350
which immunoglobulins do B cells and plasma cells produce respectively?
B cells - IgM
| plasma cells - IgG, IgA
351
what is myeloma?
it's a blood cancer resulting in abnormal proliferation of plasma cells and build up of paraprotein
352
what are the classic symptoms of myeloma?
CRAB:
- high calcium
- renal failure
- anaemia
- bone lesions
353
what is a rise in paraproteins in the blood called, if there are no symptoms indicating myeloma?
monoclonal gammopathy of uncertain significance (MGUS)
354
name some complications of paraprotein build up in myeloma
- renal disease
- hyperviscosity
- hypogammaglobulinaemia (low antibodies)
- amyloidosis
- increased risk of infections
355
if there is an abnormal build up of IgM in the blood, what is not the diagnosis and why?
it's not myeloma, as plasma cells do not produce IgM
356
what are the management options for myeloma?
- chemotherapy
- immunotherapy
- steroids
- bisphosphonates
- stem cell transplant
357
on bone marrow biopsy, what percentage of total cell count needs to be plasma cells for myeloma to be confirmed?
more than 10%
358
what type of amyloidosis is caused by multiple myeloma?
AL amyloidosis - primary amyloidosis caused by misfolding of immunoglobulin light chains
359
what protein found in the urine can help diagnose multiple myeloma? what is this protein?
Bence-Jones protein
| it's a light chain (kappa or lambda) that has spilled out of the circulation and into the urine
