Hematology Flashcards
1
Q
How much bone marrow does an adult have
A
2.5 kg
2
Q
What are the two parts of the bone marrow and what do they have in them
A
red- hemopoietin cells
yellow- fatty cells
3
Q
what changes occur to the bone marrow as you age
A
more yellow less red marrow
4
Q
how many cells per day does the bone marrow make
A
500 million so loads of room for errors
5
Q
What is leukaemia
A
malignant proliferation of hemopoietin cells
6
Q
what are two common features of leukaemia
A
diffuse replacement of healthy bone marrow cells with leukaemic cells
variable amounts of abnormal cells in peripheral blood
accumulation of leukaemic cells in liver, spleen, lymph glands, meninges, gonads
7
Q
what are the risk factors for leukaemia
A
congenital (downs increased risk)
chemotherapy
radiotherapy
benzene, Viruses e.g. HTLV and T cell leukaemia
8
Q
What are the symptoms of leukaemia
A
anaemia with fatigue, SOB, hepatosplenomegaly
thrombocytopenia with easy bruising, purpuric rash, mucosal bleeding
infections with fevers and rigours
9
Q
What is the rate of onset of symptoms of leukaemia
A
sudden usually
10
Q
what investigations do you carry out for leukaemia
A
full blood count (low RBC, low platelets, high WBC, low mature neutrophils)
biochemistry- Urea, Calcium, folate, vitamin B12
chest XR
blood film (seeing blasts, rouleux for leukaemia)
flow cytometry to see antigens on cells
virology for hep B and C and HIV
coagulation test
cytogenic analysis for genetic abnormality
bone biopsy
11
Q
What are the two forms of treatment for leukaemia
A
supportive and definitive
12
Q
What do we offer in supportive care for leukaemia
A
bone marrow support via blood transfusion and platelets
antibiotic prophylaxis and anti-fungal prophylaxis
treat symptoms e.g. nausea, constipation from treatment
psychological support
13
Q
What definitive treatment do we offer for leukaemia if intensive treatment
A
get into remission stage: high dose chemotherapy
stay in remission stage: stem cell transplant so graft cells attack cancer cells or chemotherapy for long time
14
Q
What definitive treatment do we offer for leukaemia if palliative treatment
A
low dose chemotherapy to control disease
consider quantity of life vs quality of life
15
Q
Describe what happens to leukaemic cells in acute leukaemia
A
lots of proliferation but loss of ability to differentiate so accumulation of blast cells in bone marrow which is a sign of bone marrow failure
16
Q
What is a clinical feature of bone marrow failure
A
accumulation of blast cells in bone marrow
17
Q
What happens to the peripheral WBC, RBC, platelets in acute leukaemia
A
low rbc, low platelets
wbc can be high, normal, low
18
Q
What is acute lymphoblastic leukaemia (ALL)
A
proliferation of the lymphoblast cells
19
Q
How can we classify ALL
A
B and T lymphoblast
20
Q
When does ALL become common in regards to age
A
2-4 children
15-24 teens and adults
elderly
21
Q
Which form of ALL is more common in adults, teens and children
A
Adults and teens T ALL
Children B ALL
22
Q
What is a risk factor specific for acute lymphoblastic leukaemia
A
Philadelphia chromosome abnormality
23
Q
What proportion of adults with ALL have Philadelphia chromosome abnormality? what about children
A
20-30% of adults
2% of children
24
Q
In what age group is ALL rarer but has a worse prognosis
A
adults
25
How long do male vs female adults need to be treated to maintain remission of the leukaemia
3 years for male
| 2 years for female
26
What is the commonest malignant cancer in children aged 2-4
ALL
27
What is acute myeloid leukaemia (AML)
proliferation of the myeloblast cells
28
What is the most common acute leukaemia in adults
AML
29
When does AML incidence increase
increases with age increase
30
What makes an adult more likely to develop AML
bone marrow disorders
31
Do children develop AML from primary or secondary causes more
primary AML
32
What specific thing should you check for in a blood film and why
auer rods which guide prognosis
33
What does chronic leukaemia do to the bone marrow cells
Proliferation of bone marrow cells without bone failure. i.e. cells can still differentiate
34
What is the treatment for chronic leukaemia
no cure unless bone marrow transplant
35
What is chronic myeloid leukaemia
proliferation of myeloid cells i.e. of neutrophils, eosinophils, basophils, which replace normal bone marrow cells
36
What is a risk factor for chronic myeloid leukaemia specifically
philadelphia chromosome abnormality
37
What is median survival from CML without treatment
5 years
38
What is chronic lymphocytic leukaemia
proliferation of B lymphocyte cells that are resistant to apoptosis
39
What is the median age of survival of CLL without treatment
25 years
| commonly disease of elderly and patients die with it
40
What are lymphomas
proliferation of wbc in lymph nodes or other organs in the lymphatic system
41
Where can the lymphoma spread to
blood, spleen, liver, other
42
What can cause lymphomas
```
Infections: HTLV, Epstein Barr virus, Helicobacter pylori
idiopathic
radiation
primary and secondary immunodeficiency
autoimmune disease
```
43
What are the symptoms of lymphomas
nodal or extra-nodal
compression syndrome
B symptoms: weight loss, night sweats, loss of appetite
44
Which lymph nodes are esp. effected by lymphomas
neck
axilla
groin
45
What could a lump around the neck, groin, axilla mean other than lymphoma
inflammation or infection lump
disease of underlying structures
embryonic remnant
a metastatic tumour from other site
46
How much weight must be lost to count as a symptom of lymphoma
10% of normal body weight lost in 6 months
| unintentionally
47
If a tumour metastasises to a lymph node, is that called lymphoma
no
48
How do we diagnose lymphoma and what's the name of the machine
```
haemato-oncology diagnostic service integrates:
- blood film
- bone marrow sample
- lymph node biopsy
- cytogenetics e.g. karyotype
- immunophenotype finds proteins on cell surface
- PCR
MDT to stage and grade
```
49
Give an example of a lymphoma cell we can diagnose using immunophenotype
B lymphocyte has CD20 on surface
only cell to have this
target treatment to CD20
50
What do we look at when staging lymphomas
CT scans
Bloods
PET scan (looks at where lots of glucose taken in by cells) naturally highlighted in liver, kidney, bladder, brain
51
What do we look at when assessing a patient
```
History and examination
FBC
Virology for HIV, Hep B and C
CXR
Echo
Performance status regarding treatment
```
52
What scores can you get for performance status regarding treatment
0- asymptomatic can do all activities
1- symptomatic, can walk, can do light work not strenuous
2- symptomatic, bedbound<50% of day, can walk but can't do any work, can do self-care
3- symptoms, bed bound >50% of day, can do self-care
4- symptoms, bed bound always
5- dead
53
What is a complication of lymphoma
idiopathic thrombocytopenic purpura aka immune thrombocytopenia
the immune system attacks platelets and platelet number low (usually single figures)
patient bleeds and bruises easily
54
What are the types of lymphoma
Hodgkin's and Non-Hodgkin's
55
When are the peaks in incidence of Hodgkin's lymphoma
adolescent
elderly
bimodal
56
How does Hodgkin's lymphoma present
```
painless lymphadenopathy (abnormal size, number, constituent of lymph nodes)
B symptoms
```
57
How do we diagnose Hodgkin's lymphoma
Reed-Sternberg cells presence
| large lymphocytes that may have more than one nucleus
58
How many different histological subtypes of Hodgkin's lymphoma are there
4
59
What are the stages of Hodgkin's lymphoma
```
numbers and letters (a= no symptoms, b= B symptoms)
1- one lymphoma at one site
2- two sites at same side of diaphragm
3- both sides of diaphragm affected
4- wide spread lymphoma
```
60
What chemotherapy do we use for Hodgkin's Lymphoma
```
ABVD
Adriamycin
Bleomycin
Vinblastine
Dacarbazine
```
61
What treatment do we do first for stage 1-2a of H-Lymphoma
chemotherapy and radiotherapy
62
What treatment do we do first for stage 2b-4 of H-lymphoma
chemotherapy
63
What is the no-disease prolonged survival rate with treatment for stage 1-2a and stage 2b-4 of H-Lymphoma
stage 1-2a: 70-80%
| stage 2b-4: 50-70%
64
What do we do if a patient relapses with H-lymphoma
autologous stem cell transplant
remove stem cells
high dose chemotherapy
re-introduce stem cells to build up bone marrow
65
What are the side effects of treatment of H-lymphoma
```
infertility
heart, lung problems
peripheral neuropathy
psychological
other cancer risks from treatment and general susceptibility of patient
```
66
How can we reduce unnecessary high doses of treatments for H-lymphoma
PET scan
| see which patients will respond well to treatment so give them lower doses
67
What are the three subtypes of Non-Hodgkin's lymphoma
low, high , very high grade
68
give an example of low grade NH-Lymphoma
follicular lymphoma
69
What is presentation like for Follicular lymphoma
by time of presentation, it is usually advanced
| its slow growing
70
What is the median time of survival for follicular lymphoma
9-11 years but can be longer or shorter for different patients
71
What are the treatment options for follicular lymphoma
```
nothing (immune system handles for long time)
alkylating agents
bone marrow transplant
monoclonal antibodies
combined chemotherapy
radiotherapy
radio-immunoconjugate
```
72
Can we cure follicular lymphoma
no but can be treated
73
What is an example of a high grade NH-lymphoma
Diffuse large B cell lymphoma
74
Why is Diffuse Large B cell lymphoma also known as aggressive
If not treated it and cured, it will kill the patient
75
What is the progression of symptoms like in Diffuse Large B cell lymphoma
very quickly and severely unwell quickly
| nodal presentation usually with 1/3 of patients having extra-nodal symptoms
76
What is early treatment of diffuse large B cell lymphoma
chemotherapy and radiotherapy
77
What is the advanced treatment of diffuse large B cell lymphoma
combined chemotherapy and monoclonal antibody
| R-CHOP (Rituximab-(chemotherapy drugs CHOP)
78
What is Rituximab
monoclonal antibody
targets CD20 on B cells
Mouse and human protein
Mouse protein causes side effect: High BP, rash
79
Give an example of a very high NH-lymphoma
Burkitt's lymphoma
80
What is myeloma
the malignant proliferation of plasma cells and clonal cells make one type of immunoglobulin
81
Give two plasma cell diseases associated with cancer that are not myelomas
plasmacytoma- solid tumour of plasma cells in/out of the bone marrow
Wederstorm's Macroglobulinemia- to do with IgM
82
What are the progression steps before and during myeloma
Monoclonal gammopathy of undetermined significance (MGUS)
then Smouldering Myeloma then early myeloma
then late myeloma and then plasma cell leukaemia
during the timeline there are plateau (remission) phases and relapses
83
describe monoclonal gammopathy of undetermined significance (MGUS) and myeloma relationship
not a disease stage as there is no end organ damage here but it is a stage that gives potential for disease
1% per year risk of becoming myeloma
incidentally found with monoclonal immunoglobulin usually
84
relationship of smouldering myeloma and myeloma
significant risk of smouldering myeloma becoming myeloma
85
To make a diagnosis of myeloma you need...
clonal plasma cells (due to acquired chromosomal abnormality) and end-organ damage
86
What are the key end-organ damage seen in myeloma
```
CRAB+/-
Calcium increase
Renal impairment
Anaemia
Bone disease
+/- Infection, Amyloidosis (rare), Hyperviscosity (high protein in blood, rare)
```
87
What symptoms does the high calcium lead to in myeloma?
thirst, constipation, confusion
88
Why does the renal impairment occur in myeloma?
deposition of calcium and light chains from the immunoglobulins
89
What does the renal impairment in myeloma lead to?
dehydration
90
Why does the bone disease occur in myeloma?
increased osteoclast activity and decreased osteoblast activity
so more resorption
occurs mostly in weight-bearing bones
91
How does the high calcium occur in myeloma?
more resorption from bone disease so more calcium
92
What is a severe complication that can occur from myeloma due to the bone disease?
spinal cord compression
93
Why are there more infections in myeloma?
one type of immunoglobulin, not a variety to fight a variety of infections
also less maturation of other white blood cells e.g. neutrophils
94
What is a classical sign of amyloidosis?
big tongue
95
What kind of anaemia do you see in myeloma?
normocytic or macrocytic
96
Why does anaemia occur in myeloma?
less bone marrow space for maturation of red blood cells
97
What is the other key part of the blood decreased in myeloma?
less platelet production from bone marrow
98
What does low platelets cause in myeloma?
haematoma (subcutaneous bleeding)
99
What are some symptoms of myeloma?
```
confusion
constipation
thirst
fatigue
bone pain esp. back
```
100
What are some signs of myeloma?
```
anaemia
poor renal function
monoclonal protein in urine and protein
rouloux
high erythrocyte segmentation rate
```
101
What are the aims of treating myeloma?
control disease and induce remission
control symptoms
prophylaxis and supportive care
102
What treatment options do we use for myeloma?
```
steroids
antivirals and antibiotics
biphosphates
combination chemotherapy
radiotherapy for specific lesions
Palliative care linked
```
103
What can cause spinal cord compression
Metastases and destabilisation of the spine due to tumours. commonly occurs in myeloma and plasmacytoma patients.
104
What are the symptoms of spinal cord compression
```
back pain
lower leg weakness
saddle anesthesia
high anal tone
urinary retention: residual bladder volume >200ml
neuropathy
neurological damage means too late
```
105
What do we do if we have a patient with spinal cord compression
keep patient in bed
dexamethasone to shrink tumour
Urgent MRI to see if we need surgery or radiotherapy
106
Name two serious complications of myeloma
spinal cord compression
| hyperviscosity syndrome
107
Why does hyperviscosity syndrome occur
malignant plasma cells produce lots of Ig which accumulate and as they are protein, raise the protein level in blood so becomes thick
the bigger the Ig the less needed to get this syndrome
108
What are the symptoms and signs of hyperviscosity syndrome
```
bruising and mucosal bleeding
epistaxis
ataxia (loss of voluntary control of muscle movement)
nystagmus
blurred vision
heart failure signs: pulmonary oedema, fluid overload
SOB
headaches, confusion
fatigue
```
109
What is an easy examination to do when checking for hyperviscosity syndrome
check eyes
110
What is treatment for hyperviscosity syndrome
fluids via cannula
| call haematologist
111
What is a negative side effect of chemotherapy which can lead to sudden death
tumour lysis syndrome
112
What is tumour lysis syndrome
when chemotherapy kills cancer cells, they release their intracellular components which are excreted by the kidneys so the kidneys are overwhelmed and crystallisation occurs. this and electrolyte imbalance leads to renal failure
113
What tumours are at risk particularly to tumour lysis syndrome
large tumours as more cells more death and components released
aggressive tumours as rapid turnover so more sensitive to chemo
114
What are the features of tumour lysis syndrome in the blood
hyperkalaemia
hypercalcemia
hyperphosphamia
hyperuremia
115
What are the clinical features of tumour lysis syndrome
renal failure
seizures
sudden death
116
How do you prevent tumour lysis syndrome
monitor patients that are at high risk with daily blood and urine checks for the electrolytes
vigours IV fluids
rasburicase to eliminate uric acid
117
How do we treat tumour lysis syndrome
```
IV fluids
rasburicase
dialysis if necessary
treat high potassium, don't treat high calcium
monitor urine output
```
118
What are the reference ranges for hemoglobin, Mean cell volume of RBC, WBC, neutrophils, platelets
```
hemoglobin: 131-166
MCV: 82-96
WBC: 3.5-9.5
neutrophils: 1.7-6.5
platelets: 150-400
```
119
How do we classify causes of too much of a substance in the blood
reactive/ secondary
| proliferative/ primary
120
How do we classify causes of too little of a substance in the blood
under production
| excess removal
121
What is too much red blood cells
polycythemia
122
What are the reactive causes of polycythemia
smoking
lung disease
androgen excess
altitude
123
What are the proliferative causes of polycythemia
polycythemia rubra vera
124
Why does polycythemia rubra vera occur
Myeloproliferative disorder of bone marrow
| mainly red blood cells affected but also WBC, platelets
125
What is the genetic abnormality that is associated with polycythemia rubra vera
JAK2 mutation
126
What are the clinical signs of polycythemia rubra vera
thrombosis
itchy
red face
splenomegaly
127
How do we treat polycythemia rubra vera
venesection (remove blood)
aspirin
bone marrow suppression drugs e.g. hydroxycarbamide
128
What do we call too many wbc specifically of neutrophil type
neutrophilia
129
what are the reactive causes of neutriphilia
infection esp. bacterial
inflammation
trauma
malignancy
130
What is neutrophilia
too many WBC specifically too much neutrophils
131
What are the primary causes of neutrophilia
chronic myeloid leukaemia
132
What do we call too many WBC when neutrophils are normal
lymphocytosis
133
What is lymphocytosis
too much WBC, neutrophils normal though
134
What are the reactive causes of lymphocytosis
infection esp. virus
inflammation
trauma
malignancy
135
What are the primary causes of lymphocytosis
chronic lymphocytosis leukaemia
136
What do we call low neutrophils
neutropenia
137
What does neutropenia mean
too low neutrophils
138
What are the under-productive causes of neutropenia
bone marrow failure,
BM infiltration
BM toxicity e.g. from drugs
139
What are the excess-removal causes of neutropenia
autoimmune disease
cyclical
felty syndrome
140
How do we class severity of neutropenia
normal: 1.7-6.5
mild: 1-1.7
moderate: 0.5-1
severe: <0.5
141
What are the clinical features of neutropenia sepsis
```
rigours
fever
unwell
low blood pressure (rare)
cardiovascular collapse and sudden death
```
142
Who is the patient that you always suspect neutropenia sepsis for?
patient that has had chemotherapy in last 3 months and has any of the clinical features of neutropenia sepsis
143
How do we treat neutropenia
see patient
| cannula and antibiotics: tazocin and gentamycin
144
What do we call low platelets
thrombocytopenia
145
What does thrombocytopenia mean
low platelets
146
What do we call high platelets
thrombocytosis
147
What does thrombocytosis mean
high platelets
148
What are the reactive causes of thrombocytosis
infection
inflammation
malignancy
149
What is a primary cause of thrombocytosis
essential thrombocythemia
150
What does polycythemia mean
too much red blood cells
151
What does polycythemia rubra vera cause
too much red blood cells
152
What do we call low red blood cell mass
anaemia
153
What does anaemia mean
low red blood cell mass +/- low hemoglobin concentration
154
What are the consequences of anaemia
low oxygen transport-> tissue hypoxia-> compensatory physiologicla changes -> pathological changes
155
What are the compensatory, physiological changes seen in anemia
increased perfusion - vasodilation, increased cardiac output
increased oxygen to tissue transfer
increased red blood cell production
156
What are the pathological changes seen in anaemia
```
fatty changes to myocardial tissue
fatty changes to liver
skin and nail atrophy
CNS cell death
aggregate angina conditions
```
157
Where are red blood cells produced?
bone marrow
158
How long do red blood cells survive in circulation
120 days
159
Where are red blood cells removed
spleen, liver, bone marrow, blood loss
160
How many red blood cells are removed
9 billion per day
161
What are reticulocytes
immature red blood cells
162
What is the reticulocyte test looking for
looks for immature red blood cells in blood to establish if there is an imbalance in production and removal of RBC
163
What does a high and low reticulocyte number in the reticulocyte test mean?
high reticulocyte means increased removal as BM trying to produce lots of RBC doesn't have time to mature them
low reticulocyte = increased production as BM maturing all the RBC
164
How can anaemia be classified according to what causes it
production failures
| increased cell loss, lysis or pooling
165
What are causes of production failure anaemia
chronic disorders e.g. infection, inflammation, neoplasm
haematinic deficiency: iron b12, folic acid insufficient
hypo-plastic anaemia
bone marrow infiltration e.g. leukaemia and other metastatic neoplasms to bone marrow
166
What are the causes of anaemia due to increased cell loss, pooling, lysis
acute blood loss
| haemolytic anaemia
167
How can we classify anaemia
size
| what causes it
168
How do we classify anaemia according to size
microcytic, normocytic, macrocytic
169
What causes microcytic anaemia
iron deficiency
chronic diseases: renal, heart failure, cancer
thalassemia
170
What is microcytic anaemia
small and pale RBC
171
What is normocytic anaemia
normal sized RBC
172
What causes normocytic anaemia
combined haematin deficiencies
chronic disease
Acute blood loss
173
What is macrocytic anaemia
large and dark RBC
174
what causes macrocytic anaemia
b12/folate deficiency
alcohol excess/ liver disease
hypothyroid
Haematological: bone marrow failure, bone marrow infiltration, antimetabolic therapy, haemolysis
175
Is it better to have little or lots of iron
balance
| iron is essential for formation of haem and thus RBC but too much causes deposits in myocardium, liver, pancreas
176
How do we lose iron physiologically
sweat and cells lost in GU and GI system
| uncontrolled loss
177
How do we control iron levels
via absorption
| we absorb 10% of dietary iron
178
How much iron do we need in our diet
1mg men
1.5mg children
1.5-3 mg pregnant
2mg menstruating female
179
Where is the iron in our body
60% in haemoglobin of RBC
30% in reticular-endothelial system
small % in muscle and iron-containing enzymes
small % in circulation
180
What is ferritin
iron bound to it in reticular-endothelial system
| protein-iron complex
181
what form is the iron in during excess iron states
haemosiderin
182
How much of transferrin is saturated with iron usually
1/3 so serum iron concentration is 1/3 of total-serum iron-binding capacity
183
What are the causes of iron deficiency
chronic blood loss: peptic ulcers, cancers of rectum, colon
malabsorption
malnutrition
increased requirements e.g. childhood, pregnancy
184
What do we investigate with iron deficiency
any causes to ongoing haemorrhage
heavy periods
breastfed only (breast milk low in iron)
hook worm infection check
185
What are some symptoms of anaemia
```
fatigue
SOB
palpitations
faintness
headache
```
186
How would you treat iron deficient anaemia
treat underlying cause
| iron tablets oral
187
Why do we need vitamin B12
DNA synthesis and erythrocyte formation
188
How do we absorb vitamin B12
parietal cells release intrinsic factor which binds to B12 and then the IF-B12 complex goes to iliac receptors and enters cells there.
189
How much vitamin B12 is stored in the body
2.3mg
190
How much vitamin B12 do we need per day
1ug
191
Where in our diet do we get vitamin B12 from
yogurt, milk
| usually, 20mg per day is enough
192
Who is at risk of malnutritional causes of vitamin B12 deficiency
vegans
| but would take years for it to show because stored amounts can keep us going for a long time
193
What are the causes of vitamin B12 deficiency
pernicious anaemia
congenital lack of IF
gastroectomy causing lack of IF
crohn's disease damage to ileum so lack of site of absorption
blind-looping syndrome due to bacteria competing for our B12
Ileac resectioning so loss of absorption site
malnutriiton-vegans
194
What is pernicious anaemia
causes lack of IF
autoimmune causing atrophy of gastric mucosa with the failure of IF production due to antibody to the parietal cell
other antibodies against IF: one type stop B12 to IF and one type stops IF-B12 to ileac receptors
195
What investigations to do we do when assessing B12 deficiency
antibodies against IF
| Coeliac antibodies
196
How do we treat vitamin B12 deficiency
Vit B12 replacement via IM injection
197
Why do we need folic acid
DNA synthesis
198
How much folic acid is stored in the body and where
liver mostly
| 10mg
199
How much folic acid do we need per day
200ug
| so deficiency can occur within weeks
200
What can cause folic acid deficiency
malnutrition
malabsorption
increased demand for folate: pregnancy, malignancy
drugs e.g. some anti-cancer drugs are folic acid antagonists
201
How do we investigate anaemia
```
history and examination
FBC and blood film
reticulocyte count
folate, B12, ferritin investigations
TTP (red blood cell break down product from fibrin)
```
202
What is hypoplastic anaemia
bone marrow and haematopoietic cells damaged
203
What can cause hypoplastic anaemia
aplastic anaemia (inherited or acquired e.g. from radiation)
renal failure
pure red cell aplasia (bone marrow stops making red blood cells only)
endocrine dysfunction
204
How can you divide causes of haemolytic anaemia
defects in and out of the cell
205
What are causes of haemolytic anaemia that occur outside of the RBC
```
immune haemolytic anaemia
microangiopathic haemolytic anaemia
burns
infections
hypersplenism
```
206
What happens in immune haemolytic anaemia
autoantibodies or alloantibodies against foreign antigens, attack RBC
207
What happens in microangiopathic haemolytic anaemia
RBC haemolysis occurs due to physical trauma when RBC pass through narrow or damaged vessels
208
How do burns cause haemolytic anaemia
direct damage from heat to RBC in vessels in burned areas
| burn damages the vessels so microangiopathic mechanism also
209
What infection can cause haemolytic anaemia
malaria as the pathogens burst from the erythrocytes
210
What are three types of defects inside the cell which lead to haemolytic anaemic
haemoglobinopathies
membranopathies
enzymopathies
211
describe the globin chains in adult haemoglobin
2 alpha and 2 beta globin chains
| low affinity to oxygen
212
describe the globin chains in fetus haemoglobin
2 alpha and 2 gamma globin chains
| high afinity to oxygen
213
What are haemoglobinopathies
haemoglobinopathies refer to abnormal haemoglobin caused by single point mutation that causes amino acid substitution in the alpha or beta globin chains
214
What are the two types of haemoglobinopathies and give an example for each
disorders of quality e.g. sickle cell disease
| disorders of quantity e.g. thalassemia
215
What is sickle cell disease
haemaoglobin S forms which has an abnormal beta globin chain due to single mutation on chromosome 11 from adenine to thymine leading to an amino acid substitution leaving valine in the beta chain. this causes the red blood cell to become sickle shaped.
216
What does the abnormal beta chain in red blood cells lead to in sickle cell disease
the abnormal beta globin causes the haemoglobin to not dissolve but instead to crystalise in the red blood cells during low oxygen states. This damages the red blood cell and gives it a sickle shape
217
What happens to the carriers of HbS
asymptomatic and protected against falciparum malaria
218
Other than patients who are carriers of HbS, are there other patients with abnormal HbS who are protected against falciparum malaria
Combined heterozygotes with HbS and HbC
219
What symptoms do patients with combined HbS and HbC show
milder chronic haemolytic anaemia
splenomegaly
no obstruction of microvascular
220
What are the two main consequences of sickle cell disease
chronic haemolytic anaemia (RBC last 4-5days)
| obstruction/occlusion of microvascular
221
What are the main clinical features of sickle cell disease common in adults and children
```
infections
chronic haemolytic anaemia
strokes
jaundice
splenic sequestration
splenomegaly
painful crisis
acute chest syndrome
```
222
What are some clinical features of sickle cell disease common in adults mostly
```
pulmonary hypertension
avascular necrosis
ocular disease
sickle neuropathy
leg ulcers
iron overload
```
223
Which chromosome forms globin alpha, beta
alpha 16
| beta 11
224
What is the genotype for sickle cell disease to occur
HbS homozygous
| Combined heterozygotes with HbS and HbC
225
What are two acute complications of sickle cell disease
painful crisis
| acute/sickle chest syndrome
226
What are some chronic complications of sickle cell disease
renal failure
joint damage
pulmonary hypertension
227
What causes painful crisis
cold weather, dehydration, infections precipitate it
228
What is painful crisis
pain onset 2-3 days which is manageable at first and then becomes overwhelming in arms, legs, back, ribs, chest, abdomen
229
How is painful crisis managed
analgesia and control pain
| cannula fluids IV
230
What is acute/sickle chest syndrome
tissue hypoxia leads to sickling leading to lung infarction and more hypoxia and more sickling
occurs with or after painful crisis often
231
What are some features of sickle chest syndrome
XR change, hypoxia signs
232
How do you treat sickle chest syndrome
oxygen, fluids, antibiotics
| haemotologist will usually start exchange transfusion
233
How do you treat sickle cell disease
exchange transfusion (dilates sickle cells but careful of iron overload)
hydroxycarbamide (reduces effects of sickle cells)
stem cell transplant
234
How long do sickle red blood cells last for
4-5 days
235
What is thalassemia
reduction in synthesis of alpha or beta globin chains so less haemoglobin. caused by mutation effecting expression of globin structural genes. Beta thalassemia less beta made and vice versa
236
The damage caused by thalassemia: is that due to one or both globin chains
both
the globin chain that is not synthesised enough means that less haemolgobin can be made
the globin that is synthesised normally starts to accumulate and so damages erythrocytes maturing and mature.
237
How can we classify thalassemia
according to if beta or alpha globin chain affected
according to clinical features:
major, intermedia, carrier
238
Describe the clinical manifestations of thalassemia major, intermedia and carrier
major: needs transfusion for life
intermedia: less severe anaemia can survive without constant transfusion
carrier: asymptomatic
239
How many alpha globin genes are there per red blood cell
4:
| 2 chromosome 16 and each has 2 alpha genes on them
240
What do you call the condition if all the alpha globin genes are non-functioning
what are the symptoms
hydrops foetalis
not compatible with life
dies in utero
241
What do you call the condition if 3 of the alpha globin genes are non-functioning
what are the symptoms
HbH disease
thalassemia syndrome
severe-moderate anaemia
242
What do you call the condition if 2 of the alpha globin genes are non-functioning
what are the symptoms
alpha0 thalassemia trait
| alpha+ thalassemia homozygote
243
What do you call the condition if 1 of the alpha globin genes are non-functioning
what are the symptoms
alpha+ thalassemia trait
| normal to minimum change
244
What is the genetic description for alpha0 thalassemia trait
one of the chromosome 16 has no functioning alpha genes but the other one has both functioning alpha genes
245
What is the genetic description for alpha+ thalassemia homozygote
each chromosome 16 has one functioning and one non-functioning alpha genes
246
What is the genetic description for alpha+ thalassemia trait
one chromosome 16 has one non-functioning alpha gene and one functioning alpha gene
the other chromosome has both functioning alpha genes
247
What is the genetic description for hydrops foetalis
no functioning alpha genes on either chromosome 16
248
What can cause beta thalassemia
lots of genetic lesions
249
What are the two types of beta thalassemia the genetic lesions cause
either no beta synthesis (beta0)
| or restricted but a little beta synthesis (beta+)
250
What is beta thalassemia major
severe thalassemia due to loss of two beta globin genes functioning
251
When do patients usually present with beta thalassemia major
6-12months
252
Why do patients usually present at 6-12 months with beta thalassemia major
that's the time when fetal gamma globin should have been replaced by beta globin synthesis
253
How do patients first present with beta thalassemia major
pale, crying, listless
| failure to feed, growth retardation, poor sexual health (due to deposits in gonads and endocrine organs)
254
What is the patient's signs and clinical picture in beta thalassemia
severe microcytic and hypochromic anaemia
iron overload
liver enlargement
splenomegaly
red marrow expansion due to trying to make more red blood cells due to low haemoglobin but leads to bone thinning and bone growing on outer aspect
255
How do we treat beta thalassemia major
```
iron chelation
regular and lifelong transfusion
endocrine supplementation
bone health
psychological support
```
256
What things in the long term do we monitor
endocrine monitor: diabetes, growth and puberty, gonad development
bone health: vitamin D, calcium, PTH
ferritin and haemosiderin
check heart and liver for iron deposits
257
What are membranopathies
deficiencies of proteins in membranes of red blood cells that lead to abnormal membranes with red blood cells have less survival
258
What are the two types of membranopathies
spherocytosis
| elliptocytosis
259
What interactions are damaged in spherocytosis
horizontal
260
What interactions are damaged in elliptocytosis
vertical
261
Which type of membranopathies are more common and more severe
spherocytosis
262
Why are the RBC in spherocytosis patients survive for a short time
RBC leave bone marrow biconcave but due to abnormal membrane become spherical so get stuck in the microcirculation of spleen so spend longer time so are prematurely phagocytosis
also the spherical shape means the cell is more sensitive to osmotic stress
263
What are two complications of membranopathies
jaundice
| gallstones
264
How can we treat membranopathies
folic acid supplements
| splenectomy (heal anaemia fully)
265
How bad is the haemolytic anaemia in patients with membranopathies
mild to moderate with occasional exacerbations e.g. due to infections
266
What is enzymopathies
deficiency in enzymes needed for red blood cell survival to protect against oxidant compounds
267
How do the enzymes in the red blood cell aid it
protect against oxidative compounds
| fuel the red blood cell
268
Give two examples of enzymopathies
glucose-6-phosphate dehydrogenase deficiency
| pyruvate kinase deficiency
269
What is glucose-6-phosphate dehydrogenase deficiency
low G6PD which usually reduces glutathione which protects RBC against oxidative damage
270
Why is G6PD needed in the RBC
to protect haemoglobin and membrane against oxidative damage
271
How is G6PD deficiency inherited
X linked inheritance
| some women can be affected
272
What symptoms does a person with G6PD deficiency experience
asymptomatic with crisis sometimes
| crisis characterised by haemolysis, jaundice, anaemia
273
What are treatment options for G6PD deficiency
crisis usually self-limiting
| mostly avoid oxidative drugs, broad beans and infection which lead to crisis and more cell damage usually
274
What drugs do you avoid with a person with G6PD deficiency
```
quinolone
nitrofurantoin
primaquine
dapsone
sulphonamide
```
275
How is pyruvate kinase deficiency inherited
autosomal recessive inheritence
276
What is a virus that is particularly bad for a person with haemolytic anaemia
parvovirus
277
What does parvovirus do the RBC
interferes with bone marrow so less produced for roughly a week
only serious if already have previous haemolytic anaemia as numbers of RBC suddenly drop
278
What are the three phenotypes of anaemia that can protect against falciparum malaria
Carrier of HbS sickle cell
Patient with combined HbS and HbH
Carrier of G6PD deficiency gene
279
How is membranopathies inherited
autosomal dominance
280
What do we mean when we say disorders of blood coagulation and blood homeostasis
Blood coagulation- disorder of coagulation system
| Blood homeostasis- disorder of platelets
281
Where do platelets come from
bone marrow
| megakaryocyte cytoplasm fragmentation
282
What stimulates platelet formation
thrombocytopenia produced from the liver
283
How is thrombocytopenia levels controlled
TPO binds to platelets and megakaryocytes
when platelets are low there is more free TP
so more free TPO binds to megakaryocytes and causes fragmentation so more platelets and more TPO bound and less free TPO
284
Why can platelets flow close to the endothelium in vessels
disc shape
285
Why do platelets have a disc shape
flow close to endothelium
286
How many platelets do we make per megakaryocyte
4000
287
How long do platelets live for
7-10 days
288
Where are platelets removed
spleen by splenic macrophages
289
What is platelets role in primary blood homeostasis
when exposed to collagen and vwf
platelets change shape and release granule content:
ADP, fibrinogen, calcium, thrombin
platelets aggregate by cross-linking with fibrin
form negatively charged layer that coagulation factors can bind to
290
What are the important receptors on the surface of platelets
```
thromboxane A2
P2Y12
Glycoprotein 2b3a, 1a, 1b
ABO
Human platelet antigen (HPA)
MHC class 1
```
291
How is thromboxane A2 made
inside platelet by cyclooxygenase-1 (COX-1)
292
What does thromboxaneA2 do
vasoconstriction
| aggregate platelets
293
What does P2Y12 get activated by
ADP
294
What does P2Y12 do
activate GP receptors
| activate platelets amplify
295
What are platelet glycoprotein activated by and which receptors specifically
collagen (GP1a)
296
What do platelet glycoprotein receptors do and which receptors specifically do this
bind to vwf and release dense and alpha granules
| GP2B3A, 1B
297
What kind of disorders can cause primary homeostasis disorders and which is more common
small vessel and platelet
| platelet more common
298
what investigations do you carry out for platelet disorders
FBC
Blood film
Platelet function assay (check function after giving aggregating agent)
flow cytometry
299
What symptoms are there for platelet dysfunction
mucosal bleeding- nose, gums, meninges
easy bruising
purpura
traumatic haematoma
300
What can cause bleeding
```
injury
disorder of vascular
platelet not functioning properly
low platelet number
coagulation disorder
```
301
What is the difference between platelet disorder bleeding and coagulation disorder bleeding
coagulation disorder bleeding: spontaneous haematoma not traumatic like platelet dysfunction
rare purpura
rare mucosal bleeding unless urinary tract
joint bleeding common in severe
bleeding after surgery delayed not immediate like platelet dysfunction
302
what can cause platelet dysfunctions
low number of platelets but normal function (thrombocytopenia)
platelets normal number but not functioning properly
303
What can cause normal numbers but reduced function of platelets
medication e.g. aspirin
congenital abnormality
von Willibrand disease (low VWF activity)
urea
304
What is thrombocytopenia
low platelets <150x10^9/L
| caused by increased destruction or reduced production of platelets
305
How low do the platelets have to get to cause increased traumatic bleeding
40-50x10^9
306
How low do the platelets have to get to cause spontaneous skin and mucous bleeding
<20x10^9
307
How can thrombocytopenia be classified
by what causes it
| increase in destruction or decrease in production
308
What are the causes of failure to produce platelets
```
congenital- absent, low, dysfunctional megakaryocytes
infiltration of bone marrow
low production from bone marrow due to:
low folic acid/b12
low thrombopoietin e.g. from liver disease
toxin e.g. alcohol
medicine e.g. chemo
infections e.g. HIV, TB
```
309
What are the causes of increased destruction of platelets
hypersplenism- high portal pressure, splenomegaly
autoimmune: primary, secondary immune thrombocytopenia
drug induced immune thrombocytopenia- e.g. heparin induced
consumption
310
What does consumption mean in regards to platelets
platelets highly active so die quicker and production can't keep up so low platelets
311
What are the types of consumptions that cause thrombocytopenia
disseminating intravascular coagulopathy
thrombotic thrombocytopenic purpura
major haemorrhage
haemolytic uremic syndrome
312
What occurs in immune thrombocytopenia
IgG bind to platelets so more opsonisation of platelets for spleen to destroy
313
What are the differences between primary and secondary thrombocytopenia
primary after infection immunisation usually in children, acute
secondary, associated with infection e.g. HIV, malignancy, chronic
314
What are the clinical signs of immune thrombocytopenia
haemorrhage, bruises, purpura
315
How do we diagnose immune thrombocytopenia
exclude other causes
| find underlying cause
316
How do we treat immune thrombocytopenia
steroids
treat underlying cause
platelets (not long term because IgG will do same to new ones)
tranexamic acid to stop the breakdown of fibrin
317
When must we not give tranexamic acid
urinary tract mucosal bleeding
318
How does DIC occur
after sepsis, trauma, malignancy etc. cytokines released
activate systemic clotting cascade so consumption occurs
so less platelets so bleeding
so more activation of clotting cascade so thombosis in microvascular occurs and organ failure
319
What are the main clinical signs for DIC
haemorrhage and signs of organ failure
320
What do the DIC investigations show
```
low platelets
high D-Dimers
low fibrinogen
high pro-thrombin time
+/- organ failure
```
321
How do we treat DIC
underlying cause
clotting factors
platelets
fibrinogen
322
What is unusual about heparin-induced thrombocytopenia
causes thrombosis
323
What happens in heparin-induced thrombocytopenia
heparin and platelet factor 4 form a complex that IgG binds to. This heparin-PF4-IgG complex activates platelets leading to over-activity and consumption
324
What does heparin-induced thrombocytopenia cause
thrombosis
| necrosis
325
What is the presentation of heparin-induced thrombocytopenia
dramatic drop in platelet numbers 5-10 days after taking heparin
326
Who is most at risk of heparin-induced thrombocytopenia
cardiac bypass recovery patients
| patients on unfractionated heparin
327
How do you treat heparin-induced thrombocytopenia
immediately stop heparin
give other anti-coagulation drugs
never give heparin again
328
What is AMDAT13
VWF cleaving protease
| metalloproteinase enzyme cleaves VWF
329
Why does thrombotic thrombocytopenic purpura occur
immune system inhibits AMDATS13 so over-activity of platelets and consumption
causes thrombosis
330
Where are thrombosis more likely to occur in thrombotic thrombocytopenic purpura
microvascular thrombosis esp in kidney, brain, heart
331
How do you treat thrombotic thrombocytopenic purpura
plasma exchange to replace AMDATS13
| immunosuppression medication
332
Name 3 coagulation disorders all inherited
Haemophilia A
Haemophilia B
VWF deficiency
333
Name one acquired condition that leads to coagulation disorders
vitamin K deficiency
334
What is the difference between haemophilia A and B
A is a deficiency in factor 8
| B is a deficiency in factor 9
335
How are haemophilia A and B inherited
X linked recessive
336
How are the genders affected by haemophilia A and B
Males affected
| Female carriers have 50% of normal factor level
337
How are haemophilia A and B treated
Clotting factor concentrates
338
Where is VWF synthesised
Vascular endothelial cells
| megakaryocytes
339
How is VWF disease inherited
Autosomal dominance inheritence
