haematology Flashcards
1
Q
plasma cell dycrasias
A
a spectrum of progressively more severe monoclonal gammopathies in which a clone or multiple clones of pre-malignant or malignant plasma cells over-produce and secrete an abnormal monoclonal antibody into the blood stream
2
Q
2 examples of monoclonal gammopathy of undetermined significance (MGUS)
A
plasmacytomas:
- tumours consisting of abnormal plasma cells
- myeloma
- solitary, multiple solitary or extramedullary plasmacytoma
Waldenstrom’s macroglobulinaemia:
-IgM related
3
Q
MGUS
A
myeloma protein (abnormal antibody) is found in the blood
MIg <30g/L
no significant increase in bone marrow plasma cells
no organ impairment
CAN LEAD TO MULTIPLE MYELOMA
4
Q
multiple myeloma
A
neoplastic proliferation of bone marrow plasma cells
5
Q
multiple myeloma: characteristics
A
monoclonal protein in serum or urine
lytic bone lesions
excess plasma cells in bone marrow
CRAB end organ damage- calcium, renal, anaemia, bone
6
Q
multiple myeloma: pathogenesis
A
- accumulation of malignant plasma cells in bone marrow causes it to fail
- the malignant cells produce excess of one type of immunoglobulin (IgG=55%, IgA=20%)
- low variety of Ig causes immunosuppression
7
Q
multiple myeloma: epidemiology
A
average age of diagnosis =70
more common in afro-caribbeans
1% of all cancers
13% of haem cancers
8
Q
multiple myeloma: incidence/prevalence
A
incidence= 40/million/year
prevalence 180-279/million
9
Q
multiple myeloma: presentation OLD CRAB
A
old age
Calcium elevated
Renal failure, proteinuria
Anaemia- neutropenia or thrombocytopenia causes infection, bleeding, fatigue and pallor
Bone lytic lesions- back pain and fractures
10
Q
multiple myeloma: FBC investigation
A
normocytic normochromic anaemia
raised ESR
rouleaux formation of blood film
11
Q
multiple myeloma: U&E investigation
A
high calcium
high alkaline phosphatase
bence-jones protein present
12
Q
multiple myeloma: imaging investigations
A
lytic lesions
pepper-pot skull
fractures
osteoporosis
13
Q
multiple myeloma: bone marrow biopsy
A
increased plasma cells
14
Q
multiple myeloma: cure or treatment
A
incurable disease
aim of treatment is to achieve plateau phase, control the symptoms and supportive measures
15
Q
multiple myeloma: treatment
A
chemotherapy, steroids and bisphosphonates
treat end organ damage and infections
16
Q
leukaemia
A
presence of rapidly proliferating immature blood cells (precursors of white or red) in the bone marrow that are non-functional
17
Q
what does leukaemia cause
A
wasting energy on non-functioning cells
space taken up in bone marrow
bone marrow unable to produce normal cells
when bone marrow is filled, leukaemia cells enter blood
18
Q
leukaemia: types
A
- Acute lymphoblastic leukaemia (ALL)= small lymphocyte that becomes B and T cells
- Acute myeloid leukaemia (AML)= myeloblast
- Chronic myeloid leukaemia (CML)= basophil, neutrophil, eosinophil
- Chronic lymphatic leukaemia (CLL)= B cells
19
Q
leukaemia: risk factors
A
congenital- very rare, down’s syndrome (1-2% get AML)
environmental= radiotherapy, chemo, benzene/other chemicals
20
Q
acute lymphoblastic leukaemia: epidemiology
A
common between 2-4 years old
most common cancer in childhood
if proliferation is all B cells- children
all T cells- adults
21
Q
acute lymphoblastic leukaemia: presentation
A
- marrow failure (anaemia, thrombocytopenia, infection)
- bone marrow infiltration causes bone pain
- liver/spleen infiltration results in hepatosplenomegaly
- node infiltration causes lymphadenopathy
22
Q
acute lymphoblastic leukaemia: investigations
A
FBC/blood film
CXR/CT to see for mediastinal and abdo lymphadenopathy
Lumbar puncture to see for CNS involvement
23
Q
acute lymphoblastic leukaemia: treatment
A
blood/platelet transfusions treat infections IV fluids chemo marrow transplant ALLOPURINOL- prevents tumour lysis syndrome
24
Q
acute myeloid leukaemia: epidemiology
A
most common leukaemia in adults
associated with radiation and Down’s syndrome
Progresses rapidly with death in 2 months if untreated
25
acute myeloid leukaemia: presentation
gum hypertrophy
hepatomegaly and splenomegaly
marrow failure- anaemia, thrombocytopenia, infection
26
acute myeloid leukaemia: diagnosis
WCC raised but can be low or normal
| diagnosis depends on bone marrow biopsy but differentiation from ALL is based on microscopy and immunophenotyping
27
acute myeloid leukaemia: complications
infection is the major issue- septicaemia
28
acute myeloid leukaemia: treatment
```
blood/platelet transfusions
treat infections
IV fluids
chemo
marrow transplant
ALLOPURINOL- prevents tumour lysis syndrome
```
29
chronic myeloid leukaemia: epidemiology
exclusively a disease of adults
mainly occurs between 40-60 years old
slight male predominance
80% have Philadelphia chromosome which has tyrosine kinase activity- stimulates cell division
30
chronic myeloid leukaemia: presentation
```
symptomatic anaemia
splenomegaly- abdo discomfort
weight loss
palor
fever
gout due to purine breakdown
```
31
chronic myeloid leukaemia: diagnosis
blood count- high WCC, low Hb, low platelets
| bone marrow aspirate- hypercellular
32
chronic myeloid leukaemia: treatment
stem cell transplant
| oral imatinib- specific tyrosine kinase inhibitor
33
chronic lymphocytic leukaemia: epidemiology
most common leukaemia
mainly occurs late in life
genetic mutations influence risk
pneumonia can also be a triggering event
34
chronic lymphocytic leukaemia: presentation
often no symptoms
may be anaemic
if severe- weight loss, sweats, anorexia
enlarged, rubbery, non-tender nodes
35
chronic lymphocytic leukaemia: diagnosis
blood count- raised WCC with high lymphocytes
| blood film- smudge cells seen in vitro
36
chronic lymphocytic leukaemia: complications
autoimmune haemolysis
increased infection due to low IgG
marrow failure
37
chronic lymphocytic leukaemia: progression
death is often due to complication of infections
| may transform into aggressive lymphoma- Richter's syndrome
38
chronic lymphocytic leukaemia: treatment
blood transfusion
stem cell transplant
chemo/radiotherapy
human IV immunoglobulins
39
chronic lymphocytic leukaemia: prognosis
rule of thirds
1/3 never progresses
1/3 progresses slowly
1/3 progresses quickly
40
lymphoma
disorder caused by malignant proliferations of lymphocytes
41
lymphoma: locations
accumulate in lymph nodes causing lymphadenopathy
| can also be found in blood, bone marrow, liver and spleen
42
lymphoma: aetiology
most cases unknown
immunodeficiency- primary (e.g. ataxia telangiectasia) or secondary (e.g. HIV, transplants)
infections
autoimmune disorders
43
lymphoma: symptoms
loss of appetite
loss of weight
night sweats
44
lymphoma: signs
hepatosplenomegaly
| lymph node enlargement
45
lymphoma: investigations
blood film and bone marrow
lymph node biopsy
immunophenotyping
imaging
46
lymphoma: assessing a patient
```
history/exam
bloods
CXR
echo
PFTs
performance status
```
47
lymphoma: WHO performance status
0= asymptomatic
1=symptomatic but only restricted by strenuous activity
2= symptomatic <50% in bed during day
3= symptomatic >50% in bed but not bed bound
4=bed bound
5= death
48
lymphoma: subtypes
hodgkin's
| non-hodgkin's
49
hodgkin's lymphoma: presentation
painless
lymphadenopathy
(B symptoms) sweats, weight loss
50
hodgkin's lymphoma: diagnosis
reed-sternberg cell: 4 histological subtypes
51
hodgkin's lymphoma: stages
1= one place
2= 2 areas or more, same side of diaphragm
3= lymph nodes on both sides of diaphragm
4 spread to multiple places
A= absence of B symptoms
B=presence
52
hodgkin's lymphoma: treatment
depends on stage
ABVD- adriamycin, bleomycin, vinblastine, dacarbazine
relapse responds to marrow transplant
53
hodgkin's lymphoma: treating stage 1-2A
short course combo of chemo followed by radiotherapy
70-80% prolonged disease free survival
54
hodgkin's lymphoma: treating stage 2B-4
combination chemotherapy
| 50-70% prolonged disease free survival
55
hodgkin's lymphoma: late effects
```
infertility
cardiomyopathy (anthracyclines)
lung damage (bleomycin)
peripheral neuropathy (vinca alkaloids)
psychological issues
```
56
non-hodgkin's lymphoma (NHL)
presentation, subtypes, treatments and outcomes have a much larger variety
57
low grade/indolent NHL
e.g. follicular lymphoma
slow growing
usually advanced at presentation
average survival is 9-11 years
58
low grade/indolent NHL: treatment
```
do nothing!
alkylating agents
purine analogues
combination chemo
monoclonal antibodies
radiotherapy
bone marrow transplant
```
59
high grade/aggressive NHL
e.g. diffuse large B cell lymphoma
usually nodal presentation but 1/3 have extranodal involvement
patients usually unwell with short history
60
high grade/aggressive NHL: treatment
early= short course chemo+radiotherapy
advanced= combination chemo and monoclonal antibodies
61
monoclonal antibodies
rituximab
anti-CD-20 targets CD20 expressed on cell surface of B cells
minimal side- effects
62
lump in the neck- differential diagnosis
infected or inflamed lymph nodes
malignant lymph nodes
thyroid
embryologic remnant
63
anaemia
reduced haemoglobin levels
64
normal haemoglobin ranges
male= 131-166g/L
| female=110-147g/L
65
anaemia: acute consequences
reduced oxygen transport
tissue hypoxia
compensation- increased perfusion, oxygen transfer and red cell production
66
anaemia: pathological consequences
myocardial fatty change
fatty change in liver
skin and nail atrophic changes
CNS cell death
67
normal red blood cell cycle
produced in bone marrow
life span 120 days
removed in spleen, liver, bone marrow or blood loss
68
types of anaemia
microcytic
normocytic
macrocytic
69
anaemia: mean corpuscular volume
the size of red blood cells, used to determine the type of anaemia
normal: male=81.8-96.3fl, female= 80-98.1fl
70
microcytic anaemia
small, often hypochromic red blood cells
low MCV
71
microcytic anaemia: causes
iron deficiency
chronic disease
thalassaemia
72
microcytic anaemia: iron deficiency
tests= ferritin or iron studies
| treat this with iron supplements (ferrous sulphate)
73
microcytic anaemia: chronic disease
investigate clinically and in a lab
| often renal failure or infections
74
normocytic anaemia
normal MCV but haematocrit and haemoglobin is low
75
normocytic anaemia: causes
acute blood loss
chronic disease
combined haematinic deficiency (iron, B12, folate)
76
macrocytic anaemia
red blood cells are larger than normal
| bigger MCV
77
macrocytic anaemia: causes
B12/folate deficiency
alcohol excess/liver disease
hypothyroid
78
anaemia: B12 deficiency
IF antibodies
schilling test
coeliac antibodies
treat with B12 replacement
79
haemoglobinopathies
disorders of quality such as sickle cell
| disorders of quantity such as thalassaemia
80
sickle cell disorders
mutated Hb distorts RBCs into crescent shape at low oxygen levels
arise from homozygous state (SS) or combined heterozygous (SC or Sb)
81
sickle cell pathogenesis
Hb S is a variant Hb arising because of a point mutation in the b globin gene
82
sickles cell carriers
symptom free
| protection against falciparum malaria
83
managing sickle cell disorders
acute complications such as sickle chest syndrome or stroke
chronic complications such as renal and joint damage
disease modification- transfusion, stem cell transplant
84
thalassaemia
heterogenous disorders- deletions(alpha thal) and mutations (beta thal)
globin chain disorders resulting in diminished synthesis of 1 or more chains
causes a decrease in Hb
85
clinical classification of thalassaemia
thal major= transfusion dependent
intermedia= can survive w/o regular transfusions
carrier= asymptomatic
86
thalassaemia major
age presented is 6-12 months
severe anaemia
1000 sufferers in UK
220,000 carriers in UK
87
thalassaemia major presentation
failure to feed
listless
crying
pale
88
thalassaemia major blood results
Hb=40-70g/L
MCV and MCH low
irregular and pale RBCs on film
ferritin normal
89
treating thalassaemia major
regular transfusions
iron chelation
endocrine supplementation
bone health
90
monitoring thalassaemia major
```
ferritin
cardiac and liver MRI
vit D, calcium PTH
thyroid
endocrine testing
```
91
morbidity and mortality from transfusional iron overload
- thalassaemia results in death during childhood if not treated with transfusions
- transfusions causes increase in body iron load as no natural means for elimination
- excess iron is deposited in the liver and spleen causing fibrosis and cirrhosis
- also deposited on glands and heart= diabetes, heart failure and premature death
92
membranopathies
deficiency of red cell membrane proteins
autosomal dominant
spherocystosis( vertical interaction) and elliptocytosis (horizontal) are most common
93
consequences of membranopathies
neonatal jaundice
mild to moderate haemolytic anaemia w/ occasional exacerbations during infection
gallstones
94
parvovirus and haemolytic anaemias
common infection in children
occurs in epidemics
leads to decreased RBC production
dramatic drop in patients who have reduced red cell lifespan
95
enzymopathies
lead to shortened red cell lifespan from oxidative damage
| G6PD deficiency and pyruvate kinase deficiency are most common
96
glucose 6 phosphate dehydrogenase deficiency
caused by mutations within G6PD gene
most are asymptomatic
X-linked but females also affected
african, middle eastern, mediterranean and south asian
97
glucose 6 phosphate dehydrogenase deficiency consequences
haemolysis, jaundice, anaemia
usually self-limiting
symptomatic patients rate
98
primaquine and glucose 6 phosphate dehydrogenase deficiency
this drug is used for curing malaria but should not be prescribed to someone with g6pdd as it can react to cause haemolytic anaemia
99
FBC reference ranges
HB=131-166
WBC=3.5-9.5
plts=150-400
MCV= 81.8-96.3
100
polycythaemia
too many red blood cells
101
polycythaemia causes
primary cause or proliferative= polycythaemia ruba vera
| secondary/reactive= smoking, lung disease, altitude, cyanotic heart disease
102
polycythaemia ruba vera (PRV)
overactive bone marrow
mainly RBCs but also WBCs and Plts
JAK2 mutation is 95%
103
polycythaemia ruba vera (PRV) presentation
plethoric appearance
thrombosis
itching
splenomegaly
104
polycythaemia ruba vera (PRV) treatment
aspirin
venesection
bone marrow suppression drugs
105
neutrophilia
increase in number of neutrophils
106
neutrophilia causes
```
reactive= infection, inflammation, malignancy
primary= chronic myeloid leukaemia
```
107
neutropenia
abnormally low conc. of neutrophils
108
neutropenia severity
normal 1.7-6.5
mild 1-1.7
moderate 0.5-1
severe (major infection risk) <0.5
109
neutropenia caused by underproduction
marrow failure
marrow infiltration
marrow toxicity e.g. drugs
110
neutropenia caused by increased removal
autoimmune
| cyclical
111
lymphocytosis
increase in number of lymphocytes, neutrophil number normal
112
lymphocytosis causes
```
reactive= infection, inflammation, malignancy
primary= chronic lymphocytic leukaemia
```
113
thrombocytopenia
abnormally low levels of thrombocytes
114
thrombocytopenia caused by increased destruction
autoimmune
hypersplenism
drug related immune destruction
consumption of platelets
115
thrombocytopenia caused by decreased production
- congenital
- bone marrow infiltration
- reduced platelet production by bone marrow
- dysfunctional production of platelets
116
thrombocytosis
excessive number of platelets
117
thrombocytosis causes
```
reactive= infection, inflammation, malignancy
primary= essential thrombocythaemia
```
118
platelet physiology
anucleate cell, fragments from megakaryocytes
| regulated by thrombopoietin
119
platelet tests
number- FBC
appearance- blood film
function- PFA, bleeding time
surface proteins- flow cytometry
120
causes of bleeding
```
injury
vascular disorders
low platelets
abnormal platelet function
defective coagulation
```
121
clinical features of platelet dysfunction
```
mucosal bleeding
gum bleeding
easy bruising
purpura
traumatic haematomas
```
122
causes of low platelets
```
production failure (drugs, marrow suppression or failure, acquired, congenital)
increased removal (immune, consumption, splenomegaly)
```
123
congenital impaired platelet function
von willebrand disease
| platelet disorders
124
acquired impaired platelet function
uraemia
| drugs
125
immune thrombocytopenia
IgG antibodies formed against platelets and megakaryocyte surface glycoproteins
126
primary immune thrombocytopenia
may follow viral infection or immunisation
127
secondary immune thrombocytopenia
occurs in association with some malignancies such as chronic lymphocytic leukaemia
HIV/Hep C infections
128
immune thrombocytopenia: investigations
for the underlying cause
| diagnosis of exclusion
129
immune thrombocytopenia: treatment
immunosuppression
treat underlying cause
give platelets if bleeding
130
disseminated intravascular coagulation
blood clots form throughout the body, blocking small blood vessels
131
disseminated intravascular coagulation: pathophysiology
cytokine release in response to systemic inflammatory response syndrome
activates clotting cascade
132
disseminated intravascular coagulation: investigations
underlying cause
| evidence of organ failure
133
disseminated intravascular coagulation: treatment
treat underlying cause
| supportive provision of platelets, fibrinogen and clotting factors
134
thrombotic thrombocytopenia purpura
spontaneous platelet aggregation in microvasculature (brain, kidney, heart)
reduction in protease enzyme
135
thrombotic thrombocytopenia purpura: consequences
consumption of platelets
microangiopathic haemolytic anaemia
renal/CNS/cardiac impairment
136
thrombotic thrombocytopenia purpura: treatment
```
plasma exchange
immunosuppression
no platelets- increases thrombosis
90% mortality
10-20% mortality if treatment starts promptly
```
137
neutropenia and neutropenic sepsis
abnormally few neutrophils in the blood leads to increased susceptibility to infection
138
neutropenic sepsis: causes
decreased production due to problem with the bone marrow
| haematologist- chemo
139
neutropenic sepsis: features
fever
rigor
feeling unwell or off
low BP (not as common)
140
neutropenic sepsis: when to suspect
if they had chemo in the last 3 months
present with fever
chills/rigor
isolated hypotension
141
neutropenic sepsis: what to do
see patient
put in cannula
give antibiotics
142
neutropenic sepsis: early management
first dose of antibiotics is important
| if in doubt give them antibiotics
143
sickle cell crisis: features
- precipitated by dehydration, cold weather and/or infection
- gradual onset over a few days
- then unbearable pain in arms, back, chest or abdo
- poor prognosis if: chest pain, severe abdo pain or neurological symptoms
144
sickle cell crisis: what to do
see patient
control the pain
put in cannula and start fluids
145
sickle cell/acute chest syndrome
cycle of hypoxia, sickles and lung infarction
146
acute chest syndrome: features
new signs on chest xray
| hypoxia
147
acute chest syndrome: what to do
see patient
give oxygen, fluids, antibiotics
call haematologist
148
spinal cord compression
occurs in any malignancy due to metastases of the spine
particularly prone= myeloma patients
can be caused by plasmacytoma
149
spinal cord compression: symptoms
```
back pain
neuropathic pain
leg weakness
saddle anesthesia
loss of sphincter control
```
150
spinal cord compression: clinical signs
decreased power in legs
typically decreased reflexes
decreased sensitivity
decreased anal tone
151
spinal cord compression: what to do
keep them in bed
dexamethasone 8mg
urgent MRI
152
spinal cord compression: treatment
surgical- avoid in myeloma
| medical- radiotherapy and chemo
153
hyperviscosity syndrome
malignant plasma cells produce a lot of immunoglobulin which increases the thickness of your blood
154
hyperviscosity syndrome: symptoms
```
non specific symptoms
headache
neurological
blurred vision
fatigue
mucosal bleeding
confusion
```
155
hyperviscosity syndrome: examination
general=bruising
CVS= pulmonary oedema, evidence of fluid overload
neuro= confusion, ataxia, nystagmus
156
hyperviscosity syndrome: what to do
put in cannula
fluids
call haematologist
157
tumour lysis syndrome
chemo kills cancer cells- making them release intracellular components
this overwhelms the kidneys causing crystallisation and renal failure
158
tumour lysis syndrome: those at risk
large tumour burden= more cells to die= greater risk
| aggressive cancer= rapid cell turnover= greater risk
159
tumour lysis syndrome: features
```
blood tests
hyperkalaemia= first sign
hyperphosphataemia
hyperuricaemia
hypocalcaemia
```
160
tumour lysis syndrome: prevention
- much easier than treatment
- give vigorous IV fluids during chemo and days after
- rasburicase eliminates uric acid
- monitor bloods and urine output closely
161
tumour lysis syndrome: treatment
```
fluids
rasburicase
monitor urine output
manage electrolytes
dialysis
```
