Haematology Flashcards
1
Q
what are the symptoms and signs of haematological malignancy?
A
tiredness weight loss severe, recent night sweats bone pain bleeding bruising petechiae (non-blanching) lymphadenopathy gum swelling infiltration organomegaly
2
Q
what is the genetic abnormality that is responsible for the driving and production of leukaemia cells?
A
PML/RARA fusion gene
3
Q
what type of malignancy is a PML/RARA fusion gene normally seen in?
A
acute promyelocytic leukaemia
4
Q
describe the full diagnostic pathway of haematological malignancy
A
morphological examination of bone marrow aspirate
immunophenotyping with flow cytometry
cytogenetics
molecular diagnosis
5
Q
describe leukaemia
A
acquired series of events
expansion of an abnormal clone of cells
which accumulate in the bone marrow or blood
6
Q
what is the management of acute leukaemia?
A
resuscitation and supportive therapy central venous catheter blood product support coagulation factor support antibiotics, antivirals, antifungals antiemetics fluids and allopurinol or rasburicase (prevention of tumour lysis) specific combination chemotherapy CNS directed therapy in lymphoblastic bone marrow or stem cell transplant
7
Q
describe the stem cell transplant process
A
they must be a tissue type or a HLA match (related or unrelated)
should have a transplant if the rate of dying from readmission is greater than the rate of dying from transplant (Philadelphia positive acute lymphoblastic leukaemia)
8
Q
describe the process of obtaining a stem cell donation
A
collected from the bone marrow
collected from the peripheral blood after stimulation with G-CSF
they are infused into the patient via a peripheral vein
9
Q
what are the side effects of chemotherapy?
A
nausea and vomiting hair loss mouth ulcers pancytopenic period risk of infections and bleeding infertility
10
Q
what are the findings in CML?
A
high WCC
high neutrophils, eosinophils, basophils and myeloid precursor cells
Philadelphia chromosome (BCR/ABL fusion)
high LDH and Urate
11
Q
what is the function of the BCR/ABL protein?
A
drives CML resulting in cell proliferation and apoptosis failure
12
Q
what is the management of CML?
A
TKI inhibitors block BCR/ABL (TKI) function and lead to cell death imatinib nilotinib dasatinib bosutinib ponatinib treated long-term with BCR/ABL monitoring bone marrow transplant
13
Q
what are the symptoms of bone marrow failure?
A
anaemia
bleeding
infection
14
Q
what is the relapse rate of Ph positive ALL treated with chemotherapy?
A
100%
15
Q
what are the risk factors for AML?
A
myelodysplastic syndrome pre-existing haematological disorders down's syndrome bloom syndrome prior chemotherapy radiation tobacco smoke benzene
16
Q
what are the symptoms of AML?
A
anaemia (weakness, fatigue, pallor, malaise, palpitations, dizziness, dyspnoea, tachycardia)
thrombocytopenia (mucosal bleeding, easy bruising, petechiae/purpura, epistaxis)
neutropenia (infection susceptibility, fever, recurrent infections)
abdominal discomfort/fullness (hepatosplenomegaly)
weight loss
respiratory distress, altered mental status (leukostasis)
17
Q
what are the findings in AML?
A
deranged WCC low RBC low PLT high LDH and uric acid (increased cell turnover) deranged coagulation profile
18
Q
what is the management of AML?
A
chemotherapy - induction period, consolidation period, maintenance therapy bone marrow transplant blood cell transfusions analgesia and good oral hygiene antimicrobial prophylaxis allopurinol antiemetics
19
Q
what are the complications of AML?
A
leukostasis
tumour lysis syndrome
disseminated intravascular coagulation
20
Q
how is a diagnosis of AML made?
A
> 20% myeloid blasts in the bone marrow or peripheral blood
21
Q
what is the pathophysiology of the Philadelphia chromosome?
A
add phosphates to tyrosine residues (tyrosine kinase)
inhibition of DNA repair
22
Q
what are the symptoms of CML?
A
asymptomatic (chronic phase) upper abdominal pain (hepatosplenomegaly) poor appetite night sweats gout increased susceptibility of infection dyspnoea fatigue easy bruising/petechiae/bleeding neurological deficits
23
Q
what are the features of a blast crisis?
A
> 20% lymphoblasts or myeloblasts in the blood or bone marrow
large clusters of blasts in the bone marrow on biopsy
chloroma development
24
Q
define anaemia
A
Hb < 120g/L in females
Hb < 130g/L in males
25
what are the causes of microcytic hypochromic anaemia?
iron deficiency anaemia
thalassemias
sideroblastic anaemia
26
what are the causes of normocytic normochromic anaemia?
```
combined iron and B12/folate deficiency
acute/subacute blood loss
renal failure
anaemia of chronic disease
lead poisoning
myelodysplasia
leukaemia
other primary bone marrow disorders
```
27
what are the causes of macrocytic anaemia?
```
B12/folate deficiency
haemolytic anaemia
liver disease
hypothyroidism
alcohol
cytotoxic drugs
```
28
what factors are essential for erythropoiesis?
```
erythropoietin
thyroxine
haematopoietic growth factors
vitamin B12
folic acid
iron
functioning globin genes
```
29
define microcytic hypochromic anaemia
decreased MCV
| decreased MCH/MCHC
30
what are the features of haemolytic anaemia?
jaundice (haem breakdown product)
splenomegaly
mild-moderate red cell macrocytosis
31
what is the treatment of haemolytic anaemia?
symptomatic - blod transfusion
| cause - prednisolone, oral folic acid, second-line immunosuppression, splenectomy
32
what tests should be completed in suspected macrocytic anaemia?
serum B12
serum folate
liver function
33
how do you treatment acute macrocytic anaemia?
oral folic acid
transfusion in CV compromise or acute bleeding
supplemental thiamine (Wernicke's encephalopathy)
34
describe leucoerythroblastic reaction
immature erythrocytic and neutrophilic precursors in the blood
35
what are the causes of leucoerythroblastic anaemia?
```
metastatic carcinoma
granuloma
CML
myelofibrosis
megaloblastic anaemia
lymphoma
acute leukaemias
recovery from BM insult
severe sepsis
```
36
what are the features of thalassemia?
microcytic hypochromic anaemia
normal RBC
low MCV, MCHC, MCH
37
what tests would you perform to confirmed thalassemia?
blood film
Hb electrophoresis (HbA2 elevated)
goblin gene sequencing
38
define myeloma
a cancer of the plasma cells
| massive production of antibodies
39
describe the pathophysiology of myeloma
cancerous plasma cells migrate to the bone marrow and accumulate
surpasses the growth of the normal blood
secrete growth factors that destroy the overlying bone (lytic lesions)
40
in what way can a myeloma present?
hypercalcaemia
renal failure
anaemia
bone lesions (fractures, pepper pot skull)
41
describe MGUS
persistent paraprotein with no evidence of CRAB criteria
| require follow up as can transform into myeloma
42
what is the treatment of a myeloma?
combination of targeted biological agents
ultimately mutates until therapy is no longer effective and they die of complications
chemotherapy rarely used now
43
what are the causes of bleeding disorders?
abnormal vascular endothelium
clotting factor deficiency
platelet abnormalities
44
what are the causes of a factor VII deficiency?
oral warfarin therapy (first few days)
sepsis
congenital deficiency
early vitamin K deficiency
45
what are the causes of a prolonged PT?
factor VII deficiency
46
what are the causes of a prolonged PT and APTT?
vitamin K deficiency
oral dabigatran therapy
oral warfarin therapy
DIC
47
what are the causes of DIC?
septicaemia
meningitis
malignancy
48
what are the causes of prolonged APTT?
```
DIC
liver disease
massive transfusion
unfractionated heparin therapy monitoring
heparin contamination from line locks
oral warfarin therapy
lupus anticoagulant
VIII, IX, XI, XII deficiency
```
49
what is the cause of a prolonged APTT that 'corrects'?
clotting factor deficiency
50
what is the cause of a prolonged APTT that fails to 'correct'?
lupus anticoagulant
51
what are the symptoms and signs of haemophilia A and B?
major haemorrhage into joints
affected joint is tender, warm and distended
chronic haemorrhage causes degenerative joint changes and arthropathy
intracranial haemorrhage, intramuscular haematoma, GI haemorrhage, haematuria and haematospermia
52
describe Von Willebrands Disease
epistaxis
menorrhagia
bleeding after surgery
no haemarthrosis, muscle or spontaneous bleeds
53
name some acquired platelet disorders
anti platelet therapy
NSAIDs
SSRIs
herbal medication
very common
54
name some congenital platelet disorders
Bernard Soullier syndrome
Glanzmanns thrombasthenia
storage pool disorders
Hermansky Pudlak syndrome
very rare
55
where do lymphocytes develop from?
primary lymphoid tissue (bone marrow and thymus)
56
what are the secondary lymphoid tissues?
lymph nodes
spleen
MALT
57
what are the functions of lymphocytes?
```
antibody production
antigen presentation
immune response coordination
immune response suppression
killing virally infected cells
tumour suppression
```
58
define lymphoma
a group of diseases caused by accumulation of malignant lymphocytes with lymph nodes
non/hodgkin lymphoma
59
what are the causes of lymphoma?
```
viruses (EBV, HIV, HTLV-1, hep C)
bacteria (helicobacter pylori, chlamydia psittacosis)
immunosuppression
autoimmune disease
no cause
```
60
what are the symptoms of lymphoma?
```
lymphadenoapthy
fevers
night sweats
weight loss
fatigue
itch
```
61
what are the causes of lymphadenopathy?
```
non/hodgkins lymphoma
leukaemia
malignancy (draining)
CT disorders (RA, SLE, sarcoid)
infection
```
62
describe a small lymphocytic lymphoma on histology
small uniform lymphocytes with clumped chromatin, no obvious nucleoli
63
describe a diffuse large B cell lymphoma on histology
larger pleomorphic cells many with nucleoli
64
describe a Hodgkin lymphoma on histology
inflammatory background with reed Sternberg cells
65
describe immunohistochemistry
the most important method for immunophenotyping lymphocytes on fixed paraffin embedded material
allows visualisation of an antigen
66
describe flow cytometry
requires fresh tissue
| cells incubated with multiple flurochrome-labelled Abs and passed through laser light beam in a FACS machine
67
describe FISH
fluorophore labelled DNA probes hybridise to specific DNA sequences
detect non-random chromosomal translocations in lymphoma
68
describe the Ann Arbor staging of lymphoma
1 - single lymph nodes region
2 - 2+ sites, same side of diaphragm
3 - both sides of diaphragm
4 - diffuse involvement of extralymphatic sites
69
describe classical Hodgkin lymphoma
can present at any age but has a peak incidence in young adults
m>f
reed Sternberg cells are abnormal cells of B lymphoid lineage
70
what are the types of Hodgkin lymphoma?
classical Hodgkin lymphoma (nodular sclerosis, lymphocyte rich, lymphocyte deplete, mixed cellularity)
nodular lymphocyte predominant hodgkin lymphoma
80% of patients will be cured with standard 1st line therapy
71
describe non-hodgkin lymphoma
large group of clonal lymphoid disorders
85% B cell
15% T or NK cell
72
describe diffuse large B cell lymphoma
```
1/3 NHL in western countries
high grade lymphoma
rapidly progressive
requires urgent treatment
RCHOP 1st chemotherapy
radiotherapy for sites of bulky disease
stem cell transplantation (refractory/relapse)
```
73
what are the cells of origin of a diffuse large B cell lymphoma?
germinal centre phenotype
| activated B cell phenotype (ABC, poorer prognosis)
74
describe a double-hit DLBCL
concurrent MYC and BCL2 and/or BCL6 gene rearrangements
poor prognosis
RCHOP gives a poor outcome
requires FISH screening
75
describe follicular lymphoma
```
25% all NHL
low grade
median age of onset 60yrs
translocation t(14;18) = BCL2 gene overexpression
BCL2 has anti-apoptotic functions
```
76
what is the treatment of follicular lymphoma?
```
watch and wait
radiotherapy
chemotherapy
stem cell transplantation
median survival 12-18 years
```
grade 3b treated like high grade lymphoma
77
describe chronic/small lymphocytic leukaemia
most common (4/100,000 per yr)
>age
asymptomatic - watch and wait
treatment - cytopenia, splenomegaly, lymphadenopathy, rapid rise in WCC
associated with genetic abnormalities (13q, 11q, 17p deletions, trisomy 12)
13q - excellent prognosis
17p or TP53 gene - chemotherapy resistance
78
what are the most common treatments for lymphoma?
```
corticosteroids
chemotherapy
radiotherapy
monoclonal antibodies
targeted therapies
stem cell transplantation
CAR T-cell therapy
```
79
describe monoclonal antibodies
target particular proteins (CD20, CD22, CD19, CD52) on lymphocyte surfaces
rituximab for lymphoma
ofatumumuab and obinutuzumab for CLL
80
describe the cell-signalling pathway target treatment in lymphoma
Bruton-tyrosine kinase (BTK) inhibitors ibrutinib)
| P13K (idelalisib)
81
describe autologous stem cell transplantation
rein fusion of the patients own stem cells
rarely used as part of initial therapy
side effects - mucositis, diarrhoea, organ toxicity, infection, bleeding, morality risk 5%
82
describe allogeneic stem cell transplantation
requires HLA donor
cytotoxic and immune therapy
myeloblative or reduced intensity conditioning regimens
side effects - graft vs host disease, morbidity and mortality approaching 30%
83
describe some lymphoma emergencies
superior vena caval obstruction (venous drainage obstruction from head, arms and upper chest wall, facial swelling and dyspnoea)
hypercalcaemia
spinal cord compression
tumour lysis syndrome (rapid breakdown of tumour cells, most often in high grade lymphomas and Burkitts lymphoma)
84
what is the treatment of stage IV Hodgkin lymphoma?
ABVD adriamycin, dacarbazine, bleomycin and vinblastine
interim CT-PET post two cycles
minimum clinical response - ICE chemotherapy, 2-4 cycles followed by autologous stem cell transplantation if complete response achieved
85
what is the differential diagnosis of a soft tissue mass in chest?
lung cancer
other solid malignancy
lymphoma
sarcoid
86
what is the management of superior vena cava obstruction secondary to lymphoma?
urgent biopsy
high dose steroids with tumour lysis prophylaxis
radiotherapy
chemotherapy
87
what are the causes of mucocutaneous bleeding and delayed post-surgical bleeding
VWD
dysfunctional platelet syndrome
FXIII deficiency
88
what are the symptoms and signs of a factor deficiency in males?
atraumatic bruising
spontaneous joint bleeds
immediate surgical bleeding
89
describe an extrinsic pathway problem
prolonged PT only
| factor VII defiency
90
describe a common pathway problem
```
prolonged PT and APTT
vitamin K deficiency
oral warfarin therapy
oral dabigitran therapy
DIC
```
91
describe an intrinsic pathway problem
prolonged APTT
92
describe haemophilia A and B
A - factor VIII deficiency, males
B - factor IX deficiency, males
x-linked recessive
93
which type of Hodgkins lymphoma has the worst prognosis?
lymphocyte depleted
94
what type of Hodgkins lymphoma has the best prognosis?
lymphocyte predominant
95
what symptoms of Hodgkins lymphoma imply a poor prognosis?
weight loss >10% in the last 6 months
fever >38 degrees
night sweats
96
what do myeloma plasma cells do?
migrate towards the bone marrow and accumulate
suppresses the growth of normal blood causing anaemia
secrete growth factors that destroy the overlying bone
causing lytic lesions; fracture easily
produce light chain fragments of IgG molecules which gather in the renal tubules, causing cast nephropathy
97
describe myeloma
malignancy of plasma cells;
10% plasma cells in marrow
and
high Ca, renal impairment, anaemia, or bone lesions due to this (CRAB)
or
NEW; >60% plasma cells in marrows, very high light chains, MRI findings (SLiM)
