Haematology/ Oncology Flashcards
1
Q
what is the most common thrombophilia?
A
Activated protein C resistance aka Factor V Leiden
- heterozygotes - 5 x risk thrombosis
- homozygotes - 50 x risk
2
Q
MOA of docetaxel?
A
Acts on microtubules:
prevents microtubule depolymerisation & disassembly -> decreasing free tubulin
3
Q
SE of docetaxel?
A
Neutropenia
4
Q
What are the different types of cryoglobulinaemia?
A
3 Types: Type I (25%): monoclonal Type II (25%): mixed monoclonal and polyclonal, usually with rheumatoid factor. Type III (50%): polyclonal: usually with rheumatoid factor
5
Q
What is cryoglobulinaemia?
A
immunoglobulins which undergo reversible precipitation at 4 deg, dissolve when warmed to 37 deg.
6
Q
Type 1 Cryoglobulinaemia assoc?
A
- monoclonal
- > Waldenstrom macroglobulinaemia, Multiple myeloma
7
Q
Type II Cryoglobulinaemia assoc w?
A
mixed monoclonal/ polyclonal (usually with RF)
-> Hep C, Rheumatoid arthritis, Sjogren’s, lymphoma
8
Q
Type III Cryoglobulinaemia assoc with?
A
- polyclonal: usually with RF.
- > Rheumatoid arthritis, Sjogrens
9
Q
Symptoms/ signs of Cryoglobulinaemia?
A
- Raynauds (type I)
- Cutaneous: purpura, distal ulceration
- arthralgia
- Renal - diffuse glomerulonephritis
10
Q
Ix of Cryoglobulinaemia?
A
- Low complement (esp C4)
- High ESR
11
Q
Mx of cryoglobulinaemia?
A
Immunosuppression, plasmapheresis
12
Q
Management of SVCO?
A
- endovascular stenting usually to provide symptom relief
- often given steroids e.g. dexamethasone
13
Q
most reliable lab test to screen for hereditary angioedema inbetween attacks?
A
C4 levels
- characteristically low
*C2 also low but serum C4 most reliable and widely used screening tool
14
Q
best diagnostic test to send during acute attack of hereditary angioedema?
A
C1 inhibitor levels- low
15
Q
Management of acute attack of hereditary angioedema?
A
IV C1-inhibitor concentrate,
2nd line: FFP
- HAE does not respond to adrenaline, antihistamines or steroids.
16
Q
Prophylaxis of attacks in hereditary angioedema?
A
anabolic steroid - Danazol
Or tranexamic acid
17
Q
Diagnosis of hereditary spherocytosis?
A
- typical clinical features (FHx) + lab Ix (spherocytes)
- if equivocal: EMA binding test and Cryohaemolysis test
18
Q
Diagnosis of atypical presentations of hereditary spherocytosis?
A
electrophoresis analysis of erythrocyte membranes
19
Q
Management of acute haemolytic crisis in hereditary spherocytosis?
A
- supportive
- transfusion if necessary
20
Q
Long term management of hereditary spherocytosis?
A
folate replacement, splenectomy
21
Q
t(9;22) - Philadelphia chromosome
A
- CML (present in >95%)
- poor prognostic indicator in ALL
22
Q
t(15;17) - fusion of PML and RAR-alpha genes
A
Acute promyelocytic leukaemia
23
Q
t(8;14) - MYC oncogene
A
Burkitt’s lymphoma
24
Q
t(11;14) - deregulation of the cyclin D1 (BCL-1) gene
A
Mantle cell lymphoma
25
t(14;18) - increased BCL-2 transcription
follicular lymphoma
26
causes of warm AIHA?
- autoimmune disease: e.g. systemic lupus erythematosus*
- neoplasia: e.g. lymphoma, CLL
- drugs: e.g. methyldopa
27
Features of warm AIHA?
- usually IgG antibody
| - haemolysis at extravascular sites e.g. spleen
28
Management of warm AIHA?
steroids, immunosuppression, splenectomy
29
causes of cold AIHA?
- neoplasia: e.g. lymphoma
| - infections: e.g. mycoplasma, EBV
30
features of cold AIHA?
- usually igM antibody
- commonly intravascular haemolysis
- Raynauds/ acrocynanosis
- responds less well to steroids
31
clinical features of myelofibrosis?
- symptoms of anaemia
- massive splenomegaly
- hyper metabolic symptoms: weight loss, night sweats
32
lab findings of myelofibrosis?
- anaemia
- high WBC, Pl count
- blood film: tear drop poikilocytes
- dry tap on BM biopsy-> trephine biopsy needed
- high LDH and urate (increased cell turnover)
33
What chemical mediator is mainly responsible for the tissue oedema seen in patients in hereditary angioedema?
bradykinin
- uncontrolled release of bradykinin-> oedema of tissues
34
features of thrombotic thrombocytopenic purpura?
- fever
- fluctuating neuro signs (microemboli)
- microangiopathic haemolytic anaemia
- thrombocytopenia
- renal failure
35
pathogenesis of Thrombotic thrombocytopenic purpura?
- deficiency of ADAMTS13 (a metalloprotease enzyme) that breaks down large multimers of vWF
- abnormally large and sticky multimers of vWF cause platelets to clump within vessels
36
Causes of thrombotic thrombocytopenic purpura?
post-infection e.g. urinary, gastrointestinal
pregnancy
drugs: ciclosporin, oral contraceptive pill, penicillin, clopidogrel, aciclovir
tumours
SLE
HIV
37
features of Waldenstrom's macroglobulinaemia?
- monoclonal IgM paraproteinaemia
- systemic upset: weight loss, lethargy
- hyperviscosity syndrome e.g. visual disturbance
- hepatosplenomegaly
- lymphadenopathy
- cryoglobulinaemia e.g. Raynaud's
38
features of lead poisoning?
- abdo pain
- peripheral neuropathy (mainly motor)
- fatigue
- constipation
- blue lines on gum margin (only 20% of adult patients, very rare in children)
39
Ix of lead poisoning?
- Blood lead level
- FBC: microcytic anaemia
- blood film: basophilic stippling, clover leaf morphology
- raised serum/ urine lvls of delta aminolaevulinic acid (similar to acute intermittent porphyria)
- urinary coproporphyrin raised
40
management of lead poisoning?
```
various chelating agents are currently used:
dimercaptosuccinic acid (DMSA)
D-penicillamine
EDTA
dimercaprol
```
41
Sickle cell: what medication is taken long term to reduce incidence of complications and acute crises?
Hydroxycarbamide
- increases HbF
- makes cells less likely to sickle
- advised to not be taken in pregnancy
42
features of essential thrombocytosis?
- Pl count >600
- thrombosis and haemorrhage
- characteristic symptom is burning sensation in the hands
- JAK2 mutation in 50%
43
Management of essential thrombocytosis?
- Hydroxyurea (hydroxycarbamide) to reduce pl count
- IFN-a in younger patients
- low dose aspirin to reduce thrombotic risk
44
how to prevent haemorrhagic cystitis in those on cyclophosphamide?
Mesna (2-mercaptoethane sultanate sodium)
| - binds to and neutralises acrolein
45
what type of cancer does cyclophosphamide increase risk of?
transitional cell carcinoma
46
a Leukaemoid reaction vs leukaemia causing high WBC
- high leucocyte alkaline phosphatase score
- toxic granulation (Dohle bodies) in the white cells
- left shift of neutrophils
47
Blood film features of hyposplenism e.g. post-splenectomy, coeliac disease?
```
target cells
Howell-Jolly bodies
Pappenheimer bodies
siderotic granules
acanthocytes
```
48
1st line management of idiopathic thrombocytopenic purpura?
oral prednisolone
49
management of idiopathic thrombocytopenic purpura?
oral pred (80% of patients respond)
- splenectomy if platelets < 30 after 3 months of steroid therapy
- IV immunoglobulins
- immunosuppressive drugs e.g. cyclophosphamide
50
features of acute intermittent porphyria?
- abdominal: abdominal pain, vomiting
- neurological: motor neuropathy
- psychiatric: e.g. depression
- hypertension and tachycardia common
51
genetics of acute intermittent porphyria?
- autosomal dominant
| - defect in porphobilinogen deaminase
52
what are the toxic elements accumulated in acute intermittent porphyria?
delta aminolaevulinic acid
| porphobilinogen
53
diagnosis of acute intermittent porphyria?
- urine: raised urinary porphobilinogen + urine turns deep red in sunlight
- assay of red cells for porphobilinogen deaminase
- raised serum levels of delta aminolaevulinic acid and porphobilinogen
54
lead poisoning: what is raised in urine?
coproporphyrin level
55
what drugs may precipitate haemolysis in G6PD deficiency?
- anti-malarials: primaquine
- ciprofloxacin
- sulph- group drugs: sulphonamides, sulphasalazine, sulfonylureas
56
pathophysiology of G6PD deficiency?
↓ G6PD → ↓ reduced NADPH → ↓ reduced glutathione → increased red cell susceptibility to oxidative stress
- reduced glutathione protects RBCs from oxidative damage
57
Features of G6PD deficiency?
- neonatal jaundice is often seen
- intravascular haemolysis
- gallstones are common
- splenomegaly may be present
- Heinz bodies on blood films. Bite and blister cells may also be seen
58
diagnosis of G6PD deficiency?
G6PD enzyme assay
| - levels should be checked around 3 months after an acute episode of hemolysis to avoid false -ve result
59
IX of choice in CLL diagnosis?
Flow cytometry for immunophenotyping
| - to reveal cell surface markers typical of CLL, including CD5, CD19 and CD20.
60
Defect in Chronic granulomatous disease?
lack of NADPH oxidase -> reduces ability of neutrophils to produce reactive oxygen species
-> susceptibility to catalase-positive bacteria e.g. staph aureus and fungi e.g. aspergillus
61
features of chronic granulomatous disease?
recurrent pneumonias and abscesses
62
diagnosis of chronic granulomatous disease?
abnormal dihydrorhodamine flow cytometry test
| negative nitroblue-tetrazolium test
63
features of Chediak-Higashi syndrome?
- partial albinism
- peripheral neuropathy
- recurrent bacterial infections
- giant granules in neutrophils and platelets
64
defect in Chediak-Higashi syndrome
Microtubule polymerization defect which leads to a decrease in neutrophil phagocytosis
65
features of Leukocyte adhesion deficiency?
recurrent bacterial infections,
delay in umbilical sloughing,
absence of neutrophil/ pus at sites of infection
66
defect in Leukocyte Adhesion deficiency?
LAD1: deficiency of the (LFA-1) B-2 integrin subunit (CD18) of the Leukocyte adhesion molecule
67
Features of common variable immunodeficiency?
hypogammaglobulinaemia: Low IgG, IgE and IgA.
- FTT, recurrent infections, autoimmune and granulomatous diseases
- may predispose to lymphoma
68
Features of Bruton's Agammaglobulinaemia?
- X linked recessive
- recurrent bacterial infections
- failed maturation of B cells with low IG (No antibodies)
69
Genetic defect of Bruton's Agammaglobulinaemia?
X-linked defect in Bruton's tyrosine kinase gene -> block in B cell development
70
Features of Selective IgA deficiency
- most common primary antibody deficiency
- recurrent gastro/ resp infections
- assoc w coeliac disease (may cause false -ve coeliac screen)
- severe reactions to blood transfusions (anti-IgA abs-> anaphylaxis)
71
Features of DiGeorge's Syndrome?
CATCH - 22
Congenital heart disease - tetralogy of fallot
Abnormal facies - low set ears, cleft lip
Thymus - absent, low lvls of mature T cells -> recurrent viral/ fungal infections
Cleft palate
Hypocalcaemia
22q11.2 deletion
72
Defect in Wiskott-Aldrich syndrome?
Defect in WASP gene, X linked recessive
73
Features of Wiskott-Aldrich syndrome?
X linked recessive
- recurrent bacterial infections
- eczema
- thrombocytopenia
- Low IgM levels
- Increased risk of autoimmune disorders/ malignancy
74
CLL: Indications for treatment
- progressive marrow failure
- massive (>10 cm) or progressive lymphadenopathy
- massive (>6 cm) or progressive splenomegaly
- progressive lymphocytosis: > 50% increase over 2 months or lymphocyte doubling time < 6 months
- FLAWS: weight loss > 10% in previous 6 months, fever >38ºC for > 2 weeks, extreme fatigue, night sweats
- autoimmune cytopaenias e.g. ITP
75
CLL: Management if treatment is indicated
- fludarabine, cyclophosphamide and rituximab (FCR)
| - Ibrutinib (2nd line)
76
1st line management of thrombotic thrombocytopenic purpura?
plasma exchange
77
Microscopy findings of Burkitt's lymphoma?
'starry sky' appearance: lymphocyte sheets interspersed with macrophages containing dead apoptotic tumour cells
78
Mx of Burkitt's lymphoma?
chemotherapy
79
what medication is given before chemotherapy to reduce risk of tumour lysis syndrome?
rasburicase (a recombinant version of urate oxidase, an enzyme which catalyses the conversion of uric acid to allantoin*)
80
what medication is given before chemotherapy to reduce risk of tumour lysis syndrome?
rasburicase (a recombinant version of urate oxidase, an enzyme which catalyses the conversion of uric acid to allantoin, which is 5-10x more soluble than uric acid)
81
Haptoglobin levels in haemolytic anaemia?
- LOW haptoglobin levels
Haptoglobin binds to free haemoglobin released from lysed erythrocytes. The complexes are then removed from the plasma by the hepatic reticulo-endothelial cells. Haptoglobin levels decrease if the rate of haemolysis is greater than the rate of haptoglobin production.
82
rare drug cause of B12 deficiency?
Metformin
83
MOA of cyclophosphamide?
alkylating agent- causes cross linking in DNA
84
gold standard investigation in Paroxysmal nocturnal haemoglobinuria?
flow cytometry of blood to detect low levels of CD59 and CD55
- has now replaced Ham's test
85
features of Paroxysmal nocturnal haemoglobinuria?
- haemolytic anaemia +/- aplastic anaemia
- pancytopaenia may be present
- haemoglobinuria: classically dark-coloured urine in the morning (can occur throughout the day)
- thrombosis e.g. Budd-Chiari syndrome
86
Management of Paroxysmal nocturnal haemoglobinuria?
- blood product replacement
- anticoagulation
- eculizumab, a monoclonal antibody directed against terminal protein C5, being trialled
- stem cell transplantation
87
Cisplatin: what electrolyte abnormality as SE?
Hypomagnesaemia
88
Chemotherapy related N+V?
low risk - metoclopramide 1st line
| high risk - 5HT3R antagonists eg. ondansetron +/- dexamethasone
89
Aflatoxin (produced by Aspergillus) - increased risk of which ca?
HCC
90
Aniline dyes - increased risk of which ca?
Bladder (Transitional cell ca)
91
Asbestos - increased risk of which ca?
Mestothelioma, bronchial ca
92
Nitrosamines - increased risk of which ca?
Oesophageal and gastric ca
93
Vinyl chloride - increased risk of which ca?
Hepatic angiosarcoma
94
Ix in multiple myeloma?
- monoclonal proteins in serum and urine (bence jones proteins)
- Whole body MRI
- XR: "rain drop skull"
95
Diagnostic criteria for multiple myeloma?
1 major, 1 minor OR 3 minor
Major criteria
- Plasmacytoma
- 30% plasma cells in a bone marrow sample
- Elevated levels of M protein in the blood or urine
Minor criteria
- 10% to 30% plasma cells in a bone marrow sample.
- Minor elevations in the level of M protein in the blood or urine.
- Osteolytic lesions.
- Low levels of antibodies (not produced by the cancer cells) in the blood.
96
MX of antiphospholipid syndrome in pregnancy?
aspirin + LMWH (until 34/40 gestation)
97
metastatic spinal cord compression: UMN or LMN?
Lesions above L1 usually result in upper motor neuron signs in the legs and a sensory level. Lesions below L1 usually cause lower motor neuron signs in the legs and perianal numbness. Tendon reflexes tend to be increased below the level of the lesion and absent at the level of the lesion
98
Ix of metastatic spinal cord compression?
urgent MRI: MRI whole spine within 24h of presentation
99
Mx of metastatic spinal cord compression?
high dose oral dexamethasone
| - urgent onco assessment for consideration of radiatx or surgery
100
clinically cryoprecipitate is most commonly used to replace?
fibrinogen
101
Desmopressin- in von Hillebrands disease?
induces release of von Willebrand's factor from endothelial cells
102
SE of cisplatin?
Ototoxicity, peripheral neuropathy, hypomagnesaemia
103
Anastrozole/ letrozole -MOA?
aromatase inhibitors that reduces peripheral oestrogen synthesis
- used for ER+ve breast ca
104
SE of anastrozole/ letrozole?
osteoporosis: DEXA scan when initiating pt
- hot flushes
- arthralgia, myalgia
- insomnia
105
SEs of Tamoxifen (SERM)?
- menstrual disturbance: vaginal bleeding, amenorrhoea
- hot flushes
- venous thromboembolism
- endometrial cancer
106
Management of polycythaemia vera?
- aspirin - reduces risk of thrombotic events
- 1st line: venesection
- chemotherapy: hydroxyurea, phosphorus-32 therapy
107
What may polycythaemia vera progress to ...?
myelofibrosis, AML (risk increased w hydroxyurea)
108
immune thrombocytopenia: what are antibodies directed against?
gpIIb/IIIa or Ib-V-IX complex
109
Hereditary angioedema - what is the best screening test inbetween attacks?
c4 levels - low
110
Management of choice in thrombotic thrombocytopenic purpura ?
Plasma exchange
111
Management overview of TTP?
no antibiotics - may worsen outcome
plasma exchange is the treatment of choice
steroids, immunosuppressants
vincristine
112
most common tumour of the anterior mediastinum?
Thymoma
113
Thymoma associations?
myasthenia gravis (30-40% of pts with thymoma),
red cell aplasia,
dermatomyositis,
SLE, SIADH
114
Thymoma leading to death...? causes
compression of airway
| cardiac tamponade
115
management of hereditary angioedema?
IV C1-inhibitor concentrate- otherwise, FFP.
- Note adrenaline/ antihistamines/ steroids not useful!
116
prophylaxis of angioedema attacks in hereditary angioedema?
anabolic steroid (Danazol)
117
Hodgkin's lymphoma: most common subtype?
Nodular sclerosing (around 70%).
followed by mixed cellularity (~20%), lymphocyte predominant (~5%), lymphocyte depleted (rare)
118
Hodgkin's lymphoma: subtype with best prognosis?
Lymphocyte predominant
119
Hodgkin's lymphoma: subtype with worst prognosis?
Lymphocyte depleted
120
Hodgkin's lymphoma: subtype associated with lacunar cells?
Nodular sclerosing
121
Hodgkin's lymphoma: subtype associated with large number of Reed-Sternberg cells?
Mixed cellularity
122
Hodgkin's lymphoma: what factors are associated with poor prognosis?
- B symptoms: fever >38, night sweats, weight loss >10% in last 6 months
- male
- low albumin, Hb (<10.5), lymphocyte count (<8%)
- age >45, WCC >15
- stage IV disease
123
Essential thrombocytosis: what gene mutations are assoc?
mainly JAK-2.
| in ~20% of JAK-2 negative patients: CALR (calreticulin) gene mutation
124
Cisplatin MOA?
cross-linking in DNA
125
Cisplatin SE?
Ototoxicity, peripheral neuropathy, hypoMg
126
Hydroxyurea/ Hydroxycarbamide MOA?
inhibits ribonucleotide reductase -> Decreasing DNA synthesis
127
Hydroxyurea/ Hydroxycarbamide SE?
myelosuppression
128
Myeloma: what marker is useful for prognostication?
B2-microglobulin - useful, poor prognosis if raised.
| Low albumin -poor prognosis
129
Most common tumour causing bone mets?
Prostate
followed by breast then lung
130
Most common site of bone met
spine
then pelvis
ribs
skull
long bones
131
Poor prognostic features of AML?
- >60 yo
- >20% blasts after first course of chemo
- cytogenetics: deletions of chr 5 or chr 7
132
Associations of Acute promyelocytic leukaemia?
- t(15;17)
- Auer rods (seen with myeloperoxidase stain)
- DIC/ thrombocytopenia
- good prognosis, presents younger than other types of AML (~25yo)
133
Genetics of beta thal major?
- chr 11
| - absence of beta chains
134
Features of beta thal major?
- HbA2 + HbF raised
- microcytic anaemia
- HbA absent
135
Mx of beta thal major?
repeated transfusion -> iron overload
| - s/c infusion of desferrioxamine
136
Inheritance of antithrombin III deficiency?
autosomal dominant
137
Features of antithrombin III deficiency?
- recurrent venous thromboses
- arterial thromboses may occur
- deficiency of antithrombin III -> heparin does not work
138
Management of antithrombin III deficiency?
lifelong warfarinisation
- heparinisation during pregnancy
- antithrombin III concentrates (often used during surgery/ childbirth)
139
Ix of immune thrombocytopenic purpura?
- antiplatelet antibodies
| - bone marrow aspiration: megakaryocytes. (should be performed prior to steroid initiation to rule out leukaemia)
140
Mx of immune thrombocytopenic purpura?
1st line: oral prednisolone
- splenectomy if Pl<30 after 3 mo of steroid therapy
- IVIG
- Immunosuppressive drugs: e.g. cyclophosphamide
141
latex allergy more common in which condition?
children w myelomeningocele spina bifida
142
Latex-fruit syndrome: what fruits are implicated?
those allergic to latex also allergic to fruits: particularly banana, pineapple, avocado, kiwi, chestnut, mango, passion fruit, strawberry
143
SVC obstruction - what is the most common symptom?
dyspnoea
144
Irradiated blood products are depleted of what? and why are they used?
depleted of T lymphocytes
| - used to avoid transfusion assoc graft vs host disease caused by viable donor T lymphocytes
145
features of Porphyria cutanea tarda (PCT)?
- may be caused by hepatocyte damage e.g. alcohol, oestrogens
- classically photosensitive rash with bullae, skin fragility on face and dorsal aspect of hands
146
Defect in Porphyria cutanea tarda (PCT)?
defect in uroporphyrinogen decarboxylase
147
management of Porphyria cutanea tarda?
chloroquine
148
Ix of Porphyria cutanea tarda?
urine: elevated uroporphyrinogen and pink fluorescence of urine under Wood's lamp
149
Features of Variegate porphyria?
- auto dominant
- photosensitive blistering rash
- abdo and neurological symptoms
more common in South Africans
150
Enzyme affected in variegate porphyria?
defect in protoporphyrinogen oxidase
151
pathophysiology of methaemoglobinaemia?
Hb: oxidised from Fe2+ to Fe3+.
- normally regulated by NADH methaemoglobin reductase
- tissue hypoxia as Fe3+ cannot bind oxygen, and hence the oxidation dissociation curve is moved to the left
152
Causes of methaemoglobinaemia?
Congenital causes:
- Hb chain variants: HbM, HbH
- NADH methaemoglobin reductase deficiency
Acquired causes
- drugs: sulphonamides, nitrates (including recreational nitrates e.g. amyl nitrite 'poppers'), dapsone, sodium nitroprusside, primaquine
- chemicals: aniline dyes
153
Features of methaemoglobinaemia?
- 'chocolate' cyanosis (chocolate-colored blood)
- dyspnoea, anxiety, headache
- severe: acidosis, arrhythmias, seizures, coma
- normal pO2 on gas but decreased oxygen saturation
154
Mx of acquired methaemoglobinaemia?
IV methylene blue
155
Mx of congenital methaemoglobinaemia secondary to NADH - methaemoglobinaemia reductase deficiency?
ascorbic acid (Vitamin C)
156
Differences between transfusion related lung injury (TRALI) and transfusion associated circulatory overload (TACO)
TACO:- usually rapid transfusions/ more units
- assoc w HYPERtension
TRALI:
- assoc w HYPOtension
- assoc w fever, low WCC
157
Mx of Non-haemolytic febrile reaction post- blood transfusion?
slow/ stop the transfusion, paracetamol, monitor.
158
mx of Minor allergic reaction post blood transfusion e.g. urticaria, pruritus?
Temporarily stop the transfusion, Antihistamine
Monitor.
159
Mx of anaphylaxis post blood transfusion? e.g. Hypotension, dyspnoea, wheezing, angioedema
ie. in IgA deficiency
Stop transfusion
*IM adrenaline
ABC: oxygen, fluids
160
Mx of Acute haemolytic reaction post blood transfusion (ie. ABO incompatibility)?
Fever, abdominal pain, hypotension
Stop transfusion.
- Confirm diagnosis: send blood for direct Coombs test, repeat typing and cross-matching
- Supportive: fluid resuscitation
161
Mx of TACO post blood transfusion?
Slow/ stop tranfusion. +/- IV furosemide
162
Mx of TRALI post blood transfusion?
stop transfusion, supportive. give O2
163
Features of CML?
anaemia, lethargy, weight loss, sweating common
- splenomegaly -> abdo discomfort
- an increase in granulocytes at different stages of maturation +/- thrombocytosis
- decreased leukocyte alkaline phosphatase
- may undergo blast transformation (->AML in 80%, ALL in 20%)
164
1st line mx of CML?
imatinib
- inhibitor of the tyrosine kinase associated with the BCR-ABL defect
- very high response rate in chronic phase CML
165
Mx of CML?
Imatinib,
Hydroxyurea,
IFN-alpha
Allogenic Bone marrow transplant
166
ESR in polycythaemia vera?
low ESR
167
Diagnostic criteria for Polycythaemia vera?
- JAK2 mutation (present in 95%) -> 1st line
| - High Hct / raised red cell mass
168
Other lab features of polycythaemia vera?
Low ESR, high leukocyte alkaline phosphatase
169
what type of lymphoma is assoc w increased BCL-2 transcription?
Follicular lymphoma
| - t(14;18)
170
Peripheral neuropathy + urinary hesitancy / bladder atony - Which chemotherapy drug SE?
vincristine
171
diverse organ manifestations linked by similar histological characteristics:
e.g. riddle's thyroiditis, autoimmune pancreatitis, mediastinal/ retroperitoneal fibrosis, periaortitis, Kuttner's tumour (submandibular glands) + Mikulicz syndrome (salivary, lacrimal glands), sjogrens/ primary biliary cirrhosis
IgG4-related disease
172
BRCA 1/2 associations?
Breast cancer (60% risk)
- Ovarian Ca (55% w BRCA 1, 25% with BRCA 2)
- Prostate Ca in men (BRCA 2)
173
Which chromosomes are BRCA 1 and 2 on?
BRCA 1 = Chr 17
| BRCA 2 = Chr 13
174
Features of Li-Fraumeni Syndrome?
- auto dominant
- sarcomas and leukaemias
- sarcoma <45yo or relative w cancer <45yo + another family member w cancer <45yo/ sarcoma at any age
175
Genetics of Li-Fraumeni Syndrome?
- auto dom
| - mutations to p53 tumour suppressor
176
Family history of cancers + sarcomas
Li-Fraumeni syndrome
177
Features of Lynch syndrome?
- auto dominant
- Colon ca + endometrial cancer
- Amsterdam criteria shows high risk individuals: 3 or > family members with colorectal cancer in 2 generations. (FAP excluded, one must be diagnosed under age 50)
178
Features of Gardners syndrome?
- auto dominant
- colorectal polyps -> risk of colorectal ca
- assoc skull osteoma, thyroid ca, epidermoid cysts
- Desmoid tumours
179
genetics of Gardners syndrome?
auto dom, mutation of APC gene on chr 5
180
What extra colonic features are seen in Gardners syndrome?
skull osteoma,
thyroid ca,
epidermoid cysts/ dermoid tumours
181
disproportionately low MCV microcytic anaemia, with high ferritin
Beta thal trait
182
Good prognostic factors of ALL?
- French-American-British (FAB) L1 type
- common ALL
- pre-B phenotype
- low initial WBC
- del(9p)
183
Poor prognostic factors of ALL?
- FAB L3 type
- T or B cell surface markers
- t(9;22), Philadelphia translocation
- age <2y or >10y
- male
- CNS involvement
- High initial WBC (>100 x10^9)
- Non caucasian
184
tumour marker most associated with primary peritoneal cancer
CA 125
185
AFP - what cancers?
HCC, teratoma
186
S-100 - what cancers?
melanoma, schwannomas
187
Bombesin- what cancers?
small cell lung ca, gastric ca, neuroblastoma
188
Raynauds - assoc w which type of cryoglobulinaemia?
Type 1
189
Cryoglobulinaemia - mixed IgM and IgG
Type 2
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Reed-Sternberg cell
Hodgkins lymphoma
191
Ann-arbor staging of Hodgkins lymphoma?
I: single lymph node
II: 2 or more lymph nodes/regions on same side of diaphragm
III: nodes on both sides of diaphragm
IV: spread beyond lymph nodes
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A = no systemic symptoms other than pruritus
B = weight loss > 10% in last 6 months, fever > 38c, night sweats (poor prognosis)
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192
Haptoglobin levels during a haemolytic crisis?
accelerated break down of red blood cells releases haemoglobin which haptoglobin binds to --> reducing the levels of haptoglobin in the blood.
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e.g.s of G-CSF
filgrastim
| perfilgrastim
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When should G-CSF be considered?
those at high risk of neutropenia (>20%):
- the elderly
- specific malignancies e.g. Non-Hodgkins lymphoma, ALL
- Prev neutropenic episodes
- Receiving combination chemo and radiotx
*NOTE G-CSF not recommended for myeloid malignancies as may stimulate some cancers
195
How does HPV cause cervical cancer?
HPV 16 and 18 triggers carcinogenesis by inhibiting the tumor suppressor gene p53 and RB.
196
MGUS: Differentiating features from myeloma?
- normal immune function
- normal beta-2 microglobulin levels
- lower level of paraproteinaemia than myeloma (e.g. < 30g/l IgG, or < 20g/l IgA)
- stable level of paraproteinaemia
- no clinical features of myeloma (e.g. lytic lesions on x-rays or renal disease)
197
ix for suspected spinal mets?
with neurological features: urgent MRI whole spine
Without neurological features: whole spine MRI within 1 week
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what cancers are assoc w EBV?
Hodgkins, Burkitts lymphoma, nasopharyngeal ca
199
what cancers are assoc w H pylori?
gastric lymphoma (MALT)
200
what cancers are assoc w malaria?
Burkitt's lymphoma
201
Management of tumour lysis syndrome?
IV allopurinol OR IV rasburicase + IV fluids
202
management of smouldering multiple myeloma?
watch and wait
203
skin prick test - can be interpreted after how long?
after 15 minutes
204
Aprepitant - what is this medication?
anti-emetic, which blocks the Neurokinin 1 (NK1 receptor. used in chemotherapy induced n+V
205
Poor prognostic factors of CLL?
- male sex
- age > 70 years
- lymphocyte count > 50
- prolymphocytes comprising more than 10% of blood lymphocytes
- lymphocyte doubling time < 12 months
- raised LDH
- CD38 expression positive
- TP53 mutation
- *deletion of 17p
206
What chromosomal changes is assoc w good prognosis of CLL?
deletion of long arm of chromosome 13 (del 13q)
| - seen in ~50%
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What chromosomal changes is assoc w poor prognosis of CLL?
deletions of short arm of chromosome 17 (del 17p) seen in 5-10%
208
PET scan: looks at...?
glucose uptake
209
Causes of sideroblastic anaemia?
acquired:
- myelodysplasia
- alcohol
- lead
- anti TB medications
congenital: delta-aminolevulinate synthase-2 deficiency
210
Blood film findings of sideroblastic anaemia?
basophilic stippling of RBCs
211
bone marrow findings of sideroblastic anaemia?
Prussian blue stain: ringed sideroblasts
212
management of sideroblastic anaemia?
supportive, tx underlying cause
| - pyridoxine may help
213
most common cause of neutropenic sepsis?
staphylococcus epidermidis
| - gram +v cocci
214
features of transfusion associated graft vs host disease?
- 2-6 wks post transfusion
- diarrhoea, liver damage, rash
- pancytopenia
215
diagnosis of transfusion assoc graft vs host disease?
biopsy of skin - abundant necrotic keratinocytes
biopsy of bone marrow- marked hypocellularity with macrophage infiltration
- both can be diagnostic
216
what is IFN-a used in the management of?
hepatitis B & C, Kaposi's sarcoma, metastatic renal cell cancer and hairy cell leukaemia
217
What is hairy cell leukaemia?
rare malignant proliferation disorder of B cells
| - more common in males (4:1)
218
Features of hairy cell leukaemia?
pancytopenia, splenomegaly.
- skin vasculitis in 1/3 patients
- 'dry tap' despite BM hypercellularity
- Tartrate resistant acid phsophatase (TRAP) stain positive
219
Management of hairy cell leukaemia?
1st line: chemotherapy - cladribine, pentostatin
| 2nd line: immunotherapy - rituximab, IFN-alpha
220
what condition is associated with skin necrosis after the commencement of warfarin?
Protein C deficiency
- when warfarin is first started, biosynthesis of protein C is reduced -> temporary procoagulant state, usually avoided by concurrent heparin administration.
- thrombosis in venules-> skin necrosis
221
what chromosome are alpha-globulin genes located on?
| alpha thalassaemia
chromosome 16
222
key initial therapy in Acute promyelocytic leukaemia (APML)?
ATRA - all-trans retinoid acid +/- anthracycline (daunorubicin/ idarubicin)
- causes immature promyelocytes to mature, alleviating the symptoms of DIC.
223
management of alteplase OD/ related haemorrhage?
Tranexamic acid
| - at high concentrations, non competitive inhibitor of plasmin
224
management of chronic lead poisoning?
oral DMSA
| - 500mg twice per day
225
above what levels is suggestive of lead poisoning?
lead level above 3.4 µmol/l
226
management of acute lead poisoning?
Activated charcoal
| IV disodium EDTA
227
what test to use to estimate glucose control if HbA1c is unreliable because of disturbed erythrocyte turnover or abnormal haemoglobin type?
- quality-controlled plasma glucose profiles
- total glycated haemoglobin estimation (if abnormal haemoglobins)
- fructosamine estimation'
228
Hyper IgM syndrome causes
high IgM, low IgG and IgA
- due to defective class switching
- most common form is an X-linked recessive trait due to mutation of CD40LG gene affecting roughly 2/1,000,000 males
229
what infections are common in hyper IgM syndrome?
- often presents with recurrent infections
- PCP pneumonia
- cryptosporidium
- CMV, and may lead to liver disease
also associated with increased risk of cancers (hepatocellular carcinoma, cholangiocarcinoma and neuroectodermal tumours)
230
management of acute intermittent porphyria in acute attack?
IV haematin/haem arginate
| - IV glucose should be used if haematin/haem arginate is not immediately available
231
What medication should be given alongside fludarabine, cyclophosphamide and rituximab (FCR) in CLL?
Co trimoxazole
| - In view of fludarabine causing profound lymphopenia and increasing risk of opportunistic infections (PCP)
232
What degree of lymphocytosis in CLL suggests need for management?
> 50% increase over 2 months or lymphocyte doubling time < 6 months
233
Prophylaxis for tumour lysis syndrome?
Ensure good renal perfusion
- IV fluids prior to starting chemotherapy
- stop NSAIDs
- prophylactic IV rasburicase OR allopurinol to prevent uric acid accumulation (don’t give together as will reduce effect of rasburicase)
234
What scoring system is used for classification of tumour lysis syndrome?
Cairo-Bishop scoring system:
Laboratory TLS
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2 or more of: occurring within three days before or seven days after chemotherapy.
uric acid > 475umol/l or 25% increase
potassium > 6 mmol/l or 25% increase
phosphate > 1.125mmol/l or 25% increase
calcium < 1.75mmol/l or 25% decrease
```
Clinical TLS
laboratory tumour lysis syndrome plus one or more of the following:
- increased serum creatinine (1.5 times upper limit of normal)
- cardiac arrhythmia or sudden death
- seizure
235
Eculizumab - what vaccination should be prescribed to patients on this?
meningococcal strains A, C, W, and Y
| - due to eculizumab binding to C5
236
Fastest way to increase platelet count in immune thrombocytopenia?
IVIG
| Faster than steroids
237
Hodgkin’s lymphoma (past/ present): what type of blood products should they receive?
Irradiated
- otherwise donor T cells might cause transfusion associated Graft vs host disease where donor T lymphocytes react against pt’s lymphoid tissue causing tissue / organ damage
238
Indications for gamma irradiated blood products?
- immunocompromised marrow or organ transplant recipients
- pts w haem disorders due to undergo allogeneic marrow transplantation imminently
- intrauterine transfusions
- Hodgkin’s lymphoma
- pts treated w purine analogue drugs (E.g. fludarabine)
239
isolated prolonged APTT, reduced FvIII levels, evidence of fVIII inhibitor activity?
Acquired haemophilia A
- autoimmune disorder with formation of abs attacking clotting factors
- mixing studies: coagulation test remains abnormal due to presence of factor inhibitor. in inherited disorders w factor deficiency, addition of normal plasma restores clotting parameters
240
most useful agent in preventing the delayed phase of chemotherapy-induced emesis
Dexamethasone
