Haem / Onc 7.5 Flashcards
(378 cards)
1
Q
Alpha chains of Hb - how many genes? which chromosome?
A
- 2 separate alpha-globulin genes
- chr 16
2
Q
Alpha-thalassaemia: 1/2 absent chains, what blood picture?
A
- hypochromic, microcytic but often normal Hb
3
Q
Alpha-thalassaemia: loss of 3 chains, blood picture?
A
- Hb H disease: hypochromic microcytic anaemia
- splenomegaly
4
Q
Clinical picture if 4 absent alpha chains in thalassaemia (homozygote)
A
Death in utero: hydrops fetalis
5
Q
Commonest cell type of cervical cancer?
A
Squamous 80%
adenoca 20%
6
Q
Most important etiological factors causing cervical cancer?
A
HPV 16, 18, 33
Other RFs:
- smoking, HIV, many partners, high parity, lower socioeconomic status, cop
7
Q
Mechanism of HPV causing cervical cancer?
A
HPV 16 produces oncogene E6 - inhibits p53
HPV 18 produces oncogene E7 - inhibits RB suppressor gene
8
Q
What are the preferred opioids in pts with CKD e.g. in palliative care?
A
alfentanil
buprenorphine
fentanyl
9
Q
Conversion from oral codeine -> oral morphine?
A
Divide by 10
10
Q
Conversion from oral tramadol -> oral morphine?
A
Divide by 10
11
Q
Conversion from oral morphine -> oral oxycodone?
A
Divide by 1.5-2
12
Q
Conversion from 30mg oral morphine -> transdermal fentanyl?
A
12 microgram fentanyl patch
13
Q
Conversion from 24mg oral morphine -> transdermal buprenorphine?
A
10 microgram buprenorphine patch
14
Q
Conversion from oral morphine -> subcut morphine?
A
Divide by 2
15
Q
Conversion from oral morphine -> subcut diamorphine?
A
Divide by 3
16
Q
Conversion from oral oxycodone -> subcut diamorphine?
A
Divide by 1.5
17
Q
What is Burkitt’s lymphoma?
What are the 2 main forms?
A
High-grade B cell neoplasm
- endemic African form: typically involves maxilla/mandible
- sporadic: abdominal e.g. ileo-caecal tumours are commonest, more common in pts with HIV
18
Q
What gene translocation is associated with Burkitt’s lymphoma?
A
c-myc gene translocation, usually t(8;14)
19
Q
What are the microscopy findings in Burkitt’s lymphoma?
A
Starry sky appearance: lymphocyte sheets intersperses with macrophages containing dead apoptotic tumour cells
20
Q
Rx of Burkitt’s lymphoma?
A
Chemotherapy
- tends to produce a rapid response which may cause tumour lysis syndrome
21
Q
What can be given before chemo for Rx of Burkitt’s lymphoma to reduce risk of tumour lysis syndrome?
How does it work?
A
RASBURICASE
- recombinant version of urate oxidase, an enzyme which catalyses conversion of uric acid to allantoin, which is 5-10x more soluble than uric acid so renal excretion is more effective
22
Q
Complications of tumour lysis syndrome?
A
- hypocalcaemia
- hyperkalaemia
- hyperuricaemia
- hyperphosphataemia
- acute renal failure
(low calcium, high K, uric acid & phosphate)
23
Q
What Rx may metastatic bone pain respond to?
A
- strong opioid analgesia
- bisphosphonates
- radiotherapy
24
Q
What is beta-thalassaemia trait?
What are the features?
A
- autosomal recessive characterised by mild hypo chromic, microcytic anaemia, usually aSx
- microcytosis is characteristically disproportionate to the anaemia
- HbA2 raised >3.5%
HbA2 = variant of Hb A with 2 delta chains replacing 2 normal beta chains, is found in 1.5-3% of total Hb of healthy adults
25
What is hereditary angioedema?
autosomal dominant condition ass with low plasma levels of the C1-inhibitor protein (C1-INH)
26
What is the role of C1-INHibitor (low in hereditary angioedema)
- multifunctional serine protease inhibitor - probable mechanism is uncontrolled bradykinin release
27
Ix in hereditary angioedema?
| what is most reliable and used for screening?
- low C1-INH during an attack
- low C2 & C4, even between attacks
- LOW C4
28
Sx of hereditary angioedema?
- attacks may be preceded by painful macular rash
- painless, non-pruritic swelling of subcut/submucosal tissues
- may affect upper airways, skin or abdo organs (can present as abdo pain due to visceral oedema)
- urticaria not usually a feature
29
Acute Rx of hereditary angioedema?
- IV C1-inhibitor concentrate (FFP if not available)
30
Prophylaxis of hereditary angioedema?
anabolic steroid DANAZOL may help
31
MoA of cyclophosphamide?
| Adverse effects?
Akylating agent - causes cross-linking in DNA
- haemorrhagic cystitis
- myelosuppression
- transitional cell carcinoma
32
MoA of Bleomycin?
| Adverse effects?
Degrades preformed DNA
| - lung fibrosis
33
MoA of Doxorubicin?
| Adverse effects?
Stabilises DNA-topoisomerase II complex, inhibits DNA & RNA synthesis
- cardiomyopathy
34
MoA of Methotrexate?
| Adverse effects?
Inhibits dihydrofolate reductase & thymidylate synthesis
- mucositis
- myelosuppression
- liver fibrosis
- lung fibrosis
35
MoA of 5-FU fluorouracil?
| Adverse effects?
Pyrimidine analogue inducing cell cycle arrest & apoptosis by blocking thymidylate synthase (works during S phase)
- myelosuppression
- mucositis
- dermatitis
36
MoA of 6-mercaptopurine?
| Adverse effects?
Purine analogue that is activated by HGPRTase, decreasing purine synthesis
- myelosuppression
37
MoA of Cytarabine?
| Adverse effects?
Pyrimidine antagonist, interferes with DNA synthesis specifically at the S-phase of cell cycle & inhibits DNA polymerase
- myelosuppression
- ataxia
38
MoA of Vincristine & Vinblastine?
| Adverse effects?
Inhibits formation of microtubules
Vincristine: reverisble peripheral neuropathy, paralytic ileus
Vinblastine: myelosuppression
39
MoA of Docetaxel?
| Adverse effects?
Prevents microtubule depolymerisation & disassembly, decreasing free tubulin
- neutropenia
40
MoA of Cisplatin?
| Adverse effects?
Causes Cross-linking in DNA
- ototoxicity
- peripheral neuropathy
- hypomagnesaemia
41
MoA of Hydroxyurea/Hydroxycarbamide?
| Adverse effects?
Inhibits ribonucleotide reductase, decreasing DNA synthesis
| - myelosuppression
42
General RFs for VTE?
- increased risk with advancing age
- obesity
- pregnancy esp puerperium
- FHx VTE
- immobility
- hospitalisation
- anaesthesia
- central venous catheter: femoral >> subclavian
43
Underlying conditions which predispose to VTE?
- malignancy
- thrombophilia e.g. activated protein C resistance, protein C&S deficiency
- heart failure
- antiphospholipid syndrome
- Behcet's syndrome
- polycythaemia
- nephrotic syndrome
- sickle cell disease
- paroxysmal nocturnal haemoglobinuria
- hyperviscosity syndrome
- homocystinuria
44
Medication RFs for VTE?
- combined OCP 3rd gen > 2nd
- HRT: VTE risk higher in women taking oestrogen + progestogen preparations vs those taking oestrogen only preparations
- Raloxifene & Tamoxifen
- antipsychotics esp Olanzapine
45
Pathophysiology of VTE in pregnancy?
Hyper coagulable state, majority occur in last trimester
- increase in factors VII, VIII, X & fibrinogen, decrease in protein S
- uterus presses on IVC causing venous stasis in legs
46
Rx of VTE in pregnancy?
- warfarin contra-indicated
| - SC LMWH preferred to IV heparin (less bleeding & thrombocytopenia)
47
Pulmonary causes of eosinophilia?
- asthma
- ABPA
- Churg-Strauss
- Loffler's syndrome
- topical pulmonary eosinophilia
- eosinophilis pneumonia
- hypereosinophilic syndrome
48
Infective causes of VTE?
- schistosomiasis
- nematodes: Toxocara, Ascaris, Strongyloides
- cestodes: Echinococcus
49
Causes of eosinophilia (except for pulmonary & infective)?
- drugs: sulfasalazine, nitrofurantoin
- psoriasis/eczema
- eosinophilic leukaemia (v rare)
50
What is the Philadelphia chromosome translocation?
t(9;22)
| >95% of pts with CML
51
t(9;22) translocation
- which malignancy?
- what is the result?
- CML >95%
| - if present in ALL, it is a poor prognostic indicator
52
What does the t(9;22) translocation lead to?
- part of the Abelson porto-oncogene is moved to the BCR gene on chromosome 22
- > BCR-ABL gene codes for a fusion protein which has tyrosine kinase activity in excess of normal
53
PML & RAR-alpha gene fusion leads to which translocation?
t(15;17)
54
t(15;17) is seen in which malignancy?
APML (M3)
55
Acute promyelocytic leukaemia (M3) is ass with which translocation?
t(15;17)
56
t(8;14) translocation is ass with which malignancy?
Burkitt's lymphoma
57
Which translocation leads to MYC oncogene translocating to an immunoglobulin gene?
t(8;14)
| Burkitt's
58
t(11;14) is ass with which malignancy?
Mantle cell lymphoma
59
Which translocation leads to deregulation of the cyclin D1 (BCL-1) gene?
t(11;14)
| Mantle cell lymphoma
60
What translocation is ass with Mantle cell lymphoma?
t(11;14)
| - deregulation of t he cynic D1 (BCL-1) gene
61
The gene encoding beta-thalassaemia major is on which chromosome?
chr 11
| - absence of beta-chains
62
Features of beta-thalassaemia major:
- how does it present?
- what sort of anaemia?
- what happens to HbA, HbA2, HbF?
- presents in 1st yr of life with failure to thrive & hepatosplenomegaly
- microcytic anaemia
- HbA Absent
- HbA2 & HbF raised
63
Rx of beta-thalassaemia major?
- repeated transfusion -> Iron overload
| - SC infusion of Desferrioxamine
64
On which chromosome are the 2 separate alpha-globulin genes located on?
each chr 16
65
What is Hb H?
| When is it found?
= 4 beta chains
| - found in severe alpha thalassaemia (loss of 3/4 chains)
66
What malignancy is ass with HTLV-1 infection?
adult T cell leukaemia/lymphoma
67
What malignancy is ass with HIV-1 infection?
high grade B cell lymphoma
68
What malignancy is ass with H pylori infection?
gastric lymphoma (MALT)
69
What malignancy is ass with malaria infection?
Burkitt's lymphoma
70
What is antithrombin III deficiency?
- autosomal dominant inherited cause of thrombophilia
- antithrombin III inhibits several clotting factors inc: thrombin, factor IX & X; mediating the effects of heparin
- therefore deficiency is a heterogeneous group of disorders, leading to inc in these clotting factors
71
Features of antithrombin III deficiency?
- recurrent venous thromboses
| - arterial thromboses do occur but are uncommon
72
Rx of antithrombin III deficiency:
- if VTE?
- during pregnancy?
- during surgery/childbirth etc?
- VTE -> lifelong warfarin
- pregnancy -> heparinisation
- antithrombin III concentrates durign surgery, childbirth etc
- N.b. pts with antithrombin III deficiency have a degree of resistance to heparin, so anti-Xa levels should be monitored carefully to ensure adequate anticoagulation
73
Commonest inherited thrombophilia?
Factor V Leiden (heterozygous) 5%. VTE RR 4
(prothrombin gene mutation 1.5% RR3
protein C deficiency 0.3% RR 10
protein S deficiency 0.1% RR 5-10
antithrombin III deficiency 0.03 RR 10-20)
74
c-myc gene translocation is ass with which malignancy?
Burkitt's lymphoma
75
What is the commonest cause of antithrombin III deficiency?
CKD (antithrombin III = particularly small protein easily lost through the nephron in CKD)
76
What electrolyte disturbance does cisplatin cause?
hypomagnesaemia
77
What is polycythaemia vera?
| when does it peak?
- myeloproliferative disorder caused by clonal proliferation of a marrow stem cell -> increase in red cell volume, often accompanied by overproduction of ***neutrophils & platelets*** as well
- incidence peaks in 6th decade
78
Features of polycythaemia vera?
- hyperviscosity
- pruritus, typically after a hot bath
- splenomegaly
- haemorrhage (2ry to abnormal platelet function)
- plethoric appearance
- hypertension in a 1/3 of pts
79
What blood tests should be done when polycythaemia vera suspected?
- FBC, blood film: raised haematocrit, and neuts, basophils & platelets raised in half of pts
- serum ferritin
- U&Es, LFTs
- JAK2 mutation
(also PRV can show a low ESR and raised leukocyte ALP)
80
When suspecting polycythaemia vera but JAK2 mutation negative and no obvious 2ry cause, what tests should be done?
- red cell mass
- arterial oxygen saturation
- abdo ultrasound
- serum erythropoietin level
- BM aspirate & trephine
- cytogenetic analysis
- erythroid burst-forming unit (BFU-E) culture
81
What are the Dx criteria for polycthaemia vera (if JAK2 +ve)?
Both need to be positive:
A1: high haematocrit (>0.52 men, >0.48 women) OR raised red cell mass (>25% above predicted)
A2: JAK2 mutation
82
What are the Dx criteria for polycthaemia vera (if JAK2 -ve)
Dx requires A1+2+3+ 1 A or 2B criteria
A1 raised red cell mass>25% or raised haematocrit >0.6M >0.56F
A2 absence of JAK2 mutation
A3 no cause of 2ry erythrocytosis
A4 palpable splenomegaly
A5 presence of an acquired genetic abnormality (exc BCR-ABL) in the haemtopoietic cells
B1 thrombocytosis plts>450
B2 neutrophil leukocytosis of neuts>10 in non-smokers, >12.5 in smokers
B3 radiological evidence of splenomegaly
B4 endogenous erythroid colonies or low serum erythropoietin
83
What are the different blood transfusion complications?
- immunological: acute haemolytic, non-haemolytic febrile, allergic/anaphylaxis
- infective
- TRALI: transfusion-related acute lung injury
- fluid overload
- other: hyperkalaemia, iron overload, clotting
84
Why do non-haemolytic febrile reactions to blood transfusion occur?
- due to white blood cell HLA antibodies
| - often the result of sensitisation by previous pregnancies or transfusions
85
Why do acute haemolytic transfusion reactions occur?
Rx?
complications?
- ABO mismatch -> massive intravascular haemolysis
- Sx start within minutes, inc fever, abdo pain, chest pain, agitation, hypotension
Rx inc stop transfusion, generous IV fluid resuscitation, inform the lab
Complications inc DIC & renal failure
86
Allergic/anaphylaxis reaction to blood transfusion
- what happens & why?
- Rx?
- hypersensitivity reactions to components within the transfusion
- Sx start within minutes and range insecurity e.g. urticaria - anaphylaxis
- urticaria - stop transfusion, give antihistamine, can restart transfusion when Sx resolve
- if severe then Rx urgently by stopping transfusion, give IM adrenaline & supportive Rx, e.g. consider antihistamine, corticosteroids & bronchodilators
87
What is the transmission risk of vCJD during blood transfusion?
- v small but present absolute risk
- all donations undergo leucodepletion to reduce any vCJD infectivity present
- plasma derivatives have been fractionated from imported plasma
- blood transfusion recipients cannot donate blood
88
What is acute intermittent porphyria?
rare autosomal dominant condition caused by a defect in PORPHOBILINOGEN DEAMINASE (enzyme involved in haem biosynthesis) -> toxic accumulation of delta aminolaevulinic acid & porphobilinogen
- classically presents with abdo & neuropsych Sx in 20-40yrs, more common in females 5:1
89
Features of acute intermittent porphyria?
abdo: pain & vomiting
neuro: motor neuropathy
psych: e.g. depression
cardiac: HTN & tachycardia common
90
Dx of acute intermittent porphyria?
- classically urine turns deep red on standing
- raised urinary porphobilinogen (between attacks, more during)
- assay of red cells for porphobilinogen deaminase
- raised serum levels of delta aminolaevulinic acid & porphobilinogen
91
Absorption of vitamin B12?
- binds with intrinsic factor (secreted from parietal cells)
- active absorbed in terminal ileum
- small amount passively absorbed without being bound to intrinsic factor
- mainly used in body for red blood cell development & maintenance of nervous system (myelin)
92
Causes of vitamin B12 deficiency?
- poor diet
- pernicious anaemia
- post-gastrectomy
- terminal ileum disorders e.g. Crohn's, blind-loop
- metformin (rare)
93
Features of vitamin B12 deficiency?
- macrocytic anaemia
- sore tongue & mouth
- neuro Sx e.g. ataxia
- neuropsych Sx e.g. mood disturbances
94
Rx of vitamin B12 deficiency?
- 1mg IM hydroxocobalamin 3x/wk for 2 wks then 1x/3months if no neuro involvement
- is also deficient in folic acid it's important to treat B12 first (to avoid precipitating subacute combined degeneration of the spinal cord)
95
What is Wiskott-Aldrich syndrome?
1ry immunodeficiency due to combined B & T cell dysfunction
- X-linked recessive
- mutation in WASP gene
96
Features of Wiskott-Aldrich syndrome?
- recurrent bacterial infections e.g. chest
- eczema
- thrombocytopenia
- low IgM levels
97
What leads to a raised leucocyte ALP?
- leukaemoid reactions (left-shift of immature WBCs)
- infections
- myelofibrosis
- polycythaemia vera
- steroids, Cushing's
- pregnancy, OCP
98
What leads to a low leucocyte ALP?
- CML
- pernicious anaemia
- infectious mononucleosis
- paroxysmal nocturnal haemoglobinuria
99
RFs for development of nausea & vomiting after chemo (although common)?
- age<50
- anxiety
- concurrent use of opioids
- type of chemo used
100
Rx for chemo-related nausea & vomiting?
Low-risk: metoclopramide
| If high-risk: 5HT3 receptor antagonists e.g. ondansetron are effective, esp if combined with dexamethasone
101
MoA of Aprepitant
Antiemetic which blocks the neurokinin 1 receptor - a substance P antagonist
- licensed for chemo-induced nausea & vomiting & for prevention of post-op nausea & vomiting
102
Infective causes of generalised lymphadenopathy?
- infectious mono
- HIV inc seroconversion
- eczema with 2ry infection
- rubella
- toxoplasmosis
- CMV
- TB
- roseola infantum
103
Neoplastic causes of generalised lymphadenopathy?
- leukaemia, lymphoma
104
Non-infective/neoplastic causes of generalised lymphadenopathy?
autoimmune - SLE, RA
graft vs host disease
sarcoid
- drugs: phenytoin, also allopurinol, isoniazid
105
What is antiphospholipid syndrome?
Acquired disorder of predisposition to venous & arterial thromboses, recurrent fetal loss & thrombocytopenia
- can be 1ry or 2ry e.g. SLE
106
Complications of antiphospholipid syndrome in pregnancy?
- recurrent miscarriage (aPL is present in 15% of women with recurrent miscarriage)
- IUGR
- pre-eclampsia
- placental abruption
- pre-term delivery
- VTE
107
Rx of antiphospholipid syndrome in pregnancy?
- Start Aspirin 75mg when pregnancy confirmed (urine)
- Start LMWH after fetal heart on US -discontinue at 34wks
- increases live birth rate 7X
108
5 types of sickle cell crises?
- thrombotic, painful
- sequestration
- acute chest
- aplastic
- haemolytic
109
Cause of thrombotic sickle cell crisis?
- precipitated by infection, dehydration, deoxygenation
- painful/vaso-occlusive crises
- infarcts occur in various organs inc bones (e.g. AVN hip, hand-foot syndrome in children, lungs, spleen, brain)
110
What happens in a sequestration sickle cell crisis?
- sickling within organs e.g. spleen/lungs causes pooling of blood with worsening of anaemia
- sickling causes spleen to enlarge causing also pain
- more common in early childhood as repeated sequestration & infarction of spleen gradually leads to an auto-splenectomy
- may lead to severe anaemia, marked pallor & cardiovascular collapse due to loss of effective circulating volume
111
What happens in a acute chest sickle cell crisis?
- dyspnoea, chest pain, pulmonary infiltrates, low PO2
- commonest cause of death after childhood
- 'fever +/- resp Sx, + new pulmonary infiltrates on CXR'
112
What happens in a aplastic sickle cell crisis?
- parvovirus infection
| - sudden fall in Hb
113
What happens in a haemolytic sickle cell crisis?
- fall in Hb due to an increased rate of homeless (rare)
114
Features of SVC obstruction?
- dyspnoea (commonest Sx)
- swelling of face, neck, arms, sometimes conjunctival & periorbital oedema
- headache: often worse in mornings
- visual disturbance
- pulseless jugular venous distension
115
Causes of SVC obstruction?
common malignancies inc: NSCLC, lymphoma
other: metastatic seminoma, Kaposi's sarcoma, breast ca
Also: aortic aneurysm, mediastinal fibrosis, goitre, SVC thrombosis
116
Rx of SVC obstruction?
General: Dexamethason, balloon venoplasty, stenting
Small cell: chemo + RT
Non-small: RT
117
What is Hodgkin's lymphoma?
| Age distribution?
Malignant proliferation of lymphocytes characterised by the presence of Reed-Sternberg cell
- Bimodal in 3rd & 7th decades
118
What Sx imply poor prognosis in Hodgkin's lymphoma?
B Sx
- weight loss >10% in 6months
- fever >38C
- night sweats
119
Histological type of Hodgkin's lymphoma - commonest? What cells are ass?
Nodular sclerosing 70%
- ass with lacunar cells
- good prognosis, more common in women
120
Histological type of Hodgkin's lymphoma - 2nd commonest? What cells are ass?
Mixed cellularity 20%
- ass with large number of Reed-Sternberg cells
- good prognosis
121
Histological type of Hodgkin's lymphoma - best prognosis?
Lymphocyte predominant 5%
122
Histological type of Hodgkin's lymphoma - worst prognosis?
Lymphocyte depleted (rare)
123
Factors other than B Sx ass with poor prognosis in Hodgkin's lymphoma?
```
age>45
stage IV disease
Hb <10.5
lymphocyte <600 or <8%
male
albumin <40
WCC >15,000
```
124
What is idiopathic thrombocytopenia purpura?
Immune-mediated reduction in platelet count with Ab against the glycoprotein IIb-IIIa or Ib complex
125
Ix in ITP?
what is on BM aspirate?
why should it be done before starting Rx?
Antiplatelet autoAb (usually IgG)
- megakaryocytes in the marrow
- do BM aspirate before steroids to rule out leukaemia
126
Rx of ITP?
- Oral Prednisolone (80% respond)
- Splenectomy if plts<30 after 3months steroids
- IV immunoglobulins
- immunosuppressive drugs e.g. cyclophosphamide
127
Features of a 2-level DVT Wells score?
Active cancer with Rx within 6m/palliative 1
Paralysis, paresis/recent plaster immobilisation of lower extremities 1
Recently bedridden for 3days+ or major surgery within 12wks 1
Localised tenderness along distribution of deep venous system 1
Entire leg swollen 1
Calf swelling at least 3cm >aSx side 1
Pitting oedema confined to Sx leg 1
Collateral superficial veins (non-varicose) 1
Prev doc DVT 1
Alternatuve Dx at least as likely as DVT -2
DVT likely if 2+
128
What to do if DVT likely i.e. 2level Wells score 2+?
- US proximal leg veeins within 4h (if negative do a D-dimer)
- do D-dimer if can't have US legs within 4h, and give LMWH whilst waiting (which should be done within 24h)
129
What to do if DVT unlikely i.e. 2level Wells score <2?
- D-dimer
- if +ve then proximal leg vein US within 4h
- if can't be done then give LMWH whilst waiting
130
Rx of DVT?
LMWH/Fondaparinux at Dx - continue at least 5 days or more until INR is >2 for at least 24h
- warfarin within 24h, cont at least 3months - extend if unprovoked
131
Rx of DVT in active cancer?
LMWH 6 months
132
What Ix do people who have an unprovoked DVT/PE need?
| What if they are aged >40?
- Hx & full Ex
- CXR
- urinalysis
- bloods to inc FBC, LFTs, calcium
- CT abdo-pelvis
133
When to consider thrombophilia testing?
- consider testing for antiphospholipid Abs if unprovoked DVT/PE?
- consider testing hereditary thrombophilia if someone has an unprovoked DVT/PE, and they have a 1st degree relative who has had a DVT/PE
134
What are the different types of tumour markers?
- mAbs against carbohydrate/glycoprotein tumour Ags
- tumour Ags
- enzymes e.g. ALP, neurone specific enolase
- hormones e.g. calcitonin, ADH
135
What malignancies are AFP ass with?
hepaticellular carcinoma
| teratoma
136
What malignancies are S-100 ass with?
melanoma
| schwannomas
137
What malignancies are bombesin ass with?
SCLC
gastric ca
neuroblastoma
138
What is multiple myeloma?
Neoplasm of bone marrow plasma cells
| peak incidence age 60-70
139
Clinical features of myeloma?
- bone disease: bone pain, osteoporosis + path fractures (typically vertebral), osteolytic lesions
- lethargy
- infection
- hypercalcaemia
- renal failure
- others: amyloid e.g. macroglossia, carpal tunnel, neuropathy, hyperviscosity, high total protein
140
Ix for myeloma:
- what is in serum & urine?
- what is in bone marrow?
- what is done to look at bone?
- what may be seen on X-ray?
- monoclonal proteins IgG/IgA, Bence-Jones in urine
- increased plasma cells in bone marrow
- historically a skeletal survey, but now whole-body MRI
- Xray: 'rain-drop skull' (pepper pot is different)
141
What are the Dx criteria for multiple myeloma?
- requires 1 major + 1m
- or 3minor
in someone with signs/Sx
Major:
1. plasmacytoma (Bx)
2. 30% plasma cells in BM
3. elevated M protein levels in blood/urine
Minor:
1. 10-30% plasma cells in a BM sample
2. minor elevations in M protein in blood/urine
3. osteolytic lesions (on imaging)
4. low levels of Abs (not produced by cancer cells) in blood
142
What is the 1ry factor that leads to hypercalcaemia in myeloma?
what are other much less contributing factors?
***Increased osteoclastic bone resorption caused by local cytokines released by myeloma cells*** e.g. IL-1, TNF
Others inc: impaired renal function, increased renal tubular Ca reabsorption, elevated PTH-rP levels
143
Palliative care prescribing: agitation & confusion
- 1st line drug?
- other options?
- palliative end-stage?
Haloperidol
others: chlorpromazine, levomepromazine
Palliative: midazolam
144
Genetics of haemophilia?
X-linked recessive disorder of coagulation
- upto 30% have no FHx
- A is deficiency of factor VIII
- B is lack of factor IX
145
Features of haemophilia?
- haemoarthroses, haematomas
| - prolonged bleeding after surgery/trauma
146
Blood tests in haemophilia?
```
Prolonged APTT
(normal bleeding, thrombin & PT time)
```
147
What is the commonest tumour of the anterior mediastinum?
Thymomas
| - usually detected between 6th & 7th decades
148
Associations of thymomas?
| What are the causes of death?
- myasthenia gravis 30-40%
- red cell aplasia
- dermatomyositis
- also: SLE, SIADH
- airway compression, cardiac tamponade
149
What is ITP: immune thrombocytopenia?
Immune-mediated reduction in platelet count
| - Abs directed against the glycoprotein IIb/IIIa or Ib-V-IX complex
150
Acute ITP:
who is it more commonly seen in?
when may it occur?
course?
Children, M=F
May follow infection/vaccination
- usually self limiting course over 1-2wks
151
Chronic ITP:
who is it more commonly seen in?
course?
- young/middle-aged women
| - relapsing-remitting course
152
What is Evan's syndrome? (think ITP)
ITP in ass with autoimmune haemolytic anaemia
153
Features of spinal cord compression?
- Back pain, may be worse lying down & coughing (earliest & commonest Sx)
- LL weakness
- Sensory changes: loss & numbness
- Neuro signs depending on level of the lesion (Above L1 = UMN legs with sensory level, below L1 = LMN signs in legs with perianal numbness with tendon reflexes increased below the level and absent at the level)
154
Rx of spinal cord compression?
High-dose oral dexamethasone
Urgent MRI
Urgent onc assessment for consideration of RT/surgery
155
Spinal cord compression - who does it affect?
Onc emergency, 5% of cancer pts
Extradural compression e.g. due to vertebral body mets is commonest
Also lung, breast, prostate common
156
PET scan:
- what is the radio tracer?
- what does it demonstrate?
- what are its uses?
- FDG = fluorodeoxyglucose
- glucose uptake shows 3d image of metabolic activity, which is combined with e.g. CT
- helps evaluate 1ry & possible metastatic disease
- cardiac PET not used mainstream currently
157
AIHA: autoimmune haemolytic anaemia
- what is it characterised by?
- causes?
Positive DAT: direct antiglobulin Coombs test
- most commonly idiopathic
- but also infection, drugs, lymphoproliferative etc
158
What is Warm AIHA?
where does intent to occur?
Rx?
IgG causes haemolysis best at body temp
- Extravascular sites e.g. spleen
- Steroids, immunosuppression, splenectomy
159
Causes of warm AIHA?
Autoimmune: SLE
Neoplasia e.g. lymphoma, CLL
Drugs e.g. Methyldopa
160
What is Cold AIHA?
where does intent to occur?
Rx?
IgM causes haemolysis best at 4 deg C - features may inc Sx of Raynaud's 7 acrocyanosis
- mediated by complement and more commonly intravascular
- pts respond less well to steroids
161
Causes of Cold AIHA?
Neoplasia e.g. lymphoma
| Infection e.g. mycoplasma, EBV
162
What is Meig's syndrome?
Ovarian fibroma ass with pleural effusion & ascites
163
Causes of a megaloblastic macrocytic anaemia?
B12 deficiency
| folate deficiency
164
Causes of a normoblastic macrocytic anaemia?
- etoh, liver disease
- reticulocytosis
- myelodysplasia
- pregnancy
- hypothyroidism
- drugs e.g. cytotoxic
165
When does acute myeloid leukaemia occur?
1ry disease or
2ry transformation of a myeloproliferative disorder
- more common over age 45
166
Features of AML?
```
(BM failure)
Anaemia: pallor, lethargy, weakness
Neutropenia: WCC can be v high but functioning neutrophils low, leading to frequent infections etc
Thrombocytopenia: bleeding
Also: bone pain, splenomegaly
```
167
3 poor prognostic features of AML?
>60yrs
>20% blasts after 1st course of chemo
cytogenetics: deletions of chromosome 5 or 7
168
Acute promyelocytic leukaemia M3
- what translocation is it associated with & what does it lead to?
- when does it present?
- what is seen with myeloperoxidase stain?
- what is often seen on bloods at presentation?
- t(15;17) -> fusion of PML & RAR-alpha genes
- younger, average age 25yrs
- AUER RODS
- - DIC or thrombocytopenia
- good prognosis
169
What is the FAB classification of AML?
| M0 - M7
```
M0 undifferentiated
M1 without maturation
M2 with granulocytic maturation
M3 ACUTE PROMYELOCYTIC
M4 granulocytic & monocytic maturation
M5 monocytic
M6 erytholeukaemia
M7 megakaryoblastic
```
170
What happens to Hb after intravascular haemolysis?
Intravascular haemolysis -> free Hb released -> binds to haptoglobin -> haptoglobin becomes saturated
- > so other free Hb binds to albumin -> methaemalbumin (detected by Schumm's test)
- > free Hb excreted in urine as Hburia & haemosiderinuria
171
Causes of intravascular haemolysis?
- red cell fragmentation: heart valves, TTP, DIC, HUS
- paroxysmal nocturnal haemoglobinuria
- G6PD deficiency
- Cold AIHA
172
Causes of extravascular haemolysis?
- Hbopathies: sickle cell, thalassaemia
- Hereditary spherocytosis
- Haemolytic disease of newborn
- Hot (warm) AIHA
173
What is the commonest inherited thrombophilia in Europeans?
Factor V Leiden
174
What does factor V leiden disease effective mean?
= Activated protein C resistance
175
What is the genetics of factor V leiden?
Gain of function mutation in the factor V leiden protein -> mis-sense mutation
-> activated factor V (a clotting factor) is inactivated 10X more slowly by activated protein C than normal
= activated protein c resistance
- heterozygotes 5% 4-5x inc risk of venous thrombosis
- homozygotes 10x inc risk but prevalence 0.05%
176
What is the most useful marker of prognosis in myeloma?
B2 microglobulin
177
What is the international prognostic index stages for myeloma?
stage I 62median months survival:
B2 micro globulin <3.5
Albumin >35
stage II 45 months: not I/III
Stage III 28months: B2 micro globulin >5.5
178
What is the tumour marker most associated with primary peritoneal cancer
CA-125
179
What is thrombocytosis?
| What are the causes?
Abnormally high platelets, usually >400
1. Reactive: acute phase reactant
2. Essential, or as part of another myeloproliferative disorder e.g. CML, PRV
3. Malignancy
4. Hyposplenism
180
What is essential thrombocytosis?
Where megakaryocytic proliferation results in an overproduction of platelets
- myeloproliferative disorder, overlapping with CML, PRV, myelofibrosis
181
Features of essential thrombocytosis?
Platelets >600
JAK2 mutation +ve in 50%
Both venous/arterial thrombosis & haemorrhage can be seen
Characteristic Sx = burning sensation in hands
182
Rx of essential thrombocytosis:
what is widely used?
what can be used in younger pts?
what may be used to reduce thrombotic risk?
HYDROXYUREA/HYDROXYCARBAMIDE widely used to reduce platelet count
INTERFERON-alpha in younger
Low-dose aspirin
183
```
66y.o. woman referred by GP with anaemia, feeling gen unwell for past 3 wks.
Bloods show:
Hb 8.7
MCV 87
Plt 198
WBC 5.3
Further tests:
Reticulocytes 5.2%
DAT positive, IgG only
Film - spherocytes, reticulocytes
```
Non-Hodgkin's lymphoma
- warm haemolytic anaemia
- ( no suggestion of autoimmune disease, CLL or methyldopa)
184
What is neutropenic sepsis defined as?
When does it occur?
What are the commonest pathogens?
Neuts < 0.5 in someone with anticancer Rx +
- temp >38C
- or other signs/Sx consistent with clin significant sepsis
Most commonly occurs 7-14days after chemo
Gram-positive organisms, most frequently staph epidermidis
185
Prophylaxis of neutropenic sepsis?
a FLUOROQUINOLONE, if anticipated
186
Rx of neutropenic sepsis?
Abx immediately if suspected (don't wait for FBC)
- Tazocin +/- vancomycin
- if still febrile/unwell after 48h then alternative Abx e.g. Meropenem +/- vancomycin
- if not responding after 4-6days, consider Ix for fungal infections e.g. HRCT -> start AMPHOTERICIN B empirically
- may be a role for G-CSF in selected pts
187
What is MGUS: Monoclonal gammopathy of undetermined significance?
What are the features?
= benign paraproteinaemia & monoclonal gammopathy
- usually aSx
- no bone pain/increased risk of infections
- ***10-30% have a demyelinating neuropathy***
188
Differentiating features of MGUS from myeloma?
- normal immune function
- normal beta-2 micro globulin levels
- lower level of paraproteinaemia than myeloma (<30 IgG, <20 IgA)
- stable level of paraproteinaemia
- no clinical features of myeloma e.g. lytic lesions on X-ray, renal disease etc
189
What are the features of Hodgkin's lymphoma?
- lymphadenopathy 75% - painless, non-tender, asymmetrical
- systemic 25% - weight loss, pruritus, night sweats, fever (Pel-Ebstein)
- etoh pain in HL
- normocytic anaemia, eosinophilia
- raised LDH
- patchy BM infiltration
190
What is the Ann-Arbor staging of Hodgkin's lymphoma?
| How to subdivide each stage to A/B?
I single LN
II 2+ LNs/regions on same side of diaphragm
III nodes on both sides of diaphragm
IV spread beyond LNs
```
A = no systemic Sx except pruritus
B = weight loss>10% in last 6m, fever>38C, night sweats (poor prognosis)
```
191
What is ALL?
Malignancy of lymphoid progenitor cells affecting B/T cell lineage -> arresting of lymphoid cell maturation & proliferation of immature lymphoblast cells -> BM & tissue infiltration
- commonest childhood cancer, peaks age 2-5yrs
- 80% of childhood leukaemia
192
What are the good prognostic indicators in ALL?
- FAB L1 type
- common ALL
- pre-B phenotype, precursol B-ALL
- low initial WBC
- del(9p)
- trisomy 4, 10, 17
- t(12;21) & t(1;19) translocation
193
What are the poor prognostic indicators in ALL?
- FAB L3 type
- T/B cell surface markers
- Philadelphia translocation t(9;22)
- age<2 or >10yrs
- male sex
- CNS involvement
- high initial WBC >100
- non-Caucasian
- hyPOdiploid
194
What is the management of aplastic anaemia?
Supportive:
- blood products
- prevention & Rx of infection
ATG & ALG (anti-thymocyte globulin & anti-lymphocyte globulin)
Stem cell Tx
- allogeneic Tx have 80% success rate
195
ATG & ALG (anti-thymocyte globulin & anti-lymphocyte globulin) for aplastic anaemia Rx:
- how is it prepared?
- what else if given with it?
- inject human lymphocytes in animals
- highly allergenic, may cause serum sickness with fever, rash, arthralgia etc -> STEROID cover given
- other immunosuppressants may also be given e.g. ciclosporin
196
Conditions ass with Target cells?
- sickle cell, thalassaemia
- IDA
- hyposplenism
- liver disease
197
Conditions ass with Tear-drop poikilocytes?
myelofibrosis
198
Conditions ass with spherocytes (round, lack of central pallor)?
- hereditary spherocytosis
| - AIHA
199
Conditions ass with basophilic stippling?
- thalassaemia
- sideroblastic anaemia (BM produces ringed sideroblasts instead of healthy erythrocytes)
- myelodysplasia
- lead poisoning
200
Conditions ass with Howell-Jolly bodies?
hyposplenism
201
Conditions ass with Heinz bodies?
- G6PD deficiency
| - Alpha-thalassaemia
202
Conditions ass with schistocytes (helmet cells)?
- intravascular haemolysis
- mechanical heart valve
- DIC
203
Conditions ass with pencil poikilocytes?
iron-deficiency anaemia
204
Conditions ass with Burr cells (echinocytes)?
- uraemia
| - pyruvate kinase deficiency
205
Conditions ass with acanthocytes?
abetalipoproteinaemia
206
Conditions ass with hypersegmented neutrophils?
megaloblastic anaemia
207
Blood film in hyposplenism?
- target cells
- Howell-Jolly bodies
- Pappenheimer bodies
- siderotic granules
- acanthocytes
208
Blood film in IDA?
- target cells
- pencil poikilocytes
- dimorphic film of mixed microcytic & microcytic cells if combined with B12/folate deficiency
209
What are the 3 indication of blood product that is CMV-negative & irradiated?
- granulocyte transfusions
- intra-uterine transfusions
- neonates upto 28days post-expected delivery date
210
What is the 1 indication for CMV negative (but not irradiated) blood product?
pregnancy: elective transfusions during pregnancy (not during labour/delivery)
211
What are the 3 indications for irradiated (but not CMV-negative) blood product?
- BM/stem cell Tx
- immunocompromised e.g. chemo.congenital
- pts with prev Hodgkin's disease
212
How is CMV transmitted in blood products?
- via leukocytes
- as most blood products (except granulocyte transfusions) are now leucocyte-depleted, CMV-negative products are rarely required
213
Why are irradiated blood products sometimes needed?
- To avoid transfusion graft vs host disease, caused by engraftment of viable donor T lymphocytes
214
FFP: fresh frozen plasma (150-220ml):
- when is it needed?
- when may it be used prophylactically?
- what is the universal donor?
- when PT or APTT > 1.5 and clinically significant without major haemorrhage
- prophylaxis if invasive surgery with risk of significant bleeding
- universal donor = AB blood (lacks any anti-A or anti-B Abs)
215
What does cryoprecipitate contain?
when is it suited?
when may it be used prophylactically?
15-20ml of: conc factor VIIIc, von willebrand factor, fibrinogen, factor XIII & fibronectin, produced by further processing of FFP
- clinically most commonly used to replace fibrinogen
- most suited if fibrinogen concentration <1.5 in clinically significant without major haemorrhage
- e.g. DIC, life failure, low fibrinogen 2ry to massive transfusion, emergency situation for haemophiliacs or von willebrand disease
- prophylaxis if invasive surgery with risk of significant bleed with fibrinogen <1.0
216
When is PCC: prothrombin complex concentrate used?
- emergency reversal of anticoagulation in severe bleed or head injury with suspected intracerebral haemorrhage
- prophylaxis in emergency surgery depending on circumstance
217
What is IgG4-related disease?
- raised IgG4 conc in tissue & serum, can be in any organ system of diverse organ manifestations linked by similar histopathological characteristics
- e.g. Riedel's thyroiditis, AI pancreatitis, mediastainl/retroperitoneal fibrosis, periaortitis/periarterities/inflammatory aortic aneurysm, Kuttner's tumour of submandibular glands, Mikulicz syndrome of salivary&lacrimal glands, maybe sjogrens & PBC
218
What is the commonest inherited bleeding disorder?
| inheritance?
Von Willebrand's disease
- majority autosomal dominant
- characteristically behaves like a platelet disorder i.e. epistaxis & menorrhagia more common (haemarthroses & muscle haematomas rare)
219
What are the 3 types of von Willebrand disease?
1: partial reduction in vWF (80%)
2: abnormal form of vWF
3: total lack of vWF (autosomal recessive)
220
What is the role of von WIllebrand factor?
- large glycoprotein forming massive multimers unto 1,000,000 Da in size
- promotes platelet adhesion to damaged endothelium
- carrier molecule for factor VIII
221
Ix of von Willebrand disease?
- what is prolonged
- what may be reduced
- when is platelet aggregation defective
PROLONGED BLEEDING TIME
- APTT may be prolonged
- factor VIII may be mod reduced
- defective platelet aggregation with ristocetin
222
Rx of von Willebrand disease?
- Transexamic acid for mild bleeding
- DDAVP: desmopressin raises levels of vWF by inducing vWF release from Weibel-palade bodies in endothelial cells
- Factor VIII concentrate
223
Man with type 1 von WIllebrand's disease due to have tooth extracted at dentist next wk - what is most appropriate Rx to reduce risk of bleeding?
Desmopressin
224
What is the most common hereditary haemolytic anaemia in people of northern European descent?
hereditary spherocytosis
225
What is hereditary spherocytosis?
autosomal dominant defect of red blood cell cytoskeleton
- normal biconcave disc replaced by sphere-shaped RBC
- leads to reduced RBC survival as it is destroyed by the spleen
226
What is the presentation & features of hereditary spherocytosis?
- failure to thrive, neonatal jaundice
- gallstones. splenomegaly common
- aplastic crisis precipitated by parvovirus
- degree of haemolysis is variable - can be precipitated by infection
- elevated MCHC
227
How to Dx hereditary spherocytosis?
If Dx equivocal?
If atypical presentation
What was prev recommended Ix?
- FHx, typical clinical features, lab Ix of spherocytes, raised MCHC, raised reticulocytes then additional tests not required
- If equivocal then do cryohaemolysis test & EMA binding
- if atypical then electrophoresis analysis of erythrocyte membranes is method of choice
- used to be osmotic fragility test but it is unreliable
228
Rx of hereditary spherocytosis?
- folate replacement
| - splenectomy
229
What are the most common types of transformations seen in patients with polycythaemia vera?
Myelofibrosis + AML (5-15% progress to either, risk of acute leukaemia increased with chemo Rx)
230
What is the most significant cause of morbidity & mortality in polycythaemia?
thrombosis
231
Rx of polycythaemia vera?
Aspirin
Venesection 1st line Rx
Hydroxyurea = slight inc risk of 2ry leukaemia
Phosphorus-32 therapy
232
What is sideroblastic anaemia?
Where red cells fail to completely form haem (where biosynthesis takes place partly in mitochondria)
- > iron deposits in mitochondria that form a ring around the nucleus (ring sideroblast)
- congenital/acquired
233
What is the congenital cause of sideroblastic anaemia?
| What are the acquired causes?
Delta-aminolevulinate synthase-2 deficiency
- myelodysplasia
- etoh
- lead
- anti-TB meds
234
Ix of sideroblastic anaemia ?
- hypochromic microcytic anaemia
| - BM: sideroblasts & increased iron stores
235
Rx of sideroblastic anaemia ?
supportive, Rx underlying causes
| PYRIDOXINE may help
236
Which stain should be applied to a blood film when you suspect sideroblastic anaemia?
Perl's stain - shows ring sideroblasts
237
What is the pathogenesis of TTP: thrombotic thrombocytopenia purpura?
- abnormally large & sticky multimers of vWF cause platelets to clump within vessels
- deficiency of ADAMTS13 (metalloprotease enzyme) which breaks down large multimers of vWF
- overlaps with haemolytic uraemia syndrome
238
Features of TTP?
- rare, typically adult females
- fever
- fluctuating neuro signs (micro emboli)
- thrombocytopenia
- MAHA: microangiopathic haemolytic anaemia
- renal failure
239
Causes of TTP?
- post-infective e.g. urine, GI
- pregnancy
- tumours
- SLE
- HIV
- drugs: ciclosporin, OCP, penicillin, clopidogrel, aciclovir
240
What is the commonest red blood cell enzyme defect? What is the inheritance?
G6PD deficiency
- commoner in Mediterranean & African
- X-linked recessive (only affects males)
241
What is the pathophysiology of G6PD deficiency?
Reduced G6PD -> reduced glutathione -> increased red cell susceptibility to oxidative stress
242
Features of G6PD deficiency?
- neonatal jaundice
- intravascular haemolysis
- gallstones comon
- splenomegaly may be present
- Heinz bodies on film
243
Dx of G6PD deficiency?
G6PD enzyme assay
244
Precipitants of G6PD deficiency?
```
Broad (fava) bands
Drugs:
- anti-malarial PRIMAQUINE
- Ciprofloxacin
- Sulph drugs - sulphonamides, sulphasalazine, sulfonylureas
```
245
Features of lead poisoning?
- abdo pain, fatigue, constipation
- peripheral neuropathy (motor)
- blue lines gum margin (20% adults, v rare children)
246
```
Ix of lead poisoning:
serum lead level?
FBC?
blood film?
others?
urine?
```
- blood lead level >10 significant
- microcytic anaemia
- basophilic stippling & clover-leaf morphology on film
- raised serum & urine delta aminolaevulininc acid (makes it difficult to differentiate with acute intermittent porphyria)
- raised urinary coproporphyrin
247
Rx of lead poisoning?
```
Chelating agents e.g.
DMSA dimercaptosuccininc acid
D-penicillamine
EDTA
dimercaprol
```
248
What is Waldenstrom's Macroglobulinaemia?
Lymphoplasmacytoid malignancy characterised by the secretion of a monoclonal IgM paraprotein
- uncommon, seen in older men
249
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
(think organomegaly e.g. spleen, with NO bone lesions)
250
Features of iron deficiency anaemia?
koilonychia
atrophic glossitis
angular stomatitis
post-cricoid webs
251
Rx of hiccups in palliative care?
Chlorpromazine
| - haloperidol, gabapentin also used, dexamethasone if hepatic lesions
252
What is hairy cell leukaemia?
Rare malignant proliferation disorder of B cells, more common in males 4:1
253
Features of hairy cell leukaemia?
- pancytopenia, splenomegaly
- skin vasculitis in 1/3
- 'dry tap' despite BM hypercellularity
- TRAP stain +ve (tartrate resistant acid phosphotase)
254
Rx of hairy cell leukaemia?
1st line Chemo: cladribine, pentostatin
2nd line Immunotherapy: rituximab, IFN-alpha
- splenectomy sometimes required
255
What is IFN-alpha useful for?
- produced by leukocytes, with antiviral action
| - hep B, hep C, Kaposi's sarcoma, metastatic RCC, hairy cell leukaemia
256
What is the philadelphia chromosome?
translocation between long arm of chr 9 & 22 t(9;22)(q34;q11)
- > part of ABL proto-oncogene from chr 9 fused with BCR gene from chr 22
- > resulting BCR-ABL gene codes for a fusion protein which has XS tyrosine kinase activity
257
Presentation of CML?
60-70yrs
- anaemia - lethargy
- weight loss & sweating common
- splenomegaly may be massive - abdo discomfort
- spectrum of myeloid cells in peripheral blood
- decreased leukocyte ALP
- may undergo blast transformation (AML 80% ALL 20%)
258
Rx of CML?
IMATINIB 1st line
- hydroxyurea
- IFN-alpha
- allogenic BM Tx
259
MoA of Imatinib?
- inhibitor of tyrosine kinase ass with the BCR-ABL defect
| - v high response rate in chronic phase CML
260
What cancers may show raised bombesin?
SCLC
gastric ca
retinoblastoma/neuroblastoma
261
A petechial skin rash combined with a slightly elevated APTT and reduced factor VIII activity - most likely Dx?
von Willebrand's disease
262
What is CLL?
monoclonal proliferation of well-differentiated lymphocytes, which are almost always B cells 99%
- commonest leukaemia in adults
263
Features of CLL?
- often none
- bleeding, infections
- anorexia, weight loss
- lymphadenopathy more marked than CML
264
Complications of CLL?
- anaemia
- hypogammaglobulinaemia -> recurrent ifnections
- WARM AIHA in 10-15%
- transformation to high-grade lymphoma (Richter's transformation)
265
Ix for CLL?
Smudge cells on film
| Immunophenotyping = Dx Ix of choice!!
266
What leads to recurrent infections in CLL?
hypogammaglobulinaemia
267
Relative causes of polycythaemia?
- dehydration
| - stress: Gaisbock syndrome
268
2ry causes of polycythaemia?
COPD
altitude
OSA
XS erythropoietin: cerebellar haemangioma, hypernephroma, hepatoma, uterine fibroids
269
How to differentiate between true (1ry/2ry) polycythaemia with relative polycythaemia?
Red cell mass studies,
| In true polycythaemia total red cell mass >35 in males, >32 in females
270
How can 1ry immunodeficiency disorders be classified?
According to component of immune system they affect
- neutrophils
- B cells
- T cells
- Combined B & T cell disorders
271
What are the main neutrophil 1ry immunodeficiency disorders?
- chronic granulomatous disease
- Chediak-Higashi syndrome
- Leukocyte adhesion deficiency
272
What are the main B cell 1ry immunodeficiency disorders?
- common variable immunodeficiency
- Bruton's (x-linked) congenital agammaglobulinaemia
- Selective IgA deficiency
273
What are the main T cell 1ry immunodeficiency disorders?
DiGeorge syndrome
274
What are the main combined B & T cell 1ry immunodeficiency disorders?
- severe combined immunodeficiency
- ataxic telangiectasia
- Wiskott-Aldrich syndrome
275
What is the underlying defect in chronic granulomatous disease?
Lack of NADPH oxidase reduces ability of phagocytes to produce reactive oxygen species
- rec pneumonias & abscesses esp catalase-positive bacteria & fungi
- negative nitroblue-tetrazolium test
- abnormal dihydrorhodamine flow cytometry test
276
What is the underlying defect in Chediak-Higashi syndrome?
Microtubule polymerisation defect which leads to a decrease in phagocytosis
- affected children have partial albinism & peripheral neuropathy
- rec bacterial infections
- giant granules in neutrophils & platelets
277
What is the underlying defect in Leukocyte adhesion deficiency?
Defect in LFA-1 integrin (CD18) protein on neutrophils
- rec bacterial infections
- delay in umbilical cord sloughing may be seen
- absence of neutrophils/pus at sites of infection
278
What is the underlying defect in common variable immunodeficiency?
Many varying causes, Nb is a B cell disorder
- hypogammaglobulinaemia is seen
- may predispose to autoimmune disorders & lymphoma
279
What is the underlying defect in Bruton's x-linked congenital agammaglobulinaemia?
Defect in Bruton's tyrosine kinase (BTK) gene that leads to a severe block in B cell development
- X-linked recessive
- rec bacterial infections
- absence of B cells with reduced Igs of all cases
280
What is the underlying defect in selective IgA deficiency?
Maturation defect in B cells
- commonest 1ry Ab deficiency
- rec sinus & resp infections
- ass with coeliac disease, may cause false negative coeliac Ab screen
- severe reactions to blood transfusions may occur (anti-IgA Abs -> anaphylaxis)
281
What is the underlying defect in DiGeorge syndrome?
22q11. 2 deletion -> failure to develop 3rd & 4th pharyngeal pouches (T cell disorder)
- congenital heart disease, LDs, hypocalcaemia, rec viral/fungal diseases, cleft palate
282
What is the underlying defect in severe combined immunodeficiency?
Many varying causes, commonest = X-linked, due to defect in common gamma chain (protein used in IL-2 receptors etc). Other causes inc adenosine deaminase deficiency
- rec infections due to viruses, bacteria, fungi
- reduced Tcell receptor excision circles
- stem cell Tx may be successful
283
What is the underlying defect in ataxic telangiectasia?
Defect in DNA repair enzymes
- autosomal recessive
- cerebellar ataxia, telangiectasia, rec chest infections & 10% risk of developing malignancy, lymphoma/leukaemia
- combined B & T cell disorder
284
What is the underlying defect in Wiskott-Aldrich syndrome?
Defect in WASP gene
- -linked recessive
- rec bacterial infections, eczema, thrombocytopenia
- low IgM levels
- inc risk of autoimmune disorders & malignancy
285
Commonest tumours causing bone metastases?
prostate
breast
lung
286
Commonest sites of bone metastases?
```
Vertebrae
pelvis
ribs
skull
long bones
```
287
Features of bone metastases?
bone pain
pathological fractures
hypercalcaemia
raised ALP
288
Breast cancer RFs?
- BRCA1, BRCA2 - 40% lifetime risk of breast/ovarian
- 1st degree relative breast ca Dx when premenopausal
- nulliparity, 1st pregnancy>30yrs
- early menarche, late menopause
- combined HRT, cocp
- past breast ca
- not breastfeeding
- ionising radiation
- p53 gene mutations
- obesity
- prev surgery for benign disease
289
Carcinogen Aflatoxin (produced by aspergillum) for what cancer?
liver - HCC
290
Carcinogen aniline dyes for what cancer?
bladder TCC
291
Carcinogen asbestos for what cancer?
mesothelioma
| bronchial ca
292
Carcinogen nitrosamines for what cancer?
oesophageal
| gastric
293
Carcinogen vinyl chloride for what cancer?
hepatic angiosarcoma
294
Whats the biggest RF for cervical cancer? which subtypes?
HPV
| 16, 18, 33
295
What are koilocytes in cervical cancer?
Infected endocervical cells that undergo changes, leading to:
- enlarged nucleus
- irregular nuclear membrane contour
- nucleus stains darker than normal (hyperchromasia)
- perinuclear halo may be seen
296
Poor prognostic factors in CLL?
```
male
age >70
lymphocyte >50
prolymphocytes >10% blood lymphocytes
lymphocyte doubling time <12months
raised LDH
CD38+
```
297
What chromosomal change in CLL is the most common abnormality seen in 50%, ass with good prognosis?
del 13q = deletion of long arm chr 13
298
What chromosomal change in CLL is associated with a poor prognosis?
del 17p = deletion of part of short arm of chr 17, seen in 5-10%
299
35y.o. woman who is 16wks pregnant attends AMU with 1st seizure - uncomplicated pregnancy so far.
Febrile, HR 86, BP 125/86
Bloods:
Hb 69 Plts 43 WCC 7.4
Na 137 K 4.9 Ur 18 Cr 278
Urine dip negative for protein & ketones
Schistocytes on blood film
What is the Dx?
TTP: thrombotic thrombocytopenic purpura
- acquired inability to cleave vWF multimers
- can be prompted by pregnancy
- leading to platelet deposition & widespread coagulation
- ADAMTS13 is the protein responsible
- schistocytes on blood film can indicate intravascular haemolysis (MAHA in TTP)
300
What is cryoglobulinaemia?
When Igs undergo reversible precipitation at 4deg C, dissolve when warmed to 37deg C
- 1/3 are idiopathic
301
What are the 3 types of cryoglobulinaemia?
I monoclonal 25%
II mixed mono & polyclonal 25%, usually with rheumatoid factor
III polyclonal 50%, usually with RF
302
What is type I cryoglobulinaemia?
| What are the associations?
monoconal IgG/IgM
| - myeloma, Waldenstrom macroglobulinaemia
303
What is type II cryoglobulinaemia?
| What are the associations?
mixed mono & polyclonal, usually with RF
| - hep C, RA, Sjogren's, lymphoma
304
What is type III cryoglobulinaemia?
| What are the associations?
polyclonal, usually with RF
| - RA, Sjogren's
305
What are the Sx of cryoglobulinaemia?
- Raynauds only in type I
- cutaneous: vascular purpura, distal ulceration
- arthralgia
- renal involvement (diffuse glomerulonephritis)
306
Rx of cryoglobulinaemia?
- immunosuppression
| - plasmapheresis
307
IVDU with hep C, purpuric rash, +ve RF, reduced complement levels - what is the Dx?
cryoglobulinaemia type II (ass with hep C)
308
What are the indications for Rx in CLL?
- progressive marrow failure: worsening anaemia, thrombocytopenia etc
- massive >10cm or progressive lymphadenopathy
- massive >6cm or progressive splenomegaly
- progressive lymphocytosis: >50% increase over 2months or lymphocyte doubling time <6months
- B Sx
- autoimmune cytopaenias e.g. ITP
309
What is Rx of CLL when in indicated?
Rx of choice = FCR
Fludarabine
Cyclophosphamide
Rituximab
310
What are the fundamentals of initial Rx in an acute chest sickle cell crisis?
- O2 for Spo2>95%
- IVF to maintain euvolaemia
- adequate analgesia
- INCENTIVE SPIROmetry in all presenting rib/chest pain
- Abx to cover atypical
- early consult with critical care team & haem (senior haematologist will decide whether a simple/exchange transfusion is necessary, with guidelines suggesting target Hb 100-110
311
TTP: what is the Rx of choice?
| What else can be used?
PLASMA EXCHANGE can be life-saving
| - steroids, immunosuppressants, Vincristine can be used after Rx with PEX complete
312
What is the classic pentad of TTP?
- thrombocytopenia
- microvascular haemolysis
- fluctuating neuro signs
- renal impairment
- fever
313
What is myelofibrosis?
Myeloproliferative disorder thought to be caused by hyperplasia of abnormal megakaryocytic
- > release of PDGF is thought to stimulate fibroblasts
- haematopoiesis develops in liver & spleen
314
Features of myelofibrosis?
- elderly person with Sx of anaemia is commonest presenting Sx
- massive splenomegaly
- hypermetabolic Sx: weight loss, night sweats
315
Lab findings in myelofibrosis?
- anaemia
- high WCC & plt in early disease
- tear-drop poikilocytes in early disease
- unobtainable BM Bx - 'dry tap' therefore trephine Bx needed
- high rate & LDH (reflection of increased cell turnover)
316
Most useful follow-up Ix to detect testicular teratoma disease recurrence?
AFP & beta-hCG
317
MoA of cisplatin?
Causes cross-linking of DNA
318
What sort of homeless does hereditary spherocytosis cause?
EXTRAvascular
319
Drug causes of pancytopenia?
```
Abx: Trimethoprim, chloramphenicol
Anti-rheum: gold, penicillamine
Carbimazole
Anti-epileptics: crabamazepine
Sulfonylureas: tolbutamide
Cytotoxics
```
320
What is protein C deficiency?
| What are the features?
- autosomal dominant condition leading to increased risk of thromboses
- VTE
- skin necrosis after warfarinisation (when 1st started, protein C biosynthesis is reduced -> temp procoagulant state ->thrombosis in venues -> skin necrosis
321
What is the most common clinically significant primary immunodeficiency?
CVID: common variable immunodeficiency
| IgA deficiency is more common, but most are aSx
322
Features of CVID: common variable immunodeficiency?
- raised serum Igs
- heterogeneous clinical features
Usually 3 of:
- hypogammaglobulinaemia of 2+ isotypes (low IgG/A/M). IgG more likely to be deficient than IgM
- rec sinopulmonary infections
- impaired functional Ab responses e.g. absent isohaemagglutinins, poor responses to protein/polysaccharide vaccines etc
323
What is the best screening test in-between attacks of hereditary angioedema?
serum C4
324
MoA of cyclophosphamide?
alkylating agent that causes cross-linking of DNA
325
what is Mesna ? (cyclophosphamide)
2-mercaptoethane sulfonate Na
- acrolein is a metabolite of cyclophosphamide that's toxic to urothelium
- mesna binds to it & inactivates to to help prevent haemorrhagic cystitis
326
Adverse effects of cyclophosphamide?
haemorrhagic cystitis (incidence reduced by use of hydration & mesna)
myelosuppression
TCC
327
Features of Falcon anaemia?
```
autosomal recessive
aplastic anaemia
inc risk of AML
neurological
skeletal abnormalities: short stature
cafe au lait spots
```
328
Causes of hyposplenism?
```
splenectomy
sickle cell
coeliac, dermatitis herpetiformis
Graves disease
SLE
amyloid
```
329
Ix of choice for CLL?
immunophenotyping
330
What is paroxysmal nocturnal haemoglobinuria?
Acquired disorder leading to haemolysis (mainly intravascular) of haem cells
- thought to be caused by increased sensitivity of cell membranes to complement due to a lack of GPI: glycoprotein glycosyl-phosphatidylinositol
- more prone to venous thrombosis
331
Pathophysiology of paroxysmal nocturnal haemoglobinuria?
GPI is like an anchor which attaches surface proteins to the cell membrane
- complement-regulating surface proteins e.g. DAF: decay-accelerating factor, are not properly bound to the cell membrane due to a lack of GPI
- thrombosis thought to be caused by a lack of CD59 on platelet membranes predisposing to platelet aggregation
332
Features of paroxysmal nocturnal haemoglobinuria?
- acquired, chronic intrinsic haemolytic anaemia
- RBCs, WBCs, platelets or stem cells may be affected -> pancytopenia
- Hburia: dark urine in the morning classically
- thrombosis e.g. Budd-Chiari syndrome
- aplastic anaemia may develop in some
- +ve Ham test
333
How to Dx paroxysmal nocturnal haemoglobinuria: what is the gold standard?
what used to be used?
* **Flow cytometry of blood to detect low levels of CD59 & CD55***
- Ham's test: acid-induced haemolysis (normal RBCs don't)
334
Rx of paroxysmal nocturnal haemoglobinuria?
- blood product replacement
- anticoagulation
- Eculizumab, a mAb directed against terminal protein C5, being trialled & may help reduce intravascular haemolysis
- stem cell Tx
335
What is the Ix if you otherwise can't Dx hereditary spherocytosis on Hx, FHx etc alone?
EMA binding test - uses flow cytometry to determine the amount of fluorescence (reflecting EMA bound to specific transmembrane proteins) derived from individual red cells
336
Sx & findings of spinal metastases?
- unrelenting lumbar back pain
- any thoracic/cervical back pain
- worse with sneezing, coughing, straining
- nocturnal
- ass with tenderness
337
If Sx & findings of spinal metastases (without neuro features) what is next best step?
Whole MRI spine within 1 week (24h if neuro Sx & suspect for SCC)
338
What is the main purpose of requesting irradiated food product?
Reduces the risk of transfusion graft vs host disease as it is T-cell depleted
339
What are the porphyrias?
Abnormality in enzymes responsible for biosynthesis of haem
- results in overproduction of intermediate compounds (porphyrins)
- can be acute/non-acute
340
AIP: acute intermittent porphyria
- what is the enzyme defect?
- how does it typically present?
- what happens to urine?
- defect in porphobilinogen deaminase - autosomal dominant
- female in 20-40s with abdo Sx & neuropsych Sx
- HTN & tachycardia common
- urine turns deep red on standing
341
PCT: porphyria cutanea tarda
- what is the enzyme defect?
- how does it classically present?
- what is elevated in the urine and what happens under Wood's lamp?
- Rx?
- uroporphyrinogen decarboxylase, commonest hepatic porphyria
- may be caused by hepatocyte damage e.g. etoh, oestrogens
- classically photosensitive rash with bull, skin fragility on face & dorsal aspect of hands
- urine: elevated uroporphyrinogen, pink fluorescence
- Rx with Chloroquine
342
Variegate porphyria: what is the enzyme defect?
how does it present?
where is it more common?
- defect in protoporphyrinogen oxidase
- photosensitive blistering rash, abdo & neuro Sx
- autosomal dominant, more common in South Africans
343
What is Mantle cell lymphoma?
What are the genetics?
What are the features?
- B-cell lymphoma
- CD5+, CD19+, CD22+, CD23-, CD10-
- ass translocation t(11;14) causing over-expression of the cyclin D1 (BCL-1 gene)
- poor prognosis, widespread lymphadenopathy
344
What is methaemoglobinaemia?
- Hb which has been oxidised from Fe2+ -> Fe3+
- normally regulated by NADH metHb reductase, which transfers electrons from NADH -> metHb resulting in reduction of metHb to Hb
- tissue hypoxia as Fe3+ can't bind O2, so oxygen dissociation curve shifts to the Left
345
Congenital causes of methaemoglobinaemia?
- Hb chain variants: HbM, HbH
| - NADH metHb reductase deficiency
346
Acquired causes of methaemoglobinaemia?
- drugs: sulphonamides, nitrates, dapsone, sodium nitroprusside, primaquine
- chemicals: aniline dyes
347
Features of methaemoglobinaemia?
- 'chocolate' cyanosis
- dyspnoea, anxiety, headache
- severe: acidosis, arrhythmias, seizures, coma
- normal pO2 but decreased oxygen saturation
348
Rx of Methaemoglobinaemia?
- congenital NADH - methaemoglobin reductase deficiency -> Ascorbic acid
- acquired -> IV methylene blue
349
What is a leukaemoid reaction?
Presence of immature cells e.g. myeloblasts, promyelocytes & nucleated red cells in the peripheral blood
- may be due to infiltration of BM causing immature cells to be 'pushed out' or sudden demand for new cells
350
Causes of leukaemoid reaction?
- severe infection
- severe haemolysis
- massive haemorrhage
- metastatic cancer with BM infiltration
351
How to differentiate a leukaemoid reaction from CML?
LR:
- high leucocyte ALP score
- toxic granulation (Dohle bodies) in the white cells
- 'left shift' of neutrophils i.e. 3 or less segments of the nucleus
CML:
- low leucocyte ALP score
352
Classic train of paroxysmal nocturnal haemoglobinuria?
1. haemolytic anaemia
2. pancytopenia
3. venous thrombosis
353
In essential thrombocytosis, apart from a JAK2 mutation, Which is the most likely other gene mutation responsible?
CALR = Calreticulin (20%)
354
What is the Ag found in heparin-induced thrombocytopenia?
PF4 (platelet factor 4) complex
355
leucocyte ALP score in myelofibrosis?
high
356
MoA of Docetaxel?
Prevents microtubule depolymerisation & disassembly, decreasing free tubular
357
What is the triad in HUS: haemolytic uraemia syndrome?
1. acute renal failure
2. MAHA
3. thrombocytopenia
358
Causes of HUS?
- post-dysentery (classically E. coli 'verotoxigenic', 'enterohaemorrhagic')
- tumours
- pregnancy
- ciclosporin, OCP
- SLE
- HIV
359
Ix in HUS?
FBC: anaemia, thrombocytopenia, fragmented blood film
U&E: acute renal failure
stool culture
360
Rx of HUS?
Supportive e.g. fluids, blood transfusion & dialysis if required
- complicated indications for plasma exchange - generally when v severe & not ass with diarrhoea
361
Haptoglobin in intravascular haemolytic anaemia?
LOW
- binds to free Hb released from lysed RBCs
- complexes removed from plasma by hepatic reticule-endothelial cells
- haptoglobin levels fall if the rate of homeless is greater than the rate of haptoglobin production
362
MoA of Capecitabine?
Antimetabolite pro-drug of 5-FU but is ORAL
363
skin necrosis after starting warfarin - what is the Dx?
protein C deficiency
| autosomal dominant
364
Dysregulation of coagulation & fibrinolysis resulting in widespread clotting - Dx?
DIC
365
Bacterial toxin initiation of apoptosis & thrombogenesis - Dx?
HUS
366
Abnormal placental perfusion & vascularisation?
Pre-eclampsia
367
Acquired inhibition of ADAMTS13, preventing cleavage of vWF multimers - Dx?
TTP
368
Cytotoxic that prevents microtubule depolymerisation & disassembly, decreasing free tubulin?
Docetaxel
| nb can cause neutropenia
369
high BANDS on FBC = high rate of granulopoiesis so increase in granulocytes at different stages of maturation
Dx?
CML
370
What malignancies are ass with EBV?
Hodgkins & Burkitt's lymphoma
| nasopharyngeal carcinoma
371
APML: what translocation is it ass with?
| what chromosomal deletions are ass with poor prognosis?
t(15;17)
| deletions of chr 5/7
372
Rx when indicated in CLL?
chlorambucil reduces lymphocyte count
| Fludarabine
373
What must you give before Fludarabine in Rx for CLL and why?
Septrin or monthly nebulised Pentamidine to reduce risk of PCP because it causes profound lymphopenia which increases risk of opportunistic infections
374
Vena-Occlusive disease?
| = complication of chemo pre-BM Tx
- fluid retention, hepatomegaly, jaundice, multi-organ failure
- Dx = US abdomen to help, Liver Bx shows centrilobular necrosis
Rx = supportive
375
ALL - Dx?
```
Blast on blood smear
BM Bx = Dx
LP to detect CNS involvement
CXR to look for mediastinal mass
U&E to check tumour lysis
Immunophenotype to establish if blast cells origin is B/T
DNA mutation testing
```
376
Before starting chemo Rx in ALL, what should be doe if blast cell count is Very high?
needs Leukapharesis to prevent slugging of capillary beds - can be life-saving
377
Test that has >95% sensitivity to Dx von willebrands?
PFA-100
378
ITP: what do you do before starting steroids?
BM aspirate to show megakaryocytes - and rule out leukaemia before starting steroids!
