Cancer Care Flashcards
Describe the epidemiology of lung cancer (how common, rank in cause of death):
2nd most common cancer
Biggest cause of cancer related deaths
What are some risk factors for lung cancer?
Smoking, airflow obstruction, age, FH, exposure to carcinogens e.g. asbestos
Describe some presenting symptoms of lung cancer:
Cough, haemoptysis, dyspnoea, chest pain, recurrent pneumonia, lethargy, anorexia, weight loss, hoarseness, clubbing
What is the criteria for referring suspected lung cancer for CXR?
> 40y with 2+ unexplained symptoms or has ever smoked with 1 symptom
What are the types of lung cancer?
Small cell (30%) Non-small cell: squamous (35%), adenocarcinoma (27%), large cell (10%)
Describe the features of small cell lung cancer:
Arise from endocrine cells and often secrete polypeptide hormones (ADH, ACTH)
Rapid growth rate means often too extensive for surgery (70%) at diagnosis and poor prognosis
Describe the features of squamous cell lung cancer:
Cavitating lesions, metastasise late, close to bronchus, hypercalcemia, clubbing, HPOA
Describe the features of adenocarcinoma of the lung:
Peripheries, common in non-smokers
Describe the features of large cell lung cancer:
Peripheries, early mets, may secrete hCG
What are some investigations that should be performed in suspected lung cancer?
FBC, U+Es, calcium, LFTs, INR
CXR, staging CT, PET
Bronchoscopy, FNA or biopsy, thoracoscopy, cytology, bone scan
What are some features of lung cancer that may be seen on CXR?
Nodule, hilar enlargement, consolidation, lung collapse, pleural effusion
What are the T stages for lung cancer (TNM)?
T1: <3cm
T2: 3-5cm
T3: 5-7cm
T4: >7cm
What are the N stages for lung cancer (TNM)?
N1: ipsilateral peribronchial and/or hilar
N2: ipsilateral mediastinal or subcarinal
N3: contralateral mediastinal or hilar, scalene or supraclavicular
What is the surgical management for lung cancer and when should it be used?
Lobectomy or pneumonectomy. Curative for stages I and II
Surgery and neo + adjuvant chemo for IIIa
When can chemotherapy be used in management for lung cancer?
SCLC responds
Used neo-adjuvant and adjuvant in NSCLC
Usually stage III/IV
When can radiotherapy be used in management for lung cancer?
Used curatively in stage I or II, patients unfit or not wanting surgery
Symptom relief
Where does lung cancer metastasise to?
Brain, bone, liver, adrenals
How can metastatic lung cancer be managed?
Palliative RT, bisphosphonates, steroids
What are some local complications of lung cancer?
Recurrent laryngeal nerve palsy, phrenic nerve palsy, SVCO, Horner’s (Pancoast), rib erosion, pericarditis, AF
What are some endocrine complications of lung cancer?
Cushing’s (ACTH), hyponatremia (ADH), hypercalcemia (PTH), gynaecomastia (HCG)
What are some neurological complications of lung cancer?
Cerebellar degeneration, myopathy, polyneuropathy, Lambert-Eaton syndrome
What is malignant mesothelioma?
Tumour of mesothelial cells that usually occurs in pleura
Associated with occupational exposure to asbestos (can have long latent period)
What are the presenting features of malignant mesothelioma?
Chest pain, dyspnoea, weight loss, clubbing, recurrent pleural effusions
Where can malignant mesothelioma metastasise to?
LNs, liver, bone, peritoneum
What investigations should be done if malignant mesothelioma is suspected?
CXR, CT, pleural fluid (bloody), histology following
thoracoscopy
What is the management for malignant mesothelioma?
Pemetrexed + cisplatin chemo
Describe the epidemiology of breast cancer (how common, rank in cause of death):
Commonest cancer in UK
3rd commonest cause of death by cancer
What are some risk factors for breast cancer?
FH, age, not breastfeeding, past breast Ca
Unopposed oestrogen (nulliparity, 1st pregnancy >30y, early menarche, late menopause, HRT, obesity)
5-10% due to BRCA1/2 mutations
What are some types of breast cancer?
Invasive ductal carcinoma (70%)
Invasive lobular (10-15%)
Medullary, colloid/mucoid, papillary, tubular, adenoid-cystic and Paget’s
How can breast cancer present?
Lump, changes in breast size, nipple discharge, nipple inversion, skin dimpling, rash around nipple, pain
What are the 2WW criteria for referring suspected breast cancer?
> 30y with unexplained breast lump
>50y with symptoms or changes to one nipple
What are the criteria for referring for genetic testing in breast cancer?
1st degree relative with breast Ca <40y
Bilateral at <50y
1st and 2nd degree relatives with breast cancer Multiple cancers at young age
What is the triple assessment for breast cancer?
Clinical examination, imaging (mammography
>40, US <40), histology/cytology (FNA or core biopsy)
When should MRI be used in the investigation of breast cancer?
Bilateral and for patients with implants who are high risk
If a pt has a known BRCA1/2 mutation, how should they be followed up?
Annual MRI 30-49y and annual mammography 50-69y
If a pt has a known TP53 mutation, how should they be followed up?
Annual MRI 20-69y
Describe the TNM staging for breast cancer:
T1: <2cm, T2: 2-5cm, T3: >5cm, T4: fixed to chest wall/peau d’orange
N1: mobile ipsilateral nodes, N2: fixed nodes
M1: distant mets
What are the surgical management options for breast cancer?
Removal of tumour by wide local excision or mastectomy ± breast reconstruction + axillary node sampling/surgical clearance
When would mastectomy be used instead of wide local excision?
Large, central and multifocal tumours or if patient choice
When would radiotherapy be used in management of breast cancer?
All patients with invasive cancer after WLE
Axillary radio if LN positive
What are the side effects of radiotherapy for breast cancer?
Skin reaction, fatigue, chest wall pain, fibrosis, atrophy, telangiectasia
When would chemotherapy be used in management of breast cancer?
Adjuvant improves survival and reduces recurrence
What are some endocrine treatments used in breast cancer?
Tamoxifen for 5yrs post op
Aromatase inhibitors e.g. anastrozole, if post-menopausal (give with osteoporosis prophylaxis)
In which patients should herceptin be avoided?
History of heart disorders
What is a sentinel lymph node biopsy (breast cancer)?
Blue dye into periareolar area or tumour, gamma probe to identify sentinel node which is biopsied and sent for histology
Decreases needless axillary clearance in LN -ve patients
Where does breast cancer metastasise to?
Bone, lung, liver, brain, adrenal, ovary
What investigations should be performed if metastatic breast cancer is suspected?
CXR, bone scan, liver USS, CT/MRI or PET-CT, LFTs, calcium
What are some management options for metastatic breast cancer?
Radiotherapy for painful bony lesions, bisphosphonates
Tamoxifen, chemo and Herceptin
Describe the screening programme for breast cancer:
2-view mammography every 3y for women aged 47-73
What are some features that may be seen on an irregular mammogram?
Irregular, spiculated, radiopaque mass, microcalcification
What are some factors that can be used to determine the prognosis of breast cancer?
Tumour size, grade, LN status, ER/PR/HER status, presence of vascular invasion
What are the management options for breast carcinoma in situ?
Surgical excision + RT, mastectomy, hormonal treatment post-excision
What are the features of Paget’s disease of the nipple?
Eczematoid change of the nipple associated with an underlying breast malignancy
What are the features of inflammatory breast cancer?
Cancerous cells block the lymph drainage resulting in an inflamed appearance of the breast
What are the features of Phyllodes tumour? How should it be managed?
Large, fast-growing masses that form from the periductal stromal cells of the breast. Treat with WLE
What are the features of fibroadenoma?
Usually <30y, painless, firm, soft and mobile lump
What is the prognosis for fibroadenoma?
1/3 regress, 1/3 stay the same, 1/3 get bigger
Observe and reassure but may remove if large (>3cm)
What are the features of breast cysts?
Common >35y esp. perimenopausal
Benign, fluid filled rounded lump which can be painful, not fixed to surrounding tissue
How should infective mastitis be treated?
Treat with Abx, may need incision and drainage if abscess
What are the features of duct ectasia?
Around menopause, ducts blocked and secretions stagnant
Green/brown nipple discharge ± nipple retraction or lump
What are the features of fat necrosis?
Fibrosis and calcification after injury to breast tissue
Scarring results in a firm lump
How can duct papilloma present?
Blood stained discharge
What are the 2WW criteria for referring suspected lung cancer?
CXR suggestive of Ca or >40y with haemoptysis
Describe the epidemiology of prostate cancer (how common, rank in cause of death):
Commonest cancer in males (80% in >80y), 4th overall
2nd most common cause of death among male cancers
What are some risk factors for prostate cancer?
Age, FH (1st degree <60y), BRCA2 mutation, black > white > Asian, testosterone
What type of cancer is prostate cancer and where does it arise?
Most are adenocarcinoma arising in peripheral prostate
What are the 2WW criteria for referring suspected prostate cancer?
DRE reveals hard, nodular prostate or PSA levels above age specific cut off
What are some presenting features for prostate cancer?
PSA test, LUTS (nocturia, hesitancy, poor stream), bone pain, ejaculatory symptoms, weight loss
What investigations are needed in the diagnosis of prostate cancer?
DRE, PSA, MRI prostate (often pre-biopsy)
TRUS (transrectal US) biopsy or transperineal biopsy (template)
What other conditions can cause a raised PSA?
UTI, prostatitis, BPH, acute urinary retention
What factors influence the management and prognosis of prostate cancer?
Age, DRE, T-stage, PSA, Gleason grade and score, MRI, bone scan
Describe Gleason grade and score:
If there is prostate cancer given Gleason grade of 3, 4 or 5
Gleason score is worked out by adding together two Gleason grades. The first is the most common grade in all the samples. The second is the highest grade of what’s left
What are the management options for prostate cancer?
Watchful waiting, active surveillance, brachytherapy,
RT, radical prostatectomy
What is watchful waiting?
Monitoring of prostate Ca that isn’t causing any symptoms
Aim is to observe the Ca over the long term, and avoid treatment unless it becomes symptomatic
What is active surveillance?
Monitoring of localised prostate cancer, rather than treating it straight away
Regular biopsies and MRIs to monitor and only treat if patient decides to or if tests show cancer is progressing. Treatment aims to cure
How can bony mets from prostate cancer be managed?
LHRH agonists and antiandrogen (bicalutamide) or surgical castration
Pred and docetaxel chemo for those with good performance status
If palliative: single dose RT and bisphosphonates
What is lead time bias?
Early diagnosis of a disease falsely makes it look like people are surviving longer
What is is length time bias?
Overestimation of survival duration due to the relative excess of cases detected that are asymptomatically slowly progressing, while fast progressing cases are detected after giving symptoms. Improved perceived prognosis
What are the most common tumours that cause bony mets?
Prostate, breast, lung
Where are the most common sites for bony mets?
Spine, pelvis, ribs, skull, long bones
How can bony mets present?
Bone pain, pathological fractures, hypercalcemia (if lytic), raised ALP
Describe the epidemiology of colorectal cancer (how common, rank in cause of death):
3rd most common solid cancer
2nd most common cause of cancer deaths
What are some risk factors for colorectal cancer?
Western diet (high fat, low fibre), age, obesity,
smoking, alcohol, FH
FAP (APC mutation), HNPCC (Lynch), IBD
What are the 2WW criteria for referring suspected colorectal cancer?
40+ with unexplained weight loss and abdo pain
50+ with unexplained rectal bleeding
60+ with IDA or change in bowel habit
How can colorectal cancer affecting the right colon present?
Weight loss, weakness, anaemia, abdo pain
How can colorectal cancer affecting the left colon present?
Constipation, pain, alternating bowel habit, rectal bleeding, changes in stool consistency, large bowel obstruction, fistula
How can colorectal cancer affecting the rectum present?
Obstruction, tenesmus, bleeding, palpable mass on rectal exam
What investigations should be performed if colorectal cancer is suspected?
FBC, LFTs, U+Es, CEA
Colonoscopy, flexi sig, CT colonography, biopsy, CT chest/abdo/pelvis, barium enema (long stricture), liver MRI
Describe the TNM staging for colorectal cancer:
T1: invading submucosa, T2: invading muscularis propria, T3: invading subserosa, T4: invasion of adjacent structures
N1: mets in 1-3 regional nodes, N2: mets in >3 regional nodes
M1: distant mets
When would a right hemicolectomy be used in management of colorectal cancer?
Caecal, ascending or proximal transverse colon cancer
When would a left hemicolectomy be used in management of colorectal cancer?
Distal transverse or descending colon cancer
When would an anterior resection be used in management of colorectal cancer?
Low sigmoid or high rectal cancer
When would an abdomino-perineal resection be used in management of colorectal cancer?
Low rectal cancer
When would chemo and radiotherapy be used in management of colorectal cancer?
Chemo - neoadjuvant/adjuvant/stage III/palliation
RT - palliation
Where does colorectal cancer metastasise to?
Liver
Also lung, bone, brain, LNs
Describe the screening programme for colorectal cancer:
Aged 60-74, faecal immunochemical test sent for home testing every 2 years
Detects human Hb in stool, colonoscopy if positive test
One off flexi sig offered at 55y
What are the risk factors for developing skin cancer?
FH, Fitzpatrick skin type I or II, red/blonde hair, high freckle density, sun exposure, sun bed, immunosuppression, Xeroderma pigmentosum
Describe the Glasgow 7-point checklist for malignant melanoma and when you should refer:
Major (2pts): change in size, shape, colour
Minor (1pt): inflammation, sensory change, diameter >6mm, crusting/bleeding
Refer if 3+
Describe the ABCDE diagnosis for malignant melanoma:
Asymmetry, border irregular, colour non-uniform, diameter >6mm, elevation
Describe the features of superficial spreading malignant melanoma:
Grow slowly, mets later, better prognosis
Growing moles on arms, legs, back and chest
Describe the features of nodular malignant melanoma:
Invade deep, mets early, worse prognosis
Red/black lump on sun-exposed skin
What are some factors determining prognosis in malignant melanoma?
Breslow thickness (depth in mm), tumour stage, ulceration
What is the management for malignant melanoma?
Excision with wide margins determined by Breslow thickness
May do SNLB
How should metastatic malignant melanoma be managed?
Chemo and ipilimumab (CTLA-4 blocker)
Describe the appearance of squamous cell carcinoma of the skin:
Ulcerated lesion, with hard, raised edge in sun exposed sites
At which sites can squamous cell carcinoma of the skin develop from (predisposing sites)?
Actinic keratoses, lips of smokers, or in long standing ulcers (Marjolin’s)
What is the management for squamous cell carcinoma of the skin?
Excision (Moh’s in high risk)
What is the commonest form of skin cancer?
Basal cell carcinoma
Describe the features of nodular basal cell carcinoma:
Pearly nodule with rolled telangiectatic edge, on face or sun-exposed site. May have central ulcer
Describe the features of superficial basal cell carcinoma:
Red scaly plaques with a raised smooth edge, often on trunk or shoulders
What is the management for basal cell carcinoma?
Excision (Moh’s if high risk), cryotherapy, topical fluorouracil or imiquimod
Describe the appearance of solar (actinic) keratoses:
On sun-exposed skin
Crumbly, yellow-white crusts
What is the risk associated with actinic keratoses?
Malignant change to squamous cell carcinoma may occur after several years
How should actinic keratoses be managed?
Cryotherapy or fluorouracil/imiquimod cream
Describe the appearance of Bowen’s disease:
Slow growing red/brown scaly plaque
How should Bowen’s disease be managed?
Cryo, topical fluorouracil, photodynamic therapy
Describe the appearance of keratoacanthoma:
Dome-shaped erythematous lesions that grow rapidly and often contain a central pit of keratin
What are lymphomas?
Disorders caused by malignant proliferations of lymphocytes
Accumulate in the LNs causing lymphadenopathy and can also be found in peripheral blood and infiltrate organs
What are the characteristic cells found in Hodgkin’s lymphoma and what is their appearance?
Reed-Sternberg cells
Mirror image nuclei
What ages does Hodgkin’s lymphoma commonly present?
Young adults (commonest cancer in 15-24y) and elderly
What are some risk factors for Hodgkin’s lymphoma?
Male, affected sibling, EBV, SLE, post-transplant
What are the 4 subtypes of Hodgkin’s lymphoma and which carries the worst prognosis?
Nodular sclerosing (70%) Mixed cellularity (20%) Lymphocyte rich (5%), Lymphocyte depleted (1%) - carries poor prognosis
What are some presenting features of Hodgkin’s lymphoma?
Lymphadenopathy with contiguous spread between regions (often cervical and mediastinal)
B symptoms
Pruritus, alcohol-induced LN pain, cough, SOB, spleno/hepatomegaly
What investigations should be performed if Hodgkin’s lymphoma is suspected?
LN excision biopsy, FBC, film, ESR, LFT, LDH, urate, calcium
CXR, PET-CT thorax, abdo, pelvis
Describe the Ann Arbor staging system:
I. Confined to single LN region
II. Involvement of two or more LN regions on same side of diaphragm
III. Involvement of LN regions on both sides of diaphragm
IV. Spread beyond the LNs e.g. liver or BM
What are B symptoms?
Weight loss >10% in last 6m, unexplained fever >38, night sweats
What is the treatment for Hodgkin’s lymphoma (quite general)?
Chemoradiotherapy
ABVD – Adriamycin (doxorubicin), bleomycin, vinblastine, dacarbazine
What are some complications of using chemoradiotherapy to treat Hodgkin’s lymphoma?
RT increases risk of secondary malignancies, IHD, hypothyroidism, lung fibrosis
Chemo: SEs, AML, NHL, infertility
What is the commonest non-Hodgkin lymphoma?
Diffuse large B-cell lymphoma
Describe low grade lymphomas and give some examples:
Indolent, often incurable and widely disseminated at
presentation, more common in middle/old age
E.g. follicular (20% of NHL), marginal zone, lymphocytic
Describe high grade lymphomas and give some examples:
More aggressive but often curable. Often rapidly
enlarging lymphadenopathy with systemic symptoms, affect patients at all ages
E.g. Burkitt’s, lymphoblastic, DLBCL
What are some presenting features for non-Hodgkin lymphoma?
Superficial lymphadenopathy
Extranodal disease: gastric, small bowel, skin, oropharynx, bone
B symptoms
Pancytopenia
What are some investigations that should be performed if non-Hodgkin lymphoma is suspected?
FBC, U+Es, LFTs, LDH, ESR, marrow and node biopsy, CT chest/abdo/pelvis
How can low grade lymphomas be managed?
If symptomless, none may be needed
RT may be curative in localised disease
Chlorambucil in diffuse disease
How can high grade lymphomas be managed?
R-CHOP – rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine (Oncovin), pred
What are some poor prognostic factors in non-Hodgkin lymphoma?
Age >60y, B symptoms, bulky disease, high LDH, disseminated disease
What is the 5 year survival for low and high grade lymphomas?
30% for high grade, >50% for low grade
What are the 2 forms of Burkitt’s lymphoma?
Endemic and sporadic
What translocation is Burkitt’s lymphoma associated with?
c-myc gene translocation, usually t(8:14)
What is the characteristic appearance of Burkitt’s lymphoma on microscopy?
‘Starry sky’ - lymphocyte sheets interspersed with macrophages containing dead apoptotic tumour cells
What virus is Burkitt’s lymphoma associated with?
Epstein-Barr
What are some differentials for lymphadenopathy?
Infective: glandular fever, HIV, rubella, TB
Neoplastic: lymphoma, leukaemia
Other: SLE, RA, sarcoid
Describe the pathophysiology of acute lymphoblastic leukaemia:
Malignancy of lymphoid cells, arresting maturation and promoting uncontrolled proliferation of immature blast cells, with marrow failure and tissue infiltration
How can ALL present?
Pancytopenia: anaemia, infection, bleeding
If infiltration: hepato + splenomegaly, lymphadenopathy
What condition is ALL associated with?
Down’s
What investigations should be performed if ALL is suspected?
FBC, U+Es, LFTs, blood film, BM biopsy, CXR, CT, LP
What supportive treatment can be given in ALL management?
Blood/platelet transfusion, IV fluids, allopurinol, Hickman line
Abx for infections
What are some definitive treatments for ALL?
Chemo
Marrow transplant
How can acute myeloid leukaemia present?
Anaemia, infection, bleeding, DIC, hepatomegaly, splenomegaly
What investigations can be used to diagnose AML?
FBC, blood film, BM biopsy (Auer rods differentiate from ALL), immunophenotyping, cytogenetic analysis
What are some complications of AML?
Infections, sepsis (particularly fungal), tumour lysis syndrome, leukostasis if high WCC (resp distress, priapism)
What is the management for AML?
Supportive: transfusions, fluids, allopurinol, lines, walking exercises
Chemo
Marrow transplant
What features in a 0-24y old require investigation with an urgent FBC to rule out leukaemia?
Pallor Persistent fatigue Unexplained fever Unexplained persistent infections Generalised lymphadenopathy Persistent or unexplained bone pain Unexplained bruising or bleeding
How can chronic lymphocytic leukaemia present?
Often no symptoms, found on routine FBC
Anaemia or infection prone (pneumonia, herpes)
Lymphadenopathy, early satiety, splenomegaly, hepatomegaly
What is the prognosis for CLL?
1/3 never progress, 1/3 progress slowly, 1/3 actively progress
What is Richter’s transformation?
Occurs when leukaemia cells enter the LN and change into a high-grade, fast-growing non-Hodgkin’s lymphoma
What haematological condition can develop in those with CLL?
Warm AIHA
What are some management options for those with CLL?
Watchful waiting - monitor FBC every 3m
Chemo and monoclonals
Stem cell transplantation
What are some symptoms of Richter’s transformation?
LN swelling Fever without infection B symptoms Nausea Abdominal pain
At what age does CLL commonly present?
65-70y
At what age does CML commonly present?
40-60y
How can CML present?
Weight loss, tiredness, fever, sweats
Gout, bleeding, splenomegaly, hepatomegaly, anaemia,
bruising, leukostasis
What investigations should be performed if CML is suspected?
FBC, urate, LDH, B12, U+E, LFTs, bone profile, PCR, FISH, cytogenetics, BM biopsy
Describe the Philadelphia chromosome:
Hybrid chromosome comprising reciprocal translocation between long arm of C9 and long arm of C22, forming a fusion gene BCR/ABL on C22, which has tyrosine kinase activity
What is the management for CML?
Imatinib, dasatinib
Stem cell transplantation
What is the pathophysiology of myeloma?
Abnormal proliferation of a single clone of plasma cells leading to secretion of Ig or Ig fragment causing dysfunction of many organs (esp. kidney)
What are the 2 main classifications of myeloma?
2/3rd IgG and 1/3rd IgA
How can myeloma present?
C – hypercalcemia R – renal impairment A – anaemia B – osteolytic bone lesions, backache Neutropenia, thrombocytopenia, infections, dehydration
How is myeloma diagnosed?
> 10% plasma cells in marrow
Monoclonal protein band on electrophoresis
Evidence on end organ damage
Bone lesions on skeletal survey
What investigations should be performed if myeloma is suspected?
FBC, blood film (rouleaux), ESR, U+E, bone profile
BM biopsy, serum or urine electrophoresis, X-rays,
whole body MRI
What supportive treatment can be given in myeloma?
Analgesia, bisphosphonates, local RT, transfusions, fluids, Abx or IV Ig infusions
What management can be given in myeloma with the aim of treating the disease?
Chemo: lenalidomide, bortezomib and dex
If fit, autologous stem cell transplant
What are some complications of myeloma?
Hypercalcemia
Spinal cord compression
Hyperviscosity
Acute renal injury
What is MGUS?
Monoclonal gammopathy of undetermined significance Causes a paraproteinaemia
What are the differentiating features between MGUS and myeloma?
Normal immune function
Normal beta-2 microglobulin levels
Lower level of paraproteinaemia than myeloma and stable level
What percentage of patients with MGUS go on to develop myeloma at 10 and 15 years?
10% and 50% respectively
In what bones does haematopoiesis take place in adults?
Vertebrae, sternum, ribs, skull and proximal long
bones
What are some congenital causes of bone marrow failure?
Fanconi anaemia, immunodeficiency syndromes, Diamond Blackfan syndrome
What are some infective causes of bone marrow failure?
EBV, HIV, Hep C, parvovirus
What are some drugs that can cause bone marrow failure?
Chloramphenicol, co-trimoxazole, sulfasalazine,
carbamazepine, phenytoin, methrotrexate
What are myelodysplastic syndromes?
Heterogenous group of disorders that manifest as
marrow failure with risk of infection and bleeding
What is the treatment for myelodysplastic syndromes?
Transfusions, EPO, allogenic stem cell transplant, chemo
What is aplastic anaemia?
Stem cell disorder in which BM stops making cells
leading to pancytopenia
What are some causes of aplastic anaemia?
Autoimmune, drugs, viruses (parvovirus, hep), irradiation, Fanconi anaemia
How should aplastic anaemia be managed?
Transfusions, marrow transplant, immunosuppression
What can cause a relative polycythaemia?
Dehydration, obesity, HTN, high alcohol, smoking
What can cause an absolute polycythaemia?
Polycythaemia vera
Secondary to hypoxia (high altitudes, CLD)
Increased EPO
What are the features of polycythaemia vera?
Malignant proliferation of a clone derived from one
pluripotent stem cell
95% have mutation in JAK2
Excess proliferation of RBCs +/- WBC and platelets
How can polycythaemia vera present?
Asymptomatic and detected on FBC
Headaches, dizziness, tinnitus, visual disturbance, itching after hot bath and erythromelalgia (burning
sensation in fingers/toes)
What investigations should be performed if polycythaemia vera is suspected?
FBC, JAK2, B12, serum ferritin, LFTs, U+Es, BM biospy, EPO level
What is the management for polycythaemia vera?
Aim to keep HCT <0.45 to decrease thrombosis risk by venesection (younger) or hydroxycarbamide if older
Aspirin 75mg daily
What can polycythaemia vera progress to and therefore how should the condition be monitored?
Transition to myelofibrosis in 30% and acute leukaemia in 5%
Monitor FBC every 3m
How can essential thrombocythaemia present?
Headache, atypical chest pain, light-headedness,
erythromelalgia, bleeding, thrombosis
What is the treatment for essential thrombocythaemia?
Aspirin and hydroxycarbamide in high risk
What is the pathophysiology of myelofibrosis?
Hyperplasia of megakaryocytes producing PDGF leading to intense marrow fibrosis and haematopoiesis in liver and spleen -> massive hepatosplenomegaly
List some causes of pancytopenia:
Aplastic anaemia, malignant infiltration, megaloblastic anaemia, myelofibrosis, hypersplenism
List some causes of neutrophlia:
Infection, inflammation, steroids, adrenaline, surgery, CML, PRV, myelofibrosis, malignancy, smoking, bleeding
List some causes of neutropenia:
Influenza, HIV, chemo, carbimazole, clozapine, anti-convulsant, SLE, BM failure
List some causes of lymphocytosis:
EBV, CMV, hep, CLL, ALL, low grade lymphoma, MI, sickle cell crisis, trauma, adrenaline, splenectomy
List some causes of lymphopenia:
Hodgkin’s and NH lymphoma, RA, SLE, chemo, burns, anorexia, renal/liver failure, aplastic anaemia, myelodysplastic syndrome
List some causes of eosinophilia:
Medication, asthma, hay fever, eczema, urticaria, hookworm, tapeworm, schistosomiasis, Hodgkin’s
List some causes of thrombocytosis:
Bleeding, infection, chronic inflammation, malignancy, trauma, post-surgery, iron def., PRV, CML
List some causes of thrombocytopenia:
Aplastic anaemia, viral infection, vit def, ITP, DIC, TTP,
heparin induced, splenomegaly, liver disease
What are some causes of massive splenomegaly?
CML, myelofibrosis, malaria, Gaucher’s
What are some causes of moderate splenomegaly?
Infection (EBV, TB), portal HTN, haemolytic anaemia, CLL, lymphoma, RA, SLE, sickle cell (children)
How can you tell that a mass in LUQ is the spleen?
Dull to percussion, enlarges towards RIF, moves down on inspiration, medial notch, can’t get above it
What investigations should be performed if splenomegaly is found?
Abdo USS, CT, FBC, LFT, LN biopsy
What are some indications for splenectomy?
Splenic trauma, hypersplenism, autoimmune haemolysis
What are some features of hyposplenism on blood film?
Howell-Jolly bodies, Pappenheimer bodies and target cells
What infective organisms are patients at risk of post splenectomy?
S. pneumoniae, H. influenzae and N. meningitidis
What management is given post-splenectomy to reduce infection risk?
Pneumococcal vaccine 2 weeks pre-op and every 5-10yrs
H. influenzae vaccine, full meningococcal vaccination course and annual influenza vaccine
Life-long prophylactic oral Abx: Pen V or erythromycin
What are some conditions that cause hyposplenism?
Sickle cell, Coeliac, Graves’, SLE, amyloid
Describe the process of taking a bone marrow biopsy and aspirate:
Trephine biopsy to remove 1-2cm core of BM, aspirate is liquid BM
Taken from posterior iliac crest and aspirate smeared on slides during the process.
The investigation of which conditions may need a bone marrow biopsy/aspirate?
Leukaemia, multiple myeloma, lymphoma, anemia, and
pancytopenia
What tests can be performed on a bone marrow aspirate?
Immunophenotyping, flow cytometry, cytogenetics, karyotyping, FISH
What are the risks of a bone marrow biopsy?
Bleeding, bruising, infection, pain, tingling in leg
What are some symptoms of hypercalcemia?
Fatigue, abdo pain, N+V, constipation, confusion,
headaches, polyuria, polydipsia
What are some symptoms of hyperviscosity?
Headache, somnolence, visual disturbance, ischemic
events
What are some ‘routine’ bloods that would be requested when investigating haem malignancies?
FBC, U+Es, LFT, CRP, Ca2+, clotting
What are some specialised bloods that may be requested when investigating haem malignancies?
Haematinics, reticulocytes, LDH, urate, Ig, flow cytometry
What are some risk factors for oesophageal cancer?
Male, diet, alcohol excess, smoking, achalasia, reflux, Barrett’s oesophagus, obesity
What is the distribution of oesophageal cancer by site?
20% in upper, 50% in middle, 30% in lower
How does the histological subtype of oesophageal cancer change by site?
Squamous cell (proximal) or adenocarcinoma (distal)
What is Barrett’s oesophagus?
Metaplasia of stratified squamous in distal oesophagus to columnar as a result of chronic GORD, therefore may progress to adenocarcinoma
How can oesophageal cancer present?
Dysphagia, weight loss, retrosternal chest pain
If upper 1/3rd: hoarseness, cough
What is the 2WW referral criteria for urgent endoscopy if oesophageal cancer is suspected?
Dysphagia
55+ with weight loss, upper abdo pain, reflux or dyspepsia
Unexplained IDA
What investigations should be performed is oesophageal cancer is suspected?
Oesophagoscopy with biopsy, CT/MRI
Describe the T staging for oesophageal cancer:
T1: invading lamina propria/submucosa
T2: invading muscularis propria
T3: invading adventitia
T4: invasion of adjacent structures
How should oesophageal cancer be managed?
T1/2: radical curative oesophagectomy ± neo-adjuvant
chemo
If surgery is not indicated, chemoradiotherapy
What are some risk factors for gastric cancer?
Pernicious anaemia, blood group A, H. pylori, lower social class, smoking, diet (high salt, low vit C)
How can gastric cancer present?
Dyspepsia, weight loss, vomiting, dysphagia, anaemia, epigastric mass, hepatomegaly, jaundice, ascites, Virchow’s node, acanthosis nigrans
How should gastric cancer be investigations?
Gastroscopy + multiple ulcer edge biopsies Endoscopic US
CT/MRI +/- staging laparoscopy
How can gastric cancer be managed?
Surgical resection/removal (gastrectomy)
Combination chemo + herceptin
What is the main histological subtype of pancreatic cancer?
Ductal adenocarcinoma
How can pancreatic cancer present?
Painless jaundice, steatorrhea, upper abdo pain, weight loss
How should pancreatic cancer be investigated?
LFTs, USS abdo, pancreas specific CT, CA19-9
How can pancreatic cancer be managed?
Surgical resection, neoadjuvant chemo/RT, biliary stenting, pancreatin replacement
What are the main types of testicular cancer?
Seminoma 55% (30-65y)
Teratoma 33% (20-30y)
Mixed germ cell tumour 12%
Lymphoma
What are some risk factors for testicular cancer?
Undescended testis, infant hernia, infertility
How can testicular cancer present?
Painless testis lump, hydrocele, pain, abdo mass, dyspnoea (lung mets)
What investigations should be performed if testicular cancer is suspected?
USS, alpha-fetoprotein, beta hCG, LDH, CXR, CT
How can testicular cancer be managed?
Radical orchidectomy
Seminoma are v radiosensitive
Chemo for teratomas
What are some causes of haematuria (think neoplastic v non-neoplastic)?
Cancer – RCC, upper tract TCC, bladder Ca, advanced prostate Ca
Stones, infection, inflammation, BPH
Nephrological (glomerular)
What investigations should be performed in a patient presenting with haematuria?
Urine dip, eGFR, albumin/creatinine ratio, MSU, US, flexi cystoscopy, urine cytology
What are some risk factors for renal cell carcinoma?
Smoking, obesity, dialysis
How can renal cancer present?
Incidental
Haematuria, loin pain, abdo mass, anorexia,
malaise, weight loss, pelvic-ureteric obstruction
What investigations should be performed if renal cell carcinoma is suspected?
BP, FBC, ESR, U+E, calcium, ALP, urine dip, cytology
USS, CT/MRI abdo pelvis, CXR (cannon ball mets)
What are some management options for renal cell carcinoma?
Partial or radical nephrectomy
Cryotherapy, radiofrequency ablation, anti-angiogenesis (sunitinib) if not for surgery
What are the main two types of bladder cancer?
> 90% are transitional cell carcinomas
Squamous cell may follow schistosomiasis
What are some risk factors for bladder cancer?
Smoking, aromatic amines (rubber industry, painters, mechanics), chronic cystitis, schistosomiasis, pelvic irradiation
How can bladder cancer present?
Painless haematuria, recurrent UTIs, voiding irritability
What investigations should be performed if bladder cancer is suspected?
Cystoscopy and biopsy
Urine cytology, CT urogram, MRI, renal USS
Describe the T staging of bladder cancer:
Ta: tumour confined to epithelium T1: in submucosa or lamina propria T2: invades muscle T3: into perivesical fat T4: adjacent organs
How should Tis/Ta/T1 bladder cancer be managed?
TURBT
Intravescial BCG if high grade or multiple small tumours or use mitomycin C
How should T2-3 bladder cancer be managed?
Radical cystectomy ± neoadjuvant + adjuvant chemo
RT allows preservation of bladder
How should T4 bladder cancer be managed?
Palliation chemo/RT
How should high and low risk bladder cancer be followed up?
High risk: every 3m for 2y then every 6m
Low risk: after 9m then yearly cystoscopy
How can renal cell carcinoma present with varicoele?
Rarely, invasion of left renal vein compresses left testicular vein leading to varicocele
Following radical cystectomy, how can the bladder be replaced?
Replacement of bladder with ileal conduit or orthotopic reconstruction from small bowel
What is the mechanism used by radiotherapy in the treatment of cancer?
Ionising radiation to cause damage to DNA preventing cell division and leading to cell death
Direct action on DNA or indirectly through production of free radicals
When may palliative radiotherapy be used?
Brain metastases, spinal cord compression, visceral compression, bleeding, bone pain
What are the different methods by which radiotherapy can be delivered?
Conventional external beam RT
Stereotactic RT
Brachytherapy
Radioisotope therapy
Over what time frame do early reactions to radiotherapy occur?
2w into treatment to 2-4 weeks after
What are some examples of early reactions to radiotherapy?
Tiredness Skin reactions Mucositis N+V, diarrhoea Dysphagia Cystitis
Over what time frame do late reactions to radiotherapy occur?
Months-years after treatment
What are some examples of late reactions to radiotherapy?
Spinal cord myelopathy
Pneumonitis
Xerostomia, strictures, fistula
Urinary frequency, vaginal stenosis, dyspareunia, erectile dysfunction, infertility
Hypothyroidism
Secondary cancers
Skin pigmentation, telangiectasia, lymphoedema
What factors need to be taken into account when deciding the dose for chemotherapy?
Surface area, BMI, liver and renal function, performance status
By what routes can chemotherapy be administered?
Usually given IV
Can be PO, SC, intralesional, intrathecal, topical
Why might combination chemotherapy be given?
Combinations of drugs with different MoA and different SE profiles reduces likelihood of resistance and toxicity
What is adjuvant treatment?
Given after other initial treatment to reduce risk of relapse
What is neo-adjuvant treatment?
Shrink tumour and optimise outcomes prior to main treatment
What are some examples of alkylating agents?
Cyclophosphamide, chlorambucil
What are some examples of angiogenesis inhibitors?
Aflibercept, sunitinib
What are some examples of antimetabolites?
Methotrexate, 5-FU
What are some examples of antitumour antibiotics?
Doxorubicin, mitomycin, bleomycin
What are some examples of topoisomerase inhibitors?
Etoposide
What are some examples of vinca alkaloids and taxanes?
Vincristine, vinblastine, docetaxel
What are the main side effects of chemotherapy (general)?
Vomiting, diarrhoea Mucositis, pneumonitis Alopecia Fatigue, chemo-brain Rashes Neutropenia, tumour lysis syndrome Beau’s lines, infertility
What are some specific side effects associated with cyclophosphomide?
Haemorrhagic cystitis (hydration and use Mesna), TCC
What specific side effect is associated with bleomycin?
Lung fibrosis
What specific side effect is associated with doxorubicin?
Cardiomyopathy
What are some specific side effects associated with methotrexate?
Mucositis, liver fibrosis, lung fibrosis
What are some specific side effects associated with 5-FU?
Mucositis, dermatitis
What are some specific side effects associated with vincristine?
Peripheral neuropathy, paralytic ileus
What are some specific side effects associated with cisplatin?
Ototoxicity, peripheral neuropathy, hypomagnesemia
What is extravasation of chemotherapy and how may it present?
Inadvertent filtration of a drug into subcutaneous or subdermal tissue
Tingling, burning, pain, redness, swelling
How should extravasation of chemotherapy for DNA binding drugs be managed?
Stop infusion, aspirate any residual drug
Dry cold compress to vasoconstrict and decrease spread
How should extravasation of chemotherapy for non-DNA binding drugs be managed?
Stop infusion, aspirate any residual drug
Dry warm compress to vasodilate and increase distribution
What are some mechanisms by which cancer cells can become resistant to chemotherapy?
Decreased drug uptake e.g. altered folate receptor for methotrexate Increased drug efflux – P-glycoprotein Increased DNA repair Alteration of drug target Increased catabolism Increased drug detoxification
What are some examples of monoclonal antibodies used in cancer treatment and which cancers are they used in?
Herceptin (HER2) in breast and gastric VEGF inhibitors (bevacizumab) in ovarian and bowel EGFR inhibitor (cetuximab) in bowel
How do checkpoint inhibitors work?
Some cancer cells make high levels of proteins that turn T-cells off
Checkpoint inhibitors block this process and reactivate and increase the body’s own T-cell population, enhancing the immune systems own ability to recognise and fight cancer cells
What are some examples of checkpoint inhibitors used in cancer treatment and which cancers are they used in?
CTLA4 inhibitor (ipilimumab) in melanoma PD-1/PD-L1 inhibitors (nivolumab, pembrolizumab/azetolizumab) in melanoma, lung and renal
How does a PET-CT scan work?
Uses a non-specific radioactive tracer (FDG) which highlights areas of increased metabolism, cell proliferation or hypoxia
Therefore, accumulates in cancer cells > non-cancer cells
How does a bone scan work?
Detects abnormal metabolic activity in osteoblast cells using technetium-99m
What should be co-prescribed with opioids?
Anti-emetics and laxatives
What are some side effects of opioids?
Drowsiness (transient), N+V (transient), constipation, dry mouth
What are some signs of opioid toxicity?
Sedation, resp depression, hallucinations, myoclonic jerks, delirium
What is the management for opioid toxicity?
May need O2 and naloxone
What opioids should be prescribed if a patient has renal impairment?
Alfentanil/buprenorphine
How should opioid dose be calculated (slow release and breakthrough)?
Add up 24 hours’ worth of morphine = total daily dose
TDD/2 = new morphine slow release dose
TDD/6 = new morphine PRN breakthrough dose
What is the conversion ratio between oral and subcut dose of opioids?
Subcut dose is half corresponding oral dose
What is the conversion ratio between codeine and morphine?
10:1
What is nociceptive pain and how does it present?
Normal NS with an identifiable lesion causing tissue damage
Can be somatic (sharp, throbbing, localised) or visceral (ache, poorly localised)
What is neuropathic pain and how does it present?
Malfunctioning NS, where pain is due to nerve structure damage
Stabbing, shooting, burning, stinging
Describe the WHO analgesic ladder:
Non-opioid e.g. paracetamol
Opioid for mild to moderate pain e.g. codeine, tramadol, co-codamol
Opioid for moderate to severe pain e.g. morphine, oxycodone, fentanyl
What drugs are effective in neuropathic pain?
NSAIDs, amitriptyline, pregabalin, benzos, steroids
What are some causes of N+V in cancer patients?
Chemo, constipation, hypercalcaemia, oral candidiasis, GI obstruction, drugs, severe pain, infection, renal failure, RICP, anxiety
What is the MOA of cyclizine and when is it effective?
Anti-histamine, anticholinergic, central action Intracranial disorders (RICP), bowel obstruction
What is the MOA of metoclopramide and when is it effective?
Blocks central chemoreceptor trigger zone, peripheral
prokinetic effects so good for gastric stasis
What is the MOA of domperidone and when is it effective?
Peripheral antidopaminergic
Gastric stasis
What is the MOA of haloperidol and when is it effective?
Dopamine antagonist
Drug or metabolically induced nausea
What is the MOA of ondanestron and when is it effective?
Serotonin antagonist
Chemo/RT related nausea
When is dexamethasone effective in treating N+V?
Bowel obstruction and RICP
What are some causes of constipation in cancer patients?
Opioids, hypercalcemia, dehydration, drugs, intra-abdominal disease, immobility, weakness, obstruction
What are some examples of stimulant laxatives?
Senna, bisacodyl
What are some examples of osmotic laxatives?
Macrogol, lactulose
What are some examples of softener laxatives?
Sodium picosulfate, docusate
What are some cause of breathlessness in cancer patients?
Infection, effusion, anaemia, arrhythmia, thromboembolism, COPD, heart failure, SVCO
What are some causes of pruritis in cancer patients?
Renal failure, hepatitis, polycythaemia, cholestasis, haem malignancy, paraneoplastic, primary skin disease, drug reaction
What are some signs that can be used to recognise a dying patient?
Weak, gaunt, drowsy, disorientated, poor oral intake,
abnormal breathing patterns (Cheyne-Stokes), worsening mobility, poor communication
What are the anticipatory meds given at end of life? and what are each used for?
Morphine: for pain Haloperidol: agitation and N+V Midazolam: agitation and anxiety Levomepromazine: N+V Glycopyrronium: troublesome resp secretions
What are some reversible causes of agitation at end of life?
Pain, dehydration, retention, hypercalcemia, infection
What are the features of neutropenic sepsis?
Temp >38 and neutrophil count <0.5
Drowsiness, confusion, tachycardia, hypotension, tachypnoea
What is the most common day of chemo for neutropenic sepsis to occur?
Day 10
What is the management for neutropenic sepsis?
Sepsis 6 with IV abx (tazocin) within 1h
What cancers is spinal cord compression particularly associated with?
Lung, prostate, breast, myeloma
Which region of the spine does spinal cord compression usually affect?
Thoracic in 70%
What are some features of spinal cord compression?
Back pain (nocturnal, with straining), limb weakness, difficulty walking, sensory loss, bowel/bladder dysfunction
What investigation needs to be performed urgently if spinal cord compression is suspected?
MRI of whole spine
What management options are there for spinal cord compression?
Dexamethasone with PPI
Radiotherapy within 24h of MRI diagnosis
Decompressive surgery in fit pts
What are the cancers associated with superior vena cava obstruction?
Lung (75%), lymphoma, mets (e.g. breast), thymoma
What are some features of superior vena cava obstruction?
SOB, swelling of face, neck, trunk and arm, stridor, cough, headache, engorged neck + chest wall veins
What investigations should be performed if SVCO is suspected?
CXR, CT with contrast
What is the management for SVCO?
Prop up, O2, dexamethasone
SVC stent
Chemo/RT
What are the two main causes of hypercalcemia in cancer patients?
PTH-related peptide produced by tumour (80%), osteolytic mets with local release of cytokines (20%)
What are the features of hypercalcemia?
Weight loss, nausea, polydipsia, polyuria, constipation, abdo pain, dehydration, weakness, confusion, seizure
How should hypercalcemia be managed?
Rehydration, bisphosphonates
What is the pathophysiology of tumour lysis syndrome?
Chemotherapy for rapidly proliferating tumours (leukaemia, lymphoma, myeloma) leads to cell death and hyperuricemia, hyperkalaemia, hyperphosphatemia, hypocalcaemia, raised creatinine
What are some complications of tumour lysis syndrome?
AKI, seizures and arrhythmias
What are some risk factors for tumour lysis syndrome?
Pre-existing renal dysfunction, hypovolemia
What are some features of tumour lysis syndrome?
Day 3-7 post chemo
N+V, diarrhoea, anorexia, lethargy, anuria, HF, arrhythmias
What is the management for tumour lysis syndrome?
Hydration, allopurinol or rasburicase
Haemodialysis last resort
What are the most common cancers associated with brain mets?
Lung, breast, colorectal, melanoma
What are some features of brain mets?
Headache (worse in morning, coughing, bending)
Focal neuro signs, ataxia, fits, N+V, papilloedema
What is the management for brain mets?
Urgent CT/MRI
Dexamethasone 16mg/24h
Stereotactic RT
Neurosurgery
What is the model used for breaking bad news?
SPIKES
Setting, perception, invitation, knowledge, empathy, summary
What is the aim of cancer screening programmes?
Pick out those who need further investigation to rule out or diagnose a cancer, in the hope the early diagnosis and treatment results in better outcomes
What are the risks of screening programmes?
Anxiety, harm, cost
False positives resulting in further invasive tests
False negatives conferring inappropriate reassurance
What is the aim of the MDT in cancer management?
Coordinate high quality diagnosis, treatment and care Make a recommendation on the best initial treatment for the cancer
What are the criteria for urgent CXR when suspecting lung cancer?
> 40y and: recurrent chest infection, clubbing,
supraclavicular/cervical lymphadenopathy, thrombocytosis, two symptoms
What are the criteria for urgent CT pancreas?
> 60y plus weight loss plus any of: diarrhoea, back pain,
abdo pain, nausea, constipation, new-onset diabetes
What are the 2WW referral criteria for suspected gynae cancer?
Ascites, pelvic mass, >55y with PMB
What are some features suggestive of hereditary cancer syndromes?
unusual early age, multiple primary cancers, clustering of cancers in relatives, cancers in multiple generations, rare tumours
What is the lifetime risk of breast cancer associated with BRCA1 and BRCA2 mutations?
55-65% and 45% respectively
What is Lynch syndrome and what cancers are sufferers at risk of?
Mismatch repair genes mutated
Lifetime risk of CC is 80%
Increased risk of gynae and GI cancers
How should those with Lynch syndrome be monitored?
Colonoscopic surveillance (every 2y) from 25-75y
What is familial adenomatous polyposis?
Mutations in APC gene
Multiple colorectal adenomas which undergo malignant transformation
How should those with familial adenomatous polyposis be monitored?
Surveillance sigmoidoscopy from 12y and prophylactic surgery usually <25y
List some examples of paraneoplastic syndromes:
Hypercalcemia, SIADH, Cushing’s, Lambert-Eaton, acanthosis nigricans
What cancers is alpha-fetoprotein a tumour marker in?
Germ cell/testicular, hepatocellular
What cancers is bombesin a tumour marker in?
Small cell lung, gastric, neuroblastoma
What cancer is calcitonin a tumour marker in?
Medullary thyroid
What cancer is CA-125 a tumour marker in?
Ovarian
What cancer is CA19-9 a tumour marker in?
Pancreatic
What cancer is CA15-3 a tumour marker in?
Breast
What cancer is CEA a tumour marker in?
Colorectal
What cancers is hCG a tumour marker in?
Germ cell/testicular, gestational trophoblastic
What cancers is S-100 a tumour marker in?
Melanoma, schwannoma
At what level of Hb should pt receive red cell transfusion?
70g/L
Over what time period should red cells be transfused (non-urgent)?
90-120 mins
At what level should platelets be transfused?
<20
Pre-surgery aim >50
When should FFP be transfused?
Major haemorrhage or used to correct clotting
defects e.g. DIC, warfarin overdose, liver disease
What are some early transfusion complications?
Acute haemolytic reactions Anaphylaxis and allergic reactions Bacterial contamination Febrile reactions Fluid overload Transfusion related acute lung injury
What are some delayed transfusion complications?
Infections (hep, HIV)
Iron overload
GVHD
Post-transfusion purpura
What are some complications of massive blood transfusions?
Low platelets, hypocalcaemia, low clotting factors,
hyperkalaemia, hypothermia
What precautions should be taken when transfusing in a patient with heart failure?
Give each unit over 4h with furosemide with alternate units
When are CMV negative blood products given?
Neonates and pregnant women
When are irradiated blood products given?
Neonates
BM/stem cell transplants
Immunocompromised
With/previous Hodgkin’s lymphoma
What are some signs of acute haemolytic reaction during transfusion?
Agitation, rapid increased temp., hypotension,
flushing, abdo/chest pain, DIC
How should acute haemolytic reaction during transfusion be managed?
STOP transfusion, treat DIC
What are some signs of bacterial contamination of transfusion product?
Rapid increase in temp, hypotension, rigors
How should bacterial contamination during transfusion be managed?
STOP transfusion, broad spec Abx
What are some signs of TRALI?
Dyspnoea, cough, CXR white out, hypoxia
How should TRALI be managed?
STOP transfusion, give 100% O2, treat as ARDS
Remove donor from donor panel
What are some signs of transfusion associated circulatory overload?
Dyspnoea, hypoxia, tachycardia, JVP, creps
How should TACO be managed?
SLOW or STOP transfusion
O2 and diuretic
How should non-haemolytic febrile transfusion reaction be managed?
SLOW or STOP transfusion
Anti-pyretic, monitor closely
When should metoclopramide be avoided?
Bowel obstruction, Parkinson’s
What are some causes of microcytic anaemia?
IDA, thalassemia, lead poisoning, sideroblastic
What are some causes of normocytic anaemia?
Anaemia of chronic disease, CKD, aplastic anaemia, haemolytic anaemia, acute blood loss
What are some causes of macrocytic anaemia?
B12 def., folate def., alcohol, liver disease, hypothyroidism, reticulocytosis, myelodysplasia
What are some causes of iron deficiency anaemia?
Blood loss (menorrhagia, GI bleed) Inadequate dietary intake Poor intestinal absorption Increased iron requirements (children, pregnancy)
What are some presenting features in IDA?
Fatigue, SOB, palpitations, pallor, koilonychia
What investigations may be performed to investigate IDA?
FBC, blood film
Serum ferritin
TIBC/transferrin (high, reflecting low iron stores)
Endoscopy
How should IDA be treated?
Treat underlying cause
Oral ferrous sulfate, iron rich diet (leafy veg, meat), IV iron
Describe the pathophyisology of sickle cell anaemia:
Polar amino acid glutamate is substituted by non-polar valine in each of the two beta chains
In the deoxygenated state the HbS molecules polymerise and cause RBCs to sickle
Sickle cells are fragile and haemolyse; they block small BVs and cause infarction
What is the inheritance pattern of sickle cell anaemia?
Autosomal recessive
How can sickle cell anaemia be investigated?
Haemoglobin electrophoresis
Describe thrombotic sickle cell crisis:
Painful or vaso-occlusive crises, infarcts in various organs
Precipitated by infection, dehydration, deoxygenation
Describe sequestration sickle cell crisis:
Sickling within organs such as the spleen or lungs causes pooling of blood with worsening of the anaemia
Describe aplastic sickle cell crisis:
Infection with parvovirus, sudden fall in Hb
Describe acute chest syndrome sickle cell crisis:
Dyspnoea, chest pain, pulmonary infiltrates, low pO2
What is the management for sickle cell crisis?
Analgesia e.g. opiates, fluids, O2, Abx if infection, blood transfusion
How is B12 absorbed?
Absorbed after binding to intrinsic factor (from
parietal cells in the stomach) and is actively absorbed in the terminal ileum
What are some causes of B12 deficiency?
Pernicious anaemia, post gastrectomy, vegan or poor diet, Crohn’s
What are the features of B12 deficiency?
Macrocytic anaemia, sore tongue and mouth, neurological symptoms: e.g. ataxia, neuropsychiatric symptoms: e.g. mood disturbances
How should B12 deficiency be managed?
1 mg of IM hydroxocobalamin 3x/week for 2 weeks, then once every 3m
What is warm AIHA?
Antibody (usually IgG) causes haemolysis best at body temp and haemolysis tends to occur in extravascular sites e.g. spleen
What are some causes of warm AIHA?
Autoimmune disease (SLE) Neoplasia (lymphoma, CLL) Drugs (methydopa)
How should warm AIHA be managed?
Steroids, immunosuppression and splenectomy
What is cold AIHA?
Antibody (usually IgM) causes haemolysis best at 4°C Haemolysis is mediated by complement and is more commonly intravascular
What are some causes of cold AIHA?
Neoplasia (lymphoma), infections (mycoplasma, EBV)
What are the components of a haemolysis screen?
FBC, smear, LDH, LFTs, haptoglobin, reticulocytes
What are some hereditary causes of haemolytic anaemia?
Spherocytosis, G6PDH def., sickle cell, thalassemia
What are some acquired causes of haemolytic anaemia?
Autoimmune, transfusion reaction, haemolytic disease of newborn, methyldopa
HUS, DIC, pre-eclampsia, prosthetic valves
In what conditions may target cells be seen on blood film?
Sickle-cell/thalassaemia
IDA
Hyposplenism
Liver disease
In what conditions may ‘tear-drop’ poikilocytes be seen on blood film?
Myelofibrosis
In what conditions may spherocytes be seen on blood film?
Hereditary spherocytosis, AIHA
In what conditions may Howell-Jolly bodies be seen on blood film?
Hyposplenism
In what conditions may Heinz bodies be seen on blood film?
G6PDH def., alpha thalassemia
In what conditions may pencil poikilocytes be seen on blood film?
IDA
In what conditions may schistocytes be seen on blood film?
Intravascular haemolysis, mechanical heart valve, DIC
In which clotting condition would there be: increased APTT, normal PT, normal bleeding time?
Haemophilia
In which clotting condition would there be: increased APTT, normal PT, increased bleeding time?
vWB disease
In which clotting condition would there be: increased APTT, increased PT, normal bleeding time?
Vit K def.
What pathways are tested by APTT and PT?
APTT tests intrinsic and common pathways
PT tests extrinsic pathway
What conditions cause a prolonged APTT?
Def. in the tested factors e.g. FVIII or FIX in
haemophilia A and B respectively
DIC and heparin
What conditions cause a prolonged PT?
Warfarin, severe liver disease, vitamin K def, DIC and sepsis
Describe the management of a DVT with heparin and warfarin:
LMWH given at diagnosis
Warfarin should be given within 24h of the diagnosis LMWH continued for at least 5d or until the INR ≥ 2.0 for at least 24h
Warfarin should be continued for at least 3m. 6m if unprovoked
What are some causes of DIC?
Sepsis
Trauma
Obstetric complications e.g. amniotic fluid embolism or HELLP syndrome
Malignancy
What results of investigations would be diagnostic of DIC?
Low platelets, prolonged APTT, PT and bleeding time, fibrin degradation products raised
What is the most common thrombophilic condition?
Factor V Leiden
What is the inheritance pattern for G6PDH deficiency?
X-linked recessive
What is the inheritance pattern for hereditary spherocytosis?
Autosomal dominant
What infection can precipitate a haemolytic crisis in hereditary spherocytosis?
Parvovirus
What drugs can precipitate haemolysis in G6PDH def.?
Primaquine, ciprofloxacin, sulphonylurea, sulfasalazine
Describe haemophilia A and B:
X-linked recessive
A is due to a def. of factor VIII
B lack of factor IX
What are the some signs of haemophilia?
Haemoarthroses, haematomas, prolonged bleeding after surgery or trauma, prolonged APTT
What is the most common inherited bleeding disorder?
von Willebrand disease
What is the role of von Willebrand factor?
Promotes platelet adhesion
Carrier molecule for factor VIII
What are the three types of von Willebrand disease?
Type 1 (80%): partial reduction in vWF Type 2: abnormal form of vWF – poor platelet adhesion or interaction Type 3: total lack of vWF
What is the management for von Willebrand disease?
Tranexamic acid for mild bleeding
Desmopressin
Factor VIII concentrate
