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Miscellaneous Flashcards

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1
Q

What is polycythaemia vera?

A

Myeloproliferative disorder

Caused by clonal proliferation of haematopoietic progenitor cells

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2
Q

What is primary polycythaemia?

A

Due to mutation - inherited or acquired

Main cause is polycythaemia vera

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3
Q

What is secondary polycythaemia?

A

Due to increased EPO production

Hypoxia induced rise:
smoking, CLD, COPD, obesity, OSA

Inappropriate EPO rise
Renal cell cancer, Wilm’s
Adrenal tumours

Illicit EPO use

Androgen use, testosterone replacement

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4
Q

What is relative polycythaemia?

A

Increase in haematocrit or Hb count in presence of normal red cell mass
Decrease in plasma volume

Dehydration e.g. diarrhoea, vomiting, diuretics use

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5
Q

What is the pathogenesis of polycythaemia vera?

A

98% patients have JAK2 mutation - tyrosine kinase

V617F mutation, mutations in exon 12

Mutations result in proliferation of haematopoeitic precursors

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6
Q

What are the clinical features of polycythaemia vera?

A

Some asymptomatic with raised Hb/haematocrit incidentally on blood tests

If presenting symptomatic - may have gradual creeping onset, non-specific due to increased blood viscosity

Headache, visual disturbance
Tinnitus, itching, fatigue
Vertigo, paraesthesia

Bruising, excoriation, conjunctival infection, splenomegaly, erythromelalgia

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7
Q

What are the investigations for polycythaemia vera?

A

FBC raised Hb or haematocrit

Raised serum EPO suggestive of secondary polycythaemia

Raised WCC and platelet count suggestive of PV

Serum ferritin, serum uric acid

Genetic testing for JAK2 V617F in exon 14 or mutations in exon 12

Bone marrow biopsy to distinguish PV from secondary polycythaemia

USS to identify splenomegaly, identify renal or hepatic tumours;
CT, MRI, PET-CT

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8
Q

When can a diagnosis of polycythaemia vera be made following investigations?

A
  1. High haematocrit (> 0.52 in men, > 0.48 in women) OR raised red cell mass (>25% above predicted)
  2. Mutation in JAK2
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9
Q

What is masked polycythaemia vera?

A

Haemoglobin and haemtocrit count normal despite presence of disease

Typically occurs in setting of iron deficiency where effect of JAK2 mutation blunted

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10
Q

What is the management of polycythaemia vera?

A

Reduce complications, symptoms and reduce risk of transformation to myelofibrosis or acute leukaemia

Maintain haematocrit at <0.45

Venesection - 200-500mls at a time

Low dose aspirin, 75mg once daily to reduce thrombotic events

Cytoreduction therapy in high risk patients -
hydroxycarbamide (antimetabolite)
or interferon-alpha, ruxolitinib and busulfan

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11
Q

Who can be considered for cytoreductive therapy?

A

Age >65 years and/pr
Prior PV associated arterial or venous thrombosis

Also considered in low risk with 
Thrombocytosis
Progressive splenomegaly
Progressive leucocytosis
Poor tolerance of venesection
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12
Q

What is Budd Chiari syndrome?

A

Hepatic vein thrombosis

Lead to tender hepatomegaly, ascites, and sudden severe abdominal pain

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13
Q

What complication can arise from Polycythaemia Vera?

A

AML transformation

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14
Q

What is primary myelofibrosis?

A

Proliferation of haematopoietic stem cells in the marrow and at other sites leading to fibrosis

Marrow is replaced with scar tissue

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15
Q

At what age is primary myelofibrosis most prevalent?

A

60yo

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16
Q

What signs and symptoms are commonly seen in primary myelofibrosis?

A

Typically elderly present with anaemia
B Symptoms
Massive splenomegaly

\+/-
Spontaneous bleeding
DCIS
Oesophageal varices
Petechiae
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17
Q

What investigation findings would you expect with myelofibrosis?

A

Anaemia
WCC and platelets high in early disease then low

Bone marrow aspiration = dry tap
So need to do trephine biopsy

“Tear drop” poikilocytes (RBC’s) on blood film

Poikilocytosis - varying sizes of red blood cells
and immature red and white cell blasts

High urate and LDH

Homozygous JAK2 or MPL mutation

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18
Q

How is primary myelofibrosis managed?

A

Allogenic stem cell transplant is the only cure

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19
Q

What is the palliative/symptomatic management for primary myelofibrosis?

A

Red cell transfusion/EPO for anaemia

hydroxyurea or splenectomy - splenomegaly

prednisolone - cytopenic

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20
Q

What are the complications of primary myelofibrosis?

A

progress to blast phase - like AML
portal hypertension
splenic infarct
immune deficiency

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21
Q

What is essential thrombocythaemia?

A

Failure in platelet production regulation

Malignant megakaryocyte proliferation

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22
Q

At what age do people get essential thrombocythaemia?

A

60yo

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23
Q

What are the common signs and symptoms of essential thrombocythaemia?

A

Burning sensation in hands

Mixed thrombosis and bleeding in any system:
Dusky extremities
TIA and amaurosis fugax
Arterial and Venous thrombosis (leg, MI, hepatic, renal)
Bleeding - GI, gums, eyes, urinary

Sweating/Fever
Hepato/splenomegaly

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24
Q

Why can you see bleeding in essential thrombocythaemia?

A

clotting factors run out

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25
How do you diagnose essential thrombocythaemia?
Diagnosis of exclusion
26
What is found in investigations of essential thrombocythaemia?
Platelet count >600 High WCC, RBC but low Hb thrombocytes on blood spear hypercellular bone marrow with giant megakaryocytes and increased reticulin Impaired platelet aggregation Philadelphia chromosome absent Heterozygous JAK2 or MPL mutation
27
What factors puts a patient with essential thrombocythaemia at high risk?
>60yo History of thrombosis Very high platelet count
28
How do you manage Essential Thrombocythaemia patients?
Aspirin Hydroxyurea Interferon-alpha
29
Why is hydroxyurea used in essential thrombocythaemia?
anti-metabolite --> reduce platelets
30
What are the main complications of essential thrombocythaemia?
Thrombosis Haemorrhage AML transformation
31
What is encompassed in a VTE?
Pulmonary embolism (PE): acute/chronic occlusion of pulmonary arteries. Clot breaks off and travels to the lungs (emboli). Deep vein thrombosis (DVT): acute/chronic occlusion of deep vein(s). Commonly affects the lower limbs through the formation of a clot forms (thrombus).
32
Where can a DVT be located?
Distal - below popliteal trifurcation, can resolve spontaneously without symptoms Proximal - above popliteal, may affect popliteal, femoral or iliac veins 50% develop PE within 3 months Other - name according to vessel or location of thrombus
33
What can cause a DVT?
Provoked - transient or persistent risk factors, typically within three months of event Unprovoked - no identifiable risk factor, not easily correctable
34
What are some of the risk factors for VTE?
``` Intrinsic factors Hx of DVT Cancer Obesity Acquired or inherited thrombophilia Inflammatory disorders Varicose veins Smoking Male sex Older age >60 years ``` ``` Transient factors Hospitalisation Recent major surgery Recent major trauma Significant immobility Hormone therapy e.g. COCP or HRT Long distance flights Dehydration Acute infection Pregnancy + 6 weeks PP ```
35
What is Virchow's triad?
Pathophysiology of DVT based on this Venous stasis Hypercoaguable state Endothelial injury
36
What are the clinical features of DVT?
Classically with painful, unilateral leg swelling Warm to touch, surrounding erythema Calf asymmetry - diameter >3cm increases likelihood Venous distention Oedema Tenderness along deep veins
37
What are some examples of thrombophilias?
``` Antiphospholipid syndrome (this is the one to remember for your exams) Antithrombin deficiency Protein C or S deficiency Factor V Leiden Hyperhomocysteinaemia Prothombin gene variant Activated protein C resistance ```
38
What VTE prophylaxis is given when admitted to hospital?
If at increased risk LMWH e.g. enoxaparin unless contraindicated (active bleeding or existing anticoagulation with warfarin or NOAC) Antiembolic stockings (unless significant peripheral arterial disease)
39
What is the Well's score and its meaning?
10 criteria, score 0-9 Score >2 - DVT likely, proximal leg vein US within 4 hours or d-dimer, interim anticoagulant, US in 24 hrs Score <1 - DVT 5% D-dimer If positive, proceed to leg vein US testing
40
What is the d-dimer test?
D-dimer is fibrin degradation product | Created when blood clots broken down by fibrinolytic system
41
What should be done if d-dimer positive but scan negative?
Interim anticoagulation should be stopped Patient offered repeat proximal leg vein ultrasound in 6-8 days Looks for possible extension of a distal DVT into the proximal veins that require treatment
42
What anticoagulation is given in DVT?
LMWH DOACs Vit K antagonists e.g. warfarin If stable, no renal impairment or co-morbidities - apixiban, rivaroxaban Active cancer DOAC e.g. edoxaban Renal impairment LMWH If starting warfarin, must have two consecutive INR readings >2 before stopping LMWH (bridging therapy)
43
What long term management is required for DVT?
Minimum of 3 months 3-6 months for active cancer Exploration of cause if unprovoked DVT Thrombophilia testing Cancer
44
What is a classical complication of DVT?
Most concerning is PE Post thrombotic syndrome - chronic swelling, pain, skin changes from venous stasis
45
What cell lineages are affected in myeloproliferative diseases?
Myelofibrosis - haematopoietic stem cell Polycythaemia vera - erythroid cells Megakaryocyte - essential thrombocytopenia
46
What is myelofibrosis and its pathophysiology?
Can be result of primary myelofibrosis, PV or ET. Proliferation of cell line causes fibrosis of bone marrow, replaced by scar tissue - because cytokines released from proliferating cells e.g. fibroblast growth factor. Means haematopoiesis starts to occur elsewhere - liver and spleen Hepatomegaly, splenomegaly, portal hypertension If occurs round the spine can cause spinal cord compression
47
What is the presentation of myeloproliferative disorders?
Can be asymptomatic Fatigue, weight loss, night sweats, fever Anaemia, splenomegaly, abdo pain, portal hypertension - ascites, varices, abdo pain Low platelets Thrombosis
48
What are three key signs on examination in polycythaemia vera?
Conjunctival plethora - excessive redness to the conjunctiva in the eyes A 'ruddy' complexion Splenomegaly
49
What is myelodysplastic syndrome?
Caused by myeloid bone marrow cells not maturing properly Not producing healthy blood cells Causes anaemia, neutropenia, thrombocytopenia
50
Who is myelodysplastic syndrome more common in?
Those over 60 | Patients who have previously had treatment with chemo or radiotherapy
51
What is the management of myelodysplastic syndrome?
Watchful waiting Supportive treatment e.g. blood transfusions if severely anaemia Chemotherapy Stem cell transplant Risk of transforming into acute myeloid leukaemia
52
What are differentials of abnormal or prolonged bleeding?
Thrombocytopenia (low platelets) Haemophilia A and haemophilia B Von Willebrand Disease Disseminated intravascular coagulation (usually secondary to sepsis)
53
What is the management for ITP?
Prednisolone (steroids) IV immunoglobulins Rituximab (a monoclonal antibody against B cells) Splenectomy
54
What is HIT?
Heparin induced thrombocytopenia Development of antibodies against platelets in response to exposure to heparin Target protein on the platelets called platelet factor 4 Binds to platelets, activates clotting mechanisms Causes hypercoaguable state Leads to thrombosis Breaks down platelets, causes thrombocytopenia
55
What are the functions of the spleen?
Production and maturation of T, B and Plasma cells Removal of unwanted bacteria - encapsulated Reservoir for blood cells
56
How does splenomegaly present?
LUQ mass Early satiety Abdominal discomfort Pancytopaenia
57
What is noted on examination of a splenic mass?
Heads towards RLQ Moves on respitation Dull to percuss Can't palpate above
58
What causes MASSIVE splenomegaly?
``` CML Myelofibrosis Malaria Gaucher's syndrome (hereditory) Visceral Leischmaniasis (parasite) ```
59
What FBC results would you see with hyperspenism and why?
Pancytopaenia due to pooling and destruction of cells
60
Where are blood cells destroyed in the spleen?
Reticulo-endothelial system
61
How does hypersplenism present?
Anaemia Infection Bleeding
62
What are the causes of splenomegaly?
Haematological: malignancies, haemolytic anaemia, sickle cell sequestration crisis Infectious: Hep, TB, malaria, EBV Congestive: HF, splenic vein obstruction, liver cirrhosis, Budd-Chiari Abscess or cyst Autoimmune/inflammatory: SLE, RA, sarcoid
63
What are the indications for splenectomy?
Spontaneous rupture Hypersplenism Malignant Infiltration Idiopathic thrombocytopaenic purpura
64
What are the complications of splenectomy? How could you prevent the consequences of one of these complications?
thrombocytosis --> peak within 7-10 days. Give prophylactic aspirin infection with encapsulated bacteria
65
Give examples of encapsulated bacteria
Haemophilus Influenzae Neisseria Meningitidis Streptococcus Pneumoniae Salmonella Typhi
66
If a patient has raised Hb but low circulating volume, what is this indicative of?
Relative polycythaemia i.e. concentrated lower plasma volume caused by burns, dehydration, fluid loss --> apparent Hb rise
67
You find a raised Hb and then note that circulating volume, WCC and platelets are all high, what does this indicate?
primary polycythaemia - usually polycythaemia vera
68
Hb and circulating volume high WCC and platelets low What does this indicate?
secondary polycythaemia Hypoxia = EPO release (COPD, local renal hypoxia, sleep apnoea, altitude) EPO production increased (Cushings, cerebellar haemangioma) Exogenous intake (often athletes)
69
What diseases can cause increased EPO production?
``` hydronephrosis Polycystic kidneys/liver Renal/Hepatic carcinoma Cushings Cerebella haemangioma ```
70
What are signs of primary causes of raised platelets?
symptoms + hepatosplenomegaly
71
What can cause a raised platelet count?
``` Reactive: infection, surgery Iron deficiency anaemia Myeloproliferative disorder Other malignancy Hyposplenism ```
72
What can cause a low platelet count (thrombocytopenia)?
Marrow damage: malignancy, virus, alcohol Increased clearance: DIC, TTP, ITP, HELLP Splenomegaly eg malaria, liver cirrhosis Dilutional following red cell transfusion
73
What can cause neutropenia?
``` Drugs: clozapine, carbimazole Virus: HIV, EBV Marrow failure: malignancy Reduced B12 or folate Immune diseases: RA, SLE Benign ethnic neutropenia ```
74
What can cause neutrophilia?
reactive: infection, inflammation (IBD, RA) malignancy: myeloproliferative, CML Hypo/asplenism Hypoxia Drugs: lithium, steroids
75
What can cause lymphadenopathy
Malignancy Infection Granulomatous diseases: TB, sarcoid Collagen vascular diseases: SLE, RA, sjogrens
76
where is a bone marrow sample often taken from?
Posterior superior iliac crest
77
What is the difference between a bone marrow aspiration and a trephine?
aspiration is liquid portion of the marrow | trephine take a solid piece
78
What is advanced care planning and what is an advanced decision to refuse treatment?
Care planning: not legally binding but sets out the persons wishes on any aspect of future care ADRT: legally binding if valid and applicable. It states which treatments under which circumstances a person does not wish to have
79
What is lead time bias?
Cancer picked up early so although screening appears to prolong life, life is not prolonged just time with cancer is longer
80
What is length time bias?
Screening picks up slow growing cancers that the person may never have noticed or been harmed by. Screening appears to prolong life of those found +ve whereas actually it may never have harmed them
81
In what cancers can Cushing's syndrome be seen
SCLC NSCLC Pancreatic cancer
82
What causes Cushing's syndrome?
Excess production of ACTH precursors
83
How does Cushing's syndrome present?
Rapid onset weakness Hyperpigmentation Metabolic disturbance
84
How is Cushing's syndrome treated?
Depend on cancer Bilateral adrenalectomy OR Metyrapone
85
What cancers can cause hypercalcaemia?
NSCLC Head and neck cancers Renal tumours
86
What cancers cause peripheral neuropathy?
``` SCLC Myeloma Hodgkins Breast GI ```
87
How do cancers cause peripheral neuropathy?
Autoimmune axonal degeneration/demyelination
88
What are key investigations for investigating metastatic disease of unknown primary?
FBC, U&Es, LFT, calcium, urinalysis, LDH Chest-xray CT chest abdomen pelvis AFP and hCG ``` Myeloma screen if lytic bone lesions Endoscopy directed towards symptoms PSA in men CA 125 in women with peritoneal malignancy or ascites Testicular US in germ cell tumours Mammography ```
89
What cancers if AFP associated with?
Liver cancer, germ cell tumours e.g. testicular cancer
90
What is B2M associated with?
Myeloma CLL Lymphoma
91
What is bHCG associated with?
Choriocarcinoma | Germ cell tumours
92
What is CA15-3 and CA27.29 associated with?
Breast cancer
93
What is CA19-9 associated with?
Pancreas, gallbladder, bile duct, gastric cancers
94
What is CA125 associated with?
Ovarian cancer
95
What cancer is calcitonin associated with?
Medullary thyroid cancer
96
What is CEA associated with?
Carcinoembryonic antigen | Associated with colorectal cancer
97
What is CgA associated with?
Neuroendocrine tumours Chromogranin A
98
What is fibrin/fibrinogen in the urine associated with?
Bladder cancer
99
What is LDH associated with?
Melanoma, leukaemia, lymphoma
100
What is PSA associated with?
Prostate cancer

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