Cancer + bleeding disorders

Question 1

Chronic myeloid leukaemia summary card

Answer 1

Uncontrolled proliferation of granulocyte precursors in BM but slower than AML caused by Philadelphia chromsome in 80% pts (t(9,22) - BCR-ABL fusion gene)
- asymptomatic, may present with gout, hyperviscosity, (headache, visual disturbance, thrombotic event), hypermetabolic (wt loss, sweaty, malaise), BM failure
- increased WCC (>100x1o^9)
- massive splenomegaly in 90% cases

Question 2

Acute myeloid leukaemia summary card

Answer 2

Blast cells do not go on to form promyelocyte -> myelocyte -> neutrophils etc
- present with bone failure
- accumulation of myeloblast cells (>20%) on blood film; AUER RODS present
- RFs: irradiation, Downs’, anti-cancer drugs, increased incidence with age
- promyelotic, aggressive subtype due to t(15;17), associated with DIC

Question 3

Chronic lymphocytic leukaemia summary card

Answer 3

Accumulation of mature incompetent lymphocytes as they are unable to undergo apoptosis
- associated with autoimmune thrombocytopenia + anaemia = Evan’s syndrome
- asymptomatic largerly, may present with bone marrow failure, enlarged non-tender lymphadenopathy, hepatosplenomegaly
- Blood film shows SMEAR/SMUDGE cells (cells are so fragile)

Question 4

Acute lymphoblastic leukaemia summary card

Answer 4

Uncontrolled proliferation of lymphoblasts, most commonest cancer of childhood (75% under 6yo)
- 75% are B cell ALL
- present with bone failure (low Hb + plts but high WCC)
- T cell enlargers thymus leading to mediastinal compression thus wheeze
- hepatosplenomegaly, enlarged lymph nodes, swollen testes

Question 5

What do you see in bone marrow failure?

Answer 5

Anaemia
- fatigue, pallor, SOB
Neutropenia
- recurrent infections
Thrombocytopenia
- bleeding and easy bruising

Question 6

If the pt has the following, which leukaemia do they have?
a) Auer rods on blood film
b) Smear cells on blood film
c) Child with easy bruising, splenomegaly and a wheeze
d) t(15;17) mutation
e) t(9;22) mutation

Answer 6

a) AML
b) CLL
c) ALL
d) AML myelotic subtype
e) CML

Question 7

Buzzword differences between the lymphomas

Answer 7

Hodgkin’s
- Reed Sternberg cells (Owl’s eyes)
- painful after alcohol ingestion
Non-Hodgkin’s
- HIV, SLE, Sjorgen’s association (EBV assoc. w/ both HL and NHL)
Burkitt’s (subtype of NHL, B cell)
- African child
- starry sky appearance under microscope

Question 8

Hodgkin’s lymphoma summary card

Answer 8

Malignant proliferation of lymphocytes occuring in 20-30 or >50 yo (bimodal)
- association with EBV (50% cases)
- painless enlarging mass in neck/axilla/groin, becomes painful after alcohol
- non-tender firm rubbery lymphadenopathy, fever, night sweats, wt loss, +/- hepatosplenomegaly
- Lymph node biopsy with Ann Arbour staging shows Reed Sternberg cells (Owl’s eyes)

Question 9

Non-Hodgkin’s lymphoma summary card

Answer 9

Malignancy of lymphoid cells in lymph nodes WITHOUT Reed-Sternberg cells
- 85% are B cells, 15% are T/NK cells
- associated with EBV, HIV, SLE, Sjorgen’s syndrome
- increased incidence with age
- painless, enlarging mass in neck/axilla/groin, bone marrow failure, hepatosplenomegaly, sore throat, headache, shin rashes (more common to have organ involvement than B sx)
- lymph node biospy and Ann Arbour staging

Question 10

Burkitt’s summary card

Answer 10

Subtype of NHL B cell
- occurs in large lymph node in the jaw, fast-growing
- buzzword: African child
- under microscope a starry sky appearance is seen

Question 11

What is multiple myeloma?

Answer 11

Haematological malignancy characterised by proliferation of plasma cells and production of monoclonal immunoglobulin (IgG/IgA)

Question 12

What results in multiple myeloma?

Answer 12

Unknown cause, potential viral trigger
RFs: ionising radiation, HIV, agricultural work, occupational chemical exposure (benzene, herbicides)

Question 13

How may multiple myeloma present and why?

Answer 13

> 70yo from Afro-Carribean > Caucausian > Asian

C alcium
- tired, thirsty, polyuria, nausea, constipation
R enal impairment
- Ig deposits in kidney, present in 20% cases
A naemia
- neutropenia, thrombocytopenia as BM infiltrated by plasma cells
B one pain/lesions
- increased osteoclast activation due to myeloma cell signalling in the back/ribs

Question 14

What is MGUS?

Answer 14

Monoglonal gammopathy of unknown significance
- pre-malignant condition
- accumulation of some monoclonal plasma cells
- absent CRAB features

Question 15

Ix for multiple myeloma

Answer 15

Bloods
=> increased ESR, CRP, urea/Cr, calcium, normal ALP
Blood film
=> rouleax formation
Serum/urine electrophoresis
=> Bence Jone proteins*
Serum monoclonal protein
=> >30g/L
BM aspirate
=> increased plasma cella (>10%)

Question 16

Compare the haemophilias

Answer 16

X-linked genetic disorder
Haemophilia A = FVIII (more common)
Haemophilia B = FIX
Both lead to a prolonged APTT and factor assays confirm the diagnosis

Question 17

How do haemophilias present?

Answer 17

Presents in children after surgery/trauma
- excessive bleeding/bruising
- haematuria, haemarthrosis, haematomas (increased risk of compartment syndrome/nerve palsies)
- O/E signs of IDA, joint deformity, pallor

Question 18

What are the types of von Willebrand disease?

Answer 18

Type 1 (AD): reduced levels of normal vWF
Type 2 (AD): defective vWF
Type 3 (AR): complete lack of vWF and decreased FVIII
- most severed; bleeding into joints + soft tissues

Question 19

How may vWD present?

Answer 19

More superficial bleeding compared to haemophiliacs
Bruising, epistaxis, menorrhagia
Increased gum bleeding post tooth extraction
Prolonged bleeding from minor wounds

Question 20

Ix for vWD

Answer 20

APTT = increased
PT = normal
Bleeding time = increased
vWF levels = low
platelets = normal
FVIII = low

Question 21

What is DIC?

Answer 21

Disseminated intravascular coagulation is when there is a systemic activation of coagulation, which leads to:
1) intravascular deposition of fibrin => thrombosis of small and mid-size vessels with organic failure (ischaemic organ damage)
2) depletion of platelets and coagulation factors => bleeding

Question 22

What type of anaemia is caused by DIC and how?

Answer 22

Microangiopathic haemolytic anaemia (MAHA)
- the fibrin deposits in mircocirculation cause RBCs to flow against pressure thus they become fragmented
- peripheral blood film would show schistocytes

Question 23

How might DIC present?

Answer 23

Acute, onset => sepsis, trauma, obstetric complication, malignancy

Pt is severely unwell with underlying disease sx and evidence of bleeding:
a) ACUTE => petechiae, purpura, ecchymores, epistaxis, mucosal bleeding, haemorrhage, respiratory distress
b) CHRONIC => deep venous/arterial thrombosis or embolism

Question 24

Ix for DIC show

Answer 24

FBC = low platelets, low Hb
Clotting = low fibrinogen, increased PT/APTT, increased fibrin degredation products
Peripheral blood film = schistocytes (MAHA)

Question 25

A 5 year old boy of Indian ethnic origin presented with lymphadenopathy and a mediastinal mass on CXR.
WBC: 180 x 109/L
Hb: 93 g/L
Plts: 43 x 109/L
Blood film shows blast cells

What is the most likely cause of the mediastinal mass?
a) Thymoma
b) Acute myeloid leukaemia
c) Acute lymphoblastic leukaemia
d) Haemorrhage into the mediastinum
e) Pneumonia with leukaemoid reaction

Answer 25

c) Acute lymphoblastic leukaemia

Question 26

An 83 year old man with no abnormal physical findings is found to have a high white cell count and high lymphocyte count on a blood test.
A blood film is requested and it is found to have smear cells.

What is the most likely diagnosis?

a) Acute lymphoblastic leukaemia
b) Chronic lymphocytic leukaemia
c) HIV infection
d) Infectious mononucleosis
e) Whooping cough

Answer 26

b) Chronic lymphocytic leukaemia

Question 27

A 1 year old boy presented to A&E department with a swollen right elbow following minor trauma. On examination and radiology there was no evidence of bony injury. He was sent home.
3 days later he was brought back with increased pain and swelling. Joint aspiration yielded haemorrhagic fluid.
A coagulation screen was performed which showed a normal PT and a prolonged APTT of 96 seconds (NR 24-35s). The prolonged APTT was corrected by mixing the infant’s plasma with normal plasma.

What is the most likely diagnosis?
a) Disseminated intravascular coagulation
b) Von Willebrand’s disease
c) Haemophilia
d) Autoimmune thrombocytopenia
e) Fracture of the elbow

Answer 27

c) Haemophilia

Question 28

A 16 year old boy presents to his GP complaining of nosebleeds and bleeding after brushing his teeth. He is unsure of how long it has been going on for but decided to seek advice after having to continually excuse himself from lessons. On examination you notice he has some skin bruises. A blood test shows a prolonged bleeding time and APTT. Platelet count and PT are normal.

What is the most likely diagnosis?
a) Von Willebrand disease
b) Liver disease
c) Disseminated intravascular coagulation
d) Congenital afribrinogenaemia
e) Haemophilia

Answer 28

a) von Willebrand disease