Haematology / Oncology

Question 1

Vit K dependent clotting factors

Answer 1

II
VII
IX
X

Question 2

Presentation of ALL

Answer 2

• Bone pain at night
• Weight loss, fever
• Recurrent sore throat
• Petechial rash
• Pancytopenia

Question 3

Complication of chronic transfusions

Answer 3

Iron overload - no mechanism for excretion of excess iron

Question 4

Causes of microcytic anaemia

Answer 4

Iron deficiency
Thalassaemia
Anaemia of chronic disease

Question 5

Causes of normocytic anaemia

Answer 5

Bleeding
Haemolysis
BM failure
Anaemia of chronic disease
Renal failure - reduced EPO
Transient erythroblastopenia of childhood

Question 6

Causes of macrocytic anaemia

Answer 6

B12/ folate deficiency
Diamond-Blackfan
Liver disease
Hypothyroid

Question 7

Blood results in iron deficiency anaemia

Answer 7

Low Iron / ferritin
High Transferrin
Hypochromic, microcytic anaemia

Question 8

Causes of red cell aplasia

Answer 8

LOW RETICULOCYTES
- Diamond Blackfan anaemia
- Transient erythroblastopenia of childhood around 2y, triggered by infection.
- Parvovirus B19 induced aplastic anaemia (esp if already have haemolysis)

Question 9

Genetics and features of Diamond-Blackfan Anaemia

Answer 9

Dominant. Mutation RP519.
- Macrocytic anaemia as young infant
- Low reticulocytes
- 50% physical abnormalities - craniofacies, cleft, thumb abnormalities, growth restriction
- BM - low erythroid precursors. Other cell lines normal.
- High HbF and eADA
- Tx: steroids, RBC Tx, HSCT

Question 10

Acquired causes of haemolysis

Answer 10

• AI - idiopathic, SLE, JIA
• Microangiopathic - HUS
• Infection - malaria, sepsis
• Hypersplenism
• Burns
• Poisoning - lead, arsenic
• Allo-immune - haemolytic disease of the newborn

Question 11

What does positive Direct Coomb’s Test mean?

Answer 11

Immune mediated haemolytic anaemia

Question 12

Features of G6PD deficiency

Answer 12

X-linked recessive. More African, Asian, Mediterranean.
Eps of haemolysis triggered by oxidising agent eg broad bean, moth ball, co-trimoxazole, nitrofurantoin
Ix - G6PD enzyme assay, ‘bite cells’

Question 13

Features of hereditary spherocytosis

Answer 13

Dominant. Defect spectrin. More caucasian.
Defective spherical RBC –> destroyed –> gallstones, splenomegaly, jaundice
Ix: Film = spherocytes
Tx: folic acid. Splenectomy >5y following vaccines

Question 14

Features of AI haemolytic anaemia

Answer 14

50% idiopathic. Other causes: lymphoma, leukaemia, SLE, UC, mycoplasma
Destruction of RBC due to auto-Ab
Warm / cold - temp at which Ab reacts
Tx: Steroids, immunosuppression, remove cause

Question 15

Features of pyruvate kinase deficiency

Answer 15

Recessive. Rare.
Rigid cells –> haemolysis
Film - prickle cells
Pyruvate kinase assay
Tx - splenectomy

Question 16

Features of alpha thalassaemia

Answer 16

Alpha globin deletion Ch 16. Deletion 3 copies = HbH disease, 4 copies –> hydrops / death
Presents: Microcytic hypochromic anaemia, splenomegaly, jaundice
Ix: Film with brilliant cresyl blue stain / liquid chromatography

Question 17

Features of beta thalassaemia

Answer 17

Trait - 1 copy affected, Major - both copies affected.
Presents 12-18m. Severe anaemia, frontal bossing / maxillary swelling, hepatosplenomegaly
Ix: Microcytic hypochromic anaemia, target cells, nucleated RBC
Tx: Tx + desferrioxamine, ?splenectomy, BM transplant

Question 18

Genetics of sickle cell disease

Answer 18

Point mutation of beta-globin gene
Recessive. More African, Caribbean, Middle East, India
- Sickle cell anaemia - Homozygous mutation (HbSS)
- HbSC disease - Single beta cell mutation, HbC mutation
- S Beta thalasseamia - Beta globin and beta thalassaemia mutations

Question 19

Features of sickle cell associated with increased risk of painful crisis

Answer 19

High haematocrit
Low levels of HbF

Question 20

Presentations of sickle cell diseases

Answer 20

Chronic haemolytic anaemia and sickle cell crisis:
- Painful veno-occlusive eps eg dactylitis
- Sickle chest crisis
- Splenic / hepatic sequestration
- Aplastic crisis secondary to Parvovirus B19
- Cerebral infarction
- Increased risk infection - hyposplenism

Question 21

Management of sickle cell

Answer 21

1. Avoid precipitants - cold, dehydration, exercise
   - BD penicillin prophylaxis and Imms
   - Folic acid
   - Blood Tx and iron chelation
   - Crisis: Hydration, analgesia, ABx, O2

Question 22

Causes of BM failure / pancytopenia

Answer 22

• Inherited: Fanconi’s Anaemia, Schwachman-Diamond syndrome
• Infection eg HIV, EBV, CMV, Hep C/E
• Chemicals / radiation
• AI
• Acute leukaemia
• BM infiltration lymphoma / solid tumours
• Drugs - chemo
• Ostepetrosis

Question 23

Features of Fanconi Anaemia

Answer 23

Recessive. Mutation FANC / BRCA 2
DNA repair disorder, more cancer
BM failure
Short, microcephaly
Hyperpigmentation
Anomalies - upper limb, renal, genital
Ix: Chromosomal breakage test

Question 24

Features of Leukaemia

Answer 24

ALL - Lymphoid. Boys >girls. More common.
AML - Myeloid. Boys=Girls. Auer Rods.
Presentation:
- BM failure
- Tissue infiltration - bone pain, hepatosplenomegaly, lymphadenopathy, soft tissue lumps, englarged testes, mediastinal mass
- BM / CSF blasts

Question 25

Genetic syndromes with increased risk of leukaemia

Answer 25

Down's Fanconi anaemia NF1 Noonan Wiskott-Aldrich

Question 26

Tumour lysis syndrome features

Answer 26

Hyperkalaemia Hyperphosphataemia High urate Hypocalcaemia Leukaemia - rapid breakdown of blast cells

Question 27

Definition of polycythaemia and significance

Answer 27

Haemocrit >65% 00> hyperviscosity

Question 28

What does PT test?

Answer 28

EXRINSIC pathway. Play Tennis outside. Clotting factors II, V, VII, X Abnormalities: Liver disease, DIC, Vit K deficiency, warfarin

Question 29

What does APTT test?

Answer 29

INTRINSIC pathway. Play Table Tennis inside. II, V, VII, IX, X, XII, XI Abnormalities: Lupus anticoagulant, VWD, Haemophilia, heparin, antiphospholipid

Question 30

Pathophysiology of Haemophilia

Answer 30

X-linked recessive. Females have mild Sx. - Haemophilia A = Factor VIII deficiency (more common) - Haemophilia B = Factor IX deficiency

Question 31

Presentation of Haemophilia

Answer 31

Neonates - IVH, bleeding Mod - severe bleeding Spontaneous bleeding into joints / muscles --> arthritis Bleeding with procedures Bleeding easily Markedly deranged APTT, normal PT NB clotting factor assays

Question 32

Treatment of Haemophilia

Answer 32

Recombinant factor concenentrates Desmopressin

Question 33

Normal function of von Willebrand factor

Answer 33

1. Platelet adhesion 2. Bind and stabilise factor VIII - protect from proteolytic degredation

Question 34

Pathophysiology and presentation of Von Willebrand Disease

Answer 34

Dominant / recessive. Mutation Ch 12 --> reduced production of VWF / abnormal VWF Presents: - Menorrhagia - Bruising - Excessive bleeding from procedures - Epistaxis - Prolonged APTT, PT normal - Low factor VIII - disrupted VWF binding - Abnormal VWF ristocetin cofactor assay

Question 35

Management of Von Willebrand Disease

Answer 35

Mild - TXA Severe - desmopressin prophylaxis (increased factor VIII / platelet aggregation), VWF concentrate, esp prior to surgery

Question 36

Pathophysiology / presentation / Tx DIC

Answer 36

- Trigger (eg sepsis, malignancy, trauma) --> excessive and unregulated activation of clotting system --> fibrin clots and consumption of clotting factors / platelets. - Presents: Bleeding ++, thromboembolic complications - Ix: Prolonged PT and APTT, high fibrinogen, low platelets - Tx: Cause, transfusion

Question 37

What is lupus anticoagulant?

Answer 37

Ab that develops following infection (measles, adenovirus, mycoplasma) Prolonged APTT, normal PT. APTT with 50:50 mixing --> remains abnormal in LA Usually self-resolves.

Question 38

Pathophysiology / features / Tx of ITP

Answer 38

- AI destruction of platelets. - Presents: Petechiae, purpura, epistaxis, superficial bleeding - Tx: Pred, IV immunoglobulin, Plt Tx Chronic >6m --> Rituximab / monoclonal AB

Question 39

Causes of thrombosis in children (rare)

Answer 39

- Central line - Malignancy - DIC - SLE / sickle cell - Trauma - Polycythaemia - Chickenpox (low protein S) - Inherited deficiency of anticoagulants: Antithrombin, Protein C, Protein S - Factor V Leiden mutation - prevents protein C from binding

Question 40

What are naturally occurring anticoagulants and where do they act?

Answer 40

Antithrombin - Thrombin, factor V Protein C - Factor VI, VIII Protein S - enhance protein C

Question 41

What is Li-Fraumeni Syndrome?

Answer 41

Cancer pre-disposition syndrome Mutation and loss of function p53 tumour suppressor gene. FHx breast / brain cancer, sarcoma