question 1

For each clinicopathological description, select the most likely diagnosis from the alphabetical list. Each option can be used once, more than once or not at all.

 

a.     Bernard-Soulier Syndrome

b.     Glanzmann Thrombasthenia

c.      Grey Platelet Syndrome

d.     Hermansky-Pudlak Syndrome

e.     MYH9-Related Disorder

f.      Von Willebrand Type 1

g.     Von Willebrand Type 2B

h.     Von Willebrand Pseudo Type 2B

i.       Von Willebrand Type 2M

 

i.     A 3 year old adopted boy, originally from Peurto Rico, is referred to the clinic for troublesome nosebleeds. He is also seen in the gastroenterology clinic for colitis.

 

Hb 156, WBC 10.1, Plt 202, MPV 8 fl (normal)

Normal clotting profile.

Light Transmission Aggregometry (LTA): Absence of second wave aggregation to ADP. The ratio of ADP/ATP is reduced.

 

ii.     A 23 year old woman is due removal of an impacted salivary gland stone under the ENT surgeons. She had significant bleeding from a laceration to her lower gums at the age of 8. She has had menorrhagia since menarche.

 

Hb 132, WBC 8.8, Plt 110

PT 11, APTT 33, FGN 3.8

VW Antigen 42 (normal), RiCOF 14 (low), FVIII 0.38 iu/ml (normal)

VwF Multimer analysis – Absent high and few intermediate multimers, but maintained triplet pattern.

PFA-100 >300 seconds (non-closure)

Ristocetin Induced Platelet Aggregation (RIPA):

- 0.5mg (Low dose) ristocetin, Patient platelets + cryoprecipitate = 88%

- 0.5mg (Low dose) ristocetin, Patient plasma + washed platelets = 20%

 

iii.     A 23 year old woman is referred by the obstetricians for recurrent miscarriages. She has had recurrent bleeding episodes since childhood including needing a transfusion post-tonsillectomy.

 

Hb 100, WBC 7.3, Plt 257, MPV 10 fl (normal)

PT 100, APTT 94, TT 56

PFA-100 >300 seconds (non-closure)

Light Transmission Aggregometry (LTA): No aggregation with ADP, Adrenaline or Collagen, but 73% aggregation with 1.5mg/ml of ristocetin.

 

question 2

 

For each clinicopathological description, select the most likely diagnosis from the alphabetical list. Each option can be used once, more than once or not at all.

 

j.       Bernard-Soulier Syndrome

k.      Chediak-Higashi Syndrome

l.       GATA 1

m.    Glanzmann Thrombasthenia

n.     Grey Platelet Syndrome

o.      Hermansky-Pudlak Syndrome

p.     MYH9-Related Disorder

q.      Quebec Syndrome

r.      Paris-Trousseau-Jacobsen Syndrome

s.      Scott Syndrome

t.       Velocardiofacial Syndrome

u.     Von Willebrand Type 1

v.      Von Willebrand Type 2B

w.    Von Willebrand Pseudo Type 2B

x.      Von Willebrand Type 2M

y.      Wiskott-Aldrich syndrome

 

Questions:

 

i.     A ten-year-old boy re-presents with recurrent episodes of petechiae and spontaneous nose bleeds. He had been seen in clinic in the past when he first started bruising. He was observed for a time before being discharged from regular follow-up.

 

Platelet count 80, large forms seen on film.

PFA-100 time >300 seconds

LTA  shows failure to aggregate with ristocetin, but normal results with the other agonists.

 

ii.     A 20 year old is seen in clinic and reports life-long easy bruising and bleeding. They have never required more than first aid to treat the bleeding.

 

Platelet count 110, MPV 15fl.

Electron microscopy shows giant, abnormal alpha granules.

 

iii.     A two-year-old boy is admitted to paediatric intensive care with pneumonia. This is his third admission in the last six months. On examination there is widespread eczema with secondary bacterial infection.

 

Platelet count 50, MPV 5fl

 

iv.     A 15 year old girl has had a mild bleeding disorder since a young age, which has recently become more problematic with menorrhagia.

 

Platelet count 100, MPV 15 gl with large misshapen forms seen.

Electron microscopy shows an absence of alpha granules.

 

v.     A 20 year old man has been referred to ENT clinic for a polpectomy. He gives a history of easy bruising, frequent epistaxis and reports bleeding heavily after an appendectomy as a child.

 

Platelet count 160

PFA-100 closure time >300 seconds

LTA – a partial response to ristocetin only.

Flow cytometry confirms low GpIIb/IIIa density.

 

question 3

For each of the following scenarios, select the translocation most likely to be associated with the diagnosis. Each answer can be used once, more than once, or not at all.

 

a. t(1;19)

b. t(1;22)

c. t(2;5)

d. t(3;14)

e. t(4;11)

f. t(11;14)

g. t(12;21)

h. inv(16)

 

i. A 52 year old man presenting with a six week history of night sweats, weight loss and small volume cervical and groin lymphadenopathy. Biopsy of a cervical lymph node shows a lymphoid infiltrate that is CD30+, CD4+, CD8+. A NPM1-ALK fusion gene is detected by FISH.

ii. A 63 year old man presents with loss of appetite and lethargy. A staging CT scan demonstrates splenomegaly and widespread small volume lymphadenopathy. His full blood count shows a lymphocytosis with Hb 105 and plt count 100. Flow cytometry of the peripheral blood identifies a lymphoid population that is CD19+, CD20+, CD5+. The subsequent lymph node biopsy stains positive for cyclin D1.

iii. A 25 year old woman admitted with fever and lethargy is found to be pancytopenic. Her blood film shows blast cells, which are CD34+, CD33+, HLA-DR+ on immunophenotyping. Bone marrow aspiration confirms the diagnosis and the morphology also reveals an eosinophilia, with several forms containing cytoplasmic crystals.

iv. A 65 year old female presents with a 4 month history of left eye proptosis and progressive visual loss. MRI shows a homogenous, well circumscribed lesion displacing adjacent orbital structures. Biopsy of the lesion demonstrates a CD20+, CD10-, CD23-, CD5- lymphoid infiltrate.

v. A 10 year old boy presents with a 2 week history of right hip pain and lethargy. His blood film shows blasts, which are TdT+, CD19+, CD10+, CD2-, CD3- by flow.

 

question 4

Regarding the timing of cell free fetal DNA (cffDNA) testing for RhD negative mothers, which of the following statements is correct?

a. ccfDNA can be used to D type fetal cells from 14+2 weeks and Rh C,c,E,e and Kell from 16 weeks

b. ccfDNA can be used to D type fetal cells from 11+2 weeks and Rh C,c,E,e and Kell from 16 weeks

c. ccfDNA can be used to D type fetal cells from 11+2 weeks and Rh C,c,E,e and Kell from 14 weeks

d. ccfDNA can be used to full Rh + Kell type fetal cells from 12 weeks

e. ccfDNA can be used to full Rh + Kell type fetal cells from 14 weeks

 

question 5

A 20 year old woman is being transfused red cells following a postpartum haemorrhage after the birth of her first child. During the transfusion the patient notices that the blood being transfused is Rh D positive, whereas she knows herself to be Rh D negative (as is her newborn). 100ml has been transfused. What is the correct course of action to prevent alloimmunisation?

a. Give 125IU of IM Anti-D per 1ml transfused

b. Give 100IU of IV Anti-D per 1ml transfused

c. Give 1500-2500IU of IV Anti-D and assess D+ cells by flow cytometry after 48 hours. Give further doses of anti-D as required until no detectable D+ cells remain.

d. Offer red cell exchange to patient.

e. No action is required.

 

question 6

Which of the following is the correct vaccination schedule for hyposplenic patients?

a. Hepatitis B, Men ACWY, Men B, Men C/Hib, Pneumococcal, Seasonal Influenza

b. Men ACWY, Men B, Men C/Hib, Seasonal Influenza

c. Men B, Men C/Hib, Pneumococcal, Seasonal Influenza, Shingles

d. Men B, Men C/Hib, Pneumococcal, Seasonal Influenza

e. Men ACWY, Men B, Men C/Hib, Pneumococcal, Seasonal Influenza

 

question 7

In the following scenarios of patients with DAT negative haemolysis, select the most likely diagnosis. Each answer can be used once, more than once, or not at all.

 

a. Hereditary Spherocytosis

b. Hereditary Elliptocytosis

c. Hereditary Pyropoikilocytosis

d. Overhydrated Hereditary Stomatocytosis

e. Dehydrated Hereditary Stomatocytosis

f. Cryohydrocytosis

g. Familial Pseudohyperkalaemia

h. South East Asian Ovalcytosis

 

i. Asymptomatic man with Hb 118g/l. Gel electrophoresis shows a defect in glycophorin 4.1.

ii. Asymptomatic woman with Hb 125g/l. Serum potassium 7.9mmol. Her father is from Thailand.

iii. A child with Hb 90g/l and moderate, chronic haemolysis that has resulted in outpatient haematology review. Gel electrophoresis shows reduced band 3 and protein 4.1. EMA binding by flow cytometry shows a patient:control ratio of 0.7.

iv. 6 month infant with Hb 70g/l. Blood film shows red cell fragmentation. EMA binding by flow cytometry shows patient:control ratio of 0.5.

v. Asymptomatic adult who reports problems with anaemia in childhood. His father is from Thailand.

 

question 8

Select the most appropriate red cell product specifications for each of the following scenarios. All products can be assumed to be ABO and Rh D compatible with the recipient (and mother where applicable) and negative for any clinically significant antibodies. Each answer can be used once, more than once, or not at all.

a. Processed day 0 of collection, Known Donor, High Titre Anti-A/B negative, HbS neg, K neg, CMV neg, Irradiated, up to 5 days old, Hct 0.7-0.85, suspended in CPD.

b. Irradiated, up to 35 days old, suspended in SAG-M.

c. Processed day 0 of collection, Known Donor, High Titre Anti-A/B negative, HbS neg, K neg, up to 35 days old, suspended in SAG-M.

d. Processed day 0 of collection, Known Donor, High Titre Anti-A/B negative, HbS neg, K neg, CMV neg, Irradiated, up to 35 days old, Hct 0.7-0.85, suspended in SAG-M.

e. Processed day 0 of collection, Known Donor, High Titre Anti-A/B negative, HbS neg, K neg, Irradiated, up to 35 days old, suspended in SAG-M.

f. Processed day 0 of collection, Known Donor, High Titre Anti-A/B negative, HbS neg, K neg, CMV neg, Irradiated, up to 5 days old, Hct 0.5-0.6, containing 100-120ml plasma, suspended in CPD.

g. Processed day 0 of collection, Known Donor, High Titre Anti-A/B negative, HbS neg, K neg, Irradiated, up to 5 days old, Hct 0.5-0.6, suspended in CPD.

 

i. A 10 year old boy requiring transfusion for post-operative anaemia after scoliosis surgery.

ii. A 5 day old neonate requiring red cell exchange for haemolytic disease of the fetus/newborn.

iii. An intrauterine transfusion is requiring for fetal anaemia in haemolytic disease of the fetus/newborn.

iv. A 5 year old girl requiring transfusion 15 days post allogeneic stem cell transplant for AML.

v. A 60 year old man requiring transfusion for a GI bleed. He received cladribine ten years previously for hairy cell leukaemia.

 

Question 9

Which of the following gene mutations is associated with transient leukaemia of Down Syndrome (TL-DS)?

 

a. NPM1

b. GATA1

c. FLT3-ITD

d. RUNX1

e. CEBPA

 

question 10

You are referred the blood film for a six day old neonate with a white cell count of 75 x10e9/l. The film reveals 15% immature cells which are pleomorphic with prominent nucleoli and basophilic, blebbed cytoplasm. The neonatologist tells you that the patient has a papular rash, hepatomegaly and was diagnosed prenatally with Down Syndrome.

Which of the following is the most like immunophenotype of the abnormal peripheral blood cells?

 

a. CD79a+, CD20+, CD5+, CD200+

b. TdT+, CD2+, CD3+, Cd7+

c. CD34+, CD33+, CD15+, HLA-DR+

d. TdT+, CD19+, CD10+, CD20+

e. CD34+, CD33+, CD36+, CD7+

 

question 11

Which one of the following is the most appropriate scenario in which to recommend the use of hydroxycarbamide in sickle cell anaemia in children?

 

a. As a 1st line therapy for the primary prevention of stroke, regardless of TCD velocities

b. As a 1st line therapy for the primary prevention of stroke in the presence of raised TCD velocities

c. As a 1st line therapy for the secondary prevention of stroke instead of transfusion

d. As a 2nd line therapy for the secondary prevention of stroke, after an initial period of transfusion

e. As a 2nd line therapy for the primary prevention of stroke, after an initial period of transfusion

 

question 12

Select the most appropriate diagnosis for each of the following cases

 

a. Type 1 Hereditary Haemochromatosis

b. Aceruloplasminaemia

c. Hyperferritinaemia-Cataract Syndrome

d. Type 4a Haemochromatosis (Ferroportin Disease)

e. African Iron Overload

f. Type 2 Haemochromatosis (Juvenile)

g. Neonatal haemochromatosis

h. Benign Hyperferritinaemia

i. Atransferritinaemia

j. Gaucher Disease

 

i. Upon retiring, a 65 year old man emigrates to the UK after spending his working life in Zimbabwe. At a first visit appointment with the GP he reports drinking 40 units/week of the local beer throughout his working life. Serum ferritin 3000 ug/l, transferrin saturations 40%, ALT 70, GGT 120, Bili 15.

ii. A 40 year old woman presents to her GP with fatigue. On examination her spleen is enlarged 7cm below the costal margin. Hb 100, platelets 130, neutrophils 1.0, ferritin 700 ug/l. Subsequent investigation finds that her white cell enzyme activity is at 15% of normal.

iii. A 40 year old man of British ethnicity is found to have a raised fasting blood sugar at a routine appointment with his GP. Subsequent tests reveal: Serum ferritin 1,500ug/l, Transferrin saturations 75%, ALT 90, Bili 30.

iv. A 20 year old man is referred to the neurologists by his GP with a history of progressive unsteadiness on his feet. Serum ferritin 1000, transferrin saturations 60%. An MRI scan of his brain shows iron deposition in the basal ganglia.

v. A 50 year old woman presents to her GP with generalised joint pains and fatigue. Serum ferritin 2,000 ug/l, transferrin saturations 40%. Subsequent investigation identifies mutation in the SCL40A1 gene.

 

Question 13

When considering the use of an oral bisphosphonate as bone protection, which of the following patients starting steroids for a new diagnosis of ITP are the most suitable candidates?

Select one or more from the following:

 

a.   A 55-year-old woman noted to have a collapse of the T12 vertebrae on an x-ray five years ago.

b.   A 10-year-old girl, previously fit and well

c.   A 67-year-old with a pre-imaging intermediate risk FRAX score, who is subsequently found to have normal femoral neck bone mineral density (BMD).

d.  A 71-year-old man, previously fit and well

e.   A 67-year-old woman, previously fit and well