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

question 14

In each of the following scenarios select the most appropriate drug from the list below, assuming entry into a clinical trial is not available. Each answer may be used once, more than once or not at all.

a. Enasidenib

b. Gemtuzumab Ozogamacin

c. Nivolumab

d. Liposomal Daunorubicin + Cytarabine

e. Midostaurin

f. Pracinostat

g. Azacitidine

h. Ivosidenib

i. A previously fit and well 62 year old woman presents with a short history of lethargy and easy bruising. Her full blood count shows Hb 55g/l, WBC 180x10e9/l and Plt 32x10e9/l. A bone marrow aspirate demonstrates 95% blasts and the subsequent immunophenotype is consistent with acute myeloid leukaemia. She is started on hydroxycarbamide and five days later her WBC has fallen to 30x10e9/l. The FISH report is now available and shows a (del)5q. The patient would like to consider any alternatives to the current standard of care.

ii. A 69 year man is referred by his GP with a 9 month history of progressive lethargy and more recently he has been suffering with recurrent minor epistaxis. A recent full blood count has shown Hb 75g/l, WBC 1.2x10e9/l, Plt 40x10e9/l. A bone marrow aspirate shows hypocellular particles with dysplastic erythroid precursors and 26% blasts. The blasts express a myeloid phenotype on flow cytometry. Following discussion of available treatment options, the patient expresses a wish not to undergo intensive inpatient therapy but would like to consider any alternative treatment which might control his leukaemia.

iii. A 55 year old woman has started daunorubicin plus cytarabine (DA) chemotherapy for acute myeloid leukaemia. It is now day seven of treatment and her molecular cytogenetics have identified a FLT3-ITD mutation. She asks if any additional treatment is available to her.

iv. A 26 year old man is diagnosed with acute myeloid leukaemia. Flow cytometry of the peripheral blood shows the following blast cell phenotype: CD34+, HLA-DR+, CD133+, CD33+, CD3-, CD19-. His karyotype identifies inv(16). After initial control of his WBC with hydroxycarbamide he is ready to start intensive induction therapy and the patient asks if any other treatment is available in addition to DA chemotherapy.

Question 15

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. Adult T-Cell Leukaemia (ATL)

b. Angioimmunoblastic T-Cell Lymphoma (AITL)

c. ALK negative Anaplastic Large Cell Lymphoma

d. ALK positive Anaplastic Large Cell Lymhpoma

e. Enteropathy-associated T-Cell Lymphoma (EATL)

f. Extranodal NK/T-Cell lymphoma, nasal type

g. Hepatospenlic T-Cell Lymphoma

h. Large Granular Lymphocytic Leukaemia (LGL)

i. Peripheral T-Cell Lymphoma, Not otherwise specified (PTCL, NOS)

j. T-Cell Acute Lymphoblastic Leukaemia (T-ALL)

k. T-Cell Prolymphocytic Leukaemia (T-PLL)

 

i. A 65 year old man is admitted with epistaxis. He gives a short history of night sweats and rapid weight loss. Hb 100g/l, plt 50x10e9/l, WBC 5.0x10e9/L. CT scan of the trunk reveals small volume para-aortic lymphadenopathy and bilateral adrenal masses. Adrenal biopsy demonstrates a monomorphic lymphoid infiltrate, positive for CD2, cytoplasmic CD3, CD56 and EBER. Negative for surface CD4, CD8 and surface CD3. A subsequent bone marrow biopsy confirms marrow involvement.

ii. A 28 year old man gives a two week history of right hip pain, night sweats and weight loss. Hb 130g/l, plt 57x10e9/l, WBC 90x10e9/L. CT imaging shows a 9cm anterior mediastinal lymph node mass and hepatosplenomegaly. Flow cytometry of the peripheral blood identifies an abnormal lymphoid population which are positive for cytoplasmic CD3, CD5, CD7, CD9 and weakly positive for TdT. Negative for surface CD3, CD4, CD8, CD34 and HLA-DR.

iii. A 49 year old woman presents with a six week history of itch, lethargy, night sweats and progressive neck and axillary lymphadenopathy. Examination reveals hepatosplenomegaly. Hb 100g/l, plt 170x10e9/l, WBC 5.0x10e9/L. A subsequent axillary lymph node biopsy demonstrates a paracortical polymorphic infiltrate of small to medium sized lymphocytes. These cells are positive for CD2, CD3, CD4, CD5, CD10, CXCL13 and PD-1.

iv. A 22 year old woman is referred to clinic with a rapidly enlarging lymph node in her right groin. She has no B symptoms. Her full blood count is normal except for a mild lymphopenia. PET-CT reveals FDG uptake in the right groin and para-aortic lymph nodes. A lymph node biopsy shows a diffuse infiltrate of medium-large sized lymphoid cells with frequent mitotic and apoptotic bodies. The cells are positive for CD2, CD3, CD4 and strongly positive for CD30. They are negative for CD8, CD56, ALK, CD10 and PD1.

v. A 67 year old man with a past history of rheumatoid arthritis has an incidental finding of neutropenia. He is not currently on any medication for this rheumatoid. Examination reveals 5cm splenomegaly below the costal margin. Hb 130g/l, plt 205x10e9/l, WBC 3.0x10e9/L, neutrophils 0.5x10e9/L. He remains neutropenic over the following six months and requires treatment for two infections in that time. A peripheral blood film shows large lymphoid cells containing coarse azurophilic granules. Bone marrow biopsy demonstrates an interstitial lymphoid infiltrate accounting for 30% of cells seen on the trephine. These cells are positive for CD3, CD8, CD57 and KIR. Negative for CD5, CD7.

Question 16

For each of the following scenarios, select the most likely causative antibody from the list below. Each answer may be used once, more than once or not at all.

 

a. IgG Anti-c

b. IgG Anti-e

c. IgG Anti-E

d. IgM High titre Anti-I

e. IgM Low titre Anti-I

f. IgG Anti-P

i. A 42 year old man presents with pre-syncopal symptoms on standing, which have occurred following three weeks of increasing lethargy. He is pale with jaundiced sclera and a palpable spleen tip. He has no past medical history and is not on any medication. Hb 55g/l, plt 210x10e9/l, WBC 6.5x10e9/l, Bilirubin 68, LDH 500. Examination of the blood film reveals marked polychromasia and spehrocytosis. The direct antiglobulin test (DAT) is IgG 4+ positive and negative for C3d. His red cell Rh phenotype is R1R1.

ii. A 60 year old woman attends her GP for a well woman check. The blood film is passed to you for medical review. There is marked cell agglutination, with a normal platelet count and unremarkable white cell appearances. The DAT is negative. The GP is surprised when you phone for further information, reporting that the patient is entirely well with no complaints.

iii. A 20 year old man who had recently recovered from influenza re-presents with a new fever, acute back pain and lethargy. Hb 67g/l, plt 310x10e9/l, WBC 5.4x10e9/l. His urine dipstick is positive for blood but subsequently microscopy is reported as normal. The DAT is 3+ positive for C3d. Further serological tests identify a biphasic antibody. The patient recovers fully after two weeks of supportive care.

iv. A 65 year old woman is referred by her GP. For the third winter running she has suffered with painful fingers when outside despite wearing gloves. Her fingers become discoloured during these episodes. She feels more fatigued during these winter months. Hb 105g/l, plt 190x10e9/l, WBC 4.2x10e9/l. Blood film shows red cell agglutination and the DAT is 3+ positive for C3d.

 

Question 17

Which of the following medications has been most commonly associated with drug-induced immune haemolytic anaemia?

 

a. Aspirin

b. Omperazole

c. Fluconazole

d. Bisoprolol

e. Ceftriaxone

question 18

Which of the following genetic features has the poorest median survival for patients diagnosed with myelofibrosis?

a. JAK2 V617F mutation

b. CALR mutation

c. MPL W515 mutation

d. ‘Triple Negative’ status

question 19

A 70yo man presents with progressive lethargy and report purpuric lumps on his chest that appeared in the last 2-3 weeks. Hb 100, plt 70, WBC 0.9. Bone marrow aspirate demonstrates medium sized blasts with eccentric nuclei and 'tail-shaped' cytoplasm containing vacuoles. Flow cytometry shows the following immunophenotype: Positive for CD4, CD56, CD123 and CD303. Negative for MPO, CD13 and CD33.

What is the likely dx?

a. T Prolymphocytic Leukaemia

b. B Prolymphocytic Leukaemia

c. T Acute Lymphoblastic Leukaemia

d. Blastic Plasmacytoid Dendritic Cell Neoplasm

e. Acute Myeloid Leukaemia

f. Acute MyeloMonoblastic Leukaemia