My masterclass 2016 hematology

Q1.
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A 54 year old woman was found on a routine full blood count to have Hb 22g/dl (normal range 11.5-16.5 g/dl)
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and haematocrit 61% (normal range 37-47%). The white cell count, white cell differential and platelet count
were normal. A blood count taken 8 years previously had been entirely normal. She was otherwise fit and
well, with no past medical history of note. She was a non-drinker and had never smoked. On examination she
was plethoric and her spleen was palpable 3cm below the costal margin.

Which genetic test is most likely to provide the diagnosis?

A Inversion of chromosome 16
B JAK2 V617F mutation
C Monosomy chromosome 7
D Translocation t(9;22)
E Trisomy chromosome 21

Answer comments

This woman almost certainly has polycythemia rubra vera. Over 95% of cases of polycthemia rubra vera have
the JAK2 V617F mutation. This mutation also occurs in 50% of patients with Idiopathic Myelofibrosis and 50%
of patients with Essential Thrombocythemia.

Inversion of chromosome 16 may occur in Acute Myeloid Leukaemia and is a favourable prognostic marker.
Monosomy chromosome 7 may occur in Acute Myeloid Leukaemia or Myelodysplasia and is an unfavourable
prognostic marker. Translocation t(9;22) also known as the Philadelphia chromosome occurs in Chronic
Myeloid Leukaemia and in some cases of Acute Lymphoblastic Leukaemia. Trisomy chromosome 21 is the
genetic basis of Downs Syndrome in which there is an increased incidence of Acute Leukaemia.
Q2.

A 46 year old tree surgeon was stung on the right hand by a wasp whilst at work. He presented to the ED with a
swollen right arm. He had no other medical history and took no regular medications. Examination revealed pulse
90/min, BP 130/85 mmHg, respiratory rate 14/min, oxygen saturation 98% on air, and his chest was clear with no
wheeze. His right arm was swollen and there was erythema around the sting site. He was treated with intravenous
chlorpheniramine, the swelling improved over a couple of hours, and he was discharged home with a three day
course of prednisolone 20mg od. He returned to be assessed in a medical follow up clinic.

What management would be appropriate?

A Education and training in use of adrenaline (epinephrine) auto-injectors
B Reassure that no further treatment is required
C Skin prick tests to bee and wasp venom
D Specific IgE blood tests to bee and wasp venom
E Venom immunotherapy

Answer comments

Large local reactions without any features of anaphylaxis are common and may be very dramatic (eg involve a whole
limb). They do not predict future systemic anaphylaxis and are not an indication for adrenaline autoinjectors or
immunotherapy.

The rate of venom sensitization to venom in patients with occupational exposure is over 50% and doesn’t change
management, hence specific IgE is not required. However, patients who have a systemic reaction should have specific
IgEs performed to confirm the allergen and be assessed for specific immunotherapy. Skin prick testing is not
considered first line as there is a risk of inducing anaphylaxis.
Q3.

A 24 year old woman presented to the Emergency Department following a generalized seizure. Her partner
reported that she had been unwell for the preceding few days with abdominal pain and headaches, and that her
behaviour had been a bit ‘odd’. He said that she had no previous medical history of note, no history of diarrhoea
or recent travel, took no regular or prn medications, and did not use any recreational drugs. He said that she was
not pregnant.

On examination she was pyrexial (38°c) and she appeared to have PV bleeding and haematuria.

A full blood count showed Hb 82 g/L, wcc 8.2x109/L, plts 12x109/L. The blood film comment read ‘No evidence of
platelet clumping. Schistocytes ++. Results phoned through to medical staff’. Biochemistry results demonstrated
renal impairment.

What investigation should be performed to confirm the diagnosis?

A ADAMSTS13 assay
B Autoantibody screen
C CT/MRI brain
D Pregnancy test
E Renal biopsy

Answer comments

Thrombotic Thrombocytopaenic Purpura (TTP) is a rare but life threatening condition caused by a deficiency of
von Willebrand factor (VWF) cleaving protein, (ADAMTS) which results in microthrombi formation. The diagnosis
of TTP should be treated as a medical emergency. The initial diagnosis of TTP should be made on clinical history,
examination and routine laboratory parameters of the patient, including blood film review. Severely reduced
ADAMTS13 activity (< 5%) ± the presence of an inhibitor or IgG antibodies, confirms the diagnosis. Blood must be
taken prior to treatment to assess baseline ADAMTS13 activity.
Q4.

A 59 year old man was found collapsed at home and admitted to hospital, where he was diagnosed with pneumonia
and acute kidney injury (AKI). He had a past medical history of excess alcohol intake although had been abstinent for
the last two months. He took no regular medication.

On examination he had a low BMI and weighed 45kg. He was rousable to voice but non-coherent. Vital signs
included temperature 38.8°c, pulse 110/min, BP 95/40 mmHg, respiratory rate 22/min, arterial oxygen saturation
86% (breathing room air). Blood test results included Hb 103 g/dl, WBC 22.9x109/L Plt 217x109/L, PT 18 secs
(normal range 11.5-13), creatinine 457 ?mol/L (70-150). Bilirubin 32 ?mol/L (3-17), ALT 1400iu/L (3-35), Alk phos
358iu/L (30-35), CRP 95mg/L.

He was commenced on antibiotics (Tazocin and clarithromycin), given IV vitamin K, and transferred to ICU for
haemofiltration. Prostaglandin was administered to prevent the haemofiltration line from clotting off.

Three days later he developed blue toes and the clinicians suspected microvascular events. Blood tests showed Hb
95g/L WBC 21.2x109/L Plt 44x109/L. PT 22secs, APTT 52secs (33-36) Fibrinogen 5.7 (2.5-5.5), creatinine 221 ?mol/L,
Bilirubin 71 ?mol/L, ALT 1100iu/L, Alk phos 217iu/L, CRP 134mg/L.

What is the most likely cause for his thrombocytopaenia?

A Disseminated Intravascular Coagulation
B End stage liver disease
C Heparin Induced Thrombocytopaenia
D Sepsis
E Thrombotic Thrombocytopaenic Purpura

Answer comments

Thrombocytopaenia is a common finding in critical care and can be caused by all of these conditions. The additional
deranged clotting results are in keeping with DIC or liver disease. Although DIC usually presents as haemorrhage,
<10% present with microthrombi alone. The most common cause of DIC in critical care is sepsis.
Q5.

A 76-year-old man had refractory anaemia for 3 years, requiring blood transfusion every 6 weeks. His white cell
count (WCC) normally ran at 3 x 109/l, platelets at 88 x 109/l, and mean corpuscular volume (MCV) 110 fl. He was
admitted as an emergency with a chest infection and his full blood count revealed Hb 10.2 g/dl, MCV 116 fl, platelets
22 x 109/l, WCC 77 x 109/l (neuts 1.3 x 109/l). There was no obvious blood loss. What is the most likely cause?
A Folate deficiency
B Iron deficiency
C Mycoplasma pneumonia
D Occult gastrointestinal blood loss
E Transformation to acute leukaemia

Answer comments

The MCV is often raised as a feature of myelodysplasia and has not changed significantly here. The sudden collapse
in platelets and rise in WCC signifies progression of the disease. The neutrophil count is low, so the other white cells
are probably leukaemic. Although a pneumonia could in exceptional circumstances cause a WCC of 77 x 10 9/l, the
neutrophil count would be much higher. About 40% of patient with myelodysplasia will transform into leukaemia.
Q6.

A 28 year old man with sickle cell disease presented two days after an exchange transfusion with abdominal pain,
dark urine and dysuria. Examination revealed scleral jaundice. Blood tests demonstrated a drop in haemoglobin from
82 to 42 g/L. Bilirubin was increased. No antibodies were detected on a repeat group and screen (G&S). The Direct
Antiglobulin Test (DAT) was negative.

What diagnosis should be considered?

A Acute transfusion reaction
B Alloimumunisation
C Hyperhaemolytic transfusion reaction
D Sickle cell crisis
E Urinary tract infection

Answer comments

Patients with haemoglobinopathies are often multi-transfused. They are at increased risk of acute transfusion
reactions and alloimmunisation, the latter of which is inadvertently increased when clinical teams fail to inform the
blood bank of their diagnosis. Unexpected falls in Hb may be associated with hyperhaemolytic transfusion reactions,
where both donor and recipient red cells are haemolysed resulting in severe and sometimes life threatening
anaemia.
Q7.

A 24 year old woman presented to the Emergency Department following a generalized seizure. Her partner reported
that she had been unwell for the preceding few days with abdominal pain and headaches, and that her behaviour
had been a bit ‘odd’. He said that she had no previous medical history of note, no history of diarrhoea or recent
travel, took no regular or prn medications, and did not use any recreational drugs. She was not pregnant.

On examination she was pyrexial (38°c) and she appeared to have PV bleeding and haematuria.

A full blood count showed Hb 82 g/L, wcc 8.2x109/L, plts 12x109/L. The blood film comment read ‘No evidence of
platelet clumping. Schistocytes ++. Results phoned through to medical staff’. Biochemistry results demonstrated
renal impairment.

What is the treatment of choice?

A Blood transfusion
B Fresh frozen plasma transfusion
C Methyprednisolone (intravenous)
D Plasma exchange
E Platelet transfusion

Answer comments

Thrombotic Thrombocytopaenic Purpura (TTP) is a rare but life threatening condition caused by a deficiency of von
Willebrand factor (VWF) cleaving protein, (ADAMTS). This results in microthrombi formation in areas of high shear
stress e.g. kidneys, brain, heart.

Daily plasma exchange is the mainstay of treatment and has reduced mortality rates, from over 90% to 10 –20%. It
allows removal of autoantibodies and repletes ADAMTS13. Plasma exchange has been shown to be superior to
plasma infusion. Platelet transfusions are contraindicated unless there is life-threatening bleeding.
Q8.
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A 62-year-old
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later he was
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extension with hepatosplenomegaly. Full blood count revealed haemoglobin 9 g/dL, white blood
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count 120 x 109/L, and platelets 102 x 109/L. His serum calcium was markedly elevated. His blood film is shown
(see image). What complication has developed?

See image
A Acute Myeloid leukaemia
B Chronic Myeloid Leukaemia
C Leukaemoid response to infection
D Plasma cell leukaemia
E Reactive plasmacytosis

Answer comments

Plasma cell leukaemia (primary or secondary) is a recognized complication of plasma cell disorders. Patients
have more than 20% plasma cells in peripheral blood or an absolute plasma cell count of 2000 u/L. There is
hepatosplenomegaly, and elaboration of IL-6 and other cytokines. Cytogenetic abnormalities are frequent. The
disease is fulminant and treatment is usually unsuccesful. Some patients have responded for brief periods to
intensive chemotherapy with stem cell transplantation.
Q9.

A 59 year old man was found collapsed at home and admitted to hospital, where he was diagnosed with pneumonia
and acute kidney injury (AKI). He had a past medical history of excess alcohol intake although had been abstinent for
the last two months. He took no regular medication.

On examination he had a low BMI and weighed 45kg. He was rousable to voice but non-coherent. Vital signs
included temperature 38.8°c, pulse 110/min, BP 95/40 mmHg, respiratory rate 22/min, arterial oxygen saturation
86% (breathing room air). Blood test results included Hb 103 g/dl, WBC 22.9x109/L Plt 217x109/L, PT 18 secs
(normal range 11.5-13), creatinine 457 ?mol/L (70-150). Bilirubin 32 ?mol/L (3-17), ALT 1400iu/L (3-35), Alk phos
358iu/L (30-35), CRP 95mg/L.

He was commenced on antibiotics (Tazocin and clarithromycin), given IV vitamin K, and transferred to ICU for
haemofiltration. Prostaglandin was administered to prevent the haemofiltration line from clotting off.

Three days later he developed blue toes and the clinicians suspected microvascular events. Blood tests showed Hb
95g/L WBC 21.2x109/L Plt 44x109/L. PT 22secs, APTT 52secs (33-36) Fibrinogen 5.7 (2.5-5.5), creatinine 221 ?mol/L,
Bilirubin 71 ?mol/L, ALT 1100iu/L, Alk phos 217iu/L, CRP 134mg/L.

What additional investigation would be most helpful in grading the severity of his diagnosis?
A Activated partial thromboplastin time (APTT)
B ADAMSTS13 level
C D-dimer
D Lactase dehydrogenase (LDH)
E Peripheral blood film

Answer comments

The diagnostic scoring system for Disseminated Intravascular Coagulation (DIC) is appropriate to use in patients with
an underlying disorder known to be associated with DIC. The DIC score can be calculated by combing the

absolute platelet count,

degree of prolongation of PT,

Fibrinogen level and

elevation of fibrin-related marker (e.g. d-dimer or fibrin degradation products).

A score of 5 or more is consistent with overt DIC.

Q10.

A 32 year old man was found to have an isolated lymphocytosis (25 x 109/l) on a full blood count when he registered
to be a bone marrow donor. Immunophenotyping was performed and confirmed a diagnosis of chronic lymphocytic
leukaemia. He was well, with no abnormalities on examination. A CT scan of chest, abdomen and pelvis revealed
mild splenomegaly but no lymphadenopathy.

Which is the most appropriate initial treatment?

A Allogeneic bone marrow transplantation
B Chlorambucil
C Observation
D Prednisolone
E Rituximab (anti-CD20 antibody)

Answer comments

This is Stage A CLL. The indications for active treatment of CLL depend on the stage and activity of the disease (bulky
or rapidly progressive disease or disabling systemic symptoms). There is no evidence that earlier treatment of
asymptomatic or early stage disease is beneficial, irrespective of the age of the patient.
Q11.

A 35-year-old African woman presented with a 2-week-history of feeling unwell, malaise, aches and pains. Physical
examination showed pallor and a palpable spleen 3cm below the costal margin. There was no joint swelling. Her full
blood count revealed Hb 10 g/dL, WBC 3.1x109/L, lymphocyte 0.9x109/L, platelet count 45x109/L, and the blood
film showed few blasts with Auer rods.

What is the diagnosis?

A Acute lymphoblastic leukaemia
B Acute myeloid leukaemia
C Aplastic anaemia
D Myelodysplasia
E Sickle cell disease

Answer comments

The presence of blasts and Auer bodies are in keeping with a diagnosis acute myeloid leukaemia. Sickle cell disease
and aplastic anaemia are not causes of splenomegaly.
Q12.

An 18-year-old man presented with oozing from the site of a wisdom tooth extraction earlier that day. He gave a past
and family history of epistaxis, but no other episodes of bleeding. Blood tests revealed Hb 14 g/dl, WBC 8 x109/L,
platelet count 250 x109/L, prothrombin time 13 sec (NR 12-16), APTT 33sec (NR 23-31), bleeding time 12 min (NR 3-
9), Factor VIII 90% of normal.

What is the diagnosis?

A Disseminated intravascular coagulation
B Haemophilia A
C Haemophilia B
D Vitamin K deficiency
E Von Willebrand’s disease

Answer comments

Von Willebrand disease (VWD) is the most common inherited bleeding disorder, affecting up to 1% of the population
as assessed by random laboratory screening, although less than 5% of these individuals are appreciably
symptomatic. It is characterized by mutations that lead to an impairment in the synthesis or action of von Willebrand
factor (VWF). Most cases are transmitted as an autosomal dominant trait that affects males and females equally.
There are also acquired forms of VWD that are caused by several different pathophysiological mechanisms.
Q13.

A 54-year old man presented with lethargy and tiredness. Investigations showed haemoglobin 9g/dl (NR 12.5-16),
MCV 106fL (NR 80-100), Leucocyte count 4.6 x 109/L (4-11) and platelets 98 x 109/L (NR 150-400).

Which of the following findings in the patient's history or examination would make Vitamin B12 deficiency a likely
diagnosis?
A Coeliac disease
B Diabetes mellitus (Type II)
C Epilepsy
D Heavy alcohol use
E Hypothyroidism

Answer comments

This man has a macrocytic anaemia with evidence of mild pancytopenia, suggesting megaloblastic change. Both folic
acid and vitamin B12 deficiency can result in this. Vitamin B12 deficiency can be autoimmune (pernicious anaemia)
and is associated with other organ specific autoimmune diseases such as hypothyroidism and vitiligo.
Q14.

A 44-year-old woman with type I von Willebrand’s disease who was otherwise completely healthy was about to have
a dental extraction. Her baseline results were as follows: platelets 201 x 109/l (normal), Factor VIII is 18%, RAg 18%
and RiCof 18%. Regarding haemostasis, what would you recommend before the procedure?
A Give DDAVP
B Give factor VIII
C Give tranexamic acid
D Give vitamin K
E No specific therapy is required

Answer comments

This woman is at increased risk of bleeding. Ideally we would like her factor VIII level to be above 30% at the time of
dental extraction. DDAVP will cause the factor VIII level to rise approximately three-fold (i.e. to about 60%) and
should be followed by 3 days of tranexamic acid, which acts to prevent clot break down.
Q15.
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A 19 year old woman presented with a 2 day history of bleeding from her gums. She had been fit and well until a
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few months
PACES previously, since when she had been tired and had a grumbling throat infection. On closer questioning
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she revealed that her menstrual period had been ongoing for the last 3 weeks, which was not typical for her.

On examination she had swollen, inflamed tonsils. There was no palpable organomegaly or lymphadenopathy.
Blood tests showed Hb 96g/L, WCC 4.2x109/L, platelets 80x109/L. A peripheral blood film demonstrated
hypergranular blasts. A clotting screen was reported as PT 18 secs (normal 11.5-13), APTT 108 secs (normal 33-36),
and D-dimer >5000.

What is the most likely diagnosis?

A Acute lymphoblastic leukaemia
B Acute promyelocytic leukaemia
C Glandular fever
D Hodgkins lymphoma
E Mononucleosis syndrome

Answer comments

Acute promyelocytic leukaemia (APML) is a form of Acute Myeloid Leukaemia (AML) associated with abnormal
coagulation and disseminated intravascular coagulation (DIC). The classic cytogenetic abnormality is t(15:17).
Prognosis overall is good although risk of haemorrhagic death at presentation is high. There is a need to start all-
transretinoic acid (ATRA) as soon as the diagnosis is suspected.
Q16.

A healthy asymptomatic 55-year-old man, with no abnormalities on physical examination, was found to have a
platelet count of 55x109/L and 58x109/L on two occasions. Other elements of his full blood count were normal. A
bone marrow aspirate was cellular, with normal appearance and numbers of erythroid and myeloid precursors. There
were normal to increased numbers of megakaryocytes, many of which appeared large and immature. A diagnosis of
idiopathic thrombocytopenic purpura was made.

What is the most appropriate treatment?

A Immunoglobulin (IV)
B Methylprednisolone (IV)
C Observation
D Prednisolone (oral)
E Splenectomy

Answer comments

In contrast to ITP in children, spontaneous remissions are unusual in adults, occurring in 9% in one series. All adults
with severe and symptomatic thrombocytopenia are usually treated with glucocorticoids, although most patients do
not achieve a sustained normal platelet count after glucocorticoids are discontinued. Adults presenting with mild and
asymptomatic thrombocytopenia, with platelet counts greater than 30-50x109/L, appear to have a stable and benign
course without treatment. Data from case series suggest that fewer than 20% of such patients develop more severe
thrombocytopenia and require treatment following 3-7 years of follow-up.
Q17.
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A 37 year old woman was found to have a high platelet count (650 x109/L) on a routine full blood count, with
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all other parameters being normal. She was completely asymptomatic, with no past medical history, and there
were no abnormalities on examination No infectious or inflammatory cause was found and a diagnosis of
essential thrombocythaemia (ET) was made.

Which is the best initial management?

A Chlorambucil
B Hydroxyurea
C Low molecular weight heparin
D Observation
E Warfarin

Answer comments

Younger patients who present with ET and no history of thrombosis or any cardiovascular risk factors (smoking,
obesity, hypertension, diabetes) can simply be obseved or treated with aspirin alone. ET can present with
bleeding or thrombotic complications and anti-coagulation may be indicated in some but not all cases.
Q18.

A 50 year old woman became acutely short of breath four hours after an elective total hip replacement. During the
operation she had required a 4 unit blood transfusion due to excessive bleeding, but she had been
haemodynamically stable since and was transferred to the orthopaedic ward shortly before she deteriorated. She
had a past medical history of osteoarthritis and a surgical history of two previous caesarean sections. Her regular
medications were co-codamol and ibuprofen. She had no drug allergies and no previous transfusion history.

On examination she was acutely short of breath. Observations showed a temperature of 36.8 degrees, pulse
120/min, BP 130/90 mmHg, and respiratory rate 33/min. Oxygen saturation on air was 80%, rising to 93% on 15L
oxygen. Urine output was good. A portable chest X-ray showed bilateral pulmonary infiltrates.

What is the most likely diagnosis?

A Acute haemolytic transfusion reaction (AHTR)
B Delayed haemolytic transfusion reaction (DHTR)
C Transfusion associated circulatory overload (TACO)
D Transfusion associated dyspnoea (TAD)
E Transfusion related acute lung injury (TRALI)

Answer comments

TRALI is characterised by acute respiratory distress associated with hypoxia and bilateral pulmonary infiltrates. It
occurs during or <6 hours post transfusion and lasts <4 days. Treatment is supportive with oxygen and ventilation. It
is more common with plasma products and thought to be caused by donor HLA antibodies triggering complement
activation and cytokine release.
Q19.

A 55 year old woman presented to the Emergency Department with well demarcated, black blistering over her left
breast. She had noticed reddening and discomfort of the area over the preceding two days, followed by the
development of purple spots that morning.

She had no other haemorrhagic symptoms. She denied recent travel, trauma or infections. She had a past medical
history of obesity and osteoarthritis. Following a period of prolonged immobility she had recently been diagnosed
with an above-knee deep vein thrombosis (DVT) and had commenced warfarin therapy 5 days prior to presentation.
Additional regular medications included paracetamol and ibuprofen. Her warfarin was stopped as Coumadin-induced
skin necrosis was suspected.

Which investigation is recommended?

A Activated protein C assay performed at presentation
B Functional Protein C assay performed one month after warfarin cessation
C Functional Protein S assay performed at presentation
D Prothrombin time performed performed one month after warfarin cessation
E Quantitative Protein C assay performed at presentation

Answer comments

Coumadin or warfarin-induced skin necrosis is a rare but well recognized complication of anticoagulant therapy with
lesions appearing where significant underlying subcutaneous fat tissue is present. The risk is higher in those patients
with an underlying protein C (and possibly S) deficiency. Warfarin causes a reduction in the vitamin-K-dependent
Proteins C and S, so deficiency should be excluded after VKA treatment has been withdrawn.
Q20.
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A 54-year-old woman diagnosed with low grade B cell non Hodgkin's lymphoma, previously treated with
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chemotherapy and radiotherapy for relapsed disease, presented with 8 cm splenomegaly and bone marrow
involvement. Despite this she had a normal full blood count: Hb 13.4g/dl, Wbc 8.0 x 109/l and platelets of
347 x 109/l and no B symptoms. A splenectomy was carried out with good benefit and she remained in good
partial remission for 18 months.

At a routine clinic follow-up she had the following blood count: Hb 8.4g/dl, mcv 124fl, Wbc 11x109/l and
platelets 287 x 109/l, retics 12%. Coombs test was negative. Examination was unremarkable apart from a
tinge of jaundice. Her blood film was as shown (see image). What complication has occurred?

See image
A Accessory spleen
B Auto-immune haemolytic anaemia
C Disease progression
D Gastrointestinal blood loss
E Myelodysplasia

Answer comments

This woman has developed Coombs negative autoimmune haemolytic anaemia with hyperbilirubinaemia and
reticulocytosis. The blood film shows spherocytosis. This can occur at any stage of the disease ( quiescent
phase or active progression). The presentation may precede, occur simultaneously with, or follow the
diagnosis of lymphoma. It is also more common with the use of Fludarabine, a purine analogue recently used
in such conditions. Treatment is with steroids. Treatment related myelodysplasia requires exclusion, but the
anaemia with reticulocytosis is against this option.
Q21.
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A 74 year old woman was admitted with a short history of vomiting, jaundice and malaise. She had a past medical
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history of CKD stage 3, atrial fibrillation and hypertension, and she attended the haematology outpatient
department three times a year having been diagnosed with cutaneous T-cell lymphoma 15 years ago and Chronic
Lymphocytic Leukaemia (CLL) 5 years previously. She had received no previous treatment for her CLL and had
required only active monitoring of her disease. Her regular medications were bisoprolol 5mg od, Ramipril 5mg od.

On examination she was jaundiced, pale and lethargic. There was no palpable lymphadenopathy. The abdomen
was soft and non tender with splenomegaly of 3 finger breadths.

Blood tests showed Hb 60g/L WBC 41.5x10/9L Plt 155 x109/L. Bil 40 ?mol/L, ALT 16 iu/L, Alk Phos 42 iu/L, Albumin
32 g/L. CRP 24 g/L. eGFR 64ml/min. Direct antiglobulin test showed IgG++++ C3b/d -.

What is the most likely diagnosis?

A Cold Autoimmune Haemolysis
B Cold haemoglutinin disease
C Drug induced haemolysis
D Idiopathic haemolysis
E Warm autoimmune haemolysis

Answer comments

The strongly positive DAT with IgG shows this to be a warm autoimmune haemolytic process. Taking into account
the history, this is most likely to be secondary to her CLL rather than being idiopathic or drug induced. Treatment is
initially with steroids +/- blood transfusion.
Q22.
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A 24 year old woman presented to the Emergency Department with abdominal pain and vomiting. She had a
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past medical history of congenital heart disease and had a metallic prosthetic heart valve in situ. Her regular
medication consisted of warfarin 4mg daily, and her INR was 3.0 (target 3.5). A pregnancy test was positive.

What advice should you give her regarding her anticoagulation?

A She can continue her warfarin safely during the first and third trimester of her pregnancy.
B She should continue her warfarin during pregnancy as the risks of alternative anticoagulation
outweigh the benefits.
C She should stop warfarin during her pregnancy and receive a fixed treatment dose of LMWH
according to her weight.
D She should stop warfarin during her pregnancy and receive a treatment dose of LMWH titrated to her
anti Xa levels.
E She should stop warfarin during her pregnancy and remain off anticoagulation.

Answer comments

Warfarin causes congenital malformations and foetal death when administered during pregnancy. Warfarin is
contraindicated in pregnancy in the first and third trimester. Women of child-bearing age who are taking
Warfarin tablets should use effective contraception during treatment. Dosing of LMWH is initially based on
weight, however, requirements increase as the pregnancy progresses and dosage must be titrated against peak
anti Xa levels.
Q23.
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A 35-year-old woman with known chronic idiopathic thrombocytopenia purpura (ITP) attended the haematology
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day care unit because she had noted fresh rectal bleeding. She was pale and had clearly lost a significant amount of
blood. Her platelet count on arrival was 5 x 109/l. Aside from blood transfusion, which treatment should be given?
A Immunoglobulins (IV)
B Methylprednisolone (IV)
C Platelet transfusion
D Tranexamic acid (PO)
E Vincristine (IV)

Answer comments

Platelet transfusions are generally not indicated in patients with ITP because the transfused platelets are destroyed
by the patient's antibodies. However, they are indicated when there is significant acute bleeding. Other treatments
will take longer to work, but may be administered simultaneously.
Q24.

A 68-year old man with long-standing Crohn’s disease presented with severe megaloblastic anaemia. Red cell folate
was markedly reduced.

What is the most important aspect of treatment?

A Start oral folic acid
B Start oral folic acid and intramuscular hydroxocobalamin
C Start oral folinic acid
D Start oral folinic acid and intramuscular hydroxocobalamin
E Start intramuscular hydroxocobalamin

Answer comments

Giving folic acid may unmask vitamin B12 deficiency and precipitate the sudden onset of neurological complications,
hence it is important to check for and treat Vitamin B12 deficiency before commencing folic acid replacement.
Q25.

A 30 year old man presented with a one month history of tiredness and increasing shortness of breath. On
examination he appeared pale, with the only other abnormal finding being painless splenomegaly. His full blood
count was as follows: Haemoglobin: 10.4 g/l, white cell count 350 x 109/l, platelet count 105 x 109/l. A diagnosis of
Chronic myeloid leukaemia (CML) was made.

Which is the recommended first line (non-emergency) treatment strategy?

A Hydroxyurea
B Imatinib
C Interferon
D Stem cell transplantation from an HLA-matched sibling
E Stem cell transplantation from an HLA-matched unrelated donor

Answer comments

The management of CML has changed dramatically since this imatinib (a tyrosine kinase inhibitor, TKI) was
introduced into clinical trials, and subsequently practice, in 1998. Due to the ability of this drug to keep the BCR-ABL
molecule in an inactive configuration, it is able to reverse the blood and marrow abnormalities rapidly, and can
‘clear’ the cytogenetic abnormality (Ph chromosome) from the bone marrow in up to 80% of patients. This drug is
not, however, thought to offer a cure in most patients, as withdrawing the drug results in a return of the
abnormalities. It is therefore necessary to continue the drug long term in those who acheive a good response with
minimal side-effects. Stem cell transplant using either a sibling or unrelated donor is a curative treatment for CML.
Since the widespread use of the tyrosine kinase inhibitors this strategy is less commonly used and reserved for
patients who are intolerant to TKIs or achieve a sub-optimal response to these agents. Even if a patient elects to
have a transplant they would usually be treated with a TKI or a period of time first. Hydroxyurea can be used
acutely to reduce the blood counts. Interferon is less commonly used in CML but can be used for disease control in
those intolerant of other therapies.
Q26.
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A 35 year old woman was diagnosed with acute myeloid leukaemia and received 4 courses of standard
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chemotherapy on the current MRC trial. Two weeks after completing chemotherapy she presented with shortness
of breath and ankle oedema. Investigations showed that she had a dilated cardiomyopathy.

Which drug is most likely to be the cause of the cardiomyopathy?

A Amsacrine
B Cytarabine
C Doxorubicin
D Etoposide
E Fludarabine

Answer comments

Anthracyclines include Adriamycin (doxorubicin) and Mitozantrone. They were originally designed as antibiotics
and inhibit topoisomerize 2, which is a DNA repair enzyme, also intercalating between DNA base pairs to disrupt
DNA templates. They are usually given intravenously and cause major myelosuppression, emesis, alopecia and
mucosal damage. Cardiotoxicity is significant, and transient ECG changes occur in a third of patients. Patients
should not receive more than 450 mg/m2 of doxorubicin during a lifespan as cardiomyopathy and heart failure
are dose dependent.
Q27.
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A 28 year old man with sickle cell disease presented two days after an exchange transfusion with abdominal pain,
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dark urine and dysuria. Examination revealed scleral jaundice. Blood tests demonstrated a drop in haemoglobin
from 82 to 42 g/L. Bilirubin was increased. No antibodies were detected on a repeat group and screen (G&S). The
Direct Antiglobulin Test (DAT) was negative.

What treatment should be commenced urgently?

A Blood transfusion
B Ciprofloxacin (intravenous)
C Exchange transfusion
D Immunoglobulin (intravenous) and methylprednisolone (intravenous)
E Plasma exchange

Answer comments

Transfusion complications in patients with haemoglobin disorders are common. Unexpected falls in Hb may be
associated with hyperhaemolytic transfusion reactions, where both donor and recipient red cells are haemolysed
resulting in severe and sometimes life threatening anaemia. The mechanism is poorly understood.
Hyperhaemolysis may occur in combination with alloimmunisation. Treatment is with IV immunoglobulin and
methylprednisolone. Transfusion should ideally be avoided as it may worsen the clinical picture.
Q28.
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A 42 year old publican presented with a 4 day history of increasing tiredness, lethargy and bruising, and a 24
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hour history of nausea and blood blisters in the mouth. His wife reported that in the last 6 hours he had
appeared mildly confused and had suffered a spontaneous nose bleed lasting 25 minutes. He had no past
medical history of note. On admission he had a low grade fever (38.0C), but had no photophobia and no neck
stiffness. Shortly after this examination he suffered a grand mal seizure.

A full blood count revealed Hb 7.7 g/dl (normal 13.5-18.0 g/dl), white cell count 7.7x10^9/l, platelet count
14x10^9/l (normal 150-400x10^9/l), with the blood film showing thrombocytopenia, micro-spherocytes and
red cell fragments. Biochemical testing showed serum bilirubin 145 umol/l (normal <18 umol/l), alanine
transaminase 55 U/l (normal <40 U/l), creatinine 407 umol/l (normal < 125 umol/l). Other haematological
indices included prothrombin time 12.2 seconds (normal 12-15 seconds), activated partial thromboplastin
time 32 seconds (normal 28-36 seconds).

Which is the most likely diagnosis?

A Leptospirosis
B Meningococcal meningitis
C Meningococcal septicaemia
D Thrombotic Thrombocytopenia Purpura
E Wernicke’s encephalopathy

Answer comments

This man has microangiopathic haemolytic anaemia (fragments and high bilirubin), thrombocytopenia, renal
failure, fever and neurological event (fit and confusion). This pentad is most in keeping with thrombotic
thrombocytopenia purpura (TTP). He has no meningism and the normal clotting makes DIC and its causes
(e.g. sepsis, meningococcal meningitis) less likely as the cause of thrombocytopenia.
Q29.
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An 82 year old woman with known COPD, type 2 respiratory failure and obesity presented with acute shortness of
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breath. She was assessed and commenced on oxygen therapy, nebulisers, steroids, antibiotics and treatment dose
LMWH. Serial arterial blood gas sampling was carried out without complication.

The next morning the nursing staff noted that she had severe bruising over her wrist and hand. On examination she
had a partial wrist drop. A clotting screen was performed and showed PT 12.6 secs (normal 11.5-13), APTT 120 secs
(normal 33-36). Similar results were obtained on repeat testing. She had a past surgical history of tonsillectomy
without complication and gave no history of epistaxis, easy bleeding or menorrhagia. A clotting screen carried out
during a previous admission showed PT 11.5 secs, and APTT 34 secs.

What is the most likely diagnosis?

A Acquired haemophilia
B Haemophilia A
C LMWH excess
D Low level factor VIII carrier
E Warfarin administration

Answer comments

The history and previous lab results exclude a congenital clotting abnormality. Warfarin excess would cause
prolongation of the PT. LMWH, in contrast to heparin, rarely prolongs the APTT and should be monitored using anti-
Xa levels. Acquired haemophilia is a rare but life threatening condition caused by the spontaneous development of
antibodies against FVIII. It is more common in the elderly, during pregnancy and in association with autoimmune
and malignant disease. Urgent treatment with steroids and FVIII bypassing agents is required.
Q30.
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A 35 year old woman presented to the Emergency Department with a short history of gum bleeding and
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drowsiness. On examination she had numerous visible bruises and her GCS was reduced (9/15). Blood tests
showed Hb 11.2 g/dL WBC 2.1 x 109/L (Neutrophils of 1.1 x 109/L), platelets 3 x 109/L, APPT 72 sec (normal 32-
38), PT 32 sec (normal 11-14). An urgent CT scan of her head showed that she had suffered an intra-cranial
bleed.

Which diagnosis is most likely?

A Acute lymphoblastic leukaemia
B Acute myeloid leukaemia
C Aplastic anaemia
D Idiopathic thrombocytopenic purpura
E Warfarin overdose

Answer comments

Acute myeloid leukaemia of M3 type classically presents with bleeding, marked thrombocytopenia and a DIC.
This is a medical emergency. There is a high risk of death at the time of presentation, due usually to an
inadequately managed coagulopathy or catastrophic bleed (e.g. intracranial). Patients should be managed
aggressively with platelet and clotting factor support. The chromosomal translocation that is characteristically
found makes the disease responsive to treatment with ATRA (all- trans-retinoic acid), which is started prior to
the administration of chemotherapy as soon as the diagnosis is suspected. If patients survive their presentation,
then prognosis is good