Haematology/Oncology

Question 1

What is Wiskott Aldrich Syndrome?

Answer 1

Wiskott-Aldrich syndrome causes primary immunodeficiency due to a combined B- and T-cell dysfunction

Question 2

What is the genetic mutation in Wiskott Aldrich Syndrome?

Answer 2

X-linked recessive

Question 3

What mutations causes Wiskott Aldrich?

Answer 3

Mutation in the WASP gene

Question 4

What are the clinical features of Wiskott Aldrich?

Answer 4

recurrent bacterial infections (e.g. Chest)
eczema
thrombocytopaenia
low IgM levels

Question 5

What is myelofibrosis?

Answer 5

a myeloproliferative disorder thought to be caused by hyperplasia of abnormal megakaryocytes

the resultant release of platelet derived growth factor is thought to stimulate fibroblasts haematopoiesis develops in the liver and spleen

Question 6

What are the features of myelofibrosis?

Answer 6

e.g. elderly person with symptoms of anaemia e.g. fatigue (the most common presenting symptom)
massive splenomegaly
hypermetabolic symptoms: weight loss, night sweats etc

Question 7

What are the lab findings in myelofibrosis?

Answer 7

anaemia
high WBC and platelet count early in the disease
‘tear-drop’ poikilocytes on blood film
unobtainable bone marrow biopsy - ‘dry tap’ therefore trephine biopsy needed
high urate and LDH (reflect increased cell turnover)

Question 8

What does this blood film indicate?

Answer 8

Tear drop poikilocytes

Question 9

What is hereditary angioedema?

Answer 9

Hereditary angioedema (HAE) is an autosomal dominant condition associated with low plasma levels of the C1 inhibitor (C1-INH, C1 esterase inhibitor) protein. C1-INH is a multifunctional serine protease inhibitor - the probable mechanism behind attacks is uncontrolled release of bradykinin resulting in oedema of tissues.

Question 10

How do you ix hereditary angioedema?

Answer 10

C1-INH level is low during an attack
low C2 and C4 levels are seen, even between attacks. Serum C4 is the most reliable and widely used screening tool

Question 11

What are the symptoms of hereditary angioedema?

Answer 11

attacks may be proceeded by painful macular rash
painless, non-pruritic swelling of subcutaneous/submucosal tissues
may affect upper airways, skin or abdominal organs (can occasionally present as abdominal pain due to visceral oedema)
urticaria is not usually a feature

Question 12

What is the mx of hereditary angioedema?

Answer 12

Acute:
1) HAE does not respond to adrenaline, antihistamines, or glucocorticoids
2) IV C1-inhibitor concentrate, fresh frozen plasma (FFP) if this is not available

Prophylaxis: anabolic steroid Danazol may help

Question 13

In a patient with hereditary spherocytosis what is seen in their blood film post splenectomy?

Answer 13

Howell-Jolly bodies

Question 14

What are the features of hereditary spherocytosis?

Answer 14

-most common hereditary haemolytic anaemia in people of northern European descent
-autosomal dominant defect of red blood cell cytoskeleton
-the normal biconcave disc shape is replaced by a sphere-shaped red blood cell
-red blood cell survival reduced as destroyed by the spleen

Question 15

What is the presentation of hereditary spherocytosis?

Answer 15

failure to thrive
jaundice, gallstones
splenomegaly
aplastic crisis precipitated by parvovirus infection
degree of haemolysis variable
MCHC elevated

Question 16

How do you diagnose hereditary spherocytosis?

Answer 16

the osmotic fragility test was previously the recommend investigation of choice. However, it is now deemed unreliable and is no longer recommended
the British Journal of Haematology (BJH) guidelines state that ‘patients with a family history of HS, typical clinical features and laboratory investigations (spherocytes, raised mean corpuscular haemoglobin concentration [MCHC], increase in reticulocytes) do not require any additional tests
if the diagnosis is equivocal the BJH recommend the EMA binding test and the cryohaemolysis test
for atypical presentations electrophoresis analysis of erythrocyte membranes is the method of choice

Question 17

What is the mx of hereditary spherocytosis?

Answer 17

acute haemolytic crisis:
-treatment is generally supportive
-transfusion if necessary
longer term treatment:
-folate replacement
-splenectomy

Question 18

What are the differences between hereditary spherocytosis and G6PD deficiency?

Answer 18

Question 19

What is cryoglobulinemia?

Answer 19

Immunoglobulins which undergo reversible precipitation at 4 deg C, dissolve when warmed to 37 deg C. One-third of cases are idiopathic

Question 20

What are the types of cryoglobulinemia?

Answer 20

Three types
type I (25%):
monoclonal - IgG or IgM
associations: multiple myeloma, Waldenstrom macroglobulinaemia
type II (25%)
mixed monoclonal and polyclonal: usually with rheumatoid factor
associations: hepatitis C, rheumatoid arthritis, Sjogren’s, lymphoma
type III (50%)
polyclonal: usually with rheumatoid factor
associations: rheumatoid arthritis, Sjogren’s

Question 21

What are the features of cyroglobulinemia?

Answer 21

Raynaud’s only seen in type I
cutaneous
vascular purpura
distal ulceration
ulceration
arthralgia
renal involvement
diffuse glomerulonephritis

Question 22

What are the investigations seen in cryoglobulinemia?

Answer 22

low complement (esp. C4)
high ESR

Question 23

What is the mx of cryoglobulinemia?

Answer 23

treatment of underlying condition e.g. hepatitis C
immunosuppression
plasmapheresis

Question 24

What is CLL?

Answer 24

Chronic lymphocytic leukaemia (CLL) is caused by a monoclonal proliferation of well-differentiated lymphocytes which are almost always B-cells (99%). It is the most common form of leukaemia seen in adults.

Question 25

What are the features of CLL?

Answer 25

often none: may be picked up by an incidental finding of lymphocytosis
constitutional: anorexia, weight loss
bleeding, infections
lymphadenopathy more marked than chronic myeloid leukaemia

Question 26

What are the ix for CLL?

Answer 26

Question 27

What does this blood film show?

Answer 27

Smudge cells seen in CLL

Question 28

Hyposplenism is associated with which GI condition?

Answer 28

Coeliac’s

Question 29

What are the blood film features seen in hyposplenism?

Answer 29

target cells
Howell-Jolly bodies
Pappenheimer bodies
siderotic granules
acanthocytes

Question 30

What blood film features are seen in IDA?

Answer 30

target cells
‘pencil’ poikilocytes
if combined with B12/folate deficiency a ‘dimorphic’ film occurs with mixed microcytic and macrocytic cells

Question 31

What is neutropenic sepsis?

Answer 31

Neutropenic sepsis is a relatively common complication of cancer therapy, usually as a consequence of chemotherapy. It most commonly occurs 7-14 days after chemotherapy. It may be defined as a neutrophil count of < 0.5 * 109 in a patient who is having anticancer treatment and has one of the following:
a temperature higher than 38ºC or
other signs or symptoms consistent with clinically significant sepsis

Question 32

What is the aetiology of neutropenic sepsis?

Answer 32

coagulase-negative, Gram-positive bacteria are the most common cause, particularly Staphylococcus epidermidis
this is probably due to the use of indwelling lines in patients with cancer

Question 33

What is the prophylaxis for neutropenic sepsis?

Answer 33

if it is anticipated that patients are likely to have a neutrophil count of < 0.5 * 109 as a consequence of their treatment they should be offered a fluoroquinolone