Haematology for Clinical
Finals
Paul Greaves: Consultant Haematologist, BHRUT,
Romford
21 cases, 88 MCQs,
and a framework to guide your cramming
The whole of haematology in 2 hours...
In 21 cases, 88 MCQs and a framework to hang your cramming
on...
Haematology is 5 things:
1.
2.
3.
4.
5.
Clotting
Transfusion
Cancer
Red cell
Dire emergencies you must never mess up
CLOTTING is 5 things
1.
2.
3.
4.
5.
PT, APTT and two ways to make a clot
How to use heparin, warfarin and NOACs
What to do with a bleeding patient taking anticoags
Bleeding tendency
Clotting tendency
TRANSFUSION is 5 things
1.
2.
3.
4.
5.
Red cells: ABO, Rh and K
Plasma
Platelets (and thrombocytopenia)
Tranexamic Acid
Cryo, Fibrinogen, The stuff in a locked cupboard
➢
octaplex, novoseven, factor concentrates
CANCER (Leukaemia, Lymphoma, Myeloma, MPD) is 5
things
1.
Presentation
➢
lumps, organomegaly, bone marrow failure, infection
2. Diagnostics
➢
scans, bone marrow, biopsy, blood film, flow, cytogenetics
3. Treatment
➢
chemo, radio, targeted antibodies, targeted molecules
4. Supportive care
➢
antiemetics, mouth-care, antimicrobials, bisphosphonates,
psychosocial
5. Emergencies
➢
sepsis, tumour lysis, leukostasis, cord compression
RED CELL is 5 things
1.
2.
3.
4.
5.
Haematinics
Haemoglobin/opathy
Haemolysis
Haemochromatosis
5 things to NEVER MESS UP
1.
2.
3.
4.
5.
Massive Transfusion and transfusion reactions
Sepsis, Tumour Lysis & Hypercalcemia
Cord Compression
Sickle Chest crisis
Dangerous thrombocytopenias
Never Miss
Tumour lysis syndrome: Hyperphos, hypocalc, Oliguria
Prevent with allopurinol, rasburicase and generous IV fluids
Cord Compression: Back pain, known malignancy (or suspected), neurology
Suspect with low index of suspicion
Steroids (unless a new diagnosis), image, radiotherapy, neurosurgery
Thrombotic Thrombocytopenic Purpura
Anaemia, jaundice, thrombocytopenia, fever, renal fx, Neurological
IV lines and straight to pheresis centre for PLEX +/- chemotherapy
Acute transfusion reaction
Unwell on a transfusion -> STOP it, ?adrenaline needed
check BAG, BAND, BLOOD;
involve HDU, Hydrate, inform lab, send samples,
Never Miss: the dangerous thrombocytopenias
Always ask for a blood film and check medication history
Are they bleeding? Or may they have a clot?
Could they have a bone marrow failure or immunological syndrome?
Pregnancy-Associated
○ Liver function? Proteinuria? Hypertension?
○ Think HELLP / Eclampsia spectrum
Heparin Induced Thrombocytopenia & Thrombosis (HITT)
Thrombotic Thrombocytopenic Purpura (TTP)
○ Anaemia, jaundice, thrombocytopenia, fever, renal fx, Neurological
○ IV lines and straight to pheresis centre for PLEX +/- chemotherapy
28, Bangladeshi, FEMALE, TATT
NR
What do you look for?
Hb
62
120 - 160 g/l
MCV
65
80 - 100 fl
Further tests?
MCH
17
26 - 33 pg/c
Treatment?
RDW
20
12 - 15%
WCC
11
4 - 10 x109/l
Nph
8
2 - 8 x109/l
LC
3
1 - 4 x 109/l
Plt
550
150 - 450 x 109/l
What do you ask?
88, WHITE BRITISH, FEMALE, TATT
NR
What do you look for?
Hb
62
120 - 160 g/l
MCV
65
80 - 100 fl
Further tests?
MCH
17
26 - 33 pg/c
Treatment?
RDW
20
12 - 15%
WCC
11
4 - 10 x109/l
Nph
8
2 - 8 x109/l
LC
3
1 - 4 x 109/l
Plt
550
150 - 450 x 109/l
What do you ask?
28, BLACK BRITISH (Ghanaian parents), FEMALE, TATT
NR
What do you look for?
Hb
102
120 - 160 g/l
MCV
55
80 - 100 fl
Further tests?
MCH
23
26 - 33 pg/c
Treatment?
RDW
14
12 - 15%
WCC
11
4 - 10 x109/l
Nph
8
2 - 8 x109/l
LC
3
1 - 4 x 109/l
Plt
400
150 - 450 x 109/l
What do you ask?
58, White British, MALE, TATT
NR
What do you look for?
Hb
102
120 - 160 g/l
MCV
70
80 - 100 fl
Further tests?
MCH
23
26 - 33 pg/c
Treatment?
RDW
19
12 - 15%
WCC
11
4 - 10 x109/l
Nph
8
2 - 8 x109/l
LC
3
1 - 4 x 109/l
Plt
400
150 - 450 x 109/l
What do you ask?
Microcytic Anaemia
MICROCYTIC is IDA or THAL TRAIT
IDA is DIET, GYNAECOLOGY or GUT
investigate the cause
Don’t Transfuse if you don’t have to
Ferritin is a guide not an absolute: CONTEXT!
SO WHAT is THALASSEMIA?
Alpha or Beta? : Excess of the ‘other’ globulin is pathogenic
Trait/Minor, Intermedia or Major: number of copies lost
Haemolysis, Ineffective RBCpoiesis, Extramedullary
Haematopoiesis
Skeletal Deformity & Endocrinopathy
Iron Overload Syndrome & Viral transmission risk
TRANSFUSION with AGGRESSIVE CHELATION is MAINSTAY of therapy
MCQ Time… Microcytic Anaemia
1 Which ONE of the following may be used to treat iron deficiency?
3 Which ONE of the following statements regarding oral iron therapy is TRUE?
A Ferric sulphate
A Slow‐release preparations are indicated for patients with gastrointestinal disorders
B Desferrioxamine
B Treatment should be given with vitamin C
C Ferrous gluconate
D Erythropoietin
C The maximum dose is 200 mg ferrous sulphate three times daily
D It is best given at night
E It is routinely indicated in pregnancy
4 Which ONE of these statements is NOT TRUE concerning erythropoietin?
2 Which of the following is NOT TRUE about sideroblastic anaemia?
A 90% of the hormone is made in the liver
A It may be inherited
B It contains a hypoxia response gene
B It is most frequently caused by myelodysplasia
C One stimulus to production is a low atmospheric oxygen level
C It may be caused by folate deficiency
D Levels in blood are high if a tumour secreting erythropoietin is causing polycythaemia
D It may respond to erythropoietin
but are low in severe renal disease or polycythaemia vera
MCQ Time… Thalassemia
4 Which ONE of these statements is TRUE
about β‐thalassaemia major?
A It presents at birth
1 Which ONE of the following is NOT a feature of
B It is caused by a defect in α globin synthesis
thalassaemia intermedia?
C It is associated with splenomegaly
o
A It may be due to homozygous β thalassaemia
3 Which ONE of the following
B It may be associated with extramedullary
statements is TRUE about
haemopoiesis
β‐thalassaemia trait?
C It is usually associated with splenomegaly
A It is associated with a raised
D It may cause iron overload
haemoglobin A2 level
B It is associated with iron overload
2 Which ONE of the following is used to monitor
C It is associated with a
transfusion iron overload?
reticulocytosis
A Bone marrow biopsy
D It is associated with splenomegaly
D It is associated with an increased risk of bone
infarction
5 Which ONE of the following is NOT TRUE
about a-thalassaemia?
A It may cause haemoglobin H disease
B It causes a microcytic hypochromic blood
picture
B Serum ferritin
C It ameliorates β‐thalassaemia
C Magnetic resonance imaging
D It is a cause of hydrops fetalis
D Lung function
E It is rare except in the Far East
88, WHITE BRITISH, FEMALE, Collapse, Jaundiced,
Confused
Key
tests in
macrocytic anaemia?
Hb
42
120 - 160 g/l
MCV
130
80 - 100 fl
MCH
RDW
How to treat without
causing harm?
Secondary tests
28
25
ALP
100
40 - 120 IU/L
ALT
35
5-50 IU/L
BR
25
5 - 16
mcmol/L
LDH
2000
>450 IU/L
26 - 33 pg/c
12 - 15%
9/
WCC
3
4 - 10 x10 l
Nph
1.8
2 - 8 x109/l
LC
1.2
1 - 4 x 109/l
Plt
55
150 - 450 x 109/l
B12/folate
deficiency…?
48, Jamaican, Female, Collapse, Jaundiced, Confused
Splenomegaly
Reticulocytosis
Hb
42
120 - 160 g/l
MCV
110
80 - 100 fl
MCH
Confirmatory tests?
How to treat?
Secondary tests
RDW
33
16
ALP
100
40 - 120 IU/L
ALT
35
5-50 IU/L
BR
70
5 - 16
mcmol/L
LDH
2000
>450 IU/L
26 - 33 pg/c
12 - 15%
9/
WCC
16
4 - 10 x10 l
Nph
11
2 - 8 x109/l
LC
3
1 - 4 x 109/l
Plt
450
150 - 450 x 109/l
DAT… and
haemolysis
differential?
TAKE HOME: Macrocytic Anaemia
Helpful Tests: B12, Folate, Retics, DAT, LDH, Haptoglobs
Acute: Haemolysis: Retics UP
Subacute: Folic acid ?pregnancy & Chronic: B12 ? P.A.: Retics
DOWN
Alcohol? Thyroid? Liver?
If all this is negative: suspect myelodysplasia
RAPID TRANSFUSION KILLS IN PERNICIOUS ANAEMIA
Replace B12 first THEN Folic Acid
MCQ Time… Macrocytic Anaemia
4 Causes of microcytic red cells include which
1 Which ONE of the following is associated
ONE of the following?
with pernicious anaemia?
A Alcohol
A Ileal resection
B Thyroid antibodies in serum
C Systemic lupus erythematosus
D Malabsorption of B12-intrinsic factor complex
3 Which ONE of the following is NOT
TRUE about megaloblastic anaemia?
A It is always caused by B12 or folate
cause folate deficiency?
A Antiepileptic drugs
B Veganism
C Gluten sensitivity
D Inflammation
E Pregnancy
C α‐Thalassaemia
D Increased reticulocyte count
deficiency
B Bone marrow appearances are
2 Which ONE of the following does NOT
B Renal disease
identical in B12 or folate deficiency
C It is caused by defective DNA
synthesis
D It may be caused by nitrous oxide
E It is associated with jaundice
5 Which ONE of the following causes vitamin
B12 deficiency?
A Haemolytic anaemia
B Veganism
C Widespread carcinoma
D Jejunal resection
23, White British, Male, Abdo discomfort, Jaundice
Mild splenomegaly
Reticulocytosis
Hb
95
120 - 160 g/l
MCV
82
80 - 100 fl
MCH
Confirmatory tests?
How to treat?
Secondary tests
RDW
33
16
ALP
200
40 - 120 IU/L
ALT
52
5-50 IU/L
BR
30
5 - 16
mcmol/L
LDH
500
>450 IU/L
26 - 33 pg/c
12 - 15%
9/
WCC
8
4 - 10 x10 l
Nph
6
2 - 8 x109/l
LC
3
1 - 4 x 109/l
Plt
400
150 - 450 x 109/l
DAT negative
haemolysis
differential?
68 Female, Abdo discomfort, Jaundice
Mild splenomegaly
Reticulocytosis
Hb
95
120 - 160 g/l
MCV
82
80 - 100 fl
MCH
Confirmatory tests?
How to treat?
Secondary tests
RDW
33
16
ALP
200
40 - 120 IU/L
ALT
52
5-50 IU/L
BR
30
5 - 16
mcmol/L
LDH
500
>450 IU/L
26 - 33 pg/c
12 - 15%
9/
WCC
8
4 - 10 x10 l
Nph
6
2 - 8 x109/l
LC
3
1 - 4 x 109/l
Plt
400
150 - 450 x 109/l
DAT negative
haemolysis
differential?
MCQ Time… Haemolysis!
1. Spherocytes in the blood film are a feature of
3 Which ONE of the following is NOT a cause of
which ONE of the following?
intravascular haemolysis?
A Thalassaemia major
A Rhesus incompatibility
B Autoimmune haemolytic anaemia
B ABO incompatibility
C Reticulocytosis
C Glucose‐6‐phosphate dehydrogenase (G6PD)
D Glucose‐6‐phosphate dehydrogenase (G6PD)
deficiency
deficiency
D Red cell fragmentation syndrome
5 Which ONE of the following is NOT
TRUE about glucose-6-phosphate
dehydrogenase (G6PD) deficiency?
A It commonly presents as a chronic
haemolytic anaemia
B It leads to intravascular haemolysis after
certain infections
C It protects against malaria
2. Which ONE of the following is a feature of a
chronic extravascular haemolytic anaemia?
4 Which ONE of these statements is TRUE
A Raised serum conjugated bilirubin
regarding hereditary spherocytosis?
B Low reticulocyte count
A It is caused by an inherited defect in haemoglobin
C Hypocellular bone marrow
B It is more common in males
D Gallstones
C It can be treated by splenectomy
D It is more frequent in southern Europe
D Carrier females have approximately 50%
G6PD levels
E It is a cause of neonatal jaundice
36, Black Nigerian, Male, Leg pain, Chest Pain
Known HbSS sickle cell disease
Hb
72
120 - 160 g/l
What are the priorities of
management
MCV
77
80 - 100 fl
MCH
23
26 - 33 pg/c
RDW
18
12 - 15%
WCC
22
4 - 10 x109/l
Nph
15
2 - 8 x109/l
LC
4
1 - 4 x 109/l
Plt
700
150 - 450 x 109/l
What are your targets and
guidelines?
What are the short-term
complications and how to
prevent them?
What are the long-term
complications?
What are the haemoglobinopathies
and how to diagnose them?
TAKE HOME: The Sickle Cell Syndrome
A lifelong, life-limiting, multisystemic disease
Treat without prejudice but WITH individual care plans
ADEQUATE ANALGESIA, 20 mins, 1 hr targets
YES! Bloods, Oxygen, Fluids (oral or IV), Spirometry,
NO! Pethidine, Entonox (except LAS)
MAYBE! CXR, ANTIBIOTICS, TRANSFUSION
LONG-TERM: Folic acid, Pen-V, Hydroxyurea, Transfuse,
TAKE HOME: The Sickle Cell CRISES
PAIN: Limb or Axial including SKULL or CHEST
CHEST: Pain, Hypoxia, Pulmonary Infiltrates
Oxygen, Analgesia, Antibiotics & Spirometry
Ventilatory Support, Exchange Transfusion
APLASTIC: Parvovirus (or drug); TRANSFUSE & SUPPORT!
Sequestration: Liver (or spleen); TRANSFUSE & SUPPORT!
SEPTIC: Recognise Early, Treat, Re-assess
MCQ Time… Sickle Cell Disease
3 Which of these interventions is least important in the
1 Which ONE of these statements is TRUE concerning sickle cell trait?
acute management of a sickle cell leg pain crisis
A It is a cause of anaemia
A Oxygen administration
B It protects against malaria
B Parenteral analgesia
C It occurs mainly in females
C Full blood count
D It is a cause of frequent sickle cells in the peripheral blood
D Intravenous access
2 Which ONE of the following is NOT TRUE about sickle cell anaemia?
4 Which ONE of the following is NOT TRUE about sickle
A The oxygen dissociation curve is shifted to the right (i.e. the haemoglobin
cell anaemia?
gives up oxygen more easily than normal)
A The oxygen dissociation curve is shifted to the right (i.e. the
B It is associated with stunted growth
haemoglobin gives up oxygen more easily than normal)
C It may cause ankle ulcers
B It is associated with stunted growth
D It is associated with stroke
C It may cause ankle ulcers
E It is associated with atrophy of the spleen
D It is associated with stroke
E It is associated with atrophy of the spleen
24, Female: Cough, swollen glands, Feverish, Fatigue
Hb
110
120 - 160 g/l
ALP
165
40 - 120 IU/L
MCV
92
80 - 100 fl
ALT
250
5-50 IU/L
MCH
28
26 - 33 pg/c
BR
15
5 - 16 mcmol/L
RDW
14
12 - 15%
WCC
13
4 - 10 x109/l
Nph
11
2 - 8 x109/l
LC
2
1 - 4 x 109/l
Plt
500
150 - 450 x 109/l
Haematological Malignancy
Staging / Prognostication:
EVERYONE needs:
IMAGING:
a biopsy - Lymph node, bone marrow
LYMPHOMA: CT and ‘functional’
FBC: Marrow failure often a
PET-CT
complication
Myeloma: Skeletal survey, MRI spine
Chemistry: Tumor lysis, Calcium, Liver
Molecular:
infiltration, Fitness for treatment
Immunophenotyping defines cell
HIV and Hepatitis status check
type
Autoimmune and thyroid
SUPPORTIVE CARE: Antimicrobials, BMFx, Analgesia,
Mouthcare,
Antiemetics,
Cytogenetics
determines
prognosis
Anti-TLSx
TAKE HOME:
Non-Hodgkin: Common
Lymphomas
USUALLY B CELL, High Grade or Low Grade
High Grade = DLBCL
Low Grade = Follicular lymphoma
Low grade + IgM paraprotein =
LPCLymphoma
Sometimes T cell (10%) = RASHES and BAD NEWS
BURKITT’s - rare super-highgrade, EBV
3 types: Sporadic (elderly); Endemic (Africa,
jaw, kids); HIV / immunosuppression
associated
Hodgkin: Rare (NLPHL RARER)
Teens and twenties PLUS elderly
Reed Sternberg cells; 30% EBV+
Histological subtypes x4 (usu NS or MC)
Targeted antibody: Brentuximab
(CD30)
Staged and treated the same!
Biopsy, CT or PET-CT: Anne Arbor stage
Chemotherapy mainstay
Radiotherapy for localised
BM Transplant for relapse
MCQ Time… Lymphoma
5 A 60‐year‐old man presents with
headaches and anaemia. Investigations
reveal an IgM paraprotein of 30 g/L. What
1 Which ONE of these is most
3 Which ONE of these is NOT TRUE concerning positron
is the most likely diagnosis?
useful in the staging of Hodgkin's
emission tomography (PET) scanning in Hodgkin's lymphoma?
A Burkitt's lymphoma
lymphoma?
A The radiolabel emits β‐particles
B Follicular lymphoma
A Clinical examination
B The images reflect tissue metabolic activity
C Mycosis fungoides
B Erythrocyte sedimentation rate and
C Predicts disease response if performed after only 1 course of
D Lymphoplasmacytic lymphoma
lactic dehydrogenase
treatment
C Bone marrow trephine
D Often upstages Stage I/II disease to stage III/IV
6 A 6‐year‐old boy in Kenya develops
swelling of the jaw. The mass responds
D CT scan
4 A 65-year-old woman has had a swelling in the neck for 9
rapidly to chemotherapy. What is the
2 What percentage of patients are
months. She is otherwise well with a normal FBC. Most likely
most likely diagnosis?
cured of Hodgkin's lymphoma?
diagnosis?
A Burkitt's lymphoma
A 55
A Diffuse large B‐cell lymphoma
B Follicular lymphoma
B 65
B Follicular lymphoma
C Mycosis fungoides
C 75
C Sézary syndrome
D Lymphoblastic lymphoma
D 85
D Toxoplasmosis
MCQ Time… Malignancy
Supportive 1
3 Which ONE of these is TRUE regarding fertility in relation to
treatment for malignancy?
1 Which ONE of these is NOT
2 Which ONE of these is TRUE
A Initial chemotherapy for Hodgkin's lymphoma does not usually
TRUE concerning central venous
concerning blood product support for
make women infertile
catheters used in patients with
patients undergoing treatment for
B Total body irradiation, which is used as conditioning for bone
haematological malignancies?
haematological malignancy?
marrow transplantation, does not permanently impair fertility
A If a patient has recently received
C It is easier to freeze oocytes rather than fertilized embryos
A They are associated with increased
fludarabine chemotherapy, any blood
D Sperm donation is rarely a priority in young men who require
risk of Gram‐positive septicaemia
products should be irradiated before
chemotherapy
B They can be used to take blood
administration
and administer intravenous drugs
B Platelet counts should generally be
4 Which ONE of these drugs is most valuable as an
C Chest X‐ray can be used to check
maintained above 20.109/L
antiemetic drug?
the position of the catheter
C The haemoglobin concentration should be
D It is usually placed in the inferior
kept within the normal range for age and
A Methotrexate
vena cava
gender
B Ondansetron
D Human albumin is useful for the
C Piriton
management of bleeding disorders
D Tranexamic acid
84, Female: Fatigue, Abdominal discomfort
Hb
100
120 - 160 g/l
Cr
55
40 - 120 IU/L
MCV
92
80 - 100 fl
Ca
2.3
2.2-2.6 mM
MCH
28
RDW
18 months ago..?
Hb
110
120 - 160 g/l
26 - 33 pg/c
MCV
92
80 - 100 fl
14
12 - 15%
MCH
28
26 - 33 pg/c
WCC
48
4 - 10 x109/l
RDW
14
12 - 15%
Nph
5
2 - 8 x109/l
WCC
16
4 - 10 x109/l
LC
42
1 - 4 x 109/l
Nph
5
2 - 8 x109/l
Plt
110
150 - 450 x 109/l
LC
8
1 - 4 x 109/l
Plt
140
150 - 450 x 109/l
54, Male: Fatigue, Abdominal discomfort
Hb
100
120 - 160 g/l
Cr
55
40 - 120 IU/L
MCV
92
80 - 100 fl
Ca
2.3
2.2-2.6 mM
MCH
28
RDW
18 months ago..?
Hb
110
120 - 160 g/l
26 - 33 pg/c
MCV
92
80 - 100 fl
14
12 - 15%
MCH
28
26 - 33 pg/c
WCC
48
4 - 10 x109/l
RDW
14
12 - 15%
Nph
42
2 - 8 x109/l
WCC
16
4 - 10 x109/l
LC
2
1 - 4 x 109/l
Nph
12
2 - 8 x109/l
Plt
710
150 - 450 x 109/l
LC
3
1 - 4 x 109/l
Plt
140
150 - 450 x 109/l
54, Male: Fatigue, Pruritis, Abdominal discomfort
Hb
190
120 - 160 g/l
MCV
105
80 - 100 fl
MCH
28
26 - 33 pg/c
Diagnostic Test?
RDW
14
12 - 15%
Anything else to exclude?
WCC
15
4 - 10 x109/l
Nph
13
2 - 8 x109/l
9
LC
2
1 - 4 x 10 /l
Plt
710
150 - 450 x 109/l
Hct
62
40 - 50%
‘Adjunct’ tests
Treatment?
Complications?
MCQ Time… MPD
5 Which ONE of these is NOT a cause of polycythaemia?
A Mutation of JAK‐2
B Renal disease
C Congenital heart disease
1 Which ONE of these clinical
3 Which ONE of these is a typical
features is commonly seen in
presenting FBC for chronic myeloid
patients who present with chronic
leukaemia?
myeloid leukaemia?
A Hb 3 g/dL; WBC 60.109/L; Plt 500.109/L
A Swollen cervical lymph nodes
B Hb 9 g/dL; WBC 60.109/L; Plt 400.109/L
B Enlarged spleen
C Hb 6 g/dL; WBC 12.109/L; Plt 50.109/L
C Pancytopenia
D Hb 16 g/dL; WBC 160.109/L; Plt 500.109/L
D Swelling of the gums
E Iron overload
6 Which of the these is NOT a feature of myelofibrosis?
A It causes a leuco‐erythroblastic blood film
B It may be associated with a raised platelet count
C Normal serum lactate dehydrogenase level
D It may be complicated by gout
4 Which ONE of these features is often
2 Which ONE of the following does
seen in polycythaemia vera?
NOT cause a raised platelet count?
A Nocturnal cough
A Haemorrhage
B Increased incidence of gallstones
B Chronic myeloid leukaemia
C Pruritus (itch) after a bath
C Mutation of JAK‐2
D Lymphadenopathy
D Pregnancy
D Haemoglobin abnormality
E It may cause massive splenomegaly
7 Which these is NOT a feature of polycythaemia vera?
A Splenomegaly
B Neutrophil leucocytosis
C High serum erythropoietin
D Thrombocytosis
28, MALE: ‘Flu’, Fatigue, Bone pain, and sore gums
Hb
65
120 - 160 g/l
ALP
165
40 - 120 IU/L
MCV
112
80 - 100 fl
ALT
250
5-50 IU/L
MCH
28
26 - 33 pg/c
BR
15
5 - 16 mcmol/L
RDW
18
12 - 15%
WCC
3
4 - 10 x109/l
Nph
0.9
2 - 8 x109/l
LC
1.5
1 - 4 x 109/l
Plt
40
150 - 450 x 109/l
Splenomegaly : 5 causes
Storage Disease
1. Myeloid Malignancy
Portal hypertension
2. Chronic Haemolysis
Lysis
(haemolysis)
3. Storage
Disease
Portal hypertension
ESR4. (connective
tissue)
5.
Systemic
disease:
Infection
/
Exotic (malaria/leishman/schisto)
Connective tissue
Neoplastic (Lymphoma, MPD)
TAKE HOME: Chronic
Leukaemias
CML: EXTREMELY rare!
CLL: The commonest leukaemia!
are NOTHING like each other (contrast ACUTE)All about too many mature
All about too many mature
LYMPHOCYTES
GRANULOCYTES
Often requires NO treatment
Remember: t(9;22) and BCR-ABL
TREAT when the symptoms get bad:
ALWAYS requires treatment
Lumps, Cytopenias, ‘B symptoms’
Has a MAGIC TREATMENT (Imatinib &
No magic treatment
sons)
Chemo + anti B cell (CD20) Rituximab
Can TURN INTO ANY acute leukaemia
Novel agents: Ibrutinib, Idelalisib
TAKE HOME: Acute Leukaemias
(AML/ALL)
are VERY like each other (contrast CHRONIC)
Present similarly: Bone marrow failure, infections/bleeding, leucostasis
Treated similarly: Chemotherapy +/- transplant; don’t forget the CNS
Cytogenetics are all important prognostically:
t(15;17) GOOD, monosomy 3,5,7 BAD
SUSPECT: Bone marrow failure with ‘Systemic Symptoms’, +/- leucocytosis
TREAT: DISEASE Rx: CHEMOTHERAPY, Allogeneic Transplant
ADJUVENT Rx: Analgesia, Bisphosphonates, Anticoags, Antibios
MCQ Time… Leukaemia
4 Which ONE of these is the MOST LIKELY
blood count in a patient who presents with
acute myeloid leukaemia?
1 Which ONE of these statements is most accurate
3 Which ONE of the following is NOT
A Hb 14 g/dL; white blood cell count (WBC)
concerning the approximate long-term cure rate for
TRUE about acute myeloid
270.109/L; platelets 100.109/L
acute myeloid leukaemia?
leukaemia?
B Hb 9 g/dL; WBC 2.109/L; platelets 140.109/L
C Hb 9 g/dL; WBC 27.109/L; platelets 10.109/L
A It is 30% at all ages
B It is 60% in those aged <60 years and 30% thereafter
A It may cause pancytopenia
D Hb 14 g/dL; WBC 270.109/L; platelets
C It is 60% in those aged <60 years and 10% thereafter
B It has a cure rate of >80% in some
1000.109/L
D It is 30% in those aged <60 years and 10% thereafter
subtypes
C Allogeneic stem cell transplantation is
5 Which ONE of these genetic abnormalities
2 Which ONE of these is used in treatment of
needed in all patients less than 50 years
defines a patient with acute myeloid leukaemia
relapsed acute myeloid leukaemia?
old with an HLA‐matched donor
as having an unfavourable prognosis?
A Arsenic
D It may follow myelodysplasia
A t(8;21) translocation
B Digoxin
E It may cause swelling of the gums
B Normal karyotype
C Cyanide
C Translocation of NPM gene
D Atropa belladonna
D Deletion of chromosome 7
TAKE HOME: Bone Marrow Failure
Syndromes
EXCLUDE CONGENITAL and secondary causes: Nutritional/Viral/Toxin/Radiation
Support with blood products and antimicrobial
Myelodysplastic syndrome:
prophylaxis
Aplastic Anaemia:
Sometimes curable Disease of Mid-Age
Autoimmune mechanism
Does not evolve to AML
Treatment:
Immunosuppression (ATG/CSA) + BMT
Generally incurable Disease of the elderly
Neoplastic / malignant mechanism
Frequently evolves to AML
Treatment:
Hypomethylators, Growth factors, chemo +
BMT
Sometimes Immunosuppression or
MCQ Time… Bone Marrow
Failure
1 Which ONE of these is the
2 What is the most likely treatment for a
most likely clinical picture in a
75-year-old patient with refractory anaemia
patient with myelodysplastic
and haemoglobin 9 g/dL?
syndrome associated with
A Azacytidine
isolated del(5q)?
B Stem cell transplantation
C Lenolidamide
A A man with Hb 13 g/dL and a
D Trial of erythropoietin
platelet count of 600 × 109/L
4 Which of the following does NOT cause pancytopenia?
A Iron deficiency
B Folate deficiency
C Aplastic anaemia
D Acute myeloid leukaemia
E Cyclophosphamide
5 Which ONE of these is NOT a feature of the blood count
and bone marrow in patients with aplastic anaemia?
A Abnormal ‘blast’ cells on the blood film
B Hypoplastic bone marrow with replacement by fat
C Normal appearance of neutrophils on the blood film
B A woman with Hb 10 g/dL and
3 In which patients with myelodysplastic
platelet count of 600 × 109/L
syndrome is ciclosporin most effective?
C A woman with Hb 13 g/dL and
A Low risk disease, hypocellular bone marrow
platelet count 100 × 109/L
B Low risk disease, hypercellular bone marrow
C High risk disease, hypocellular bone marrow
D High risk disease, hypercellular bone marrow
D Normochromic normocytic anaemia
6 Which of these is NOT associated with red cell aplasia?
A A raised reticulocyte count
B Parvovirus infection
C Thymoma
D Chronic lymphocytic leukaemia
64, Male, Black Nigerian: Back pain, Fatigue, Polydipsia
Hb
100
120 - 160 g/l
MCV
92
80 - 100 fl
MCH
28
26 - 33 pg/c
RDW
14
12 - 15%
WCC
6
4 - 10 x109/l
Nph
5
2 - 8 x109/l
LC
1.5
1 - 4 x 109/l
Plt
140
150 - 450 x 109/l
Cr
200
40 - 120 IU/L
Ca
3.1
2.2-2.6 mM
TAKE HOME: MYELOMA
MULTISYSTEMIC MALIGNANCY: CRAB criteria (+ infections)
Calcium, Renal, Anaemia, Bone (+Infection, Thrombus, Amyloid)
SUSPECT: Anaemia, bone pain, fatigue, high globulins, Hypercalcemia
TREAT:
DISEASE Rx: Chemo/RT, novel agents: velcade & Imids, auto BMT
ADJUVENT Rx: Analgesia, Bisphosphonates, Anticoags, Antibios
BEWARE!: Cord Compression, Pathological #, Renal Failure, Infection,
Hyperviscosity
MCQ Time…
Myeloma
5 Which ONE of these is NOT
a typical clinical feature of
systemic amyloidosis?
1 Which ONE of these is NOT
3 Which ONE of these clinical cases is an example of smouldering myeloma?
A Macroglossia
associated with
A Bone marrow plasma cells >10%, no paraproteinand lytic bone lesions
B Peripheral neuropathy
paraproteinaemia?
B Bone marrow plasma cells >10%, abnormal serum free light chain ratio and
C Cardiomyopathy
A Chronic lymphocytic leukaemia
hypercalcaemia
D Liver cirrhosis
B Lymphoplasmacytic lymphoma
C Plasma cells <1%, paraprotein in blood and osteoporosis
C Primary amyloidosis
D Plasma cells >10%, paraprotein 30 g/L in blood and no tissue damage
6 Which ONE of these is a
side-effect of treatment with
D Chronic myeloid leukaemia
4 Which ONE of these treatment strategies is most likely to be used for a
thalidomide?
2 Which ONE of these is a
64-year-old man who is diagnosed with multiple myeloma?
A Hyperactivity
relatively common complication
A Approximately four courses of chemotherapy followed by collection of autologous
B Bleeding
in multiple myeloma?
stem cells and transplant after melphalan conditioning
C Myopathy
A Acute renal failure
B Monthly courses of oral melphalan with prednisolone until the paraprotein level
D Constipation
B Cardiomyopathy
reaches a plateau, then thalidomide maintenance
C Diarrhoea
C High dose chemotherapy followed by a related donor stem cell transplant
D Pulmonary fibrosis
D Monthly courses of R‐CHOP chemotherapy
B
C
A
D
E
A: CML
B: AML
C: MM
D: CLL
E: CHL
MCQ Time…
Spleen
4 Infection risk with which ONE of these organisms is
NOT increased after splenectomy?
A Neisseria meningitides
B Clostridium difficile
1 Which ONE of these is a
2 Which is NOT associated with hyposplenism?
C Haemophilus influenzae type B
major function of the
A Coeliac disease
D Streptococcus pneumoniae
spleen?
B Inflammatory bowel disease
A Removal of the nucleus
C Sickle cell anaemia
5 Which ONE of these is a common complication
D Chronic myeloid leukaemia
within the first 2 weeks after a splenectomy?
from red cells released from
A A rise in the platelet count up to 1000 × 109/L
the bone marrow
3 Which ONE of these statements is TRUE concerning
B Monocytosis
B Production of neutrophils
management patients who have had a splenectomy?
C Hepatic encephalopathy
for release into the circulation
A Lifelong prophylactic phenoxymethylpenicillin
D Disseminated intravascular coagulation
C Storage of blood cells
recommended
which can be released at
B Patients should be advised not to travel abroad
6 Before splenectomy, which vaccines is NOT given?
times of physiological stress
C Patients should be monitored for reactivation of herpes
A BCG
D Generation of humoral
viruses such as Epstein-Barr virus and cytomegalovirus
B Neisseria meningitides
(antibody) immune response
D Inactivated vaccines such as influenza are not useful in
C Haemophilus influenzae
to encapsulated bacteria
these patients
D Streptococcus pneumoniae
38, White Female, Fatigue, Easy bruising limbs, ankle
rash
Hb
122
120 - 160 g/l
APTT
26
20 - 30 sec
MCV
92
80 - 100 fl
PT
11
9 - 12 sec
MCH
28
26 - 33 pg/c
Fib
2.3
1.5 - 4g/l
RDW
14
12 - 15%
9/
WCC
9
4 - 10 x10 l
Nph
6
2 - 8 x109/l
9
LC
3
1 - 4 x 10 /l
Plt
26
150 - 450 x 109/l
What could be
causing this?
Which
investigations?
Confirmatory tests?
38, White Female, Fatigue, Easy bruising limbs, ankle
rash
Hb
122
120 - 160 g/l
APTT
60
20 - 30 sec
MCV
92
80 - 100 fl
PT
11
9 - 12 sec
MCH
28
26 - 33 pg/c
Fib
2.3
1.5 - 4g/l
RDW
14
12 - 15%
9/
WCC
9
4 - 10 x10 l
Nph
6
2 - 8 x109/l
9
LC
3
1 - 4 x 10 /l
Plt
120
150 - 450 x 109/l
What could be
causing this?
Which
investigations?
Confirmatory tests?
38, White Female, Easy bruising, Headache, Feverish
Hb
80
120 - 160 g/l
APTT
26
20 - 30 sec
MCV
101
80 - 100 fl
PT
11
9 - 12 sec
MCH
28
26 - 33 pg/c
Fib
2.3
1.5 - 4g/l
RDW
17
12 - 15%
Cr
700
40 - 120 IU/L
Ur
36.3
2.5 - 8 mM
WCC
9
9/
4 - 10 x10 l
9
Nph
6
2 - 8 x10 /l
LC
3
1 - 4 x 109/l
ALP
100
40 - 120 IU/L
Plt
2
150 - 450 x 109/l
ALT
35
5-50 IU/L
BR
70
5 - 16 mcmol/L
LDH
2000
>450 IU/L
88, Male, Nursing home resident, Purpura, Abdo pain
Hb
80
120 - 160 g/l
APTT
>120
20 - 30 sec
MCV
65
80 - 100 fl
PT
11
9 - 12 sec
MCH
28
26 - 33 pg/c
Fib
2.3
1.5 - 4g/l
RDW
17
12 - 15%
Cr
150
40 - 120 IU/L
Ur
13.2
2.5 - 8 mM
WCC
9
9/
4 - 10 x10 l
9
Nph
6
2 - 8 x10 /l
LC
3
1 - 4 x 109/l
ALP
100
40 - 120 IU/L
Plt
480
150 - 450 x 109/l
ALT
35
5-50 IU/L
BR
20
5 - 16 mcmol/L
Neonate, Male, Post ventouse delivery, Unresponsive, Cefalhaematoma
Hb
120
160 - 180 g/l
APTT
>120
20 - 30 sec
MCV
105
100 - 110 fl
PT
11
9 - 12 sec
MCH
28
26 - 33 pg/c
Fib
2.3
1.5 - 4g/l
RDW
17
15 - 20%
WCC
23
10 - 35 x109/l
Nph
18
5 - 21 x109/l
LC
8
2 - 10 x 109/l
Which investigations?
Plt
380
150 - 350 x 109/l
Confirmatory tests?
What could be causing
this?
‘Late’ Complications?
MCQ Time… Haemophilia
5 Bleeding into mucous membranes, normal platelet
count, factor VIII moderately reduced APTT slightly
prolonged. Which disease is this most likely to be?
1 Which statement is TRUE in haemophilia?
3 Which ONE of these is NOT TRUE
A Haemophilia A
A The prothrombin time is prolonged
concerning the treatment of
B Haemophilia B
B The activated partial thromboplastin time
haemophilia A?
C Von Willebrand disease
D Immune thrombocytopenic purpura
(APTT) time is prolonged
C The thrombin time is prolonged
A Cryoprecipitate is the replacement of
D The bleeding time is prolonged
choice
6 Which ONE of these statements is NOT TRUE
E The level of von Willebrand factor (vWF) in
B The formula used for replacement
concerning von Willebrand disease?
plasma is reduced
therapy is units given = weight (kg) ×
A There is either a reduced level or abnormal function of
increment needed (U/dL) / 2
von Willebrand factor (vWF)
2 Which ONE of the following statements is
C Modern plasma‐derived replacement
B Factor VIII levels may be reduced as vWF is the carrier
NOT TRUE in haemophilia A?
therapy is heat and solvent‐detergent
for factor VIII protein
A Bleeding is mainly mucosal
treated
C It is the most common inherited bleeding disorder and
B Antenatal diagnosis is possible
D DDAVP infusion can raise raise the
inheritance is usually autosomal dominant
C Inheritance is sex‐linked
factor VIII level in mild cases by two‐ to
D Plasma derived factor VIII concentrates contain vWF and
D The disease may be acquired in some cases
fourfold within 1 hour
are the treatment of choice in most cases
Take Home: Bleeding and Bruising
Platelets abnormal: Mucocutaneous bleeds: Bruises and purpura
Clotting proteins abnormal: Joint bleeds if congenital, EVERYWHERE if
acquired
APTT abnormal: It’s heparin, Lupus or HAEMOPHILIA (acquired/congenital)
PT abnormal: It’s warfarin, Nutrition, liver or a RARE haemophilia
BOTH abnormal: It’s DIC, Liver… check fibrinogen / FDPs
BLEEDING HISTORY: structured bleeding assessment tool is better than labs
THROMBOPHILIAS
CONGENITAL: FVL, PTM, ATD, PCD, PSD
ACQUIRED: APLS, MPD
Malignancy, TRAUMA, HOSPITALISATION,
HORMONE
Secondary: Immobilisation, Smoking, Obesity
Take Home: Oral Anticoagulation
Warfarin still has its place:
Reversible (PCC NOT FFP), Well tolerated, useful with renal
impairment
ALWAYS use for valvular heart disease (especially prosthetics)
Takes 3 days to work (at least), but REVERSIBLE (Vitamin K and PCC)
Novel agents are preferable for new patients or clinic non-attenders:
Rivaroxaban most commonly (+apixiban if frail)
Dabigatran sometimes used (but GI bleeds and MIs?)
Act immediately but IRREVERSIBLE (for now… watch this space)
Take Home: Parenteral Anticoagulation
Unfractionated heparin rarely used
except for CARDIOLOGY and RENAL IMPAIRMENT
APTT monitoring required because of unpredictable pharmacokinetics
Risk of Heparin-induced Thrombocytopenia
Can be reversed with PROTAMINE (or just switched off - short half-life)
Low molecular weight heparin
Many brands, pretty much the same (dalte/enoxa/tinza-parin)
Predictably RENALLY excreted hence easy dosing (weight-based)
But unlike UFH - it’s IRREVERSIBLE (mainly) and has a 10-20 hour
MCQ Time… Clotting
3 Which ONE of these is TRUE concerning the
1 Which ONE of these is NOT a recognised
cause of disseminated intravascular
coagulation?
A Amniotic fluid embolism
B Meningococcal septicaemia
C Postoperative bed rest
D Snake bite
factor V Leiden gene mutation?
A It leads to failure of activated protein S to prolong
the APTT clotting test
B It occurs in approximately 5% of Caucasian factor V
alleles
D Homozygous inheritance carries the same
B Fibrinogen concentration is increased
C High levels of fibrin degradation products
(d‐dimers)
D PT and APTT are often prolonged
to unfractionated heparin?
A It can be given once or twice daily
B There is a reduced risk of osteoporosis
C It only has a half life of 30 minutes so is
easily reversed
D It does not need monitoring by blood tests
6 Which ONE of these statements is TRUE
concerning warfarin treatment?
A Warfarin must be stopped for 3 days prior to
2 Which ONE of these is NOT a typical
A Reduced platelet count
of low molecular weight heparin compared
C Carriers are at increased risk of bleeding
coagulation risk as heterozygous inheritance
feature of DIC?
5 Which ONE of these is NOT an advantage
4 Which ONE of these is NOT used to investigate
venous thromboembolic predisposition
A Serum cholesterol
B Anticardiolipin and anti‐β2‐GPI antibodies
C PT (prothrombin) and APTT tests
D Protein C and protein S assays
minor surgery (e.g. dental extraction)
B It is safe to use in pregnancy
C It is monitored by the APTT assay
D A target INR range of 2-3 is used for
treatment of deep vein thrombosis
58, White British, MALE, TATT
PMHx
Hb
122
120 - 160 g/l
Diabetes
MCV
102
80 - 100 fl
MCH
28
26 - 33 pg/c
Osteoarthritis
RDW
14
12 - 15%
WCC
9
4 - 10 x109/l
20-30u beer/week
Nph
6
2 - 8 x109/l
O/E
LC
3
1 - 4 x 109/l
Plt
400
150 - 450 x 109/l
Hypothyroidism
Tanned
ALP
165
40 - 120 IU/L
ALT
250
5-50 IU/L
BR
15
5 - 16 mcmol/L
Ferritin
6250
20 - 300
mcg/L
Transferrin
Sat
58
<55%
58, White British, MALE, TATT
How to confirm the diagnosis?
How to treat now?
How to manage long-term?
Further work to be done?
Iron metabolism…?
HFE
C282Y
H63D
Take Home: Iron Overload
Hyperferritinemia = ACUTE PHASE, LIVER … or iron
overload
Gut is the main regulator through HEPCIDIN and HFE
Transfusional, Ineffective Erythropoiesis or H.H.
Liver, Endocrine, Cardiac, Joint, Skin
C282Y or H63D mutated HFE gene
VENESECT if H.H.
MCQ Time… Iron
1 Which ONE of the following is
3 Which of the following statements is NOT correct?
NOT TRUE about serum iron?
A A unit of blood contains 200-250 mg iron
A It is low in inflammatory diseases
B A man needs to absorb about 1 mg of dietary iron daily
B It is raised in iron overload
C A molecule of transferrin may transport 4 atoms of iron
C It shows a diurnal rhythm
D Haemorrhage is the major cause of iron deficiency in
D It is transported in plasma by ferritin
the UK
4 Which ONE of these statements is TRUE about
2 Which of the following normally
genetic haemochromatosis?
contains >10% of body iron?
A It is dominantly inherited
A Transferrin
B It is usually caused by mutation of HFE
B Heart
C It causes excess iron in the duodenal mucosa
C Neutrophils
D It is associated with reduced saturation of transferrin
D Macrophages
5 Which ONE of these statements is NOT TRUE
concerning erythropoietin?
A 90% of the hormone is made in the liver
B It contains a hypoxia response gene
C One stimulus to production is a low atmospheric
oxygen level
D Levels in blood are high if a tumour secreting
erythropoietin is causing polycythaemia but are low
in severe renal disease or polycythaemia vera
6 Which ONE of the following organs is not
damaged by transfusional iron overload?
A Liver
B Kidneys
C Parathyroids
D Pituitary
E Heart
Take Home: Blood
Plasma (FFP):
Products
Corrects deficiencies of all clotting
factors
No good for warfarin-induced
deficiencies
Used in massive transfusion (>6 units)
Generally NOT for DIC!
Cryoprecipitate:
Fibrinogen concentrate
Good for dys/hypofibrin
Prothrombin Complex
Concentrates:
LIFE THREATENING warfarin
bleeds
Clotting factors
Once were ‘super-concentrates’
Now RECOMBINANTS (less viral risk)
Factors VIIa, VIII, IX and VWF
Generally for HAEMOPHILIA
Activated version: FEIBA
For haemophilia with
MCQ Time… TRANSFUSION
4. In 2014, 700 ‘near misses’ of transfusing the
incorrect blood product to a patient were reported
in the UK. These are the top five reasons
1 Which ONE of these infectious
3a. Which of the following is the most
discovered by root cause analysis. Which was the
agents is NOT tested for in blood
frequently reported transfusion related
commonest by far?
products?
reaction leading to major morbidity
A Hepatitis C antibody
A. Acute transfusion reactions
A Attachment of incorrect unit to patient IV line by
B Hepatitis B
B. Haemolytic transfusion reactions
administering nurse
C Gonorrhoea
C. Infected blood product
B Collection of incorrect unit from blood bank
D HIV
D. Transfusion-related acute lung injury
C Data entry error by laboratory clerical staff
E. Transfusion-associated circulatory overload
D Sampling/labelling error on initial cross match
sample
2 Which ONE of the following
transfusions is likely to cause
3b. Which most frequently leads to death?
intravascular haemolysis?
A. Acute transfusion reactions
A young woman estimated to be in her mid 20s is
A Group O blood to group A recipient
B. Haemolytic transfusion reactions
admitted to resuscitation bay with clinical shock
B Group B blood to group O recipient
C. Infected blood product
having sustained a RTA resulting in severe pelvic
C Group O blood to group AB recipient
D. Transfusion-related acute lung injury
and chest trauma. Which blood product should she
D Rh‐positive blood to a Rh‐negative
E. Transfusion-associated circulatory overload
receive…?
donor
The same, but he is a young man…?
MCQ Time… Miscellaneous Haematology
1 Which ONE of the following is NOT TRUE
2 Which ONE of the following infections
about neutropenia?
can often cause lymphocytosis?
A It may be caused by acute myeloid leukaemia
A Haemophilus influenza
B It occurs in aplastic anaemia
B Bordetella pertussis
C It is caused by aspirin
C Tuberculosis
D It is associated with systemic lupus
D Salmonella species
erythematosus
E It is a cause of mouth ulcers
3 Which ONE of these statements is TRUE
about T-lymphocytes?
2 Which ONE of the following is NOT a cause
A They express CD5
of eosinophilia?
B They synthesize immunoglobulin
A Steroid therapy
C They recognize soluble antigens
B Eczema
D They activate the complement cascade
C Hookworm
D Hodgkin's lymphoma
4 Which ONE is TRUE about B-lymphocytes?
A They secrete surface immunoglobulin
B They are divided into helper and killer cells
C They are all short‐lived
D They are the atypical lymphocytes in infectious
mononucleosis
5 Which ONE of these statements is NOT TRUE
concerning immunoglobulins?
A Each immunoglobulin has one kappa and one
lambda chain
B IgM is the largest isotype
C There are four subclasses of IgG
D The normal serum level of IgG is 6-16 g/L
That was…
Haematology for Clinical Finals
Paul Greaves: Consultant Haematologist, BHRUT,
Romford
...any questions? (now or later:
[email protected]