Haematology Flashcards
1
Q
In which type of leukaemia is lymphadenopathy most common?
A
CML
2
Q
Which type of leukaemia may produce CNS symptoms or testicular swelling?
A
ALL
3
Q
Which tests are required to make a diagnosis of ALL?
A
Flow cytometry
BM biopsy
4
Q
What is the presence of an Auer Rod on blood film diagnostic of?
A
AML
5
Q
In which haematological malignancy might “faggot cells” be present?
A
AML
6
Q
Which translocation is associated with APML?
A
T(15;17)
7
Q
Which haematological malignancy is most likely to present with DIC?
A
APML
8
Q
What is the mainstay of treatment in APML?
A
ATRA (All-trans retinoic acid)
This forces cells to differentiate and hals proliferation
9
Q
Which hamatological malignancy is most likely to present with LUQ pain?
A
CML - due to splenomegaly
10
Q
Recall 4 features of the blood film that may be seen in CML
A
Leukocytosis
Eosinophilia
Basophilia
Left shift
11
Q
Which haematological malignancy may have hypolobated megakaryocytes in the bone marrow?
A
CML
12
Q
Which translocation produces the philadelphia chromosome?
A
T(9;22)
13
Q
Which haematological malignancies are associated with the Philadelphia Chromosome?
A
Comminly CML
20-30% ALL in adults
14
Q
What is the mainstay treatment of CML?
A
Tyrosine kinase inhibitors
There are 3rd generation
Imatinib is an example of a first gen TKI
15
Q
Which haematological malignancy is most likely to present with ITP/ haemolysis?
A
CLL
16
Q
Smear/ smudge cells may be seen in which haematological malignancy?
A
CLL
17
Q
How is CLL diagnosed?
A
Flow cytometry
This identifies light chain restriction
18
Q
How is CLL similar to small lymphocytic lymphoma?
A
Same pathology, but in the blood rather than the marrow and lymph nodes
19
Q
Recall the staging of CLL
A
A - no cytopaenia, <3 areas of lymphoid involvement
B - no cytopaenia, 3 + areas of involvement
C - cytopaenias
20
Q
Describe the stage-depended consideration of treatment for CLL
A
Stage A - watch and wait
Stage B - Consider treatment
Stage C - Treat
21
Q
What are the available treatments for CLL?
A
- Ibrutinib (Bruton’s tyrosine kinase inhibitor)
- FCR (fludarabine, cyclophosphamide, rituximab)
- Stem cell transplant
22
Q
What is Richter’s syndrome?
A
Transformation of CLL to aggressive disease (ALL/ high grade lymphoma)
23
Q
What platelet level is diagnostic of essential thrombocythaemia?
A
Consistently >450
24
Q
In which myeloproliferative disorders is a JAK2 mutation present in approximately 50% of cases?
A
Essential thrombocythaemia
Myelofibrosis
25
What is the treatment for essential thrombocythaemia?
Aspirin to reduce stroke risk
| Hydroxycarbamide to lower count
26
What % of patients with polycythaemia vera have a JAK2 mutation?
95%
27
What is the treatment for polycythaemia vera?
Aspirin to reduce stroke risk
Venesection
Hydroxycarbamide to lower count
28
What might polycythaemia be secondary to?
Severe COPD
Cyanotic heart disease
Erythropoietin-secreting renal tumours
29
Which cytopaenias do you get in myelofibrosis?
Pancytopaenia
30
What might be identified on examination of someone with myelofibrosis?
Splenomegaly
31
What abnormal cell may be seen on a blood film of someone with myelofibrosis?
Tear drop poikilocytes
32
How is myelofibrosis treated?
Stem cell transplant is the only cure
| Can use ruloxinib to relieve symptoms - a JAK2 inhibitor
33
What is the most common presentation of myelodystplastic syndrome?
Incidental cytopaenia
34
At what % of blasts is myelodysplastic syndrome considered to have progressed to AML?
>20%
35
How is the risk of a myelodysplastic syndrome progressing to AML calculated?
IPSS score
36
Describe the typical presentation of Hodgkin's lymphoma
Young, cervical lymphadenopathy made worse on drinking EtOH
37
Presence of which type of cell is diagnostic of Hodgkin's lymphoma?
Reed-Sternburg cells
38
What is the most common form of Hodgkin's lymphoma?
Nodular sclerosing
39
What type of haematological malignancy is EBV associated with?
Hodgkin's lymphoma
40
How is Hodgkin's lymphoma managed?
ABVD chemo + radio
41
How does Non-hodgkin's lymphoma typically present?
With B symptoms and lymphadenopathy
42
What is the most common type of indolent Non-Hodgkin's lymphoma?
Follicular
43
What would be seen on lymph node biopsy in folliculat non-Hodgkin's lymphoma?
Large number of centroblasts
44
Which translocation is associated with follicular non-Hodgkin's lymphoma?
T(8;14) --> BCL2 gene
45
What is the main risk of treatment in high grade lymphoma?
Tumour lysis syndrome
46
What is the typical histological appearance of Burkitt's lymphoma?
Starry sky
47
Which translocation is associated with Burkitt's lymphoma?
T(8;14)
48
What are the 4 B cell subtypes of non-Hodgkin's lymphoma?
Burkitt's
Diffuse large B cell
Mantle cell
Follicular
49
What is the mainstay of treatment for diffuse large B cell lymphoma?
R-CHOP chemo
50
Which translocation is associated with mantle cell lymphoma?
T(11;14) - which causes overexpression of cyclin D1
51
Where is acute T cell lymphoma leukaemia most common?
Far East
52
Which virus is associated with ATLL?
HTLV-1
53
In which haematological malignancy are 'flower cells' seen on the blood film?
ATLL
54
Recall the name of the staging system used in lymphoma, and how each stage is defined
```
Ann Arbor staging
Stage 1 = 1 set of LN
Stage 2 = >1 set of LN, one side of diaphragm
Stage 3 = LNs both sides of diaphragm
Stage 4 = involves spleen/ BM
```
55
What is Bence Jones protein?
Myeloma paraprotein in urine
56
Recall 2 features of the blood film that may be seen in multiple myeloma
Rouleaux
| Fried egg cells (plasma cells that are immature)
57
What are the diagnostic criteria for myeloma?
Plasma cells in BM >60%
1+ lesions on MRI
Free light chain ratio > 100
58
What is smouldering myeloma?
Serum paraprotein >30
| Clonal bone marrow plasma cells 10-60%
59
What are the criteria for MGUS?
Serum paraprotein < 30
| Plasma cells <10% in BM
60
What is Waldenstrom's macroglobulinaemia?
Similar to follicular lymphoma but:
Paraprotein is always IgM
Risk of hyperviscosity syndrome
61
Recall the reversing protocol for warfarin
Based on INR
- If at any point there is a major bleed --> hold warfarin, give vit K and FFP/PCC
Otherwise:
- INR <5 --> reduce warfarin dose
- INR 5-8 --> hold warfarin if no bleed, give vit K if minor bleed
INR >8 --> hold warfarin and give vit K
62
What is the reversing agent for heparin/LMWH?
Protamine sulphate
63
What is the reversing agent for DOACs?
Prothrombin complex concentrate (PCC)
64
What is the reversing agent for aspirin/ clopidegrel?
Platelet transfusion
65
Recall the dosing for red cells, platelets and FFP
Red cells: ~1 per 10g/l Hb rise
Platelets: ~1 per 25 count rise
FFP: 10-15mls/kg
66
In which blood products does rhesus status matter?
Red cells
| Platelets
67
At what temperature should platelets be stored?
Room temp
68
Over how long should red cells, platelets and FFP be infused?
Red cells: 2-3 hours
Platelets: 30 mins
FFP: 30-60 mins
69
By which class of Ig are acute haemolytic transfusion reactions mediated?
IgM
70
How can TRALI and TACO be differentiated?
TRALI may produce fever, TACO does not
| TACO --> features of heart failure, TRALI does not
71
Which blood product is most likely to cause sepsis because of bacterial contamination?
Platelets
72
How can febrile non-haemolytic transfusion reactions be prevented?
By leukodepletion
73
Which group of patients have the highest risk of anaphylactic reaction to blood products?
IgA deficient patients
74
Recall 2 clinical signs of TACO
Raised JVP
| Raised PCWP
75
What is the main clinical feature of delayed haemolytic transfusion reaction?
Extravascular haemolysis
76
By which immunoglobulin is delayed haemolytic transfusion reaction mediated?
IgG
77
Recall 3 symptoms of GVHD in blood transfusion
Skin desquamation
Diarrhoea
Liver failure
78
What is the pathophysiology of GVHD in blood transfusion?
Donor lymphocytes recognise host HLA as foreign
79
How can GVHD in blood transfusion be prevented?
Irradiating blood products for immunocompromised patients
80
What leveks of haemoglobin are considered 'anaemia' in men and women respectively?
M: <135
F: <115
81
What is a normal red cell volume?
80-100fL
82
What are the 2 most important tests to do to determine the cause of a microcytic anaemia?
Peripheral blood smear
| Iron studies
83
What are 'pencil cells' pathognomonic for?
Iron deficiency anaemia
84
What will be seen as well as anaemia on an FBC in iron deficiency anaemia?
Reactive thrombocytosis
85
Which two conditions may have basophillic stippling on a blood smear?
Thalassaemia
| Sideroblastic anaemia
86
What would iron studies show in sideroblastic anaemia?
Same as IDA: high transferrin and TIBC, low iron and ferritin
87
What are the key tests to do to investigate a macrocytic anaemia?
Peripheral blood smear
LFTs
TFTs
88
What is elevated in the serum specifically in B12 deficiency?
Methylmalonic acid
89
What is the test for pernicious anaemia?
Schilling test
90
What drug might cause folate deficiency?
Phenytoin - it impairs its absorption
91
Recall 3 causes of non-megaloblastic macrocytic anaemia
Pregnancy
EtOH use
Hypothyroidism
92
What are the most important tests to do when investigating a normocytic anaemia?
Peripheral blood smear
DAT/Coombs
CRP and ESR
93
Why would you do a CRP/ESR in cases of normocytic anaemia?
Would be raised in anaemia of chronic disease
94
Recall 2 inherited causes of haemolytic anaemia
Hereditary spherocytosis
| G6PD deficiency
95
What are the two tests for hereditary spherocytosis?
Osmotic fragility test (less specific)
| Eosin-5-maleimide test (more sensitive and specific)
96
How should hereditary spherocytosis be managed?
Folate supplementation
| Splenectomy
97
What is the inheritance pattern of G6PD deficiency?
X linked recessive
98
What is the normal role of G6PD?
Generates NADPH via pentose pathway
99
What would be seen on peripheral blood smear in hereditary spherocytosis?
Spherocytes and polychromasia
100
What would be seen on peripheral blood smear in G6PD deficiency?
Heinz bodies
| Bite cells
101
Recall 3 causes of immune haemolytic anaemia
Autoimmune (warm/ cold)
ABO incompatibility
Rh incompatibility
102
Describe the differences between warm and cold autoimmune haemolytic anaemia
Warm: IgG, extravascular haemolysis (associated with CLL, SLE and methyldopa)
Cold: IgM, intravascular haemolysis (associated with mycoplasma, EBV and Hep C)
103
How can autoimmune haemolytic anaemia be managed?
Treat cause
Steroids
Rituximab
104
Recall 3 types of non-immune acquired haemolytic anaemia
MAHA
HUS
TTP
105
What is the triad of features in MAHA?
HUS, TTP and DIC
106
How can MAHA be distinguished from DIC?
MAHA will have normal APTT, PT anf fibrinogen
107
What is the most common cause of HUS in children?
E coli O157:H7 - shiga-like toxin
108
In which type of anaemia should antibiotics always be avoided?
HUS
109
What is the usual pathophysiology of TTP?
ADAMTS13 deficiency --> decreased vWF breakdown
110
What is the triad of features in TTP?
HUS + neurology + fever
111
On which chromosomes are the alpha and beta globin chains encoded?
Alpha: 16
Beta: 11
112
What are the 3 subtypes of beta thalassaemia?
Minor/ intermedia/ major
113
What are the genotypes and corresponding phenotypes of each of the types of alpha thalassaemia?
HbBarts - 4 faulty genes - fatal in utero due to hydrops
HbB - 3 faulty genes - severe anaemia
Trait - 2 faulty genes - mild anaemia
Silent - 1 faulty gene
114
What is the mutation that causes sickle cell anaemia?
Glu--> Val at codon 6 on the beta globin chain
115
Recall some principles of management of sickle cell disease
Vaccinate against encapsulated bacteria
Supplement folate
Hydroxyurea
Supportive care in acute crisis
116
In a patient with sickle cell anaemia, what is the most common pathogen to be implicated in cases of
a) sepsis
b) osteomyelitis?
```
Sepsis = Strep pneumoniae
Osteomyelitis = salmonella
```
117
Recall some differentials for disorders of haemostasis
Primary haemostatic disorders = to do with platelet function eg. vWF disease, ITP, HIT
Secondary haemostatic disorders = to do with the coagulation cascade = haemophilia A/B, liver disease, vit K deficiency
118
Recall some differentials for thrombotic disorders
Inherited: Factor V Leiden, anti-thrombin deficiency, protein C/S deficiency
Acquired: HIT, malignancy, immobilisation
119
What is the inheritance pattern of each of the types of von Willebrand disease?
Types 1 and 2 = autosomal dominant
| Type 3 = autosomal recessive
120
What are the 3 subtypes of vWF disease?
Type 1 = too few platelets
Type 2 = qualitative deficiency
Type 3 = quantitative and qualitative deficiency
121
What would be the exected APTT and PT in vWF?
Prolonged APTT
| Normal PT
122
Differentiate the presentation of acute vs chronic ITP?
Acute: children, self-resolving, preceding infection
Chronic: adults, mostly women, longterm relapsing-remitting
123
How can severe acute ITP/ chronic ITP be treated?
Steroids
IV Ig
Splenectomy for chronic
124
What is the inheritance pattern of haemophilia?
X linked recessive
125
What is deficient in haemophilia A/B?
```
A = factor VIII
B = factor IX
```
126
How is haemophilia treated?
Replace missing factor
127
What are the typical symptoms of haemophilia?
Deep bleeding
| Haemarthroses
128
What would be the exected APTT and PT in haemophilia?
Prolonged APTT
Normal PT
(Same as vWF disease)
129
Recall 3 causes of vit K deficiency
Malabsorption
Warfarin
Antibiotic therapy
130
Which factor will be the first to be depleted in vit K deficiency?
Factor VIII
131
What would be the expected APTT and PT in vit K deficiency?
Both prolonged
132
What is the pathophysiology of factor V Leiden?
Resistance to Protein C --> failure to degrade factor V --> hypercoagulable state --> predisposition to VTE
133
What is the inheritance pattern of anti-thrombin deficiency?
Autosomal dominant
134
What is the main sign of anti-thrombin deficiency?
VTEs in weird places (eg spleen, mesenteric veins)
135
How is anti-thrombin deficiency diagnosed?
Anti-thrombin deficiency
136
How should anti-thrombin deifciency be managed?
Longterm warfarin/ argatroban
137
What is the inheritance pattern of protein C/S deficiency?
Autosomal deficiency
138
How can protein C/S deficiency affect the skin?
Associated with warfarin-induced skin necrosis: initial hypercoagulable state -> ischaemia of skin vessels
139
How is protein C/S deficiency diagnosed?
Protein C/S assay
140
How should protein C/S deficiency be managed?
Longterm argatroban
141
What are the key investigations to do in any microcytic anaemia?
Peripheral blood smear
Iron studies
142
What are the expected results of iron studies in thalassaemia?
All normal
143
What are the key differentials in microcytic anaemia?
IDA
Thalassaemia
Siderblastic
144
What are the key investigations to do in macrocytic anaemia?
Peripheral blood smear (to see if megaloblastic or not)
LFTs (alcohol?)
TFTs (hypothyroid)
145
What specific marker is elevated in B12 deficiency but not folate deficiency?
Serum methylmalonic acid
146
What type of anaemia can be caused by phenytoin use?
Folate deficiency --> megaloblastic
147
What 2 tests would be positive in hereditary spherocytosis?
Osmotic fragility
Eosin-5-maleimide
148
What are the 2 abnormal cells that can be seen in G6PD in a peripheral blood smear?
Heinz bodies
| Bite cells
149
What are the difference between hot and cold AIHA?
Warm: mediated by IgG, associated with CLL, causes extravascular haemolysis
Cold: mediated by IgM, associated with mycoplasma/ EBV/ Hep, --> intravascular haemolysis
150
How can MAHA and DIC be distinguished?
MAHA has normal APTT, fibronogen and PT
151
What are the 5 elements of TTP?
```
MAHA
Thrombocytopaenia
Acute renal failure
Neurological symptoms
Fever
```
152
Which inherited clotting disorder carries the highest risk of clots?
Antithrombin deficiency
153
What is the most common mode of inheritance of VWD?
Autosomal dominant
154
By which class of Ig is ABO incompatibility mediated?
IgM
155
With which type of transfusion is bacterial contamination most likely?
Platelets (stored at warmer temp)
156
What disorder is most strongly associated with predisposition to anaphylactic reaction to transfusion?
IgA deficiency
