Haematology DA Flashcards
(222 cards)
1
Q
Lymphoma -> Jaundice?
A
Compression bile duct
Liver involvement
AIHA
2
Q
Cancer causing secondary polycythaemia
A
Renal cell carcinoma
Liver cancer
3
Q
Low ferritin
Low transferrin sat
High TIBC
A
IDA Lab findings
4
Q
Anaemia is characterised by the presence of red and white cell precursors
A
Leucoerythroblastic anaemia
5
Q
Tear drop red blood cells (aniso- and poikilocytosis)
Nucleated RBCs
Immature myeloid cells
A
Leucoerythroblastic anaemia
6
Q
Causes of Leucoerythroblastic anaemia
A
BONE MARROW INFILTRATION:
Leukaemia / Lymphoma / Myeloma
Solid tumours
Myelofibrosis
Miliary TB, severe fungal infection
7
Q
dry tap on BM aspirate
A
Myelofibrosis
8
Q
Anaemia caused by reduced red blood cell survival
A
Haemolytic anaemia
9
Q
Anaemia
Raised reticulocytes
Raised unconjugated bilirubin
Raised LDH
Low haptoglobins
A
Haemolytic anaemia
10
Q
Inherited Haemolytic anaemia
A
Hereditary spherocytosis (membrane problem)
G6PD deficiency (enzyme problem)
Sickle cell disease, thalassemia (haemoglobin problem)
11
Q
Acquired Haemolytic anaemia
A
Immune-mediated
Non-immune mediated
12
Q
DAT +ve
A
haemolytic anaemia is mediated through immune destruction of red cells
13
Q
Spherocytes
A
Autoimmune haemolytic anaemia
14
Q
Causes of Autoimmune haemolytic anaemia
A
Cancer involving the immune system (e.g. lymphoma)
Disease of the immune system (e.g. SLE)
Infections (disturbs the immune system)
15
Q
Non-immune haemolytic anaemia
A
Infection (e.g. malaria)
Microangiopathic haemolytic anaemia (MAHA)
16
Q
Usually caused by underlying adenocarcinoma
Red cell fragments
Low platelets
DIC/bleeding
A
MAHA features
17
Q
MAHA MOA
A
An underlying adenocarcinoma produces procoagulant cytokines that activate the coagulation cascade
This leads to DIC and the formation of fibrin strands in various parts of the microvasculature
Red cells will be pushed through these fibrin strands and fragment
NOTE: always consider underlying adenocarcinoma in any patient presenting with MAHA
18
Q
Causes of secondary polycythaemia
A
Cancer (renal, hepatocellular, bronchial)
High altitude
Hypoxic lung disease
Congenital cyanotic heart disease
19
Q
Acute vs chronic leukaemia?
A
Chronic - mature white cells are raised
Acute - immature blast cells are raised
20
Q
causes of neutrophilia
A
Corticosteroids (due to demargination)
Underlying neoplasia
Tissue inflammation (e.g. colitis, pancreatitis)
Myeloproliferative/leukaemia disorder
Infection
21
Q
Brucella
Typhoid
Viral
??
A
No neutrophilia
22
Q
Band cells
A
immature neutrophils
23
Q
Presence of band cells indicate what?
A
presence of immature neutrophils (band cells) show that the bone marrow has been signalled to release more WBCs
24
Q
Band cells
Toxic granulation
Clinically: infection/inflamm
A
Reactive neutrophilia
25
Neutrophilia
Basophilia
Immature myelocytes
Splenomegaly
Myeloproliferative disorder
26
Neutrophilia
Myeloblasts
AML
27
Causes of monocytosis
Bacteria: TB, Brucella, typhoid
Viral: CMV, VZV
Sarcoidosis
Chronic myelomonocytic leukaemia
28
Causes of reactive eosinophilia
Parasitic infection
Allergy (e.g. asthma, rheumatoid arthritis)
Underlying neoplasms (e.g. Hodgkin’s lymphoma, T cell lymphoma, NHL)
Drug reaction (e.g. erythema multiforme)
29
FIP1L1-PDGFRa fusion gene
Chronic eosinophilic leukaemia
30
Pox viruses
basophilia
31
causes of reactive lymphocytosis
Infection (EBV, CMV, toxoplasmosis, rubella, HSV)
Autoimmune diseases (NOTE: these are more likely to cause lymphopaenia)
Sarcoidosis
32
Blood film: viral infection vs leukaemia/lymphoma?
Viral infection: reactive or atypical lymphocytes (EBV)
CLL or NHL: small lymphocytes and smear cells
33
raised Hb concentration and raised haematocrit
polycythaemia
34
caused by a lack of plasma (associated with alcoholism, obesity and diuretics)
Relative polycythaemia
35
Philadelphia positive
CML
36
caused by an excess of erythrocytes
True polycythaemia
37
Philadelphia negative
polycythaemia vera
essential thrombocythaemia
primary myelofibrosis
38
AML vs Myelodysplastic syndromes
Acute myeloid leukaemia (blasts >20%)
Myelodysplastic syndromes (blasts 5-19%)
39
Types of myeloid malignancy
Acute myeloid leukaemia
Myelodysplastic syndromes
Chronic myeloid leukaemia
Myeloproliferative disorders
40
Tyrosine kinase
myeloproliferative disorders
41
Genes in Myeloproliferative disorders
JAK2 (V617F)
Calreticulin
MPL
42
JAK2 V617F mutation
Polycythaemia vera (100%)
Primary myelofibrosis and Essential thrombocythaemia (60%)
43
Mutated JAK2
constitutively active in the absence of EPO thereby driving cell replication in the absence of a stimulus
44
Often incidental
Hyperviscosity: headaches, visual disturbance, stroke, fatigue, dyspnoea, light-headedness
Increased histamine release: aquagenic pruritis, peptic ulceration
Polycythaemia vera
45
Tx for polycythaemia vera - reduce Hct and thromobosis risk?
Reduce haematocrit (aim for <45%) - venesection, cytoreductive therapy (hydroxycarbamide)
Reduce thrombosis risk - control Hct, aspirin, keep platelets < 400x109/L
46
Characterised by sustained thrombocytosis > 600 x109/L
Essential thyrombocythaemia
47
Megakaryocyte lineage - chronic myeloproliferative disorder
Essential thrombocythaemia
48
Incidental finding (50%)
Thrombosis (arterial and venous) - CVA, TIA, DVT, PE, gangrene
Bleeding (mucous membrane and cutaneous)
Headaches, dizziness, visual disturbance
Splenomegaly (modest)
Essential thrombocythaemia
49
Tx for Essential thrombocythaemia
Aspirin
Hydroxycarbamide
Anagrelide (rarely used)
50
MOA of Anagrelide
specifically inhibits platelet function but rarely used because of side-effects
51
Hydeoxycarbamide MOA
Antimetabolite that suppresses cell turnover
52
Cytopaenias (anaemia, thrombocytopaenia)
Thrombosis
MASSIVE splenomegaly
Hepatomegaly
Hypermetabolic state (FLAWS)
Primary myelofibrosis
53
Survival primary myelofibrosis
3-5 yrs
54
Poor prognostic indicators - primary myelofibrosis
Severe anaemia
Thrombocytopaenia
Massive splenomegaly
54
Trephine biopsy:
Increased reticulin and collagen fibrosis
Prominent megakaryocyte hyperplasia and clustering
New bone formation
Primary Myelofibrosis
55
Leucoerythroblastic picture
Tear drop poikilocytes (Dacrocytes)
Giant platelets
Circulating megakaryocytes
Primary Myelofibrosis
56
Mutations in Primary myelofibrosis
JAK2 and Calreticulin
57
Characterised by extramedullary haemopoeisis
Reactive bone marrow fibrosis
Primary myelofibrosis
58
Tx for primary myelofibrosis
Transfusions
Hydroxycarbamide
Ruxolitinib - JAK2 inhibitor
Allo stem cell transplant
Splenectomy - symptom relief
59
Leucocytosis (MASSIVE)
Normal or raised Hb and platelets
CML
60
Neutrophils
Basophils
Myelocytes (NOT blasts)
CML
61
CML timeline
5-6 years STABLE phase
6-12 months ACCELERATED phase
3-6 months BLAST CRISIS
62
translocation between 9;22
CML -> Philadelphia chromosome - 22q derivative chromosome
63
Bcr-Abl fusion gene
CML - means that the tyrosine kinase component is constitutively activated thereby driving cell proliferation in the absence of a stimulus
64
BCR-ABL tyrosine kinase inhibitors
CML:
- Some people fail to achieve a complete cytogenetic response
- Non-compliance
- Side-effects (fluid retention, pleural effusion)
- Loss of major molecular response (due to resistance mutations)
65
BCR-ABL inhibitors
Imatinib
Dasatinib , Nilotinib
Bosutinib
66
Cancer of monoclonal plasma cells
Abundance of monoclonal immunoglobulin
Osteolytic bone lesions
Anaemia
Infections (due to deficient polyclonal response)
Kidney failure (due to hypercalcaemia)
Multiple myeloma
67
MGUS?
Premalignant MM
68
MGUS Blood film
Serum M <30g/L
Bone marrow clonal plasma cells <10%
No lytic lesions
No myeloma organ or tissue impairment
No evidence of B-cell proliferative disorder
69
Myeloma vs Lymphoma
IgA or G = Myeloma
IgM = Lymphoma
70
Most common haem malignancy
B cell lymphoma
71
Second most common haem malignancy
Multiple myelomma
72
Mayo criteria
Risk stratification MGUS
73
Smouldering myeloma
Between MGUS and Myeloma
74
Hyperdiploidy
IGH rearrangements (heavy chain gene translocations)
MM development mechanisms
75
Centroblast
Activated B cell
76
CRAB
MM symptoms:
Hypercalcaemia (>2.75 mmol/L)
Renal failure (creatinine >177μmol/L or eGFR <40ml/min)
Anaemia (Hb <100g/L or drop by 20g/L)
Bone lesions (One or more bone lytic lesions in imaging
77
Myeloma defining event
BM plasma cells ≥60%
Involved : uninvolved FLC ratio >100
>1 focal lesion MRI >5mm
78
Criteria for MM diagnosis
≥10% plasma cells in bone marrow + ≥1 CRAB or myeloma defining event
79
Survival in MM
3-4 years
80
Immature plasmablastic cell
Prominent nucleoli
Reticular chromatin
Less abundant cytoplasm
81
Normal plasma cells
Nucleus is pushed to one side of the cell
Clumped chromatin
Large cytoplasm (low nuclear-to-cytoplasmic ratio)
82
+ ve CD138 and CD38
MM:
CD138 - commonly used diagnostic marker
CD38 - can be targeted by monoclonal antibodies
83
-ve CD19, -ve CD20 and surface Ig neg
MM
84
+ve CD20
B cell lymphoma and CLL
85
Cast nephropathy - caused by high serum FLC, which is filtered and precipitates in tubules
Hypercalcaemia - nephrocalcinosis
MM
86
AKI and MM?
20-50% AKI at diagnosis
87
Bence jones protein
MM
88
MM -> AL amyloidosis?
Light chains have the potential to misfold and deposit = Amyloid
89
Congo red
Amyloid stain
90
Nephrotic (70%)
Proteinuria, Oedema
Unexplained HF - (10%)
Raised NT-pro-BNP
Abnormal Echo and cardiac MRI
Sensory Neuropathy
Abnormal LFTs (9%)
Macroglossia
Malabsorption plus GI symptoms
Amyloidosis
91
MM Tx?
Cyclophosphamide
Daratumumab
Steroids
Thalidomide
Bortezomib
92
MOA of thalidomide
down-regulates pro-survival cytokines and induces apoptosis
93
anti-CD38 antibody
Daratumumab - anti-CD38 antibody, binds to cell surface of plasma cells causing complement activation and cell lysis/death
94
Prevalence NHL and HL?
NHL = 80%
HL = 20%
95
Oncogenes in Lymphoma/Leukaemia
Bcl2
Bcl6
Cyclin D1
c-Myc
96
H. pylori lymphoma
Gastri MALT - marginal zone NHL of the stomach
97
Sjogren's lymphoma
marginal zone NHL of the parotid
98
Coeliac disease Lymphoma
small bowel T cell lymphoma, enteropathy-associated T cell NHL
99
HTLV1
Human T lymphocytrophic virus -> Lymphoma/Leukaemia
100
Loss of T cell function -> lymphoma?
EBV established latent infection in B cells which is kept in check by cytotoxic T cell
Loss of T cell function (e.g. HIV, post-transplant immunosuppression) can lead to EBV-driven lymphoma
101
a crescent-shaped region where naïve unstimulated B cells are found
Mantle zone - Lymph node
102
where naïve B cells will eventually migrate, and mature B cells will end up in the medulla
Germinal centre - Lymph node
103
CD3, CD5
T cell markers
104
CD20
B cell marker
105
WHO classification of lymphoma
Hodgkin lymphoma:
Classical
Lymphocyte predominant
Abnormal B cells
Non-Hodgkin lymphoma:
B cell (MOST COMMON) - (Precursor B cell neoplasm) (Peripheral B cell neoplasm (low and high grade))
T cell - (Precursor T cell neoplasm) (Peripheral T cell neoplasm)
106
11;14 translocation
Mantle cell lymphoma
107
2;5 translocation
Anaplastic large cell lymphoma
108
Follicular lymphoma
Small lymphocytic lymphoma (CLL)
Marginal zone lymphoma
Low-grade lymphoma
109
Diffuse large B cell lymphoma
Burkitt’s lymphoma
Mantle cell lymphoma
High-grade lymphoma
110
positive staining for CD10 and Bcl2
Follicular lymphoma
111
14;18 translocation involving Bcl2 gene
Follicular lymphoma
112
Cells are CD5 and CD23 positivie
Small cell lymphoma
113
Richter transformation
Small lymphocytic lymphoma -> high grade lymphoma/leukaemia
114
Arise mainly in extra-nodal sites, arise from post-germinal centre memory cells
Marginal zone lymphoma
115
middle aged male
Disseminated disease
Lymph in GI tract
Mantle cell lymphoma
116
Mantle cell lymphoma survival?
3-5 yrs
117
Show aberrant expression of cyclin D1 and CD5
Mantle cell lymphoma
118
"Angular / clefted nuclei"
Mantle cell lymphoma
119
Cyclin D1 overexpression
Mantle cell lymphoma
120
Jaw or abdominal mass in children and young adults
Burkitt's lymmphoma
121
EBV lymphoma
Burkitt's
122
Starry sky appearance
Germinal cells
Burkitt's
123
c-Myc translocation (8;14, 2;8 or 8;22)
Burkitt's lymphoma
124
Middle-aged and elderly patients with lymphadenopathy
Diffuse large B cell lymphoma
OR
T cell lymphoma - more aggressive
125
p53-positive and high proliferation fraction
Poor prognosis Diffuse Large B Cell Lymphoma
126
T cell lymphomas
Adult T cell leukaemia/lymphoma - HTLV1
Enteropathy-associated T cell lymphoma - Coeliac disease
Cutaneous T cell lymphoma (mycosis fungoides)
Anaplastic large cell lymphoma
127
Children and young adults with lymphadenopathy - aggressive
Anaplastic large cell lymphoma
128
Large epithelioid lymphocytes
Anaplastic large cell lymphoma
129
2;5 translocation
Anaplastic large cell lymphoma
130
Alk-1 protein expression
Good prognosis Anaplastic large clel lymphoma
131
differences between Hodgkin and Non-Hodgkin Lymphoma
Hodgkin is more localised (usually one nodal site)
Hodgkin spreads contiguously to adjacent to adjacent lymph nodes
132
Young and middle-aged patients with only a single group of lymph nodes involved
Associated with EBV
Hodgkin's Lymphoma
133
Reed sternberg cells?
Bi / multi - nucleated abnormal lymphocyte
134
Hodgkin cell?
Mononucleated abnormal lymphocyte
135
+ve CD15 and CD30, (CD20 negative)
Hodgkin's lymphoma - classic
136
Isolated lymphadenopathy
NO association with EBV
nodular lymphocyte predominant Hodgkin lymphoma.
137
B cell rich nodules with scattered around L&H cells
lymphocyte predominant Hodgkin lymphoma
138
Positive = CD20
Negative = CD15, CD30 (unlike classical Hodgkin lymphoma)
Lymphocyte predominant Hodgkin's lympgoma
139
B symptoms
Fever
Night Sweats
Weight loss
140
Lymphoma stages
1 = 1 group of nodes
2 = > 1 group of nodes on the same side of the diaphragm
3 = > 1 group of nodes above and below the diaphragm
4 = extranodal spread
Suffic ‘B’ if B symptoms are present
141
Stage lymphoma how?
PDG-PET/CT
142
ABVD
Hodgkin's lymphoma chemo regime:
- Adriamycin
- Bleomycin
- Vinblastine
- Dacarbazine
143
Curability of Hodgkin's
Stage I and II: >80%
Stage IV: 50%
144
LDH marker?
Of cell turnover
145
R-CHOP
Diffuse large b cell lymphoma:
R-CHOP
- Rituximab
- Cyclophosphamide
- Doxorubucin
- Vincristine
- Prednisolone
146
R-CVP
Tx for Follicular Lymphoma:
R-CVP (rituximab, cyclophosphamide, vincristine, prednisolone)
147
Epigastric pain, ulceration, bleed
B-symptoms uncommon
Gastric MALToma
148
EATL prognosis
no response to chemo
usually fatal
149
most common leukaemia in Western world
CLL
150
CLL - cells?
Prolif of mature B cells
151
Smear cells
CLL
152
Lymphocytosis
Smear cells
Normocytic normochromic anaemia
Thrombocytopaenia
Bone marrow lymphocytic replacement of normal marrow elements
CLL
153
CD19 positive
CD5 negative
Mature B cells
154
CD19 negative
CD5 positive
CD3 positive
CD4 or CD8 positive
Mature T cells
155
CD19+ and CD5+
CLL or Mantle cell lymphoma
156
Rai and BInet staging system
CLL
Binet: stages A-C depending on number of lymphoid areas (< or > 3, Hb and platelets)
157
TP53 mutation - worse prognosis
IgH V gene mutation - better prognosis
CD38 expression
CLL
158
Ig levels in CLL
Hypogammaglobulinaemia
Malignant B cells suppressing Ab production by B cells
159
Richter transformation risk of CLL
1% per year
160
Richter transformation Tc?
R-CHOP
161
TP53 intact CLL treatment?
FCR - Fludarabine, Cyclophosphamide, Rituximab
162
CAR T therapy for CLL targets?
CD19
163
Tx new options for CLL?
Bcl2 inhibitor - venetoclax
Bruuton tyrosine kinase inhibitor - Ibrutinib - p53 mutation
PI3K inhibitor - Idelalisib
164
Transient Abnormal Myelopoiesis associations?
Down's syndrome
20% develop Myeloid leukaemia in 4 yrs
165
Transient Abnormal Myelopoiesis - pathophys?
Preleukaemic blasts in bone marrow and blood of neonate
166
GLOBIN GENES:
Beta
Delta
Gamma
Epsilon
BETA - chromosome 11
167
GLOBIN GENES:
Alpha 1 and 2
Zeta
Alpha - chromosome 16
168
Hb - 2 alpha, 2 beta
HbA
169
Hb - 2 alpha, 2 delta
HbA2
170
Hb - 2 alpha, 2 gamma
HbF
171
Foetal Hb
2 zeta, 2 epsilon
Gower 1
172
Foetal Hb
2 alpha, 2 epsilon
GOver 2
173
Foetal Hb
2 zeta, 2 gamma
Portland 1
174
HbA2 level in adult healthy
< 3.5%
175
Birth Hb levels and types
1/3 HbA
2/3 HbF
176
homozygosity for HbS gene
Sickle cell anaemia
177
Howell-Jolly bodies
Splenic dysfunction -> Hyposplenism
Sickle cell anaemmia too
178
Parvovirus causes?
Aplastic anaemia
179
clinical features of beta thalassaemia major:
Anaemia → heart failure, growth retardation
Erythropoietic drive → bone expansion, hepatomegaly, splenomegaly
Iron overload → heart failure, gonadal failure
180
Beta thalassaemia major Mx
Accurate diagnosis and family counselling
Blood transfusion
Iron chelation therapy
Consider child as individual an part of family
181
Iron chelating drug
Desferrioxamine
182
Pentose shunt
G6PD def
183
Glycolytic pathway
Pyruvate Kinase Def
184
Red cell membrane abnormality
hereditary spherocytosis, hereditary eliptocytosis
- Spherocytes = spherocytosis
- Eliptocytes = eliptocytosis
185
Inherited haemolytic anaemia
Thalassaemia
Sickle cell
Pyruvate kinase def
G6PD
Hereditary Spherocytosis
Hereditary eliptocytosis
186
Acquired congenital haemolytic anaemia
Haemolytic disease of the newborn
187
Low reticulocyte count
Aplastic anaemia
188
inheritance pattern of G6PD deficiency
X-linked recessive
189
Children - Acquired Haemolytic anaemia
Autoimmune haemolytic anaemia (AIHA)
Haemolytic Uraemic syndrome
190
Positive DAT
Spherocytes on blood film
AIHA
191
Acute renal failure
Microangiopathic haemolytic anaemia
Thrombocytopenia
HUS
192
Microangiopathic hemolytic anemia
Thrombocytopenic purpura
Neurologic abnormalities
Fever
Kidney disease
TTP
193
Schistocytes
MAHA
194
Intravascular haemolysis of occuring due excessive shear forces in small vessels
MAHA
195
Haemarthrosis when starting to walk
Bruises
Excessive post-traumatic or surgery bleeding
Haemophilia A and B in infant
196
Mucosal bleeding
Bruises
Post-traumatic bleeding
vWD
197
Haemophilia A or B more common?
Haemophilia A is 4x more common than B
198
Differentials for ITP
Henoch-Scholein Purpura
Non-accidental injury
Coagulation factor defect
Inherited thrombocytopaenia
Acute leukaemia
199
Tx ITP?
Observation (most common)
Corticosteroids
High dose IVIG
IV anti-RhD (if RhD positive)
200
Most common leukaemia in children?
ALL
201
CD34
Stem cell marker
202
Risk of dying from BM transplant
>50%
203
autologous stem cell transplantation Mechanism?
Growht factor is given to the patient to stimulate the production of cells from the bone marrow
Cells are sampled from the patient’s bone marrow (some of them will be CD34+ stem cells)
These are preserved in a freezer
High-dose chemotherapy is given to the patient to eradicate their bone marrow
Stem cells are re-infused
204
Most common reasons for Autologous HSCT
Myeloma
Lymphoma
CLL
205
Allogenic Stem Cell Transplant uses?
Acute leukaemia
Chronic leukaemia
Myeloma
Lymphoma
Bone marrow failure
Congenital immune or haematological conditions
206
GvHD which transplant
Allogenic
207
equation that relates the probability of having a sibling with a matching tissue type to the number of siblings a patient has
Probability of match = 1 — (3/4) ^ number of siblings
208
HLA for Class I - Present to CD8+ (cytotoxic T cells)
HLA-A, B, C
209
HLA for Class II - Present peptide to CD4+ (Helper T cells)
HLA-DP, DQ, DR
210
Match rate with parent?
1/2
6 HLAs, 2 x parents, match rate = 1/2
211
Allogenic HSCT mechanism?
Identify disease unlikely to respond to standard treatment
Treat patient into remission
Identify donor and collect stem cells
Give patient myeloablative therapy
Infuse stem cells
Continue immunosuppression and support patient through period of cytopenia
212
GvHD - acute vs Chronic
<100 days = acute
>200 days = chronic
213
GvHD symptoms - acute
Skin - painful rash and desquamation
GI tract - abdominal pain and diarrhoea
Liver - jaundice and hepatomegaly
214
GvHD symptoms - chronic
Skin - sclerosis, ulcers, nail dystrophy
Mucosal membranes - ulcer
Lungs - bronchiolitis obliterans
Liver - dysfunction and jaundice
Dry eyes
Polymyositits
215
Treatment for acute GvHD
Corticosteroids (mainstay)
Calcineurin inhibitors: cyclosporin, tacrolismus
Mycophenolate mofetil
Monoclonal antibodies
Photophoresis
Total lymphoid irradiation
216
Prevention of GvHD
Mycophenolate is standard prevention regime
ALSO:
Methotrexate
Corticosteroids
Calcineurin inhibitors
Post-transplant cyclophosphamide
217
GvHD cells involved?
Mature lymphocytes, not stem cells
218
Neutropaenic sepsis?
Fever >38 for over an hour
Single fever >39
Patient w neutrophils <1 x 10^9
Broad-spec Abx
219
Post-HCST:
Pneumonitis
Retinitis
Colitis
Encephalitis
CMV disease post-transplant
220
CMV Tx?
Ganciclovir
221
