Haematology Flashcards
1
Q
What is leukoerythoblastic anaemia
A
Presence of nucleated red blood cells and myeloid precursors in the blood
2
Q
What see on blood film of leukoerythoblastic
A
Tear drop cells
Nucleated RBC
Myelocyte
3
Q
What could cause leukoerythoblastic
A
Malignant
- non haemaoptoetic
- leukaemia, myeloma, lymphoma
Myelofibrosis
Severe infection
- miliary TB
- severe fungal infection
4
Q
How are haemolytic anaemias classified
A
Acquired
Inherited
5
Q
Blood finding of haemolytic anaemia
A
Anaemia- raised MCV
Reticulocytosis
Bilirubinaemia
LDH up
Haptoglobin
6
Q
How to tell if haemolytic anaemia is immune
A
Spherocytes
DAT+ve
7
Q
Causes of immune haemolytic anaemia
A
SLE
Cancer- CLL, lymphoma
Mycoplasma
Adenocarcinoma
8
Q
Causes of non-immune haemolytic anaemia
A
Malaria
MAHA
9
Q
What is often underlying condition in MAHA
A
Adenocarcinoma
HUS
DIC
TTP
Pre-eclampsia
10
Q
Blood film of MAHA
A
RBC fragments- schistocytes
Thrombocytopenia
11
Q
What happens in MAHA
A
Mechanical RBC destruction for example through fibrin/plt mesh or metallic heart valve
12
Q
Differing between reactive and malignant neutrophilia
A
Reactive- toxic granulation and no immature cells
Malignant- basophilia and myelocytes in CML
13
Q
When do you get reactive eosinophilia
A
Parasitic infection
Allergic disease
Neoplasms which release eosiniphilic growth factor
Drug reactions in particular erythema multiforme
14
Q
What causes raised lymphocyte count
A
EBV,CMV, toxolplasma, rubella, herpes
Hepatitis
Autoimmune
Sarcoid
15
Q
How to determine whether reactive or malignant in B cells
A
Look at light chains- ratio of kappa and lambda
If reactive will be equal (60:40)
If malignant will be 1 predominating (99:1)
16
Q
Blood findings of iron deficiency anaemia
A
Microcytic hypochromic anaemia
Low ferritin, transferrin saturation
Increased TIBC
17
Q
What are spherocytes
A
RBC without central pallor
Are spherical and smaller
18
Q
Neutropenia and myeloblasts
A
AML
19
Q
What causes chronic eosinophilic leukaemia
A
FIP1L1-PDGFRa fusion gene
20
Q
What causes a monocytosis
A
TB, brucella, typhoid
Viral- CMV, varicella
Sarcoidosis
Chronic myelomoncytic leukaemia
21
Q
Lymphopenia causes
A
HIV
Auto-immune disorders
Inherited immune deficiencies
Chemo
22
Q
What is thrombophlebitic syndrome and when does it occur
A
Is a complication of thromboembolism
- recurrent pain
- swelling
- ulcers
23
Q
Inherited causes of VTE
A
Antithrombin deficiency
Protein S deficiency
Protein C deficiency
Factor V leiden
24
Q
How does injury to vessel wall make it prothrombotic
A
Anticoagulant molecules like thrombomodulin down regulated
Prostacyclin production reduced
Vwb factor release
25
What can causes vessel wall prothrombotic
COVID19
Malignancy
Vasculitis
Trauma
26
How does stasis promote thrombosis
Accumulation of activated factors
Promotes platelet adhesion
Hypoxia produces inflammatory effects on endothelium
- adhesion and release of VWF
27
What are the anticoagulant drugs and how are classified
Immediate
- heparins
- direct anti Xa and anti IIa
Delayed
- vit K antagonists
28
What are 3 options of heparins, their method of administration and if need monitoring
Unfractionated heparin IV and needs monitoring
LMWH subcut no monitoring
Pentasaccharide subcut no monitoring
29
Long term disadvantages of heparins
Osteoporosis and injections
30
MOA of heparins
Potentiate antithrombin III which inactivates thrombin and factors 9,10,11
31
What are the DOACS
Anti-Xa
- rivaroxaban, apixaban, edoxaban
Anti- IIa
- dabigatran
32
Monitoring needed for DOACS
None
33
Difference in peaks of anticoagulants
DOAC and heparin 4 hours
Vitamin K a delayed
34
MOA of warfarin
Indirectly prevents the recyclin of Vit K which reduces levels of 2,7,9 and 10
35
How is warfarin given
Oral
36
Antidote for heparin
Protamine sulphate
37
Antidote for DOACs
In dabigatran is an antibody none for Xa
38
How is unfractionated heparin monitored
APTT
(anti-Xa or heparin levels in some trusts)
39
What is given as thromboprophylaxis
Tinzaparin 4500u
Enoxaparin 40mg
40
What is given as thromboprophylaxis if upcoming surgery or heparin CI
TED stockings
41
What is given sometimes to post op ortho patients
DOAC and aspirin
42
Differnece in length of DOAC given after VTE
Surgical precipitant
- no need for long term
Idiopathic with no identified risk
- long term
Minor precipitant like trauma or flights
- 3 months
43
Risk factors for myeloma
Age
Obesity
Black
44
What is MGUS and how diagnosed
Precursor to myeloma where are free light chains in blood or urine
- serum m protein less than 30g/L
- bone marrow clonal plasma cells less than 10%
- no evidence of organ damage/lesions
45
Risks of MGUS
Increased risk of osteoporosis, thrombosis, bacterial infection
Myeloma transformation if IgG or IgG
Waldenstroms lymphoma if IgM
46
How is MGUS risk stratified
MAYO
47
Difference between smouldering myeloma and MGUS
Smouldering myeloma
- M spike over 30g/L or urinary monoclonal protein over 500 mg or bone marrow clonal plasma cells over 10%
- BUT no CRAB criteria or amyloidosis
48
Typical primary genetic events leading to myeloma
Hyperdiploidy
49
Presentation of myeloma
CRAB
Calcium- hypercalcaemia sx
Renal failure- amyloidosis and nephrotic syndrome
Anaemia- pancytopenia
Bones- pain, osteoporosis, lytic lesions, fractures
50
Diagnostic criteria for myeloma
Over 10% plasma cells in bone marrow or plasmacytoma plus atleast 1 CRAB or MDE
CRAB
- calcaemia over 2.75
- creatine over 177 or eGFR under 40
- Hb under 100 or drop by 20
- one or more bone lytic lesion
MDE
- bone marrow plasma cells over 60%
- FLC ration over 100
- over 1 focal lesion
51
Imaging for myeloma bone disease
Never use X rays
Whole body CT scan
PET
MRI
52
Main surgical emergencys in myeloma
Chord compression and hypercalcaemia
53
How to manage cord compression
MRI scan
- dexamethasone
- radiotherapy
- rarely require neurosurgery
54
How can myeloma cause renal damage
High serum free light chains
Dehydration
Treatment drugs are nephrotoxic
55
Diagnostic work up for myeloma
Serum protein electrophoresis
Serum free light chains
24 hour urine collection for bence jones protein
Bone marrow aspirate and biopsy
- stain for CD138
56
What is stained for in myeloma
CD138
57
How is myeloma staged
Internaltional staging system/salmon durie
58
Most common presentation of myeloma amyloid
Nephrotic syndrome
59
What is monoclonal gammopathy of renal significance
At least 1 renal lesion causesd by free light chains
Does not meet haematological criteria for myeloma diagnosis
60
How is MGRS treated
In same way as myeloma
61
Problem of bortezomib
Neuropathy
62
Problems of carfilzomab
Thrombocytopenia and IV infusion
63
Polycythaemia in neonate/fetus causes
Twin to twin transfusion
Intrauterine hypoxia
Placental insufficiency
64
Anaemia causes in fetus/neonates
Twin to twin transfusion
Fetal-maternal-transfusion
Parvovirus B19
Haemorrhage
Dammage from irradiation, anticoagulant drugs, antibodies
65
When can some of the first mutations leading to leukaemia often occur
In utero
If twins can even pass from one twin to another
66
What is significant risk factor for congenital leukaemia (transient abnormal myelopoiesis)
Down syndrome
67
Features of congenital leukaemia
Myeloid with huge involvement of megakaryocyte lineage
68
Difference between thalassaemia and haemoglobinopathy
Thalassaemia- reduced synthesis of globin chains
Haemoglobinopathies- synthesis of abnormal globin chains
69
What are 3 types of haemoglobin and what globin chains make up them
A- alpha and beta
A2- alpha and delta
F- alpha and gamma
70
Haemoglobin proportions through life
When foetus principally F and a bit of A
As grow is A with a bit of A2
71
Triggers for sickling episodes
Hypoxia
Dehydration
Acidosis
72
Where does vascular obstruction occur in sickle cell disease
After elongation to pass from capillary bed to venule
73
Mutation in SCD
Point mutation of glutamate replaced by valine codon 6 of beta chain coding for beta globin chain on Chr 11
1 in sickle cell trait
2 in sickle cell anaemia
74
What are 4 types of sickle cell disease
Remember sickle cell disease is an umbrella term
- sickle cell anaemia HbSS
- sickle cell trait HbAS
- sickle-haemoglobin C disease HbSC
- sickle beta thalassaemia HbS/beta
75
What happens in sickle-haemoglobin C disease
Inherit one HbS and one HbC which is a defective beta chain of a different source to sickle cell disease
76
Presentation of sicke cell beta thalassaemia present
Very severely- is similar to HbSS
77
How are haemoglobinopathies and thalassaemias normally discovered
Guthrie blood spot
78
How does SCD problems differ between the ages
In younger people- hand foot syndrome very common
Splenic sequestration occurs in young as still have functioning spleen
Then in older people when spleen is fibrosed get hyposplenism which leads to increased infection risk
Infants immune system has not developed immunity to parvovirus or pneumococcus which can be deadly as susceptible to red cell aplasia
Children are growing which has immense demand for folic acid
- growth spurts require folic acid
- red cell lifespan a lot less
- hyperplastic erythopoiesis requires folic acid
79
What is splenic sequestration and how can present
When blood pools in the spleen
Severe anaemia, shock and possible death
80
Complications of iron overload
HF
Gonadal failure
81
Problems of anaemias from haemoglobinopathies and thalassaemias in children
Lead to growth retardation
HF
82
Treatment for iron overload
Chelation therapy
- desfrioxamine
- deferipone
83
Classifications of haemolytic anaemias in children
Red cell membrane
- hereditary spherocytosis
- hereditary elliptocytosis
Haemoglobin defects
- sickle cell anaemia
Glycolytic pathway
- PK deficine
Pentose shunt defects
- G6PD
84
What is most common acute leukaemia in children under 1
AML
85
How does VWB present
Mucosal bleeding
Bruises
Post traumatic bleeding
86
What is transient abnormal melopoiesis
AML resembling diseases which presents in neonates at birth or just later
Very megakaryoblastic
87
Differences between congenital leukaemia and tranisent abnormal myelopoeisis
Congenital- symptoms at birth, cell markers, high blasts
TAM- everything normal
88
What is translocation in acute promyelocytic leukaemia
t(15;17)
PML-RARA
89
How does acute promyelocytic leukaemia often present
Bleeding and DIC
90
Which chromosome duplications can lead to AML
8
21
91
Common translocations associated with AML
15;17
5;8
8;21
16;16
92
Chromosomal loss or deletion associated with AML
Deletions loss of 5/5q and 7/7q
93
What are the principles of leukaemogenesis in aml
At least 2 interacting molecular defects
Type 1- promote proliferation and survival of cells
Type 2- block differentiation
94
What chromosome inversion can lead to AML
16
95
Cytology of AML versus ALL
Both have elevated WCC blasts
AML- auer rods and granules
ALL- the blasts have blebs of cytoplasm
96
What is main accepted aetiology for AML
Unknown
97
How to tell difference between AML and ALL
Immunophenotyoping
98
What method is used for immunophenotyping in acute leukaemia
Flow cytometry
99
ALL versus AML flow cytometry
Common to all- CD34 as on precursor cells
ALL
- T lymphocytes CD3, CD4, CD8
- B-lymphocytes CD19, CD23
AML
- CD13, CD33 and MPO
100
What is AML which presents with hypokalaemia, gum and skin infiltration
Monocytic
101
Which AML often presents with CNS disease
Acute monocytic leukaemia
102
If suspect acute leukaemia what investigations do in order
Blood film to look for auer rods/granules
Immunophenotyping to look for specific markers
If no leukaemic cells in blood do a bone marrow aspirate
103
Main clue differentiating acute leukaemia in history
Lymphadenopathy very common in ALL but not AML
104
Supportive care for AML
Red cells
Platelets
FFP if DIC
Abx
105
What is used to treat DIC
FFP/cryoprecipitate
106
Chemo regime for AML
- induction of remission and maintenance
Induction of remission
- danorubicin
- cytarabine
Consolidation
- cytarabine
107
Management of AML and ALL if poor prognosis/high risk of relapse
Allo-SCT
108
Management of APML
All-trans-retinoic-acid (ATRA) and A2O3
109
What can be given for CD33 AML
Gemtuzumab- CD33 immunotherapy
110
What is given in Ph postive leukaemias
Imatinib
111
What are the differences on examination of T-ALL vs B-ALL
Thymic enlargement in ALL
112
Which genetic abnormalities are associated with good and bad prognosis in ALL
Good- hyperdiploidy
Bad- Ph chromosome (BCR-ABL)
113
What are the 2 specialised treatments for ALL
Ph-chr- imatinib
CD20- rituximab
114
Why are allopurinol and electrolytes given in acute leukaemia
Prevent TLS
115
What is TdT
Marker of immature lymphocytes
116
When are spherocytes seen
HS
Haemolytic anaemia
117
What is MCV in B12
Extremely high
118
Why do you get pancytopenia in B12 deficiency
Needed for DNA synthesis
-RBC the most rapid turnover so thats why anaemia most marked symptom
Plt and neut maturation still need B12 just not as quickly
119
What is most common cause of renal failure in myeloma
Cast nephropathy
120
What are myelodysplastic syndromes
Group of heterogenous haematopoeitic stem cell disorders which results in aberrant cells produced from myeloid lineage
Seen in elderly
121
What are ringed sideroblasts seen in
Myelodysplastic syndromes
122
What are micromegakaryocytes and platelts with hypolobated nuclei seen in
Myelodysplastic syndromes
123
What is pegler huet anomaly seen in
Myelodysplastic syndromes
124
Morophological anormalities associated with myelodysplastic syndromes
RBC- ringed sideroblasts where get nucleated blast surrounded by iron granule ring
Neutrophil- pelger huet anomaly where bilobed neutrophil
Platelet- micromegakaryotype and hypolobated nuclei
125
Difference between acute myeloid leukaemia and myelodysplastic syndromes
AML over 20% blasts
126
Prognosis of myelodysplastic syndromes
1/3 die from infection
1/3 die from bleeding
1/3 die from acute leukaemia
127
Treatment of myelodysplastic syndromes
Supportive – transfusions, EPO, G-CSF, ABx
• Biological modifiers – immunosuppressive drugs, lenalidomide, azacytidine
• Chemotherapy – similar to AML
• Allogeneic SCT
128
What is aplastic anaemia
Where bone marrow fails to produce the required number of red cells but can be pancytopenic
129
What is bone marrow described as in aplastic anaemia
Hypocellular
130
Difference between myelodysplastic syndromes and aplastic anaemia
Both have pancytopenia
In MDS there is disorder of differentiation so BM is full of blasts- hypercellular
In AA failure to produce so BM is hypocellular
131
Causes of aplastic anaemia
Primary
- inherited
- idiopathic
Secondary
- radiation
- infections- hepatitis, P19
- SLE
- drug (mainly chemo)
132
Treatment of idiopathic aplastic anaemia
Supportive- abx, transfusions and chelation if needed
If young then aim for stem cell transplant with sibling if not explore other treatment non-family
If old or donor not found then use immunosuppression
Immunosuppressive agents- ciclosporin, anti-lympocyte globulin, eltrobopag
133
What immunosuppressive agents are used for idiopathic aplastic anaemia
Anti-lymphocyte globulin
Ciclopsorin
Second line- eltrombopag
134
What are 2 inherited causes of aplastic anaemia need to know
Fanconi anaemia- most common
Dyskeratosis congeinta
135
Genetic basis of fanconi anaemia versus dyskeratosis congenita
FA- multiple genes involved
DC- abnormal and short telomeres
Inheritance- FA is AR, DC is x linked
136
When does fanconi anaemia present
5-10 years old
137
Complications of fanconi anaemia
Risk of congenital and somatic abnormalities
- short stature
- cafe au lait spots
- microcephaly
- developmental delay
- abnormality of thumbs
- hypogonadism
Cancer risk
- AML and MDS
138
Childhood aplastic anaemia with strange thumbs, short, delayed and pigmented spots
Fanconi anaemia
139
Triad for dyskeratosis congenita
Skin pigmentation
Nail dystrophy
Leukoplakia which are white areas in the mouth
140
Pancytopenia, skin pigmentation, nail issues and white patches in mouth
Dyskeratosis congenita
(nail dystrophy and leukoplakia)
141
What happens to platelets in malaria
Can drop acutely
142
What are hypersegmented neutrophils seen in
Megaloblastic anaemia- where BM produces large cells due to B12 deficiency
143
What is paroxysmal cold haemoglobinuria
Get anaemia from RBC lost in urine during an infection- measles, syphyllis, VZV
144
Haematuria versus haemoglobinuria how to tell
Centrifuge and if haematuria, RBC will sit at bottom
145
How is APML diagnosis confirmed
Cytogenetic analysis
146
Blood findings of MDS
Typically- macrocytic anaemia
Can get pancytopenia
147
What are metamyelocytes seen in
Megaloblastic anaemia
148
What is difference between megaloblastic macrocytic anaemia and non-megaloblastic
Megaloblastic is impaired DNA synthesis from folate or B12 deficiency
Non-megaloblastic is from liver disease and hypothyroidism where just slow at producing cells
149
What is rouleaux formation and what seen in
RBC stacked on one another
Myeloma
Chronic inflammation
150
What does facial plethora suggest
Is red swelling and puffiness
Polycythaemia vera
151
Which tumour produces IgM antibodies
Waldenstroms lymphoplacytic lymphoma
152
What are parts to antibody and how relate to myeloma
Common portion (Fc) (base) made up of heavy chains
Variable portion (Fab) made of kappa or lamda light chains
Myeloma get production of IgA or IgG
153
Most important drug in myeloma kidney disease treatment
Bortezomib
154
Management of myeloma
Depends if transplant eligible (under 65 or not)
Eligible
- anti-CD38 (daratumumab)
- proteasome inhibitors ( bortezomib)
- immunomodulatory drugs (lenalidomide)
Then ASCT
Non-eligible
- daratumumab
- lenalidomide
- dexamethasone
155
What is a lymphoma
A malignant tumour of lymphoid cells found in either the LN, BM, spleen or tissue specific lymphoid tissue
156
What factors involved in our immune system make it a common site for malignancy
Constant cutting and recombining TCR and Ig leads to potential for errors and point mutations
Rapid cell proliferation in response to infection increases chance of mutation
Process dependant upon apoptosis which provides opportunity for apoptosis mutations
157
What are the risk factor categories for non-hodgkins lymphoma
1. constant antigenic stimulation from bacterial infection or chronic AI conditions
2. viral infection
3. EBV infection when loss of t cell function
158
What lymphoma is associated with sjogrens
Marginal zone lymphoma of parotid gland
159
What lymphoma is associated with hashimotos
Marginal zone lymphoma of the thyroid
160
What lymphoma is asscoaited with coeliac disease
Enteropathy associated T-cell NHL
161
Example of virus causing lymphoma from direct viral integration
HTLV-1 infects T cells from vertical transmission causing adult t cell leukaemia lymphoma
Common in japanese and carribean
162
What are the 3 parts of the lymphoreticular system
Generative: generate and maturation of lymphoid cells
- thymus
- BM
Reactive: develop the immune reaction
- LN
- Spleen
Acquired: develop the local immune reaction
- extranodal lymohoid tissue in the skin, stomach etc
163
What is route of a b cell in a LN
Enters B cell area and in mantle zone is a naive B cell
Enters the germinal centre and those wich bind antigen epitopes are activated and selected
Will then enter post germinal centre
This process is why B cell lymphomas much more common
164
In lymphoma which CD suggest B cell versus T cell
T- CD3, CD5
B- CD20
165
What are the B cell NHL
Low grade
- follicular lymphoma
- small lymphocytic
- marginal zone
High grade
- diffuse large B cell
- Burkitts lymphoma
Aggressive
- mantle cell lymphoma
166
Clinical features of follicular lymphoma
Lymphadenopathy
Elderly/middle age
Very indolent
167
Molecular features of follicular lymphoma
14,18 transformation involving production of bcl-2 gene
168
Histology of follicular lymphoma
Follicular pattern or nodular appearance of germinal cell origin CD10
Stain for bcl-2/6
169
What causes marginal zone lymphomas
Chronic antigen stimulation
ie sjogrens- parotid marginal zone lymphoma
Can be treated just by removing the trigger
170
What lymphoma does chronic Hpylori infection cause
Gastric MALT lymphoma
171
Histology of large B cell lymphoma
Sheets of large lymphoid tissue (B cells)
172
What are 3 types of burkitts lymphoma
Endemic- found in africa, EBV, jaw movement and abdo mass
Sporadic- EBV, jaw less involved
Immunodeficiency- non EBV associated. HIV/post transplant
173
What presents with jaw or abdo mass in young adults
Burkitts lymphoma
174
Histology of burkitts lymphoma
Germinal centre
Starry sky appearance- macrophages containing phagocytosed lymphocytes
175
Molecular findings of burkitts lymphoma
8;14 translocation
C-myc production
176
Histology of mantle cell lymphoma
Pregerminal centre cells in mantle zone
Angular, clefted nulei
Cyclin D1 overexpression
177
Molecular findings of mantle cell lymphoma
11;14 translocation
Cyclin D1 overexpression
178
What are the NH T-cell lymphomas
Peripheral T cell lymphoma
Enteropathy associated T cell lymphoma
Cutaneous T cell lymphoma
Anaplastic large cell lymphoma
Adult T cell leukaemia/lymphoma
179
What is associated with cutaenous t cell lymphoma
Mycosis fungoides
180
Histology of peripheral t cell lymphomas
Large t lymphocytes in old people
181
Histology of anaplastic large cell lymphoma
Large epithelioid lymphocytes
182
Clinical features of anaplastic large cell lymphoma
Occurs in children young adults
Lymphadenopathy
183
Molecular findings of anaplastic large cell lymphoma
2;5 translocation
Alk-1 protein expression
184
Pain in lymph nodes after drinking and cyclical fever
Hodgkins lymphoma
Has bimodal presentation- 20-29 and over 60
185
Difference between NHL versus HL in presentation
NHL- involves multiple sites and spreds randomly anywhere
HL- single node involved and spreads to adjacent one
186
How is hodgkin lymphoma staged
Ann arbor
1- 1 node site affected (includes spleen)
2- 2 or more regions on same side of diaphragm
3- 2 or more regions on other sides of diaphragm
4- extra nodal site like like liver or BM affected (cant be spleen)
Can be A or B
B = constitutional symptoms and A they do not
187
Histology of classical Hodgkins lymphoma
Sclerosis
Reed steenberg cells and hodgkin cells
Germinal or post germinal B cell origin
EBV associated
CD15,20,30+ve
188
What are subtypes of hodgkins lymphoma
Classical
- Nodular sclerosing
- Mixed cellularity
- Lymphocyte rich and lymphocyte depleted
Nodular lymphocyte predominant
189
Histology of nodular lymphocyte predominant Hodgkins lymphoma
Germinal centre B cell
B cell rich nodules
CD20+ve only
190
How can lymphomas present
Lymphadenopathy
Extrinsinc pressure from LN
Constitutional symptoms
Recurrent infections
191
What is most common hodgkins lymphoma
Nodular sclerosing
192
How is hodgkin lymphoma investigated
Lymph node biopsy and relevant immunohistochemistry and molecular studies
PET scan to stage
193
Treatment of classical hodgkins lymphoma
ABVD
Adriamycin
Bleomycin
Vinblastine
DTIC
Long term SE- pulmonary fibrosis, cardiomyopathy
194
How is follicular NHL treated
Depends if treatment indicated by
- nodal extrinsic compression
- massive painful nodes
- recurrent infections
IF NOT WATCH AND WAIT
If any of above then R-CAVP
R- rituximab
C- cyclophosphamide
A- adriamycin
V- vincristine
P- prednisolone
195
Blood count and film findings of CLL
Massive lymphocytosis
Cytopenia
Smear cells on film
196
Flow cytometry of CLL
Normal B-cell would be CD5-ve and CD19+ve but CLL is both positive
197
In CLL prognosis which mutation is important to assess
TP53 (chr 17deletion)
Ruins prognosis
198
What is the danger of CLL
Typically very indolent however can undergo Richter transformation to diffuse large B cell lymphoma if acquires another mutation
199
Treatment of CLL
Often watchul waiting unless need
If is need
BCR inhibitor- ibrutinib
BCL2 inhibitors- venetoclax
Chimeric antigen receptor T cells
200
What is main risk of venetoclax
TLS when intiate treatment
201
What is sickle cell disease
Encompassing term for diseases associated with pathological effects of sickling
202
What happens in sickle cell beta thalassaemia
Inherit 1 beta thalassaemia globin chain
Inherit 1 sickle cell beta globin
203
What are signs of an increased erythopoietic drive
Bone expansion
Hepatomegaly
Splenomegaly
204
What are the 2 types of beta thalassaemia
Beta thalassaemia trait
Beta thalassaemia homozygosity
205
How is beta thalassaemia major treated
Transfusions
206
What can trigger G6PD
Infections
Drugs
Fava beans
207
Treatment of von willebrand disease
Lower factor purity factor VIII concentrates
208
What are signs of hyposplenism on blood film
Howell jewell bodies
Target cells (codocytes)
209
Differentials for raised Hb
Is it due to excess plasma? (relative)
True
- secondary (raised EPO)
- primary (myeloproliferative neoplasm) (low EPO)
210
How are primary causes of polycythaemia split
Ph chr negative
- essential thrombocythaemia
- polycythaemia vera
- primary myelofibrosis
Ph chr positive
- CML
211
What can cause relative/pseudo polycythaemia
Alcohol
Obesity
Diuretics
212
How is secondary polycythaemia split
Depends if EPO being raised is appropriate
Appropriate
- high altitude
- hypoxic lung disease
- cyanotic heart disease
Inappropriate
- renal disease causing increased EPO
- uterine myoma (suggested they produce EPO)
- ectopic EPO from other tumours
213
Presentation of polycythaemia vera
Visual issues
Fatigue/dyspnoea
TIA
Headaches
Aquagenic pruritus (histamine release)
Peptic ulceration (histamine release)
214
Tests for polycythaemia vera
FBC- raised Hb, can also raise plts and WCC
Low EPO
JAK2 mutation testing
215
Management of polycythaemia vera
Venesection with hydroxcarbamide
Need to control VTE risk too with aspirin
216
Essential thrombocythaemia presentation
Arterial or venous thrombosis; DVT, PE, CVA, gangrene
GI bleeding
Bleeding from mucous membranes
Headaches and dizziness
217
Management of essential thrombocythaemia
Aspirin
Hydroxycarbamide
Anagrelide to inhibit plt formation
218
What can essential thrombocythaemia progress
Leukaemic transformation
Myelofibrosis
219
Presentation of primary myelofibrosis
Cytopenias
Thrombocytosis
Splenomegaly causing budd chiari
Hypermetabolic syndrome
- wt loss
- fatigue
- night sweats
220
Blood film of primary myelofibrosis
Tear drop dacrocytes
Giant platelets
Circulating megakaryocytes
221
What mutations may be seen in primary myelofibrosis
JAK2
Calreticulin
222
Bone marrow trephine findings of primary myelofibrosis
Dry tap
Reticulin or collagen fibrosis
Megakaryocyte hyperplasia
New bone formation
223
Treatment for myelofibrosis
RBC and platelets transfusions
Hydroxycarbamide for thrombocytosis
Ruxolotininb
Allogenic SCT in high risk cases
224
Why do transfusions tend not to work in primary myelofibrosis
Splenomegaly
225
What is ruxolotinib and what used in
JAK2i
Used in primary myelofibrosis
226
What does hydroxycarbamide do
Reduce number of platelets
227
Presentation of CML
Constitutional sx
Bruising
Infections
228
Examination finding of CML
Massive splenomegaly
May have hepatomegaly
229
FBC and blood film findings of CML
Hb and plt preserved or raised
Massive leukocytosis
On film lots of neutrophils and basophils
Myelocytes (not blasts)
230
Mutation causing CML
Philadelphia chr
9:22
BCR-ABL
231
What are the phases to CML
Chronic
Accelerated/acute ( blasts 10-19%)
Blast (over 20% blasts)
232
Management of CML
Chronic phase- imatinib (TK inhibitor)
Blast phase- treat like acute leukaemia
233
How can heparin affect platelet count
Thrombocytopenia
234
What are encoded by HLA (MHC) class I
HLA-A, B, C
Recognised by CD8 cells
235
On what chromosome are HLA genes found
6
236
What are encoded by HLA (MHC) class II
HLA- DP, DQ, DR
Present to CD4 cells
237
What are the odds of a sibling being HLA identical
35%
238
How can you work out the odds of a match with a sibling
1- (3/4)^n
n=number of siblings
239
How does an autologous stem cell transplant work
1. given growth factor to promote production of stem cells
2. collect the stem cells and freeze them3
3. high dose chemo to kill any cancerous cells without issue of doing so at expense of BM as..
4. reinfuse stem cells
240
What organs does acute graft versus host affect
Skin
Liver
GI tract
241
When do you tend to use autologous stem cell transplants more often
Myeloma
Lymphoma
Normally in case of relapse
242
How is graft versus host disease prevented
Methotrexate
Cyclosporin
243
How is acute graft versus host disease treated
Corticosteroids
Can also use calcineurin inhibitors- cyclosporin A
244
Which organs does chronic graft versus host disease affect
Skin
Mucosal membranes
Lungs
Liver
Eyes
Joints
245
What is main risk factor for chronic graft versus host disease
Prior acute Graft versus host disease
246
Post stem cell transplant which organisms are most likely to cause mortality
Gram neg- pseudomonas, e coli
247
Consequences of haemolytic anaemia
Folic acid demand increased
Erythroid hyperplasia with circulating reticulocytes
Propensity to gallstones (worsened by gilberts)
Very susceptible to effects of Parvovirus B19
248
Co-inheritance of what condition increases risk of gallstones in haemolytic anaemia
Gilberts
249
Blood findings of haemolytic anameia
High bilirubin
High LDH
Low haptoglobin
250
Inheritance of HS
Autosomal dominant
25% of cases no family history
251
How to diagnose HS
Osmotic fragility test- increased sensitivty to hypertonic saline
Reduced binding of dye eosin-5-maleimidie on flow cytometry (modern method used)
252
Difference between heterozygous and homozygous hereditary elliptocytosis clinically
Hetero- no anaemia
Homo- anaemia at birth requiring exchange transfusion
253
Difference between heterozygous and homozygous hereditary elliptocytosis on blood film
Hetero- elliptocytes and oval shaped RBCs
Homo- elliptocytes, fragments of RBC and reticulocytosis
254
What is G6PD epidemiology linked to
Malaria heavy areas as is protective
255
What are bite cells seen in
G6PD
256
What are heinz bodies seen in
G6PD (blue deposits of oxidised Hb)
257
What are RBC with short projections seen in
PK deficiency
258
Pathophysiology of paroxysmal nocturnal haemoglobinuria
Acquired loss of surface GPI markers on RBC leading to chronic intravascular haemolysis at night mediated by complement
259
Presentation of paroxysmal nocturnal haemoglobinuria
Morning haemoglobinuria
Increased risk of thrombosis in particular budd chiari
260
Differentiating between Fe deficiency and anaemia of chronic disease
Low ferritin would show Fe deficinency however raised in ACD
Therefore look a transferrin which high in IDA as well as TIBC which is low in IDA
261
What causes anaemia of chronic disease
In inflammatory states hepcidin increases which sequesters GI absorption of iron and prevents release of iron from macrophages
262
Causes of pancytopenia
Non malignant
- B12/folate deficiency
- aplastic anaemia from drugs etc or idiopathic
Malignant- ONLY TIME SEE LEUKOERYTHROBLASTIC PICTURE
- bony metastases
- myeloma/lymphoma/ acute leukaemia infiltration
- myelodysplasia
263
How is CLL diagnosed
Immunophenotyping showing B cells CD5+
264
What do myeloma plasma cells produce
IgA or IgG
Can get myelomas which only produce light chains
265
What is prognostic marker of myelomas in the blood
Beta-2-microglobulin
266
What are the phases to coagulation
Initiation- formation of complex of FXa and FVa
Amplification- the amplificatory effects of thrombin
Propagation- thrombin burst creates stable fibrin clot
267
What happens in the intrinsic pathway
Starts with 12
11
9
8
10a and here joins with factor 5
268
What happens in the extrinsic pathway
Tissue factor exposed from endothelial injury leads to activation of factor 7
The complex between TF and FVIIa activates FIX and FX
269
What happens in the initiation phase
Tissue factor exposed from endothelial injury leads to activation of factor 7
The complex between TF and FVIIa activates FIX and FX
270
What to APTT, PT and TT all represent
APTT- intrinsic pathway
PT- extrinsic pathway
TT- common pathway
271
What happens in amplification phase of coagulation
The FXa /FVa complex converts small amounts of prothrombin to thrombin
This then activates FVIII, FV, FXI and platelets which themselves bind these factors
272
What happens in propagation phase of coagulation
FVIIIa/FIXa complex activates FX on surface of activated platelets which converts large amounts of prothrombin to thrombin
This creates a stable fibrin clot
273
What is difference between coagulation and platelet bleeding
Platelet- skin, mucosal petechiae and purpura
Coagulation- haematoma and joint bleeding
Post surgery/wound the bleeding is immediate in platelet
Post surgery/wound the bleeding is delayed but severe if coagulation problem
274
MOA of clopidogrel
Inhibitor of ADP receptor which prevents platelet aggregation
275
MOA of aspirin
Inhibits cyclo-oxygenase enzyme which reduces thromoxane A2 production from arachidonic acid
276
How are disorders of platelets classified
Decreased number
- decreased production (BM failure)
- decreased survival (ITP, MAHA)
- increased use (DIC)
Reduced function
- acquired (aspirin, uraemia)
- inherited (thrombasthenia)
277
What are ecchymoses typical of
Coagulation factor disorders
278
How are coagulation factor disorders classified
Inhertied
- haemophilia
- vWB disease
Acquired
- DIC
- liver disease
- Vit k deficiency or OD
279
Inheritance of vWB
Type 1 and 2- Autosomal dominant
Type 3- X linked recessive
280
Causes of Vit k deficiency
Malnutrition and malabsorption (green vedgetables)
Biliary obstruction
Abx
281
Treatment of vit k deficiency
Vitamin K
FFP
282
What is vit K needed for
Factors II, VII, IX and X
And protein S and C which is why warfarin is procoagulant initially
283
Blood findings of liver disease association coagulation disorders
High levels of VIII and VWF
Low II, V, VII, IX, X and XI
284
What can cause DIC
Malignancy
Sepsis
Trauma
Obstetric complications
Toxins
285
Blood findings of DIC
Low platelets
Low fibrinogen
Long PT, APTT, TT and INR
High D dimer
See schistocytes on blood film
286
Treatment of DIC
Platelet transfusion
FFP
Cryoprecipitate
287
Pathogenesis of DIC
Systemic activation of coagulation leads to depletion of plts and coagulation factors causing bleeding
Intravascular deposition of fibrin causing thrombosis leading to organ failure
288
Differentiating VwB disease from haemophilia A
Both have low factor 8 (as VwB bound )
Both have a high APTT but VwB can be normal
VwB will have however a low ristocetin cofactor activity and ristocetin activity
289
What happens in factor V leiden
Is mutation in FV which means protein C can't degrade it leading to increased VTE risk
Resistance to factor V
290
tHow is factor V leiden diagnosed
Protein C functionality
291
What is thromboangiitis obliterans
Vasculitis of small/medium vessels in the limbs which leads to arterial and venous thrombosis
292
Investigation for thromboangiitis obliterans
Angiogram showing corkscrew appearance
293
What happens in protein S deficiency
Reduced breakdown of activated factor 5 and 8 as this is its role
294
BM finding of essential thrombocythaemia
Megakaryocyte hyperplasia with giant platelets
295
What happens to RBC in pregnancy
Get bigger
Mild anaemia from dilution
296
What happens to platelets and neutrophils in pregnancy
Neutrophilia
Gestational thrombocytopenia but they increase in size
297
If get low MCV anaemia in pregnancy what do if known haemoglobinopathy
Check serum ferritin
If less than 30 treat with oral iron
298
Differentials for thrombocytopenia in pregnancy
Gestational
Pre-eclampsia
ITP
MAHA (HELLP, TTP etc)
299
What changes induce hypercoagulable state in pregnancy
Increase in factor VIII & VII, VwB
Reduction in protein S
300
Biggest risk factor for VTE mortality in pregnacy
BMI over 25
301
What does warfarin in pregnancy cause
Chondrodysplasia punctata in first trimester
302
Causes of DIC in pregnancy
Sepsis
Placental abruption
Amniotic fluid embolism
Pre-eclampsia
Retained dead fetus
303
How to differentiate IDA from thalassaemia trait on FBC
RBC increased in thalassaemia trait
304
Difference in antibody between anti AB and RhD
Anti- A or B is IgM
Anti-RhD- IgG
305
What antibodies cause delayed transfusion reaction
Anti-D IgG
306
Which cells should you give to RhD positive patients
RhD positive as using negative is a waste
307
Can you give RhD positive blood to a rhesus D negative person
Yes if in short supply but avoid in woman of child bearing age
308
What reaction happens against non-RhD, A and B antigens
Delayed transfusion reaction as IgG
309
How long are transfusion records kept for
30 years
310
What red cells give in emergency
O-
311
Management of a red cell transfusion
Stored at 4^C for 35 days
Must be transfused within 4 hours
Transfuse 1 unit over 2-3 hours
312
Management of platelet transfusions
Stored at 20^C for 7 days
Transfuse over 30 mins
313
What antigen must be compatible with platelet transfusion
D
314
What is maximum surgical blood ordering schedule
Planned agreement between surgeons and haem lab
315
When are plt transfusions contraindicated
Heparin induced thrombocytopenia thrombosis
HITTP
316
Indications for cryoprecipitate
When bleeding due to hypofibrinogenaemia
- liver disease
- DIC
317
What is intra-operative cell salvage
Collect lost blood
- centrifuge
- filter and wash
Reinfuse
Used in majority of surgeries including obstetric
318
When is cell salvage contraindicated
Cancer
Bowel surgery
319
When is only time have CMV negative blood
Intra-uterine or neonatal transfusions
Pregnant women
320
When give washed blood cells
Severe allergic reactions to blood
321
When is post operative cell salvage used
Knee surgery
322
Most common blood group
O
323
Which transfusion is infection most likely associated with
Platelet
If get fever during or soon after
take blood cultures and give broad spectrum abx
324
Acute reactions to transfusions
ABO haemolytic
Allergic
Infection
Febrile non-haemolytic
Resp
- TACO- transfusion associated cardiovascular overload
- TRALI- transfusion related acute lung injury
325
How are transfusions monitored
Baseline temp before
Repeat 15 mins later
After an hour
End of transfusion
326
How do febrile non-haemolytic transfusion reaction
Temp rise
Chills Rigor
327
How manage febrile non-haemolytic transfusion reaction
Paracetamol
Slow down maybe
328
What causes febrile non-haemolytic transfusion reaction
Donor WCC cytokine release
329
Presentation of allergic transfusion reactions
Mild urticarial reaction with a wheeze
330
Management of allergic transfusion reaction
IV antihistamines and slowing/stop tranfusion
331
Prsentation of ABO incompatibility post transfusion
Shocked fever
Chest, loin pain, collapse, flushing, haemoglobinuria
332
Management of ABO incompatibility
Stop transfusion
Take FBC, coagulation
Repeat x-match and DAT
Discuss with haem
333
Presentation of bacterial contamination
Restless
Fever
Shock
Collapse
334
What causes bacterial contamination
Bacterial growth may mean release of endotoxin
From donor
- GI, dental, skin infection
During processing (skin)
335
Presentation of anaphylaxis in response to transfusion
Facial, laryngeal oedema
Wheeze
Shocked
336
Presentation of TACO
SOB
Reduced sats
HR and BP up
Raised JVP
CXR- fluid overload
337
Who does TACO occur in
Cardiac failure
Renal impairment
Hypo-albuminaemia
On fluid replacement
338
What is risk factor for anaphylaxis in response to transfusion
IgA deficiency
339
How does TRALI present
SOB
Low sats
HR and BP up
Dry cough
Fever
340
MOA of TRALI
Aggregates of WBC in pulmonary capillaries
341
What is alloimunisation in transfusions
Develop an immune antibody to a RBC antigen they lack
342
Problem of alloimunisation in transfusions
In future transfusions with thay antigen will get extravascular haemolysis from IgG
343
Tests for delayed haemolytic transfusion reaction
Raised LDH, reticulocytes, Hb, DAT, haemoglobinuria
U&Es as get renal failure
344
What is transfusion assocaited graft versus host disease
Where lymphocytes from donor aren't destroyed by immune system in extremely immunosuppressed patients
345
How is transfusion assocaited graft versus host disease prevented
Irradiate the blood if immunosuppressed
346
Presentation of transfusion assocaited graft versus host disease
Diarrhoea
Liver failure
Skin desquamation
BM failure
347
Presentation of post transfusion purpura
Purpura a week after tranfusion which will resolve however can get life threatening bleeding
348
Management of post transfusion purpura
IVIG
349
Where is labelling of tube made
At the bedside
350
What do if woman at screening found to have alloantibodies for RBC antigens
Check ffDNA for antigen status of baby
Monitor mothers antibodies level
Screen for anaemia with MCA doppler
Deliver early as it gets a lot worse later in pregnancy
351
How can baby be treated for HDN
As a feotus with known anti-D antibodes in mother can give intrauterine transfusions
At birth phototherapy or exchange transfusion
352
What dose of anti-D is given at certain parts of pregnancy
After sensitising event
Before 20 weeks- 250
After 20 weeks- at least 500 but do kleihauer test to confirm
353
What other antibodies can cause HDN
ABO
Anti-D
Anti-Kell
Anti-c
354
Feature anti-kell HDN
Reticulocytosis
355
How does Group assessment in G&S work
Column agglutination technology
Get forward group whereby anti-A, anti-B and anti-D reagents mixed with patients RBCs
Get reverse group where known A and B RBCs added to patients plasma containing IgM antibodies
If is positive then get agglutination
356
How are antibodes to non-ABO antigens formed
Do not naturally occur
Will develop after exposure like in previous transfusion or pregnancy
357
What is G&S
Group and screen
Blood group identified
Screen- screen for non-ABO antibodies like Kell
358
How does screen part of G&S work
Indirect antiglobulin technique
Patients plasma mixed with 2 or 3 reagent cells which between them contain all of non AB antigens on them
If agglutination shows presence of antibodies
359
How does crossmatch work
Mix patients and donor RBCs together at 37^C for 30 mins and will pick up antibody-antigen reaction resulting in potential future extravascular haemolysis
360
What are 2 options for cross matching
Indirect antiglobulin technique
- this does full crossmatch including non ABO screen
Immediate spin
- antiglobulin reagent added to crosslink IgG antibodies
Immediate spin
- done at room temperatute for 5 mins
- only detects ABO incompatibility
361
When would you do an immediate spin for serological crossmatch
Emergency
362
What is added in indirect antiglobulin technique
Antiglobulin reagent to crosslink IgG that would not normally mix
363
What is FFP
Plasma is separated from cells and thawed
364
What is indication for FFP
Bleeding due to coagulopathy like DIC, TTP and replacement of a single clotting factor
365
What is cryoprecipitate
Concentrated FFP which gives a lot of fibrinogen
366
Red blood cell transfusion indication
Less than 70
Less than 80 if symptomatic (SOB, IHD, ECG changes)
367
What level of platelets aim for to prevent bleeding in surgery
Over 50
Over 100 if critical location like eye or CNS
368
What compatibility is important in FFP and cryo
ABO
369
Inheritance of hereditary elliptoctosis and spherocytosis
Autosomal dominant
370
What must do before giving folate supplements
Check B12 as can exacerbate neuropathy
371
Pathophysiology of sideroblastic anaemia
Body has produced too much iron it cant put into RBC so iron deposited around mitochondria
372
Causes of sideroblastic anaemia
MDS
Alcohol
Chemo and irradiation
373
MOA of venetoclax and ibrutinib
Ibrutinib- tyrosine kinase inhibitor
Venetoclax-BCL inhibitor which promotes apoptosis
374
How to remember the translocations and respective associated proteins in B cell lymphomas
In terms of aggressiveness the first number decreases and the proteins are in alphabetical order
Follicular- 14:18 + BCL-2
Mantle- 11:14 + Cyclin d
Burkitts- 8:14 + C-myc
375
Bleeding time in VWB versus haemophilia A
VWB prolonged but not in haemophilial
376
How do neutrophils appear on blood film
3x larger than RBC, multisegmented with speckly stained nucleus
377
How do monocytes appear on blood film
3x size of RBC
Kidney shaped nucleus
378
How do basophils appear on blood film
3x larger than RBC
Deep blue granules- bilobed nucleus
379
How do eosinophils appear on blood film
3x size of RBC
Reddish purple granules- bilobed nucleus
380
How do lymphocytes appear on blood film
About same size as RBC
Giant nucleus takes up most of cell with no granules
381
What is scoring system for myelodysplasia
International prognosis scoring system (IPSS)
382
What is benefit of modern ABVD treatment for hodgkin lymphoma
Infertility prevented
383
Which congenital coagulopathy has highest thrombosis risk
Antithrombin deficiency
384
What cells stain in sudan black
Myeloblasts
385
Differnece in mutations between alpha and beta thalassaemia
Alpha- deletions on chromosome 16
Beta- point mutations on chromosome 11
386
When do bite cells vs heinz bodes appear in G6PD
Heinz are early
Bite are later
387
What is indication for platelet transfusion
Platelets under 30 and with active bleeding
388
What medications can be given for TLS
Allopurinol
Rasburicase
389
What are types of VWB
Type 1- slight reduction- AD
Type 2- defective- AD
Type 3- complete absence- x linked
390
How are febrile non haemolytic reactions prevented
Leukodepletion- done in long term transfusion patients
391
What is MCV in sideroblastic anaemia
Low
392
What is difference in staining between classical NHL and lymphocyte predominant
Classical- CD15 and 30 positive
Lymphocyte predominant- CD20
393
Histology of small lymphocytic
Small B cells
CD5 and CD23
394
Which NHL has worst and best prognosis
Best- nodular sclerosing
Worst- lymphocyte depleted
395
What is bad prognostic marker for CLL
TP53
396
What can small cell lymphoma progress to
DLBC- just like CLL
397
Management of diffuse large cell
R CAVP
Rituximab
Cyclophosphamide
Adriamycin
Vincristine
Prednisolone
398
