Haematology Flashcards
1
Q
Donation order of blood products
A
O can donate to A, B and AB
A and B can donate to AB
AB can only donate to AB
2
Q
What are duffy antibodies and what pathology is associated
A
antibody which is negative on antibody testing but can cause haemolytic transfusion reactions
site of entry for plasmodium vivax into RBCs
3
Q
What does FFP contain and what is used for
A
coagulation factors
used in coagulopathies
4
Q
what does cryoprecipitate contain
A
Fibrinogen
factor 8, vWF, factor 13
used in critical bleeding, trauma, DIC, big procedures
5
Q
Platelets orignate from
A
magakaryocytes
6
Q
macrophages originate from
A
monocytes
7
Q
What does hypersegmented neutrophils indicate
A
B12/folate deficiency
8
Q
Receptors present on platelets
A
Gp1b for vWF receptor
Gp11b/111a receptor for fibriniogen
9
Q
Platelet proliferation stimulated by
A
thrombopoeitin stimulates magakaryocyte proliferation
10
Q
What are macrophages activated by
A
IFN gamma
11
Q
Most important commponent of granuloma
A
macrophages fuse to form giant cells
12
Q
Causes of eosinophilia
A
PACMAN Eats
Parasites
Asthma
Chronic adrenal insufficiency
Myeloproliferative disorders
Allergic processes
Neoplasm (hodgkins)
Eosinophilic granulomatosis with polyangitis
13
Q
Causes of basophilia
A
myeloproliferative (esp CML)
14
Q
Causes of IgE independent mast cell degranulation
A
Vancomycin, opioids and contrast
15
Q
What is mastocytosis
A
rare proliferation of mast cells in skin and organs
associated with c-KIT mutations and raised serum tryptase
high histamine causes flushing, pruritis, hypotension, abdo pain, diarrhoea and peptic ulcer disease
16
Q
NK cell surface receptors
A
CD56 and CD16
17
Q
Nk cell function
A
induces apoptosis in those not espressing MHC1
18
Q
B cell surface receptors
A
CD19, CD20, CD21
19
Q
T cell surface receptors
A
both have CD3
CD8 (cytotoxic)
CD4 (helper)
20
Q
DAT positive if
A
AIHA
21
Q
Platelet plug formation process
A
injury -> vWF binds to exposed collagen -> platelets bind to vWF via Gp1b -> platelets release ADP binds to PY12 receptor and induces Gp11b/111a on surface of platelets -> more plalets bind to Gp11b/111a and link platelets
22
Q
Mechanism of aspirin
A
irreversibly inhibits COX which inhibits TXA2 synthesis (pro-aggregation of platelets)
23
Q
MoA for clopidogrel, ticagrelor and prasugrel
A
inhibit ADP binding to P2Y12 receptor, blocks expression of G11b/111a
24
Q
Tirofiban and eptifibatide MoA
A
inhibit Gp11b/111a directly
25
Desmopressin effect on coagulation
promotes release of vWF and factor 8
26
What is in extrinsic pathway
VII to VII and tissue factor complex
27
Intrinsic pathway process
Tissue damage activates factor XII -> leads to downstream formation of IXa/VIIIa complex formation (to help process X to Xa)
28
How does C1 esterase inhibitor affect coagulation
inhibits XIIa and XIa in the intrinsic pathway
29
What is the function of protein C and S
inhibits IXa/VIIIa complex and inhibits prothrombinase (Va/Xa)
Stops coagulation cascade
30
Function of heparin, LMWH, dabigatran
direct thrombin (IIa) inhibitors (stop conversion of fibrinogen to fibrin)
31
Process how clots are broken down
cleaved by plasmin
plasminogen converted to plasmin by tPA (synthestic tPA tenectaplase, alteplase)
tPA blocked by transexamic acid
32
MoA transexamic acid
blocks tPA from processing plasminogen to plasmin
33
Vit K dependent factors
2, 7, 9, 10, protein C and S
34
Haemophilia A is def of
factor 8
x-linked recessive
35
Haemophilia B is def of
factor 9
x-linked recessive
36
haemophilia C is def of
factor 11
autosomal recessive
37
C1 esterase function
inhibits kallikrein which activates bradykinin
C1 esterase def -> hereditary angioedema
38
MoA antithrombin
mainly inhibits thrombin (IIa) and Xa
heparin enhances activity of antithrombin
39
Mechanism of factor V leiden mutation
produces factor V resistant to inhibition by activated protein C
increases clotting
40
Warfarin MoA
inhibits vit K epoxide reductase so Vit K cannot be activated
41
spur cells assoc
liver disease
vit E def
abetalipoproteinaemia
42
burr cells assoc
liver disease
ESRD
pyruvate kinase def
43
teardrop cells assoc
bone marrow infiltration
44
schistocytes association
MAHAs (DIP, TTP/HUS, HELLP) and mechanical haemolysis (valves)
45
bite cells assoc
G6PD deficiency
46
Spherocytes assoc
AIHA
hereditary spherocytosis
47
elliptocytes assoc
hereditary elliptocytosis - mutation in gene encoding for RBC membrane
48
target cells assoc
HbC disease
asplenia
liver disease
thalassemia
49
sickle cell crisis occurs when
low O2 conditions (high altitude, acidosis)
high HbS concentration (dehydration)
50
Howell-Jolly bodies assoc
functional hyposplenism (sickle)
asplenia
51
basophilic stippling assoc
sideroblastic anaemia
thalassemias
52
pappenheimer bodies assoc
siderblastic anaemia
53
heinz bodies assoc
G6pd deficiency
54
Causes of microcytic anaemia
TAIL
thalassemias
Anaemia of chronic disease
Irion def
Lead poisening
55
How to tell between intrinsic and extrinsic haemolytic anaemia
instrinsic - low hapto
extrinsic - +ve DAT
56
Causes of intrinsic haemolysis
Membrane defects - hereditary spherocytosis, PNH
Enzyme deficiencies - G6PD def, pyruvate kinase def
Haemoglobinopathies - sickle cell, HbC
57
Causes of extrinsic haemolysis
autoimmune
microangiopathic
macroangiopathic
infections
58
Difference between megaloblastic and non-megaloblastic anaemia
both MCV >100
Megaloblastic has DNA affected -> B12 def, orotic anaemia, fanconi anaemia
non - alcohol use, liver disease
59
Iron studies in iron def
low iron, low ferritin, low transferrin satn, high transferrin
60
iron studies in anaemia of chronic disease
low iron, high ferritin, low transferrin, low/normal transferrin satn
61
Iron studies in pregnancy/OCP use
high transferrin
62
How is iron absorbed
Iron is reduced to Fe2+ by DCYTB before it is absorbed by DMT1. Then bound to ferritin and moved out of cell by feroportin
63
Role of hepcidin
binds and internalises ferroprotin
decreases iron absorption
64
What regulates hepcidin
hepcidin decreased in iron deficiency, hypoxia, non-ferroportin mutations of haemochromotosis (HFE, TFR2, HAMP and HJV)
Hepcidin increased in inflammatory states, iron overload, feroportin mutated haemochromatosis
65
Signs of iron def
anaemia sx
koilonychia
pica
glossitis, cheilosis
Plummer-vinson sydrome
66
What is Plummer-vinson syndrome
iron def, esophageal webs and dysphagia
67
Population alpha thalassemia most prevalent
asian and african
68
alpha thalassemia what on peripheral smear
target cells
69
degrees of alpha thalassemia
Hb barts - 4 deletions, dead
HbH disease - 3 deletions, severe anaemia'
alpha thalassemia minor - 2 deletions, mild anaemia
alpha thalassemia minima - siletn carrier
70
population common in beta thalassemia
mediterraneans
71
Degree of beta thalassemia
beta thalassemia major - 2 absent Beta globin chains, severe anaemia, skeletal deformities, extramedullary haemotopoesis (heptosplenomegaly)
beta thalassemia intimedia - 1 absent or reduced beta globin chain with another reduced chain, variable anaemia
beta thalassemia minor - one chain reduced beta globin, mild anaemia, raised HbA2 >3.5%
72
What is luspatercept
for treatment of thalassemia, modified form of actin receptor IIb, binds TGF-beta ligands and increases differenciation and proliferation of erythroid precursors
73
how does lead poisening cause microcytic anaemia
inhibits ferrochelatase and ALA dehydrogrenase -> reduced heme synthesis
74
sx of lead poisening
lead lines on gingivae and metaphysis of bones
encephalopathy
erythrocyte basophilic stippling
abdo colic
sideroblastic anaemia
wrist and foot drops
75
treatment of lead poisening
chelation with succimer or EDTA
76
Causes of sideroblastic anaemia
genetic - x-linked defect in ALA synthase gene
acquired - myelodysplasic syndromes
reversible - alcohol, lead poisening, B6 def, copper def, drugs
77
where is B12 absorbed
terminal ileum
78
difference between folate and B12 def
folate doesn't have neurological sx
folate has raised homocysteine but normal methylmalonic acic
B12 has cord degen and raised both homocysteine and methylmalonic acid
79
Associations of HLA DR5
pernicious anaemia and hashimoto's
80
Lab indications of haemolysis
high LDH, reticulocytosis, unconjugated bili, pigmented gallstones, urobilinogen in the urine
81
Ix findings of intravascular haemolysis
low haptoglobin, schistocytes on smear
haemoglobin in urine
urinary haemosiderins
urobilinogen in urine
82
Causes of intravascular haemolysis
mechanical (prosthetic valve)
PNH
MAHAs
83
How does extravascular haemolysis occur
RBCs destroyed by macrophages in spleen -> unconjugated bili -> conjugated in liver -> urobilinogen to bowel, readbsorbed and process in liver to be excreted in urine
84
Ix findings in extravascular haemolysis
splenomegaly
spherocytes in smear
no Hb or haemosiderin in urine
can have urobilinogen in urine
85
Main mechanism of anaemia of chronic disease
inflammation raised IL6 which increases hepcidin which internalises ferroprotin and reduces iron absorption from gut
86
aplastic anaemia causes
radiation
viral
fanconi anaemia
idiopathic
drugs
87
which viruses cause aplastic anaemia
EBV, HIV, hepatitis
88
which drugs cause apastic anaemia
cholamphenicol
alkylating agents
antimetabolites
89
Cause of fanconi anaemia
Autosomal recessive DNA repair defect leading to bone marrow failure
90
Clinical features of fanconi anaemia
short stature
cafe au lait spots
thumb/radial defects
predisposition to malignancy
91
Ix findings of aplastic anaemia
low reticulocytes
elevated EPO
92
aplastic anaemia vs aplastic crisis
aplastic anaemia has pancytopenia whereas crisis has anaemia only
93
Sx of aplastic anaemia
those related to anaemia - fatigue, malaiase, pallor
thrombocytopenia - purpura, mucosal bleeding, petechiae
leukopenia - infection
94
Causes of intrinsic haemolysis
Hereditary spherocytosis
PNH
Pyruvate kinase deficiency
sickle cell
HbC disease
G6PD
95
Underlying pathology of hereditary spherocytosis
autosomal dominant
defect in proteins interacting with RBC skeleton
premature removal by spleen
EXTRAVASCULAR haemolysis
96
Sx of hereditary spheocytosis
splenomegaly
pigmented gallstones
aplastic crisis secondary to parvovirus
97
How to diagnose hereditary spherocytosis
decreased fluorescence of RBCs on EMA binding test
increased fragilty in osmotic fragility test
98
Treatment for hereditary spherocytosis
splenectomy
99
Pathology of PNH
haematopoetic stem cell mutation -> increased complement mediated intravascular haemolysis
loss of CD55 and CD59 which protect RBC from complement
occurs at night due to mild resp aciodosis when breathig slowly in sleep
100
Triad of PNH
DAT -ve (because intravascular haemolysis is -ve)
pancytopenia
venous thrombosis
101
sx of PNH
smooth muscle dystonias - dysphagia, abdo pain
pink/red morning urine
pancytopenia
venous thrombosis
Pulmonary HTN (decreased NO)
102
PNH associations
CML, aplastic anaemias
103
PNH dx
absence of CD55/59 on flow cytometry
104
PNH treatment
ravulizumab/eculizumab (targets C5 -> terminal complement)
- higher risk of meningitis from neisseria, needs abx prophylaxis (penicillin)
if bone marrow failure - allogenic stem cell transplant
105
G6PD pathology
x-linked recessive
G6PD defect -> reduced NADPH -> reduced glutathione -> increased RBC susceptibility to oxidative stress -> hameolysis to sulfa, antimalarials and fava beans
Intra and extravascular haemolysis
106
smear fings for G6PD def
heinz bodies and bite cells
107
pyruvate kinase deficiency pathology
smear findings
Autosomal recessive
pyruvate kinase defect -> reduced ATP -> rigid RBCs -> extravascular haemolysis
smear: burr cells
108
Sickle cell anaemia pathology
point mutation in Beta globin gene -> single AA substitution -> alters hydrophobic region of RBC, aggregation of Hb
intra and extravascular haemolysis
Low O2, high altitude or acidosis precipitates sickling -> vasoocclusive disease
109
XR findings in sickle cell anaemia
hair on end skull XR from increased erythropoeisis
110
complications of sickle cell anaemia
aplastic crisis with parvovirus
autosplenectomy (howell jolly bodies)
splenic infarcts, sequestration
vaso-occlusive including acute chest syndrome
focal segmental glomerulosclerosis
111
diagnosis of sickle cell anaemia
gel electrophoresis
low HbA
high HbS
high HbF
112
Treatment of sickle cell
hydroxyurea - increases HbF
blood transfusions as required
asplenia tx
folic acid
113
AIHI tests
DAT positive
usually normocytic
smear: spherocytes and agglutinated RBCs
114
difference between cold and warm AIHA
warm -> IgG mediated
cold -> IgM and complement
115
causes of warm AIHA
SLE
CLL
Beta lactams
methyldopa
116
Causes of cold AIHA
CLL
mycoplasma pneumoniae
EBV
117
treatment of warm AIHA
steriods
rituximab
splenectomy if refractory
118
treatment of cold AIHA
avoid cold
rituximab
119
causes of drug induced haemolytic anaemia
abxs (penicillins, cephalosporins)
NSAIDs
Immunotherapy
chemotherapy
120
mechanism of MAHAs
types of MAHAs
RBCs damaged passing through obstructed or narrowed vessels
DIC
TTP/HUS
SLE
HELLP
hypertensive emergency
121
findings which suggest MAHA
schistocytes on smear
122
Lead poisening pathology and symptoms
blocks heme synthesis pathway leading to accumulated by-products (like porphyia)
sx: microcytic anaemia (basophilic stippling and ringed sideroblasts in bone), peripheral neuropathy, headahce, memory loss, GI and kidney disease
123
Symptoms of acute intermittant porphyria
5 P's
painful abdomen
port coloured urine
polyneuropathy
psych disturbance
perecepitated by CYP450 induces, EtOH and startvation
124
diagnosis of Acute intermittant porphyria
measure porphobilinogen and total prophyrins as screening
elevated PBG during attack enough to diagnose
if PBG normal but porphyrins elevated -> a type of porphyria
125
treatment of prophyria
hemin
if mild can do trial of carbohydrate loading
126
What is prophyria cutanea tarda
type of porphyria causes blistering cutaenous photocensitivity in hands
can be triggered by hep C or hereditary
Tx: phlebotomy, sun avoidance, hydroxychloroquine
127
Signs of acute iron poisening
abdo pain
vomitng
anion gap metabolic acidosis
multiorgan failure
128
signs of chronic iron poisening
arthopathy, cirrhosis, cardiomyopathy, bronzing of skin, hypogonadism
129
Prothrombin time is a measure of?
common and intrinsic pathway
130
Partial thromboplastin time (PTT) is a measure of?
common and intrinsic pathway
131
Thrombin time is a measure of?
rate of conversion of fibrinogen
prolonged with anticoagulants, DIC, liver disease, reduced fibrin
132
what does mixing studies diagnose and how
Dx clotting factor deficiencies
add normal plasma to pt plasma, if corrects is clotting factor deficiency
If there is a factor inhibitor present it does not correct
133
Symtpoms of haemophilia
normal PT, prolonged PTT
easy bleeding
haemarthrosis
134
treatment for Haemophilia A B and C
A - if mild desmopressin (increases factor 8), factor 8 concentrate, emicizumab (bridges factor 9 and 10 to restore function of missing 8)
B - factor 9 concentrate
C - factor 11 concentrate
135
Vitamin K deficiency coagulation studies
prolonged PT and PTT
136
Indicated MAHA on MCQs
low Hb, schistocytes and raised LDH
137
Most common cause of isolated thrombocytopenia
ITP
138
Mechanism of ITP
anti-GpIIb/IIIa antibodies leads to destruction of platelets in spleen by macrophages
139
Hypersensitivity type associated with ITP
T2 hypersensitivity
140
Causes of ITP
idiopathic
autoimmune (SLE)
viral (HIV, Hep C)
Malignancy (CLL)
drug reactions
H pylori
141
Ix in ITP
normal PT and PTT
higher megakaryocytes on bone marrow bx
low plts
142
ITP treatment
critical bleeding -> glucocorticoids and IVIG
Severe bleeding - > glucocorticoids alone
rituximab
eltrombopag/romiplastin (TPO receptor agonist)
splenectomy for refectory ITP
143
Difference between thrombotic microangiopathies (TMA) and DIC
TMAs have no lab findings of consumptive coagulopathy (normal PT, PTT and fibrinogen)
DIC has prloned PT, PTT and reduced fibrinogen
144
Thrombotic thrombocytopenic purpura mechanism (TTP)
inhibition or deficiency of ADAMs 13 -> reduced degradation of vWF -> large vWF multimers -> increased platelet adhesion and aggregation (microthrombi formation)
145
symptoms of TTP
thrombocytopenia, MAHA (low Hb, high LDH, schistocytes), fever
plus fever and neurological sx (confusion, headache)
146
TPP bloods
normal PT and PTT, DAT -ve
Confirm Dx with ADAMS13 <10%
147
TPP treatment
PLEX
glucocorticoids
when dx confirmed -> rituximab
if severe features -> caplacizumab (monoclonal against vWF)
148
Haemolytic uraemic syndrome (HUS) mechanism
caused by shiga toxin producing E coli (STEC O157:H7) -> profound endothelial dysfunction
149
Sx of HUS
thrombocytopenia, MAHA and AKI
plus blood diarrhoea
usually in children
150
Tx of HUS
supportive care
151
What does von willebrand bind to on platelets
Gp1b
152
von willebrand disease mode of inhereitance
AD
most common inhereted bleeding disorder
153
treatment for von willebrand disease
desmopressin (releases vWF stored in endothelium)
if severe bleeding von willebrand concentrate (if not available then cryoprecipitate)
154
Pathology of DIC
widespread clotting factor activation -> thromboembolic state with excessive clotting factor consumption -> increased thrombosis and haemorrhage
155
Causes of DIC
heat stroke
snake bites
gram -ve sepsis
trauma
obstetric complications
pancreatitis
malignancy (APML)
nephrotic synrome
transfusion
156
DIC on bloods
prolonged PT and PTT
schistocytes
increased d-dimer (fibrin degredation products)
decreased fibrinogen
decreased factor 5 and 8
157
treatment of DIC
treat underlying condition
Plt if < 20
VTE prophylaxis
158
Antithrombin deficiency mechanism
can be acquired by renal failure (nephrotic syndrome)
antithrombin loss in urine -> reduced inhibition of factors 2a and 10a
159
Factor V leiden inheritance and MoA
AD
mutant factor V production resistant to degredation by activated protein C
160
Mechanism of protein C and S deficiency and manifestations
decreased ability to inactivate factors 5A and 8a
increased risk of warfarin induced skin necrosis
161
Malignancy associated with DIC
APML
162
difference between leukaemia and lymphoma
lymphoma arising from LN, leukaemia widespread bone marrow involvement
163
Cells indicating hodgkins lymphoma
Reed sternberg cells
164
CD markers present and not present in hodgkins
CD15 and CD 30
CD 20 in lymphocyte rich (non-classic)
does not have CD45
165
Histological subtypes of hodgkins lymphoma
nodular sclerosis
mixed cellularity
lymphocyte rich or poor
166
Viral asscoiation with hodkins
EBV
167
risk factors for hodgkins
age
mediastinal bulk
> 2 sites
B symptoms
168
treatment of hodgkins
ABVD, BEACOPP, RTx
if relapses > pembrolizumab (PD1), Brentuximab (CD30) or autologous SCT
169
Asscoiated conditions with hodgkins lymphoma
minimal change disease
paraneoplastic cerebellar degeneration
erythroderma
170
Burkitt lymphoma translocation
t (8:14) [B kinda looks like at 8]
cMYC translocation
171
CD Markers of burkitt lymphoma
lab findings of burkitts
CD19
very high LDH >1000
Ki67 95-100%
172
association with burkitt lymphoma
EBV
173
difference in endemic vs sporadic version of burkitt lymphoma
endemic version usually involves Jaw and occurs in Africa
Sporadic verison usually involve abdo/pelvis in 40s
174
Burkitt's treatment
low risk - EPOCH-R
high risk CODOXM, IVAC, hyperCVAD (CNS penetrating)
175
Most common non-hodgkin lymphoma in adults?
diffuse B cell lymphoma
176
mutations associated with diffuse B cell lymphoma
BCL2 and BCL6
germ centre B cells in 70%, BCL2 and CD10 (better prognosis)
activated B cell in 25%, BCL 6 and MUM 1
177
Treatment for diffuse B cell lymphoma
1st line - r-chop
2nd - platinum or cytarabine therapy, autologous SCT
3rd - CART cells, polutuzumab (anti CD79), allogenic SCT
178
Most common indolant lymphoma
follicular
179
follicular lymphoma genetics and markers
t(14:18) BCL2 translocation
present CD 19, 20 and 10
CD 23 not present
180
treatment for folicular lymphoma
limited stage - RTx
advanced - R-bendamustine (alkylating)
181
Mantle cell lymphoma genetics and markers
t(11:14) translocation of cyclin D1 and Ig CD5+
CD19 positive
aberrant CD5 expression
182
Mantle cell lymphoma treatment
if fit - R-CHOP, RDHAC and ASCT
if unfit - R bendamustine
if relapse - BKI (ibrutinib), venetoclax (BCL2 inhibitors), CART cells
183
Marginal zone lymphoma genetics (MALT)
associated with t(11:18) and chronic inflammation
mature B cells, do not express CD5 or CD10
184
MALT lymphoma treatment
localised - RTx
stage 3/4 if sx - R-bendamustine
185
Primary CNS lymphoma associated with
EBV
HIV/AIDs
186
Dx of CNS lymphoma
ring enhancing lesion on MRI, need tissue
187
Treatment for primary CNS lymphoma
MTX, tituximab plus either tenozolanide or procarbazine and vincristine
188
cause of mature T cell lymphoma
HTLV
189
CD markers for T cell lymphoma
CD5 positive
CD7 -ve
190
Most common immunoglobulin produced in multiple myeloma
IgG > IgA > light chains
191
diagnostic criteria of multiple myeloma
bone marrow plasma cells <10% or bx proven plasmacytoma plus >1 of
CRAB criteria (Ca>2.75, CrCl <40 or Creat >177, Hb <100)
biomarkers: BM plasma cells >60%, FLC ratio >100, > 1 focal lesion
192
Most common cause of AKI in multiple myeloma
light chain cast nephropathy
193
which type RTA associated with multiple myeloma
type 2
194
high risk genetic mutations in MM
17p deletion (TP53 mutation)
t(14:16)
t(4:14)
high LDH, high beta2-microglobulin
195
Multiple myeloma treatment
<70yo, induction with bortezomib, lenalidomide and dexamthasone then autologous SCT
if older, lenolidamide or bortezomib therapy
196
Waldenstroms mutation and type of immunoglobulin
MYD88 mutation
IgM overproduction
197
fundoscopy findings in waldenstroms
sasauge like veins
198
BM Bx findings in waldenstroms
>10% monoclonal B lymphocytes with plasma cell features and intranuclear inclusions
199
When do you treat in waldenstroms and what with?
if symptomatic anaemia or hyperviscosity (>40)
DRC or R-bendamustine
BTK inhibitors
200
MGUS risk of progressing to MM or waldenstroms
1-2% per year
201
Most common type of MGUS
non-IgM
IgG>IgA>free light chains
202
Difference between myelodysplastic syndrome and AML
bone marrow blasts <20% in MDS (>20% in AML)
203
Difference between types of ALL presentations
T cell - ALL presents with mediastinal mass and SVC like syndrome
B-ALL usually in children
204
Conditions assocaited with ALL
Down syndrome
205
Markers of ALL
TdT (pre-T and B cell marker)
CD10 (pre B cell markers)
206
Mutations in ALL and their associated prognosis
t(12:21) better prognosis
t(9:22) poor prognosis
207
B-ALL markers and genetics
CD19 CD 79 CD 22
usually in children, 25% have T(9:22) BCR-ABL rearrangement
208
ALL treatment
Philadelphia -ve -> vincristine, glucocorticoid and anthracycline
- younger adult with CD20 + -> add rituximab
Philidelphia +ve -> TKI
209
Most common adult leukaemia
CLL
210
Markers of CLL
CD20 CD5 B cell neoplasm
CD23
211
Difference between CLL and small LL
CLL >5x109/L malignant cells in peripheral blood
< 5 is SLL
212
CLL smear findings
smudge cells (autoimmune haemolytic anaemia)
213
Most common CLL tranformation
Richter transformation into diffuse B cell lymphoma
214
CLL associations
hypogammaglobulinaemia -> causing infections
immunodeficiency
215
Indications for treatment in CLL
marrow failure/cytopenias
symptomatic splenomegaly/lymphadenopathy
lymphocyte doubling time <6 months
autoimmune complications
constitutional sx
216
Best prognostic mutations in CLL
13q deletion
217
adverse porgnosis factors/mutations in CLL
17p or 11q mutations on FISH
unmutated immunoglobulin heavy chain (IHGV)
CD38 or ZAP70 positive
elevated beta 2 microglobulin
age >65yo
218
CLL teratment
17p mutations respond poorly to fludrabidine so give venetoclax (BCL2) and obinutuzumab (CD20)
- give same if unfit
If fit then give fludarabine regimine (2nd line venetoclax and rituximab
3rd line - BKI
219
Pathology of hairy cell leukaemia
indolent disease of mature memory B cells due to BRAFV600E mutation
- causes marrow fibrosis which leads to dry tap on aspiration of BM
220
Hairy cell leukaemia presentation
massive splenomegaly
pancytopenia
can have proximal myopathy secondary to polymyositis
221
Sensitive and specific marker for hairy cell leukaemia
annexin A1
222
treatment for hairy cell leukaemia
purine analogs - cladrabine and pentostatin
rituximab, ibrutinib
vemurafinib (inhibitor of BRAF V600E)
223
What is the second most common leukaemia
AML
224
Risk factors for AML
down syndrome
previous chemo/RTx
225
diagnosis of AML
>20% blasts in BM or blood
226
AMl presentation
cytopenias (neutropenic fevers)
bone pain
Leukostasis (capillaries blocked by malignanct cells -> organ damage)
primary tumour lysis
DIC in APML
227
Favourable mutations in AML
t(15:17) - APML
t(8:21)
Inv(16)
mutated NPM1
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intermediate risk AML mutations
mutated NPM1 with high FLT3-ITD
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adverse mutations in AML
17p abberation
mutated TP53
wild type NPM1 and high FLT-ITD
complex karyotype
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blood findings of AMPL
auer rods (crystlaised MPO)
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APML mutation
t(15:17), PML-RARA
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treatment considerations for APML
PML-RARA blocks retinoic acid induced myeloid differenciation
ATRA and arsenic forces differenciation and can induce degredation of PML-RARA
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Complications of ATRA
ADR: headaches, hepatotoxicity, cytopenias
Differenciation syndrome
- fever, oedema, pulmonary infiltrates and serotsitis
prophylaxis with prednisolone
to treat with dexamethasone
only stop ATRA if severe
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Treatment for AML
< 70yo and fit - induction 7 days of cytarabine and 3 days of daunorubicin
consolidation high dose cytarabine
if FLT3 can give midostaurin
Allogenic SCT in second remisson (if no SCT fatal)
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What is considered remission in AML
<5% blasts in bone marrow
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CML mutation
t(9:22) BCR ABL1
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3 phases of CML
chronic - neurophilia and myelocytosis in blood, increased platelets
- BM blasts <10%, <20% basophils in blood
accelerated - increased blasts in BM, splenomegaly, blasts between chronic and blast phase
blast phase - acute leukaemia, blasts >20%
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Cluse to suggest CML
proliferation of all mature myeloid lines (neutrophilia, basophilia, eosinophilia, myelocyte peak)
median WCC at dx 100
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Treatment of CML
higher risk -> 2nd gen Tyrosine kinase inhibitors (nilotinib, dasatinib ->30% risk pleural effusion)
lower risk -> 1st gen TKI (imatinib)
if relapsed 3rd gen TKI ponatinib
goals of therapy 3 monthly BCR-ABL byt 1 year <0.1%
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Polycythemia vera mutation
JAK2
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polycythemia vera sx
aquafenic pruritis, fatigue, microvascular sx (headache, lightheaded, visual disturbance, astypical chest pain)
erytheromelalgia (severe burning pain and red-blue discolouration)
mild/mod splenomegaly in some cases
associated with hyperviscosity and thromosis (splanchic thrombosis/budd-chiari
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major investigation finding in polycythemia vera
decreased EPO
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diagnostic criteria of polycytemia vera
Major - Hb >165 or HCT >0.49, BMbx showing hypercellularity, JAK2 V617F mutation (97%) or JAK2 exon 12 (3%)
minor - subnormal EPO
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major cause of mortality in polycythemia vera
thrombosis
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risk of leukaemic and myelofibrosis transofrmation in polycythemia vera
5-15% for both over 15 years
thrombosis is 5-15% in 3 years
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polycythemia vera threatment
all pt get venesection to aim for HCT <0.45
low risk - BD aspirin
high risk cytoreduction with hydroxyurea, IFN alfa, busulfan
only ruxolitinib (JAK1/2 inhibitor) if significant sx
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What is essntial thrombocytopenia
massive proliferation of megakaryocytes and platelets
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symptoms of essential thrombocytopneia
mostly asymptomatic
can have mucocutaenous bleeding due to acquired von willebrand disease
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essential thrombocytopenia diagnostic criteria
major - plt >450, BMbx megakaryocyte proliferation and no/small fibrosis, not meeting other criteria, JAK2 (55%), CALR (35%) ir MPL (<5%) mutation
minor - presence of clonal marker or absence of reactive thrombocytosis
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essential thrombocytopenia mutations
JAK2 (55%), CALR (35%) ir MPL (<5%) mutation
JAK2 and MPL most asscoiated with thrombosis
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essential thrombocytopenia risk of AML and myelofibrosis
AML <5% over 15 years
myelofibrosis 5-10%
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essential thrombocytopenia treatment
only affects thrombosis risk, not survival or transformation
low risk - observation, if risk factors aspirin
intermediate - BD aspirin, cytoreduction if CVD
high risk - cytoreduction and aspirin
anticoags if VTE
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what is primary myelofibrosis
megakaryocyte proliferation causing BM fibrosis and extramedullary haemotopoesis
atypical megakaryocyte hyperplasia -> increased TGF-beta secretions -> increased fibroblast activity -> obliteration of BM with fibrosis
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clinical findings in primary myelofibrosis
massive splenomegaly
teardrop RBCS
30% can be asymptomatic
associated with gout and renal stones (hyperuricaemia)
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diagnostic criteria of primary myelofibrosis
major - megakaryocyte proliferation and reticulin fibrosis, not meeting criteria for CML, PV, ET or MDS, presence of JAK2, CALR or MPL
minor - anaemia, slenomegaly, elevated LDH, leukoerythroblastic film
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treatment of primary myelofibrosis
intermediate 2 and high risk treated with allogenic SCT
low risk monitored
standard therapy is ruxolitinib
hydrocyurea for leukocytosis
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What is Myelodysplastic syndrome and subtypes
when blasts <20%, group of haematopeotic stem cell disorders
MDS with excess blasts -> 5-19% blasts
MDS with multilineage -> blasts <5%, 1-3 cytopenias
MDS with single lineage dysplasia -> blasts <5% and 1-2 cytopenias
MDS with isolated 5q deletion can be treated with lenolidamide
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treatment of myelodysplastic syndrome
azacitadine (inhibitrs DNA methyltransferease and induces cytotoxicity)
- delays time to death and progression to AML
259
What is langerhan's cell histiocytosis and what are sx
proliferative disorder of langerhans cells (APCs in skin), usually in children with lytic bone lesions, skin rash, recurrent otitis media or mass involving mastoid bone
cells do not stimulate T cells (functionally immature)
cells express S-100 and CD1a
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blood findings in tumour lysis syndrome
low Ca, high K, phosphate and uric acid
261
treatment of tumour lysis syndrome
allopurinol or rasburcase
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MoA of heparin
activates antithrombin which decreases activity of 2a and 10a
263
How to reverse heparin
protamine sulfate
264
mechanism of heparin induced thrombocytopenia Type 2
IgG antibodies formed against heparin bound platelet factor 4 (PF4), binds and acitvates plt and is removed by spleen -> thrombocytopenia
5-10 days post heparin administration
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Warfrain MoA
inhibits vit K epoxide reductase
266
Why is there initial hypercoagulation with warfarin
protein C has a shorter half life than factors 2 and 10. used up first, increased 2 and 10 without being inhibited -> hypercoagulation
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dabigatran reversal agent
idarucizumab
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dabigatran coags finding
raised aPTT
269
apixaban/rivaroxaban reversal agent
andexanet alfa (recombinant factor Xa)
270
apixaban/rivaroxaban coags finding
prolongs INR
271
Multiple myeloma marker
CD38
