HAEM ONC Flashcards
CML treatment= imatinib– MOA
imatinib MOA= tyrosine kinase inhibitor
CML- chromosome problem
translocation chr 9 and 22– philadelphia chromosome
TRALI vs TACO
TRALI– causes hypotension and overload signs and RAPID
TACO- slower, hypertension, overload
heparin affects which part of coagulation?
antithrombin
acute chest syndrome == which ocndition?
sickle cell crisis
most common type oh hodgkins lymphona
nodular sclerosing
monoclonal proliferation of well-differentiated lymphocytes which are almost always B-cells
CLL
combined B and T cell disorders ? (4)
WASH your b cells and t cells
Wisckott
Ataxic telangiectasia
severe combined immunodeficiency
Hyper IgM
neutrophil disorders (3)
Chronic granulomatous disease
Chediak-Higashi syndrome
Leukocyte adhesion deficiency
B cell only disorders (3)
Brutons X linked
(selective) IgA deficiency
Common variable immunodeficiency
T cell only disorder (1)
digeorge
draw toxicity bear
see photo
hereditary angioedma- inheritance and best screening test
autosomal dominant
C4 screening in between attacks
Basophilic stippling typical of?
lead poisoning
antiphospholipid syndrome management
LMWH and aspirin
most common type of inherited thrombp[hilia
factor 5 leiden heterozygous= activated factor C resistance (c for COMMON)
what is ITP
what antibodies against
Ix
reduction in the platelet count.
Antibodiesagainst the glycoprotein IIb-IIIa or Ib complex
Ix :
IgG antiplatelet antibodies
bone marrow asp- megakaryocytes
Mx:
PO prednisolone
plasma exchange IvIG
splenectomy if does not respond to steroids after3 motnhs
what is most likely to precipitate haemolysis in a patient with G6PD deficiency?
penicillin
Raynaud’s
type of cryoglobinuaemia
Type 1 cryoglobinuamiea
3 types of cryoglobinaemia and conditions associated with each type
type 1 - monoclonal- IgG, IgM
raynayds, multiple myeloma, waldenstrom
type 2 - mixed mono and polyclonal rheumatoid factor: hep c, RA, sjogrens
type 3 : polyclonal, RA,Sjogrens
Mx for cyoglobinaemia and tx
Low complement levels
high ESR
Tx:
plasma phoresis
immunosuppression
methaemoglobinaemia affects o2 and co2?
ABG:
high o2
low co2
O2 sats LOW, HIGH pao2
symptoms: headache
SOB cyanosis
medication (ABx) most likely to cause methaemoglobinaemia
co-trimoxazole
what is methamoglobinaemia
how does it affect o2 dissociation curve
Hb oxidsied to Fe2+ to Fe3+
shifts curve to the LEFT
causes of methaemoglobinaemia
MNEUMONIC CAUSES methaemoglobinaemia:
Sulphur, Nitrates and Poppers means Dappy’s Prime Pussy Dyes
treatment Methaemoglobinaemia
NADH methaemoglobinaemia reductase deficiency: ascorbic acid
IV methylthioninium chloride (methylene blue) if acquired
what type of infection associated with hereditary spherocytosis causes aplastic crisis
parvovirus B19 infection
what is seen on blood film for G6PD?
inheritance pattern?
Diagnostic test?
heinz bodies on blood film (6yo like heinz)
X LINKED recessive
Diagnostic test= Measure enzyme activity of G6PD
hereditary spherocytosis
Diagnostic test
inheritance
what is seen on bloodfilm
diagnostic test= EMA binding
aut dominant
blood film- spherocytes
adverse effects of aromatase inhibitors eg letrozole
and MOA
MOA= reduce production of oestrogen in peripheral tissues
features of TTP : ask the FAT RN
Fever
Anaemia
Thrombocytopaenia
Renal impairment
Neuro involvement
Tx TTP
Plasma exchagne
steroids
imunosuppressants
vincristine
alpha thalassemia affects ‘? chr
chromosome 16 (16 sort of looks like alpha)
if only 1 or 2 alpha chains affected- hypochromic and microcytic
IF severe= all 4 chains are affected =death in utero hydrops fetalis
how to Differentiate CML from leukaemoid reactions:
CML: leukocyte alkaline phosphatase score is low
Leukaemoid reaction; alk phos score is HIGH
high leucocyte alkaline phosphatase score
toxic granulation (Dohle bodies) in the white cells
‘left shift’ of neutrophils i.e. three or fewer segments of the nucleus
causes of leakaemoid reaction
severe infection
metastatic Ca with BM infiltration
severe haemolysis
massive haemorrhage
most common inherited bleeding disorder– inheritance pattern
von willebrands
AUT DOM
Treatment von willebrand disease
factor 8 concentrate
tranexamic acid for mild bleeding
desmopressin_ raises WVB factor
sickle cell
cause
- inheritance
- diagnosis
Inheritance= autosomal recessive
diagnosis- electrophoresis
valine substituted at position 6 of beta globin chain instead of glutamic acid
Tranplant vs graft disease: time frame
CFs
skin biopsy will show?
Tx?
2-6 weeks after transfusion
CFs diarrhoea, rash, liver damage
-skin biopsy will show abundant necrotic keratinocytes
There is no treatment, so prevention by using gamma-irradiated blood products in high-risk patients is the key.
tumour marker CA 125
ovarian
CA 19-9 tumour marker
pancreatic
CA 15-3 tumour marker
breast cancer
Alpha-feto protein (AFP) tumour marker
hepatocellular
teratoma
CEA
colorectal
S-100 tumour marker
S-100 Melanoma, schwannomas
Bombesin tumour marker
SCLC, gastric , neuroblastoma
what type of leukaemia associated with polycythaemia rubr vera
AML
most common inherited BLEEDING disorder
VWB disease
most common inherited thrombophilia= anti protein c resistance
follicular lymphona translocation?
14:18
c-myc gene translocation
Burkitts lymphoma
Burkitts lymphoma transloccation
YMCA= YMC8
8 for translocation t(8:14)
myc has the same letters (c myc gene translocation)
TLS management
HIGH VOL IV fluids
prophylactic allopurinol and also rasburicase can be used
Tx- rasburicase
DO NOT give rasburicase and allopurinol together as this red effect of rasburicase
hereditary spherocytosis abdo pain cause
likely gallstones
what is likely to develop from polycythaemia rubra vera
myelofibrosis
AML
acute intermittent porphyria vs porphyria cutaena tarda differences
porphyria cutaena tarda = photosensitive bullae
acute intermittent porphyria= presents with psych, neuro and abdominal symptoms
acute intermittent porphyria
CFs
CFs
abdominal: abdominal pain, vomiting
neurological: motor neuropathy
psychiatric: e.g. depression
hypertension and tachycardia common
classically urine turns deep red on standing
raised urinary porphobilinogen
Paroxysmal nocturnal haemoglobinuria
CFs
Ix
Mx
CFs
haemolytic anaemia
RBCs , WBCs, platelets or stem cells may be affected== pancytopenia
haemoglobinuria: classically dark-coloured urine in the morning
thrombosis e.g. Budd-Chiari syndrome
aplastic anaemia may develop
Ix:
GOLD Flow cytometry of blood - CD59, CD55
hams test = acid induced haemolysis
Mx_ blood product replacement
anticoagulation
monoclonal antibody eculizumab
stem cell transplant
low levels of CD59 and CD55 == ?
Paroxysmal nocturnal haemoglobinuria
most common cause of antithrombin III def?
CKD
ADAMTS13 ass’d with which type of vasculitis
TTP
when should skin prick testing be read
when shoud skin patch testing be read
skin prick- 15mins
skin patch- 48hrs
which type of chemo causes hypomagesia
cisplatin
meigs syndrome =
ovarian fibroma
Irinotecan MOA
Irinotecan inhibits topoisomerase I,
what is Multiple myeloma
what type of cells
and CFs
Investigations
MM = haem malignancy
clonal proliferation of plasma cells
CFs
CRABBI
Ca raised (osteoclast reabsorp)
Renal (light chain dep)
Anaemia
Bleeding (bruises)
Bone (lytic lesions)
Infection
Investigations:
XR -skull XR = raindrop lytic lesions
Urine- monoclonal band BENCE JONES protein IgA IgG
Diagnostic criteria Multiple Myeloma
either : one major criteria OR 3 minor criteria
Major criteria
Plasmacytoma (as demonstrated on evaluation of biopsy specimen)
30% plasma cells in a bone marrow sample
Elevated levels of M protein in the blood or urine
Minor criteria
10% to 30% plasma cells in a bone marrow sample.
Minor elevations in the level of M protein in the blood or urine.
Osteolytic lesions (as demonstrated on imaging studies).
Low levels of antibodies (not produced by the cancer cells) in the blood.
sickle cell crisis- ANAEMIA crises
2 types and how to differetiate them
anaemia crisis in sickle cell- 1. sequestration and 2. aplastic
Aplastic = sudden fall in Hb, low reticulocyte count , PARVOVIRUS infection
sequestration =Low Hb, increased reticulocyte count
common childhood haem malignancy
ALL
C1-INH deficiency= what condition?
hereditary angioedema
bronchial carcinoma and mesothelioma associated with exposure to WHAT
asbestos
what is mesna and when to give it
mesna prevents bladder irritation after cyclophosphamide chemo treatment
reed sternberg cell associated with?
hodgkins lymphoma
only which electrolyte is lowered in tumour lysis syndrome? all rest elevated
calcium is lowered
DOCETAXEL AND TAXANE MOA
PREVENTS microtubule depolymerisation. Creates free tubulin
sickle cell patient which medication for long term use to prevent sickle crises?
hydroxycarbamid
Bombesin tumour marker for?
SCLC, neuroblastoma, gastric ca
systemic mastocytosis investigation-
urinary histamine
CLL : is chr 17 or 13 deletion associated with GOOD prognosis
chr 13 deletion is good prognosis
CLL poor prognostic factors
male sex
age > 70 years
lymphocyte count > 50
prolymphocytes comprising more than 10% of blood lymphocytes
lymphocyte doubling time < 12 months
raised LDH
CD38 expression positive
TP53 mutation
CLL : is chr 17 or 13 deletion associated with GOOD prognosis
chr 13 deletion is good prognosis
acute intermittent porphyria
CFs
inheritance
Ix
Tx
AUT DOM
CFs
Neuro=motor neuropathy
Psych- depression
abdo pain, n+v
HTN, tachycardia
Ix= urine turns dark red on standing oxidation
URINARY POROBILLOGEN RAISED
Tx=
IV haemtin/arinate
or IV glucose
Tx CML
imatinib is now considered first-line treatment
inhibitor of the tyrosine kinase associated with the BCR-ABL defect
very high response rate in chronic phase CML
hydroxyurea
interferon-alpha
allogenic bone marrow transplant
most common bac cause of neutropenic sepsis
Staph epidermis
coagulase-negative, Gram-positive bacteria
conditions thymomas associated with (4)
myasthenia gravis (30-40% of patients with thymoma)
red cell aplasia
dermatomyositis
also : SLE, SIADH
how does desmopressin affect ppl with VWB disease
desmopressin (DDAVP): raises levels of vWF by inducing release of vWF from Weibel-Palade bodies in endothelial cells
DIC =? caused by
CFs, Ix, blood results
Causes of DIC
sepsis
trauma
obstetric complications e.g. aminiotic fluid embolism or hemolysis, elevated liver function tests, and low platelets (HELLP syndrome)
malignancy
Ix bloods:
low platelets
incr PT, incr APTT
high d dimer
low fibrinogen
BLOOD FILM=SCHISTOCYTES (helmet cells)
Lead poisoning
CFs
Ix
Tx
CFs
abdominal pain
peripheral neuropathy (mainly motor)
neuropsychiatric features
fatigue. constipation
blue lines on gum margin
Ix: lead blood level
FBC= microcytic anaemia, basophilic stippling
increased urinary coproporphyrin
Mx:
chelation
dimercaptosuccinic acid (DMSA)
D-penicillamine
EDTA
dimercaprol
how to treat severe b12 def , with NO folate deficiency
if no folate deficiency-
IM 1mg hydroxycobalamin 3x a week for 2 weeks and then once every 3 months
If folate deficient- treat b12 deficiency first
what to give pt with Von willebrand deficiency before dental procedure
desmopressin
when is leukocyte ALP raised :
leukamoid reactions
myleofibrosis
polycythaemia vera rubra
infections
steroids, cushings
pregnancy
COcp
when is leukocyte ALP low
CML
pernicious anaemia
paroxysmal nocturnal haemoglobinuria
infec mono
causes of extravascular haemolysis
Wa Ha Ha Ha
W warm autoimmune hemolytic anemia
H hemolytic disease of the newborn
H hereditary spherocytosis
H hemoglobinopathies: sickle cell, thalassemi
IgM paraproteinaemia?>?????
Tx of this condition
waldenstroms
Tx= rituximab
what actually causes methaeglobinaemia?
OIL RIG
ferrous ions (Fe2+) of haemoglobin are oxidised to the ferric (Fe3+) ions
what abx precipitates G6DP haemolysis
primaquine
ciproflocaxin
sulphonamides
suphonylureas
sulphasalazine
hyposplenism findings on blood film
Howell-Jolly bodies and siderocytes are typical blood film findings of hyposplenism
smudge cells=?
CLL- need to do immunophenotyping
transfusion of WHAT type of blood product = most likely bacterial infection
platelets
tear drop poikiolocytes= ?
myelofibrosis
beta thalassemia trait- inheritance
and major
beta thalassemia trait= aut rec
HbA2 raised
Usually asymptomatic apart from : mild hypochromic, microcytic anaemia - microcytosis is characteristically disproportionate to the anaemia
Beta thalassemia major= chr 11
Presents in 1st year of life with severe anaemia, hepatosplenomegaly and failure to thrive
Extra-medullary haematopoiesis 🡪 facial abnormality
Blood film 🡪 hypochromic, microcytic cells. Also target cells and nucleated RBCs
Mx 🡪 lifelong transfusions
good prognostic markers ALL
and poor prgnostic
good prognostic markers:
FAB 1 type
caucasian
initial low WBC
common ALL
pre B phenotype
del 9p
Poor prognostic factors
FAB L3 type
T or B cell surface markers
Philadelphia translocation, t(9;22)
age < 2 years or > 10 years
male sex
CNS involvement
high initial WBC (e.g. > 100 * 109/l)
non-Caucasian
poor prognostic features AML
> 60 yo
20% blasts after first chemo
deletion chr 5 or 7
CML chr affected
first line tx
philadelphia- 9:22
imatinib- tyrosine kinase inhibitor
BCR-ABL
smudge cells seen in ?
CLL
In ER positive breast cancer- when to use tamoxifen vs letrozole/anastrazole
Tamoxifen= ER positive PRE menopausal women
SE’s incr risk VTE and endometrial Ca
Aromatase inhibitors= ER positive POST menopausal women
staging system for lymphoma
Ann Arbor system.
Stage 1 - One node affected
Stage 2 - More than one node affected on the same side of the diaphragm
Stage 3 - Nodes affected on both sides of the diaphragm
Stage 4 - Extra-nodal involvement e.g. Spleen, bone marrow or CNS
poor prognosis lymphoma
age > 45 years
stage IV disease
haemoglobin < 10.5 g/dl
lymphocyte count < 600/µl or < 8%
male
albumin < 40 g/l
white blood count > 15,000/µl
treatment of aplastic anaemia
stem cell transplant- allogenic
anti thymocyte
anti lymphocyte
platelet tramsfusion
Leucocyte alkaline phosphatase
raised and lowered in:
Raised in
myelofibrosis
leukaemoid reactions
polycythaemia rubra vera
infections
steroids, Cushing’s syndrome
pregnancy, oral contraceptive pill
Low in
chronic myeloid leukaemia
pernicious anaemia
paroxysmal nocturnal haemoglobinuria
infectious mononucleosis
howel jolly bodies on blood film
hyposplenism
TTS deficiency
ADAMTS13
haemophilia INHERITANCE
2 types and their causes
CFs
Ix
x linked recessive
haemophilia A= factor 8 def (a sounds like 8)
haemophilia B = factor 9 def
CFs
BOYS/MEN
prolonged bleeding
haemoarthrosis
haematomas
Ix increased APTT but everything else normal
why pt with CLL has repeated pneumonia
Hypogammaglobulinaemia
acute intermittent porphyria investigation
urinary porphobilinogen
how to tell if warm or cold haemolytic anaemia
Manchester is cold and in the UK. Hence, IgM(anchester) associated cold AIHA, and leads to intravascular haemolysis (Manchester in the UK)
Ghana is hot and outside the UK. Hence cause IgG(hana) associated warm AIHA, and leads to extravascular haemolysis (Ghana outside the UK)
SLE ass’d with warm
waldenstrom’s macroglobulinaemia
Waldenstrom’s macroglobulinaemia: lymphoplasmacytic lymphoma
associated with an IgM monoclonal (paraprotein) protein in the serum. bone marrow based disease
Features
systemic upset: weight loss, lethargy
hyperviscosity syndrome e.g. visual disturbance
the pentameric configuration of IgM increases serum viscosity
hepatosplenomegaly
lymphadenopathy
cryoglobulinaemia e.g. Raynaud’s
Investigations
monoclonal IgM paraproteinaemia
bone marrow biopsy is diagnostic
infiltration of the bone marrow with lymphoplasmacytoid lymphoma cells
Management
typically rituximab-based combination chemotherapy
monoclonal IgM paraproteinaemia
bone marrow biopsy is diagnostic of ???
waldenstroms macroglobulinaemia
essential thrombocytosis: gene mutation
what is it
JAK2 mutation
Essential thrombocytosis is one of the myeloproliferative disorders: CML, polycythaemia rubra vera and myelofibrosis. Megakaryocyte proliferation results in an overproduction of platelets.
Features
platelet count > 600 * 109/l
both thrombosis (venous or arterial) and haemorrhage can be seen
a characteristic symptom is a burning sensation in the hands
a JAK2 mutation is found in around 50% of patients
Management
hydroxyurea (hydroxycarbamide) to reduce the platelet count
interferon-α is also used in younger patients
low-dose aspirin may be used to reduce the thrombotic risk
what gene mutation do all myeloproliferative disorders have
JAK2 mutation
hydroxyurea MOA=
reduce platelemt count
antimetabolite- type of chemo
used in essential thrombocytosis
topoisomerase I chemo given- what else is also given at the same time
Irinotecan
inhibits topoisomerase I which prevents relaxation of supercoiled DNA
skin necrosis following the commencement of warfarin:
CAUSED BY?
Protein c deficiency
develops necrotic skin lesions on his lower limbs and forearms.
how are haptoglobin levels affected by INTRAVASCULAR haemolytic anaemias
LOW HAPTOGLOBINS
intravascular haemolytic anaemias
G6PD def
Red cell fragments - TTP, DIC, HUS, heart valves
Paroxysmal nocturnal haemoglobinuria
Cold haemolytic anaemia (IgM , manchester is cold and IN THE UK)
CAUSES LOW HAPTOGLOBIN
extravascular haemolytic anaemias
Wa
Ha
He
Ha
Warm haemolytic anaemia (igG, Ghana is OUTSIDE of the UK and is WARM)
Haemoglobinopathies - Sickle cell, thalassemia
Hereditary spherocytosis
Haemolytic disease of newborn
ring sideroblast on blood film =?
pyridoxine b6 deficiency
can cause sideroblastic anaemia
resistance to heparin cause of thrombophilia
antithrombin 3 def
major criteria determining the use of cryoprecipitate in bleeding
low fibrinogen level
t(15;17) translocation and DIC
Acute promyelocytic leukaemia
essential thrombocytosis tx
hydroxycarbamide
arepipratant moa
neurokinin blocker
b12 and folate def= which to treat first
treat b12 injection first
and then replace folate
to avoid subacute degn sc
Features may include symptoms of Raynaud’s and acrocynaosis.
=?
Remember this for cold AIHA
Investigation cold acute haemolytic anaemia
Direct antiglobulin test
what virus causes Adult T-cell leukaemia/lymphoma
HTLV-1:
what virus causes High-grade B-cell lymphoma
HIV
what virus causes Hodgkin’s and Burkitt’s lymphoma, nasopharyngeal carcinoma
EBV
malaria can also cause burkitts lymphoma
Benign ethnic neutropaenia is common in ??
blakc ppl
heparin MOA
Activates antithrombin III.
pernicious anaemia Ix
intrinsic factor testing
folate b12
bicalutamide MOA
androgen receptor blocker
A==> Abiraterone==> Synthesis blocker
B==>Bicalutamide==>Receptor blocker
C==>Cyproterone==> Receptor blocker
what is amyloidosis and the 2 types
Positive congo red staining
AA amyloidosis = renal involvement, inflammatory- RA, SLE
AL amyloidosis= more common
MM, WM, MGUS
what would give a false negative TTG when investigating coeliac diagnosis
selective IgA deficiency- so it is important to also check endomysial IgA with TTG when testing
DIC transfuse what product
Fresh frozen plasma
FFP (
low fibrinogen is an indicator for this
Delayed haemolytic blood transfusion reaction
positive direct antiglobulin test
CFs tumour lysis syndrome
anuric/ oligouric
rosette crystals in urine
nivolumab MOA
PD1 inhibitor
causes of warm haemolytic anaemia
IgG , extravascular
idiopathic
SLE
CLL, lymphoma
methyldopa
causes of cold haemolytic anaemia
IgM, intravascular
infections = more likely to give you a cold
EBV, mycoplasma infections
low transferrin sats but high ferritin causes= ?
alcohol XS,
inflammation, liver disease
CKD,
malignancy
what type of drugs can be given in pts who are not tolerant of chemo and stem cell transplant?
thalidomide
bortezomib = proteasome inhibitor
factor 5 leiden resistance = describe how factor 5 and others are affected
factor 5 disease= slow inactivation of factor v by activated protein C
GOSRELIN MOA
gnrh agonist,, LHRH analogue
what to give to von willebrand pt going for tooth extraction
give desmopressin
avoid factor 8 conc bc risk of transfusion infection
