Haematology Flashcards
MoA of venetoclax
Bcl2 inhibitor (which is anti-apoptotic –> restores apoptosis)
A/E of Venetoclax
TLS
MoA of ibrutinib
Blocks Brutons TKI
A/E of ibrutinib
AF
Indication for venetoclax
CLL refractor to FCR chemotherapy
Treatment of MDS with 5q deletion
Lenalidomide
High risk MDS treatment strategies
HSCT eligible? - transplant
Not transplant eligible - azacitidine
MoA of idelalisib and indication
Pl3 kinase inhibitor
Refractory CLL
anti CD33?
GEmtuzumab
Add to CD33 +ve AML
What to add for FLT3 positive AML to 7+3 induction
Add midostaurin
2 main A/E of CAR-T cell
CRS
ICANS
A/E of idelalisib
Increased risk opportunistic infections
Test for Fanconi’s anaemia
Chromosome fragility studies
CAL-R mutation associated with what FBE abnormality
Elevated Plt
- ET, prefibrotic PMF
Driver mutations for myeloproliferative disorders
JAK-2 - most common
CAL-R
MPL
Highest myeloproliferative at risk of transformation to AML
CML (if untreated)
Otherwise PMF
PRV High risk
How does this affect treatment?
High risk = age > 60, thrombosis, or high WCC/Plt
Add hydroxyurea to phlebotomy aiming < 0.45 and aspirin
High risk ET
Age > 60, thrombosis, Plt > 1500, symptomatic splenomegaly
Add hydroxyurea to aspirin
Management of PRV
Low risk - aspirin and venesection aiming HCT < 0.45
High risk - add hydroxyurea
Tear drop cells
Myelofibrosis
Dry tap
Myelofibrosis
Ruxolitinib MoA
JAk-2 inhibitor
Benefits of ruxolitinib
Improves splenomegaly
Improves constitutional symptoms
A/E of ruxolitinib
Cytopaenias
Increased ifnection risk
Pitted erythrocytes
Hyposplenism
Howell Jolly Bodies
Hyposplenism
Features of hyposplenisms, should be concerned for?
OPSI - overwhelming post splenectomy infection
Functions of spleen (3)
White pulp - 2nd lymphoid organ
Red pulp - filtration (RBC’s, deformed blood cells, bacteria)
Haematopoiesis - thalassaemia and PMF
Causes of hyposplenism
Anything that can acuse damage to spleen
- SCT, hSCT
- Autoimmune
- Hepatic - ALD, cirrhosis
- Splenic vasculature changes
Features of leukaemoid reaction
Toxic granulation
Toxic vacuolation
Dohle bodies - small blue inclusions
B cell markers
CD19
CD20
Kappy/lambda
T cell markers
CD3
CD4
CD5
CD8
Stem cell marker
CD34
Inheritance vWD
Autosomal dominant
Syndrome that has acquired vWD
Heyde syndrome - AS and recurrent GI bleeds
4T’s HITS
Thrombocytopaenia - Plt drop >50%, not < 20
Timin - D5-10
Thrombus
No other cause
Interactions of Xa inhibitors
P-glycoprotien and CYP3A4
Can’t use with inhibitors - posaconazole, ketaconazole, ritonavir
Inactivated by inducers
Interactions of dabigatran
Only metabolised by P-glycoprotein
Thrombin time
- What is it
- Use
Measures final step - fibrinogen to fibrin
Useful for heparin effect:
- Elevated TT but normal reptilase time (insensitive to effects of heparin)
A globin chain - chromsome
16
B globin chain - chromosome
11
Variants of B globins that are due to 1 aminoacid substitution
HbS
HbE
HbC
Beta tetramers
HbH
Gamma tetramers
Barts
Erythema nodosum, hilar adenopathy, migratory polyarthralgia, fever
Lofgren syndrome = sarcoid
Mutton fat keratitis
Opthamic sarcoid
Lupus pernio
Indurated plaques with telangiectasias on central face/neck
White cells in donor transfusion product cause?
Febrile non-haemolytic transfusion reaction
Ab’s in donor transfusion reacting with white cells in recipient cause?
TRALI
Mechanism to minimise febrile non-haemolytic reaction
Leucodepletion
Mechanism to prevent transfusion GvHD
Irradiation
Blood product with highest risk of infection/bacterial contamination
Platelets - stored at room temperature
Hodgkins immunophenotype
CD15
CD30
Anti-CD30
Brentuximab
Complement mediate haemolysis
- other name
- type
PNH
Intravascular
FEatures of intravascular haemolysis
Free Hb
Urine free Hb
Urine haemosiderin
Chronic haemolysis - Rx to prevent aplastic anaemia
Folate
Favourable for AML
Mutated NPM1
Mutated CEBPA
Unfavourable for AML
FLT3-ITD mutated
Wild type NPM1
APLS
Lab criteria
One or more aPL antibodies 12 weeks apart
Anticardiolipin - IgG or IgM positive 12 weeks apart
Beta 2 glycoprotein - IgG or IgM positive 12 weeks apart
Lupus anticoagulant - 12 weeks apart
APLS clinical criteria
- Vascular
1 or more deep vein, arterial thrombus
- Superficial vein does not count
APLS pregnancy morbidity criteria
1 or more fetal loss > 10 weeks
3 or more fetal loss < 10 weeks
Premature birth due to pre-eclampsia, eclampsia or placental insufficiency
Smouldering myeloma criteria
M protein > 30
OR
>10% BM plasma cells
No end organ damage
MGUS criteria
M protein < 30
BM plasma cells < 10%
No end organ damage
Acute proximal DVT/PE management
3 months (for provoked/unprovoked)
Assess at 3 months chance of recurrence
When to continue anticoagulation > 3 months for DVT/PE
> 2 DVT
APLS
Active cancer
Distal (beyond popliteal) provoked DVT - length of anticoagulation
6 weeks
HbS present
No HbA
2 options?
Normal HbA2 - Beta S and Beta S
Increased HbA2 - Beta S and Beta 0
HbS present
HbA detected
2 options?
High HbA - Beta S and normal beta (trait)
High HbA2 - Beta S and Beta +
Protamine MoA
-Heparin
- LMWH
Heparin - binds heparin, forms stable salt and fully nullifies drug
LWMH - incompletely reverses anti Xa activity of LMWH
Mechanism of reduced haptoglobin in haemolytic anaemia and how cleared
Haptoglobin-Hb dimers clared by liver
Protective genetic factors for Sickle cell
Hb F levels - prevent HbS polymerisation
Alpha thalassaemia - indirectly inhibits HbS polymerisation
Gene high prevalence African people that is protective against Sickle cell crises
PKLR - pyruvate kinase
Medication increases Hb F lvels
Hydroxyurea
Medication prevents polymerisation of Hb S
Voxelotor
Anti Xa assay
- Useful for?
LMWH monitoring
Heparin monitoring with baseline high apTT
Anti X chromogenic assay
- Useful for?
Warfarin monitoring with baseline high apTT/INR
Anaemia chronic disease vs IDA + ACD
ACD - Normocytic, high ferritin, low tsats
IDA and ACD - microcytic, high/normal ferritin, low tsats
What does AT III inactivate?
IXa, Xa, XIa, XIIa
what does protein C/S inactivate?
Factor V and VIIIa
These are needed to activate thrombin
–> having lack of protein C/S means unreguated thrombin formation
NAPDH deficiency in RBC’s?
2nd to ?
Significance
G6PD deficiency (this enzyme makes NADP –> NADPH)
Lack of NADPH means more susceptible to oxidative injury
Marrow stimulating agent used in aplastic anaemia
Eltrombopag
THrombopoeitn made where?
Liver
Low (but not absent) reticulocyte count
Folate/B12/Fe/Copper deficiency
2nd causes of hypogammaglobulinaemia
- broad categories and causes
Reduce production
- drugs - steroid, rituximab
- malignancy - CLL, lymphoma, MM
Increased loss
- protein losing enteropathy
- Nephrotic syndrome
- Burns
Mutation of JAK2 in myeloproliferative disorders - what effect?
Persistent active transcription and replication of cells
