Dunedin- Haematology Flashcards
Describe anticoagulation and their targets
How to manage elevated INR in adult patients
Describe NOAC, there target, and potent drug interactions
Describe the effect of anticoagulation on PT and aPTT
rivaroxoban increases PT alot
Describe warfarin bridging before surgery:
*stop warfarin 5 days prior to surgery
*4 days prior check INR and start enoxaparen when INR is <2
*cease enoxaparen 24 hours before procedure
What is acquired haemophilia A?
-Development of a clotting factor deficiency that was not present at birth
- usually due to an autoantibody to factor VIII
- usually present with significant bleeding into skin, muscles, soft tissues and mucous membranes
Lab
- prolonged APTT which does not correct with mixing study
- low level of factor VIII + inhibitor present
What is the management of acquired factor VIII inhibitors?
*recombinant activated Factor VII
*activated prothrombin complex concentrates (FEIBA-factor VIII inhibitor bypassing activity)
Immunosuppression: cyclophosphamide, rituximab, IVIG
What is the MOA of tranxemic acid?
Binds to plasminogen and prevents the breakdown of fibrin
Management of cerebral vein thrombosis, splanchnic vein thrombosis
Cerebral vein thrombosis –> 3-6 months unless unprovoked in which case 6-12 months
What is the MOA, eg and S/E of alkylating agents
Prevent cell division cross- linking strands of DNA–> prevent DNA synthesis–> programmed cell death
eg chlorambucil, cyclophosphamide, melphalan
S/E bone marrow depression, nausea and vomiting, late cancer
What is the MOA, e.g, S/E of antimetabolites
MOA: mimic normal cell components (in S phase) –>inhibit DNA replication
E.g folate methotrexate, pyrimidine: cytarabine
S/E: mucositis, bone marrow suppression
What is the MOA, e.g, S/E of anthracyclines
MOA: Many: free-radical formation, lipid peroxidation, direct membrane effects, enzyme interactions
Examples:
* Daunarubicin, Idarubicin,
doxorubicin
Side effects:
* Cardiotoxicity,
myelosuppression, alopecia
What is the MOA, e.g, S/E of topoisomerase II inhibitor
MOA: inhibits enzyme that manages the coiling of DNA –> accumulation
E.g. etoposide
S/E: diarrhoea, mucosal, nausea
What is the MOA of mitotic inhibitors, e.g, S/E
Mechanism: blocks microtubule formation –> prevents formation of mitotic spindle
E.g Vincristine
S/E: neurotoxicity, myelosuppression
What is the MOA, E.g, S/E of BCL inhibitor
MOA: BCL-2 proteins are pro- an anti- apoptotic proteins that, in
cancer cells, are over expressed
E.g. Venetoclax
S/E TLS, neutropenia
What is the MOA, E.g S/E of PL3K inhibitors?
MOA: PI3K/AKT/mTOR pathway is part of a signalling pathway for growth control, metabolism, translation initiation
Eg: idalalisib
S/E Autoimmune dysfunction, skin
toxicity, hypertension,
hyperglycaemia
What is the MOA of TKI inhibitors
Dont need mutation for it to work
Mechanism: Binds to BCR-ABL1 of oncoprotein BCR- ABL1
Examples: Imatanib, dasatinib, Nilotinib
S/E Hypertension,
diarrheoa, LV
dysfunction, QT
prolongation
What is the MOA of proteasome inhibitors?
MOA: Proteosomes are structures
in cells that remove mis-
folded proteins and destroy
them. Blocking this causes
cell death
Examples: Bortezomib
S/E Peripheral neuropathy, Nausea, vomitting
Describe the MOA of monoclonal antibodies
MOA- cross-linking surface antigen –> cell death
Describe the lab results of Tumour Lysis syndrome
*Increased uric
acid
*Increased
potassium
*Increased
phosphate
*Decreased
calcium
What is the management of TLS
hydration
allopurinol –> reduces formation of new uric acid
Rasburicase –> converts uric acid to allantoin (readily excreted), rapidly decreases uric acid. therefore can deal with uric acid that is already formed
What are the most common indications for stem cell transplant
Autologous:
Multiple myeloma, non-hodgkins lymphoma, Hodgkins lymphoma
Allogenic
- AML, ALL, myelodysplastic syndrome, non-hodgkin lymphoma, Myeloproliferative neoplasms, severe aplastic anaemia
- BM failure, immunodeficiency (SCID), autoimmune disease, bone marrow disorders (haemoglobinopathies, thalassaemias, haemophilia)
What problems arise if there is an issue with matching donor and recipient
if donor cells attack body –> GVHD
if host cells attack donor cell –> graft rejection
MHC 1 and 2
Class 1:
- HLA-A, B-, C
- present on ALL cells
Class 2:
-HLA-DR, DQ, and DP, DM DO
- only on immune antigen presenting cells e.g dendritic cells, b cells, monocytes
Describe complications of allogenic transplant
What is CAR-T cell therapy?
Chimeric antigen receptor T cell
take patients T-cells and re-program them and then give it back
What are indications for CAR-T cell therapy
1) Relapsed refractory acute lymphoblastic leukaemia (ALL)
2) relapsed/refractory (R/R) DLBCL after failure of at least 2 prior line of therapy
3) R/R mantle cell lymphoma, after failure of therapy with a Bruton’s tyrosine kinase (BTK) inhibitor
What are complications of CAR-T cell therapy?
Cytokine release syndrome (treatment symptomatic, tociluzimab, dexamethasone, methylprednisone)
- high fever and chills
- dyspnoea
- severe N/V and/or diarrhoea
- feeling dizzy or lightheaded
- headaches
- tachycardia
- fatigue
- muscle and/or joint pain
Neurotoxicity (dexamethasone, methylprednisone)
- headache
- confusion/agitation
- seizures
- dysphagia
- loss of balance
Describe pathogenesis of cytokine storm
What is the most common lymphoma? and how is it managed
diffuse large B cell lymphoma
biopsy: mixture of large and small cells in a diffuse pattern with loss of architecture
treatment: R-CHOP
- rituximab
- cyclophosphamide
- doxorubicin (hydroxydaunorubicin)
- vincristine (oncovin)
- prednisone
+/- radiotherapy
What are examples of myeloproliferative neoplasms and lab studies
- polycythaemia vera
- essential thrombocytosis
- myelofibrosis
- CML
PLETHORA
Lab studies:
- BCR:ABL for CML
- JAK2, Cal-R, MPL
Biopsy: hypercellular, fibrosis on reticulin stain
Myeloproliferative disease management?
CML –> TKI e.g imatinib, hydroxyurea
Polycythaemia –> phlebotomy, hydroxyurea
Essentail thrombocytosis –> hydroxyurea
Myelofibrosis
- JAK1/JAK2 –> ruxolitinib
- allogenic bone marrow transplant
CLL investigations
*FBC: smudge/ smear cells
*Flow cytometry: dim surface immunoglobulin, CD5, CD19, CD20, and CD23
*FISH: del(13q14), del (11a), and del (17p)
CLL treatment
1) watch and wait
2) treat if anaemia or thrombocytopenia, painful lymphadenopathy, B symptoms, lymphocyte doubling time, autoimmune haemolytic anaemia or ITP
What are indications of treatment of multiple myeloma
Indications for treatment
* >60% plasma cells
* Serum free light chains >100
*MRI lesions >5mm
* Hypercalcaemia
*Renal failure
* Anaemia
*Lytic lesions
Multiple myeloma treatment
Chemotherapy: bortezomib plus cyclophosphamide plus dexamethasone (VCD); bortezomib plus ow doxorubicin plus dexamethasone (PAD); and vincristine plus doxorubicin plus dexamethasone (VAD).
Non-chemotherapy regimens: Thalidomide/lenalidomide and dexamethasone, carfilzomib/bortezomib; daratumumab
Autologous stem cell transplant
What are aeur rods seen in?
AML particularly APML
Genetic abnormalities in AML
*t(8;21)(q22;q22),
* inv(16)(p13;q22),
* t(16;16)(p13;q22)
Describe the treatment approach for myelodysplastic syndrome
What are investigations for follicular lymphoma
Biopsy:
* Nodular growth pattern
* Amount of centroblasts determine tumour grade
* Staining:, CD20 (or CD19), CD10, and BCL-6 and are negative for CD5 and CD23, BCL-2 (>85%)
Molecular genetics: genetics: t(14;18)
What is the clinical presentation of follicular lymphoma
- painful adenopathy
- may grow spontaneously grown and regress
-usually asymptomatic otherwise