Haematology Flashcards
What treatments can you give for HITS?
Direct thrombin inhibitors - bivalirudin, argatroban
Danaparoid
Fondaparinux
How do you diagnose progressive myeloma (symptomatic)? 2 criteria required.
Paraprotein in serum +/- urine
Evidence of end organ damage
How do you diagnose asymptomatic myeloma? 2 criteria required.
Serum paraprotein >30g/L
+/- bone marrow clonal plasma cells >10%
What are the staging criteria for multiple myeloma?
Stage I - B2-microglobulin < 3.5, albumin >35
Stage III - B2-microglobulin > 5.5, albumin any level
Which translocations confer a poorer prognosis in multiple myeloma?
T(4;14)
T(14;16)
Which translocation confers a more favourable prognosis in multiple myeloma?
T(11;14)
How is multiple myeloma treated in non-transplant candidates?
Lenalidomide + dexamethasone
Then bortezomib and melphalan/cyclophosphamide and prednisone
How is multiple myeloma treated in transplant candidates (>70)?
Induction: chemo + bortezomib + dexamethasone for 3-4 months
Then melphalan + SCT
Maintenance is steroids + thalidomide/lenalidomide
How is multiple myeloma treated in transplant candidates (<70)?
Bortezomib induction
Auto SCT
Maintenance: thalidomide/lenalidomide +/- prednisolone + bisphosphonate
What is the most common type of myeloma?
IgG in 50-65% of cases
Followed by IgA (20-25%, do less well), light chain (15-20%) and then IgM/IgD at approx 1-2%
2-3% non-secretory
Which type of patients are more likely to progress from MGUS to myeloma? 3 considerations.
IgA paraprotein more likely to progress than IgG
If serum free light chain ratio is abnormal, more likely to progress
High levels of paraprotein e.g. >15g/L
What are treatment criteria for treatment of MM? 3 criteria.
Raised calcium, renal impairment, anaemia and bone pain AND
2 lesions on MRI/low dose CT scan OR
Plasma cell >60 in bone marrow OR
SFLC ratio >100
What are typical side effects of thalidomide? Name 3.
Constipation
Thrombosis
Permanent neuropathy
Which are the highest yield areas to biopsy for AL amyloidosis?
Kidney/liver biopsy (>90%)
Fat biopsy (70-80%)
Rectal (50-70%)
BM looking at blood vessel walls (50-55%)
BM + fat = >90%
Which cytogenetic factors confer a poor prognosis in AML? Name 3.
Deletion chromosome 7q
Inversion q3 or t(3;3)
Multiple abnormalities simultaneously
Which cytogenetic factors confer a favourable prognosis in AML? Name 3.
T(15;17) - M3
Inversion q16 (monocytic, with eosinophilia)
T(8;21) (often M2)
What is Venetoclax and what can it be used in? Not sure if this will be tested.
BCL2 inhibitor
Being trialled in CLL/LG NHL (for CLL, good results with obinutuzumab)
Shows promise for NPM1 patients
In which type of AML are patients more likely to have soft tissue involvement, particularly skin and gums?
Monocytic (M4-5)
ATRA is used in the treatment of APML. What is ATRA syndrome, and how is it treated?
Release of cytokines, causing drop in O2/ARDS
Treated with dexamethasone
What are the current treatment options available for APML? Name 2.
ATRA
Arsenic - superior to ATRA/chemo for upfront treatment
- SE includes Torsades de Points
What does T-cell ALL frequently present with?
Mediastinal involvement.
Name 5 poor prognostic features in ALL.
Philadelphia chromosome t(9;22) positive
BCR-ABL fusion gene positive
High WCC
Extra-medullary disease - CNS, testes
Age - poorer in older adults, and in infants
What is the treatment course for ALL?
1 month induction - anthra/vincristine/steroid/asparaginase
1 month consolidation - cyclophosphamide/Ara-C/etoposide
1 month intensification - HD MTX or cranial XRT
Re-induction 1 month and then re-consolidation 1 month
Oral maintenance to complete 2-3 year treatment
In which patients is allogenic transplant indicated for ALL? Name 2 groups.
Adult patients in 1st complete remission if high risk
If <35 (following 1st complete remission)
Which cytogenetic factors would you expect to see in CML?
Philadelphia chromosome positive
BCR-ABL translocation
In patients that are imatinib resistant/intolerant for CML, what are the other treatments you could consider, and what are their side effects? Name 3.
Nilotinib - SE CV, prolonged QTc
Dasatinib - SE pleural effusions
Ponatinib - SE CV (recommended in some mutations e.g. T3151)
What cytogenetic factors help to differentiate mantle cell lymphoma from CLL? Name 2.
CD5 +ve
CD23 -ve
What is Binet staging for CLL?
Stage A - <3 LN groups and Hb and platelets >100
Stage B - 3 or more sites involved, Hb and platelets >100
Stage C - Hb <100 or platelets <100
Stage predicts outcome; stage A only requires treatment if systemic symptoms
What is standard treatment for CLL?
Rituximab + fludarabine/obinutuzumab + cyclophosphamide
For p17-/p53 patients - ibrutinib in addition to above
What are typical side effects of ibrutinib? Name 3.
Atrial fibrillation
Diarrhoea
Platelet dysfunction
How does hairy cell leukaemia typically present? Name 3 features.
Pancytopenia
Splenomegaly
No lymph nodes
What markers would you expect to see in hairy cell leukaemia? Name 4.
CD19 and CD 20 (B-cell)
CD25 (IL-2 receptor)
CD103
How is hairy cell leukaemia treated?
Single 7 day course of cladrabine
If BRAF +ve - consider vemurafenib
What are the 4 “classical” subtypes of Hodgkin’s lymphoma?
Nodular sclerosing - most common
Mixed cellularity
Lymphocyte rich - best prognosis
Lymphocyte depleted
What is Ann Arbor staging for Hodgkin lymphoma?
Stage I - single lymph node group
Stage II - two separate lymph nodes or organ both confined to one side of the diaphragm
Stage III - both sides of the diaphragm
Stage IV - extra-lymphatic organ involvement
B symptoms - weight loss of >10% or night sweats
How do you treat Hodgkin’s lymphoma?
Earlier stage - ABVD (adriamycin, bleomycin, vinblastine, dacarbazine)
Later - BEACOPP (bleo, etoposide, adria, cyclo, vincristine, procarbazine, pred)
Brentuximab is a recent anti-CD30; checkpoint inhibitors under consideration
Which translocation if involved in the diagnosis of Burkitt’s lymphoma?
T(14;18) - c-Myc
What are the two different types of cutaneous T-cell lymphoma? Name 2
Mycosis fungoides - initially flat eczematous lesions becoming raised
Sezary syndrome - related to mycosis fungoides, but involving all the skin with blood involvement
How do you treat cutaneous T-cell lymphoma?
Photopheresis
Alemtuzumab (anti-CD52)
How is myelofibrosis treated?
JAK2 inhibitors
Ruxolitinib can be given to both JAK2 +ve and -ve patients
Name 5 complications of polycythaemia rubra Vera.
Aqua-pruritis
Thrombosis
Bleeding
Myelofibrosis
AML
How is PRV treated?
Aspirin - reduced risk of thrombosis
Venesection - best if neuts/plts = N
Hydroxyurea if high counts
Keep PCV <0.45
In myeloproliferative neoplasms, what confers a poor prognosis?
Being “triple negative” - JAK2, calreticulin and MPL
What do you look for in terms of surface markers to diagnosis paroxysmal nocturnal haemoglobinuria?
LACK of CD55 and CD59 on RBCs/neutrophils/monocytes
What is the pathophysiology of paroxysmal nocturnal haemoglobinuria?
Clone lacking GPI anchor proteins on surface membranes of RBC/neutrophils, increased susceptibility to complement
NO depletion in microcirculation
How in PNH treated?
Eculizumab (anti-C5)
How do the different levels of gene deletion present in alpha thalassaemia?
One gene deletion - silent carrier (aa/a or aa/a-)
Two gene deletion - alpha trait (a-/a- or aa/—)
Three gene deletion - HbH disease (a-/—)
Four gene deletion - Barts hydros fetalis (—/—)
How does beta thalassaemia manifest itself?
Increased HbA2 (a2d2)
Trait (heterozygous) - asymptomatic, mild anaemia, MCV <72, HbA2 3.6% - 5% (normally <3.5%)
Major - Hb 30-70, MCV 50-70, expanded bone marrow and bony deformities, hyposplenism, iron overload resulting in cardiac failure and arrhythmias, delayed growth and puberty, transfusion dependent
Name 5 features you would expect to see in autoimmune haemolytic anaemia.
Anaemia
Reticulocytes
Bilirubin (unconjugated)
Low haptoglobin (used up removing excess Hb)
Direct antiglobulin test (i.e. Coomb’s)
In hereditary spherocytosis, in which proteins would you expect mutations to occur? Name 4.
Ankyrin
Band 3
Spectrum
Protein 4.2
What types of cells would you expect to see in G6PD deficiency? Name 3.
Bite cells
Keratocytes
Heinz bodies
What is the pathophysiology of G6PD?
Hydrogen peroxide is normally converted to water and oxygen
Lack of G6PD means hydrogen peroxide results in oxidant radicals,which damage Hb and membrane, leading to formation of Heinz bodies
Name 5 drugs/drug groups that are implicated in drug-induced oxidative haemolysis.
Sulphonamides
Dapsone
Antimalarials
Co-trimoxazole
Naphthalene
Name 3 things that can result in cold agglutinins.
EBV
Mycoplasma
Lymphoma
Cold agglutinin disease (cold agglutinins + haemolysis) are strongly associated with lymphoma.
Name 5 causes of acquired von Willebrand syndrome.
Aortic stenosis and LV assist devices
Essential thrombocythaemia - vWF consumed by very high platelet numbers
Immune-mediated
Malignancy
Hypothyroidism
What are the three different types of Von Willebrand disease?
Type 1 - reduced level of VWF protein (<30 IU/dL or <0.3 IU/mL)
Type 2 - reduced function
Type 3 - very low levels (both alleles affected)
Which blood type is more likely to result in lower levels of VWF?
Blood type O
Name 2 ways of measuring antiphospholipid antibodies.
- Lupus anticoagulant testing
2. Enzyme immunoassay (anticardiolipin abs, b2-glycoprotein I antibodies)
Name 5 drugs/drug groups that are implicated in drug-induced oxidative haemolysis.
Sulphonamides
Dapsone
Antimalarials
Co-trimoxazole
Naphthalene
Name 3 things that can result in cold agglutinins.
EBV
Mycoplasma
Lymphoma
Cold agglutinin disease (cold agglutinins + haemolysis) are strongly associated with lymphoma.
Name 5 causes of acquired von Willebrand syndrome.
Aortic stenosis and LV assist devices
Essential thrombocythaemia - vWF consumed by very high platelet numbers
Immune-mediated
Malignancy
Hypothyroidism
What are the three different types of Von Willebrand disease?
Type 1 - reduced level of VWF protein (<30 IU/dL or <0.3 IU/mL)
Type 2 - reduced function
Type 3 - very low levels (both alleles affected)
Which blood type is more likely to result in lower levels of VWF?
Blood type O
Name 2 ways of measuring antiphospholipid antibodies.
- Lupus anticoagulant testing
- Enzyme immunoassay (anticardiolipin abs, b2-glycoprotein I antibodies)
B2-glycoprotein is the major pathogenic antibody
Name 2 ways of testing of for lupus anticoagulant.
Sensitive APTT - antiphospholipid Abs prolong APTT-type test
Dilute Russell’s viper venom test (dRVVT) - venom activates Factor X - blocked by antiphospholipid antibodies
Positivity for >1 test is associated with thrombosis
What is a mixing study, and how is it interpreted?
Half a normal plasma pool is added to patient’s blood sample
50% of coagulation factors are sufficient for normal clotting times
There, if a factor deficiency is present, the prolonged APTT will correct
However, if the sample contains an inhibitor (e.g. heparin, antiphospholipid ab etc.) the admixed plasma will be inhibited
Name 3 major defects and 2 minor defects that result in familial thrombophilia.
Major 3 (heterozygotes affected) Antithrombin deficiency Protein C deficiency Protein S deficiency
Minor 2
Factor V Leiden
Prothrombin variant
Which factors are affected in haemophilia A and B respectively?
Haemophilia A - Factor VIII
Haemophilia B - Factor XI
How is haemophilia A treated? Name 3 methods.
Activated prothrombin complex concentrate
Recombinant factor VIIa (Novoseven) - bypassing need for factor VIII
Emicizumab - a bispecific antibody that mimics FVIII activity by binding to both FIX and X - used to treat patients with haemophilia A with developed inhibitors to FVIII
Name 4 conditions that can cause an isolated bilirubin elevation.
Gilbert’s syndrome (uridine diphosphoglucuronate-glucuronosyltransferase 1A1)
Crigler-Najjar Syndrome (unconjugated)
Rotor and Dubin-Johnson syndromes (conjugated)
Haemolysis (unconjugated)
