Flashcards
Haematology 3
Cards in this deck (200)
- 1when do we use warfarin?-for anticoagulation for when DOAC's are unproven or unsafe
-e.g. patients with mechanical valves, antiphospholipid syndrome or chronic kidney disease
-remember Rivar has a small renal metabolism - 2discuss warfarin's pharmacology- has a plasma half life of 36 hours
- metabolised by liver
- many drug interactions and large inter-interval dose
- causes an increased PT and APTT
-typical dose is 2-8 mg od - 3how is warfarin monitored in patients?using INR testing (patient PT/control PT)
- typical range is 2-3 - 4what major pharmacological problem does warfarin have?- it has a narrow therapeutic window
- 5briefly explain INR- an INR means we have a clotting time the same as that of a normal control
-an INR of 2 means it takes twice as long
-therefore if on anticoagulation, want to minimise the INR (warfarin) so the person doesn't bleed. - 6what is the management of a person on warfarin who is bleeding-give vitamin K1 1-3 mg po or iv if INR>8.0 for mild bleeding (8 times as long as normal)
- or factor K concentrate plus vit K1 for severe bleeding - 7before surgery, when should warfarin be stopped/restarted?- if a low thrombosis risk, stop warfarin for 5 days, restart day after surgery and give thromboprophylaxis dose of LMWH
-if a high risk, stop warfarin 5 days before, restart day after surgery BUT make sure you use LMWH as a bridge before surgery as soon as warfarin omitted 5 days before - 8essentially, what is the purpose of transfusion?- replacement of substances in the recipient from donated blood
-cells
-plasma proteins - 9approximately what proportion of preventable deaths are there from lack of blood transfusions worldwide?- around 25%
- 10what are the risks of transfusion?- unavailable blood (normally not a problem In UK)
- transfusion transmitted infections (less common)
- immunological reactions (normally from recipients Ig's)
- overloading (through iron overload/fluid overload) - 11iron overload causes what condition? - how do we prevent this?- haemochromatosis
-chelate the patient e.g. with Deferasirox - 12what is the process of selecting blood donor's?- normally healthy volunteer's
- aged 17-70 (if regular donor, no age limit)
- medically assessed- history, medication, travel (infections)
- fingerprik Hb- women Hb>125, men Hb >135 g/l (no anaemia) - 13give an overview of apheresis donation- these are normally regular donors
- selective removal of the component required (normally platelet donations)
- up to 3 doses of platelets/ donor visited - 14how might Apheresis (selective removal of blood component) be used therapeutically?- might be used in leukaemia (remove white cells)
- to exchange plasma in those who require clotting factors
- red cell replacement (such as in sickle-cell) - 15all blood donations are subject to testing for what?- ABO group
- RhD type
- HIV 1 + 2 antibodies
- hep BsAg and PCR
-hep c antibody/RNA PCR
- Syphilis antibody
-Hep E - 16only selected donations are subject to what tests?- CMV antibody
- Hep E RNA
- HTLV I antibody
- Malaria Ab
- West Nile Virus
- T Cruzi Ab
-HLA type/ HPA type
-extended red cell phenotype
-sickle cell screening - 17what occurs during processing of blood samples?- leukocyte depletion
- split into red cells, platelets, plasma for use as FFP/ cryoprecipitate
-platelets sampled for bacterial testing
- other special processes such as irradiation, washing and hyperconcentration - 18what is the main component of cryoprecipitate?- Fibrinogen
- 19what is the difficulty in transfusing granulocytes-they only live for approx. 24 hours
- 20what is the 'shelf-life' of RBC's?- 35 days at 4 degrees
- 21how quickly should RBC's be transfused after removal from fridge?- <4 hours after
- 22what solution is used to help cells to survive (RBC's)?- additive solution
-glucose
( 280ml plus/minus 60ml)
- 0.5/0.7 hct - 23what are the uses of RBC samples?- to correct anaemia's
-to account for blood loss (major) - 24how are platelets processed?- they are initially pooled (4-6 donors)
- or subject to aphaeresis from a single donor
- stored at 22celcius for 7 days
- - 25what are the uses of platelets?- in thrombocytopenia
- bleeding with low plt
- prevention of bleeding in very low plt patients
-before procedures that might induce large bleeds - 26discuss the storage and uses of FFP- frozen to -30C
- can be stored for 2 years
- to replace clotting factors if patient bleeding - 27what process is used to inactivate viruses in FFP and who are the groups who benefit?-using methylene blue/solvent detergent (octaplas)
- normally those who need a very large plasma infusion OR children - 28what is cryoprecipitate?- a precipitate that forms when FFP is thawed
-for fibrinogen replacement - 29what are the fractionated products from blood donations?- used to get specific proteins
- these are pooled concentrates from many donors
- examples include: albumin, clotting factors and immunoglobulins - 30why is there no threshold for transfusion?- if the person is functionally unaffected- transfusion unnecessary.
- therefore, only give a transfusion if functionally important to do so - 31explain the concept of a transfusion threshold, given the information above- a threshold of transfusion, which, when met, is the maximum level of transfusion that should be given
-rememeber, only give transfusion is functionally important AND remember NO TRANSFUSION IS THE SAFEST TRANSFUSION
-give the minimum transfusion to get above the threshold - 32if the patient is asymptomatic, what should you do if transfusing?-STOP (obviously)
- 33based on an RCT in North America- what group of patients did best in red cell transfusions-two sets of patients- one with a restrictive threshold, one with a liberal threshold.
- the ones with a restrictive threshold for transfusion more likely to survive
- therefore should recommend a restrictive threshold of transfusion - 34for most people, what is the best (most restrictive) threshold for red cell transfusion?- around 70g/L
- 35why might there be a higher threshold for red cell transfusion?- certain conditions might necessitate a higher oxygen carrying capacity such as radiotherapy
- made on a condition dependent basis - 36image from lecture slide to demonstrate above flashcard
- 37look at the table overleaf discussing the indications for a plasma tranfusion
- 38summary of indications for platelet transfusion
- 39fundamentally, why are blood cells immunological substances ?- they have antigens
- 40what surface antigens do RBC's present?-ABO and others
- 41what antigens do white cells have?- HLA classes i and ii
- Human neutrophil antigens - 42what antigens do platelets contain?- HLA class i
-human platelet antigens (HPA) - 43what is an antigen?- a protein that can elicit an immune response
- 44how then, does the ABO system work simply?- foreign antigens can be recognised on blood cells
-can elicit an immune response - 45what two general groups of incompatibility of transfusion are there?- major and minor
- 46describe major incompatibility- wherein the hosts antibodies (recipient) has antibodies against the transfused blood
-this tends to provide more clinical problems as it's a larger volume of antibodies in the recipient than the donor - 47describe minor incompatibilitythe transfused blood has antibodies against the recipients
-e.g. group O blood is transfused to group A patient - 48all red cells in a human contain which antigen?- the H antigen
-therefore, since the O group only contain the H antigen, this is group O
-universal group - 49how then, do we get A and B groups?- dependent on the inheritance of glycosyltransferases
-GST A converts H to A
GST B converts H to B - 50what happens in an adverse reaction to blood transfusion?- tachycardia
-temperature goes up
- haemolysis
- fatal reaction to 50ml blood - 51give some features of ABO antibodies- they are naturally occurring, developing without the need for exposure to blood
- they're present in almost all individuals
- can cause acute transfusion reactions, such as complement binding - 52what antibodies are formed in the O blood type?- anti-A and Anti B
- therefore they should only be transfused with group O blood (no antigens for A/B) - 53what antibodies are formed in the A blood group?- Anti B
-therefore transfuse A or O blood ( want to avoid B antigen) - 54what antibodies are formed in the B blood group?- anti- A
-therefore give B or O blood (want to avoid A antigen) - 55what antibodies are formed in the ABO group?-none
-can therefore transfuse AB, A, B and O - 56what proportion of people are blood group: -O -A -B -AB-44%
-42%
-10%
-4% - 57study the table that demonstrates donor plasma compatibility: platelets, FFP and cryoprecipitate
- 58despite their being ABO blood types, there are many other antigens on blood cells that mean their are many more blood groups -how many of these groups exist?->300 blood groups in 35 systems
- 59where can antibodies against other RBC's other than ABO come from?- from the foetus during pregnancy
- previous blood transfusion - 60these antibodies against RBC antigens can cause ?- immediate haemolysis (rare)
- delayed haemolysis (more common)
- haemolytic disease of the newborn - 61describe haemolytic disease of the newborn- mother's IgG crosses the placenta
-targets the IgG target antigen in the foetus.
- a second pregnancy could cause IgG attack of the foetus red blood cells, causing haemolysis (this is called fetomaternal pregnancy haemorrhage)
-these antibodies are against the RhD antigen blood group - 62how can we help to prevent haemolytic disease of the newborn?- by transfusing RhD negative blood to women
-Anti D immunoglobulin to prevent antibody formation
- treatment of foetus/ baby with RhD negative transfusion - 63what is post transfusion purpura? -example of a platelet transfusion/antibody reaction- a adverse reaction to platelet transfusion when the body produces alloantibodies against the introduced platelets antigens
-frequently happens in people lacking the HLA-1a antigen
-person creates antibodies to the HLA-1a and causes destruction of the platelets - 64what other condition has a similar cause (HLA-1a and HLA-5b)?- Neonatal thrombocytopaenia (reduced survival)
- 65give a condition in which antibodies attack granulocytes after transfusions- transfusion related lung injury
- 66describe transfusion related lung injury- a reaction of transfused antibodies to HLA class 1 and 2 + human neutrophil antigens
-these antibodies react with neutrophils in the pulmonary vasculature
-leads to acute non-cariogenic pulmonary oedema - 67give a reason why antibodies might attack plasma proteins?- during allergy and anaphylaxis
- 68simply, what is graft versus host disease?- wherein the host cells recognise grafted foreign tissue as non-self and attack
-white cells in donated blood attack HLA in the recipient blood - 69what is the prevention for graft versus host disease?- irradiated blood for certain immunosuppressed individuals
-gamma irradiated to kill off organisms prior to transfusion - 70table to show alternatives to transfusion
- 71put simply, what is lymphoma?-a cancer of lymphocytes
- 72broadly, what are the two types of lymphoma?- hodgkin's
-non-hodgkin's - 73what cells are typical findings in Hodgkin's lymphoma?- Reed Sternberg cells
- 74image of blood film with Reed Sternberg cell
- 75what two grades of non-hodgkins lymphoma are there?- high grade
-low grade - 76who is most at risk of non-hodgkin's lymphoma?- generally increased risk with increased age
-seems slightly higher in prevalence in males - 77generally, a high grade non-hodgkin's lymphoma has what type of presentation?- a short history of being unwell
-more fast growing
-but can be cured - 78low grade non-hodgkin's lymphoma presents how?-normally slower growing, can be no symptoms
-can be treated but not usually cured
- treatment is reserved for those with symptoms - 79what clincal presentations are routinely seen in those with non-hodgkin's?- enlarged lymph nodes
-B symptoms- drenching night sweats
-unexplained fevers >38C
-weight loss > 10% in the last 6 months
- fatigue, itching, symptoms relating to cytopanenia's - 80what blood tests should be given and why in patients with non-hodgkin's?- FBC- to check if white count is low but lymphocyte level is high
-renal and liver function tests- these organs are important in metabolising chemotherapy drugs
-LDH and calcium - 81what are the risk factors for non-hodgkin's lymphoma?- poor immune function,
-autoimmune diseases,
-Helicobacter pylori infection,
-hepatitis C,
-obesity,
-Epstein-Barr virus infection - 82what screening/diagnostic tools are used in non-hodgkin's lymphoma?-lymph node biopsies- to identify the site/spread
- staging scan via CT, NCAP, PET scans)- helping to decide best treatment course
-Bone marrow biopsies - 83give examples of the Ann Arbor staging of non-Hodgkins lymphoma-stages 1,2,3 and 4
-followed by either an A or B
- A if no B symptoms
-B if B symptoms - night sweats (drenching), fevers >38C and weight loss of >105 in 6/12 - 84explain stages I, II, III and IV of the Ann Arbor staging of non-hodgkins-stage 1 is involvement of a single node or group of nodes
-stage two is involvement of two sites on the same side on the diaphragm
- stage III is disease on both sides of the diaphragm. May also involve spleen/extranodal disease
-stage IV widespread extra lymphatic involvement (bone, hepatic, splenic, lung, skin) - 85what style of chemotherapy is given to those with non-Hodgkin's lymphoma-RCHOP
R – rituximab (monoclonal Ab)
C – cyclophosphamide
H – doxorubicin (hydroxydaunomycin)
O – vincristine (Oncovin ®)
P – prednisolone (a steroid). - 86RCHOP is given how often? - what is the main risk of RCHOP? -just remember that this is for high grade only- every 3 weeks
- can cause neutropenic sepsis around day 7-10
-increased risk of bacterial infections as we knock down neutrophil count
-important to check this after the first hour of RCHOP therapy - 87in high grade non-hodgkin's lymphoma, patients are given how much RCHOP if they are: 1)stage IA 2) stage IIA-IV1) RCHOP times 4 AND local radiotherapy to site of interest
2) RCHOP time 6-8 cycles with no radiotherapy - 88give some common types of low grade non-hodgkin's lymphoma-follicular lymphoma
-marginal zone lymphoma
-mantle cell lymphoma
-small lymphocytic lymphoma - 89image to demonstrate follicular lymphoma -this is a lymphoma showing follicular patterns - It is positive for the B-cell markers CD10, CD19, CD22, and usually CD20, but almost always negative for CD5.
- 90image to demonstrate marginal zone lymphoma -accounts for 12% of all B cell lymphoma's - most commonly GI tract
- 91how do we manage these kinds of low grade non-hodgkin's lymphoma's?- active monitoring- remember we cannot cure
-radiotherapy
-chemo/monoclonal antibodies/ targeted therapies
-however very important to treat based on symptoms
-if, for example, patients symptoms minor, is it worth making these worse with radiotherapy? - 92what is the distribution of Hodgkins lymphoma?- bimodal
- ages 20-30 get it
-then dip
-then 50-60 get it
-most important group is the 20-30 year olds - 93what feature on a blood film gives away a lymphoma as being Hodgkin's?- Reed Sternberg cells
-almost look binucleate in appearance - 94what system is used for staging Hodgkin's lymphoma?- Ann-Arbor
-same as non-Hodgkin's - 95what treatment is available for those with Hodgkins lymphoma?different to RCHOP
-ABVD
A – doxorubicin (Adriamycin ®)
B – bleomycin
V – vinblastine (Velbe ®)
D – dacarbazine (DTIC). - 96those with stages IA and IIA are given how much ABVD?- 2-4 cycles
-followed by radiation of the initial site - 97patients with stage IB and IIB are given how many round of ABVD?- variable, but common to start with 4-6
-then CT/PET scans are used to determine how many more cycles are needed
-option to give radiotherapy if improvement
-remember that B symptoms are important in treatment - 98those with more developed Hodgkin's are given? NB just to note that these figures are from American guidelines- ABVD at least 6 cycles and then reassessed
- 99what is the 5 year survival rate for those with Hodgkins?->85%
-remember Hodgkins can be cured - 100what common problems occur in those who have received treatment for Hodgkin's?-latent effect of the radiotherapy, leading to a second malignancy of the breast/lung, for example
- heart or lung problems
-these problems are associated with older people/women for breast cancer - 101what is myeloma?- a cancer of plasma cells
- 102briefly, what are plasma cells?- these are a type of white cell that produces antibodies (Ig's) to help to fight infection
- 103quick note, how does complement work?- in essence, binds antibodies attached to foreign antigens (humeral)
- creates a cascade leading to rapid destruction of the cell
-this is why is haemolytic disease of the newborn, IgG causes haemolysis by recruitment of complement - 104neutrophils, leukocytes in general (eosinophils, basophils etc) work how?- through phagocytosis
- 105neutrophils make up what percentage of circulating leukocytes?-50-60%
- 106which type of cell is responsible for much of the inflammatory response?- mast cells
- 107in multiple myeloma, what is the main cause?- plasma cells only producing one type of antibody
-monoclonal paraprotein which is normally not seen in healthy patients
-gives rise to a relapsing and remitting cancer type - 108how do we identify myeloma?-through immunofixation of urine and serum- looking for a monoclonal peak
- bone marrow biopsy - 109examine the immunofixation overleaf -shows an abnormal monoclonal peak
- 110what is monoclonal gammopathy of undetermined significance? (MGUS)- wherein the patient has serum monoclonal paraprotein <30g/L
-clonal bone marrow plasma cells <10%
- absence of end organ damage
-require active monitoring as might develop into myeloma - 111define MGUS?- where an abnormal amount of monoclonal paraprotein (M protein) is found in the serum
-requires monitoring as it develops into myeloma in 1.5% of patients
-remember its still a relatively low amount of gamma - 112study the graph overleaf demonstrating MGUS
- 113what is smouldering myeloma?- the monoclonal population of plasma cells produces M protein
-these cells proliferate to cause MGUS
-more aggressive proliferation= smouldering myeloma
-these patients require constant 6 monthly testing as it can quickly develop into MM - 114what do we see in the serum of someone with smouldering myeloma?- serum monoclonal protein (IgA/IgG) >= 30g/L
- OR urinary monoclonal protein >= 500mg per 24 hours
-AND/OR clonal bone marrow plasma cells 10-60%
AND absence of myeloma defining events or amyloidosis - 115how do we define if a patient has myeloma?- if someone has monoclonal protein + increased clonal plasma cells
-evidence of end organ damage (CRAB) - C= hypercalcaemia, R= Renal impairment, A= Anaemia, B = Bone lesions (lytic)
- remember that recurrent infections may be a problem - 116in terms of biomarkers, what do we see in myeloma?- 60% or greater clonal plasma cells in the bone marrow
-serum free light chain ratio of >100
- more than one focal lesion on MRI that is at least 5mm or greater in size - 117what feature on bone are you concerned about when looking at myeloma?-lytic bone lesions
-can cause "pepper-pot" skull
-very easy to fracture - 118study the radiograph overleaf -demonstrates pepper-pot skull lytic lesions
- 119another example of lytic lesions -this time on a femur
- 120how many people with myeloma will have renal impairment?- appox. 25% of individuals have this on presentation
- up to 50% will at some point have this
- 2-12% will require renal replacement therapy - 121as a side note, what common drugs are nephrotoxic?-NSAIDs
- 122how do we treat myeloma related renal impairment?- vigorously replacing/rehydrating the patient with at least 3 litres of normal saline daily
- treat precipitating events e.g. hypercalcemia/sepsis
-stop nephrotoxic drugs (NSAID's)
-administer high dose dexamethasone- good for treatment of myeloma
- lease with renal team
- treat the underlying cause - 123hypercalcaemia in myeloma is found in how many patients?- around 30% (with myeloma)
- 124what problems are associated with hypercalcaemia (in myeloma) and generally ?- CNS dysfunction (confusion, coma, parasthesia)
-muscle weakness
-pancreatitis
-constipation
-thirst, polyuria
- shortening of the QT interval on ECG - 125an ECG of some one with hypercalcaemia- remember these waves are called Osbourne waves (shown by arrows) -remember that this is a shortening of the QT interval
- 126how do we manage hypercalcaemia?- hydration with IV fluids most important
-Give Bisphosphonates- zoledronic acid/pamidronate
-treat the underlying cause - 127what is the main purpose of bisphosphonates?- reduce bone loss
-encourage osteoblasts to undergo apoptosis thereby reducing turnover of bone - 128what is hyper viscosity syndrome?- a group of signs/symptoms that stem from an increased viscosity of the blood
- 129why is this caused, in the case of myeloma?- an abnormally high level of paraprotein (particularly IgA and IgG3)
- 130what is the typical presentation of hyperviscosity syndrome in myeloma?- blurred vision
- headaches
- mucosal bleeding
-dyspnoea due to heart failure - 131due to blurred vision, you may use fundoscopy - what might you find in a patient with myeloma and has hyperviscosity syndrome?- retinal vein distension
- haemorrhages
- papiloedema - 132diagram to show difference between normal retina and papiloedema -worth asking a clinician to go through this with you
- 133in terms of number of Ig's, when do we start seeing symptoms in myeloma caused hyperviscosity syndrome?- plasma viscosity > 4 or 5 mPa
- IgM level > 30 g/L
-IgA level > 40g/L
-IgG level > 60 g/L - 134what treatment is there for hyper viscosity syndrome?- plasma exchange- physically removing the paraprotein
- isovolaemic venesection- taking a pint of blood
- giving anti myeloma therapy- takes a while to work - 135in how many cases of myeloma do you find spinal cord compression?- 5 %
- 136what signs/symptoms accompany spinal cord compression?- sensory loss
- paraesthesiae
- limb weakness
- walking difficulty
-sphincter disturbance - 137how do we respond to cord compression caused by myeloma (any cord compression)?- dexamethasone 40mg daily for 4 days- used to help manage the myeloma - most will respond to this- give before any other tests (on suspicion)
- urgent MRI whole spine
- neurosurgical review to decompress or stables spine
- local radiotherapy- if non bony lesions ASAP (within 24 hours)
-treat underlying cause with systemic therapy - 138myeloma is very difficult to cure -therefore what are the aims of therapy?- to control myeloma
-maximise quality of life
- prolong survival - 139what isn't possible in the elderly due to the risk?- bone marrow transplants- these are a treatment for <65 year olds
-therefore aim is not curative, but rather management - 140give two examples of chemotherapy agents used in myeloma- cyclophospamide
- Melphalan - 141what steroid is most commonly given in myeloma?-dexamethasone!
- 142name some immune modulatory drugs are given for myeloma?- anti-angiogenic, anti-inflammatory's, anti-proliferative
- e.g. thalidomide/lenalidomide - 143what test should be given prior to prescription of thalidomide?- a pregnancy test
- 144why are bisphosphonates used in myeloma?- to inhibit the action of osteoclasts
- e.g. zoledronic acid, pamidronate - 145what other supportive measures could be given if indicated e.g. in recurrent infections?- antibiotics
- transfusions
- give thromboprophylaxis as they are at higher risk of thrombosis - 146treatments need developing for myeloma -therefore patients with the condition should be put in....-clinical trials
-if they consent
-if ethical - 147according to Professor David Marks lecture, what definition does he give for leukaemia?- "clonal proliferation of malignant blood cells derived from primitive haemopoietic stem cells in the bone marrow
-uncontrolled expansion of the hypo functional cells in blood, bone marrow and other organs leads to suppression of normal haematopoiesis and immunity" - 148in this lecture, what are the main problems included with leukaemia?- anaemia, bleeding, susceptibility to infection
-lymphadenopathy, hepatosplenomegaly
- skin, testicular and CNS infiltration - 149what are the two acute leukaemia's and how are they described?- AML/ALL
- rapid proliferation of blast cells
- rapid onset and progression if untreated
-classically could die if untreated in circa. 2 weeks - 150what are the two chronic leukaemia's to be aware of?- CML/CLL
- proliferation of more mature precursor cells
- slower in its progression and less aggressive course
- although transformation can occur to an acute phase or more aggressive malignancy - 151image showing cell lineages (haematopoiesis) - leukaemic event can happen at any one of these stages - G-CGF= granulocyte colony growth factor -have a rough understanding of this
- 152in the aetiology of leukaemia, what endogenous factors are there?- chromosome fragility syndrome
- downs
- hereditary immune deficiency
- familial - 153What exogenous factors might be important in the aetiology of leukaemia?- radiation
-chemotherapy
- Benzene (smoking/chemical exposure)
- Viral infections
- acquired immune deficiency - 154both of these endogenous and exogenous factors that cause leukaemia effect what type of cell during haemopoiesis?- the haemopoietic stem cells
- therefore they can cause any type of leukaemia - 155how do these effects on the haemopoietic cells result in leukaemia ?- stem cells go through clonal initiation
- this goes under clonal expansion
- suppression of normal haematopoiesis occurs
-huge clonal progression leads to clinical signs of leukaemia - 156run through some of the basic epidemiology of acute myeloblastic leukaemia (AML)- commoner in adults
- incidence is 1:10000 annually
- increased frequency with age (median >70yr)
-treatment is better for younger patients, but not so good prognostically for >70 year olds - 157AML may be due to de novo mutations, however it can also be due to secondary problems -list these-to other haematological disorders e.g. myelodysplasia, myeloproliferative disorders
-could be due to therapy for cancers (common in breast) - 158graph to show incidence of AML
- 159cytochemistry is used frequently in clinical practice now: true or false?- false
- much more emphasis on flow cytometry as a means of diagnosing AML (can define the cancer easier)
- blood films still very useful - 160what is acute promyelocytic leukaemia ?- an abnormal build up of granulocytes called promyelocytes
-is a subtype of AML - 161blood film to show promyelocytes -look in the cytoplasm of these cells to identify Auer rods -notcie how the promyelocytes are also granular (GRANULOCYTES)
- 162what are Auer rods and why are they useful to us?- they are finger like projections on blood films associated to promyelocytes/myelocytes
- formed of fused neutrophilic lysosomes
- - 163in which conditions can these Auer rods be found?-acute promyelocytic leukaemia (APML)
- AML - 164what genetic changes take place in APML?- a reciprocal translocation of the 15th and 17th chromosomes
- forming the pathogenetic PML-RAR alpha fusion gene - 165what should you do immediately, according to Professor David Marks, if a patient is suspected to have APML even before blood films?- give trans retinoic acid immediately
-is a medical emergency
-if picked up and treated immediately >90% survival - 166what major investigations need carrying out for APML?- FBC- low plt and Hb counts
- WBC usually 20-100 x10^9 with blasts visit on blood film
- WBC > 50 = high risk
- bone marrow: blasts must be >= 20% of nucleated cells - 167in flow cytometry for AML, what are we looking for?- CD13+, CD33+ is helpful to confirm AML
- other aberrant markers such as CD7 are helpful to follow response - 168what is the most important prognostic indicator in AML?- cytogenetics
- 169what cytogenetic results indicate a 'good' prognosis?- INV16, t(8;21), t(15;17)
- 170what cytogenetic results give rise to poor prognoses of AML?- monosomy 7, chromosome 5, chromosome 1 and complex cytogenetics (>5 abnormalities)
-these are normally treated up front with an allograft - 171what form of chemotherapy do we give for AML?- combination
- giving cytosine arabinoside and daunorubicin (intercalating agents) - 172what chemotherapy is given for APML?-again combination
- retinoic acid/arsenic trioxide - 173what drug is important to optimise outcome in both AML and APML?- ara-C (cytarabine/cytosine arabinoside)
- 174what is the frequency of chemotherapy even for AML/APML?- 3-4 cycles
-4-6 weeks
- treatment induces a profound marrow suppression and prolonged pancytopenia - 175with this prolonged pancytopenia, what supportive care is given for AML/APML?- transfusion of red cells and platelets
- antiseptic mouthwashes, clean diet, oral prophylactic antifungals
-give prompt IV broad spectrum antibiotics
- all to support pancytopenia
- evidence for using Quinolones - 176what are the complications of treatment of AML/APML?- infection- bacterial and fungal can be fatal
- bleeding (can be fatal in CNS)
- profound weight loss
- social problems- have to be in patient for most of the 6 months, loss of employment and great stress on the family - 177what negates the best prognosis from AML/APML?- being <60
- favourable cytogenetics
- > 80% chance of cure if young and t(15;17) FLT-3- negative, NPM1 positive >60% survival. - 178what are the chances of survival if >60 years and having unfavourable cytogenetics?- <10%
- 179what is the overall complete remission rate in AML/APML?- 85%
- 45-50% cured with chemotherapy alone - 180in those with AML who are <50, what treatment can offer a good survival?- allogenic bone marrow transplantation
- if HLA-donor matched, 50-70% cure rate - 181what common problems are associated with allogenic bone marrow transplantation?- graft versus host disease/ increased mortality
- 182Which group of patients might benefit from reduced intensity conditioning (RIC) allografts?- patients who are >50
-is the therapy of choice if patient is in 2nd remission - 183graph illustrating how cytogenetics has a huge effect on AML/APML survival/ prognosis
- 184give a quick summary of ALL- primative lymphoblasts infiltrate bone marrow and circulate in blood, infiltrate liver and spleen
- 185ALL is bimodal in distribution, who is most commonly effected?- children aged 2-10
- another peak in incidence >60 years - 186what are the clinical signs of ALL?- similar to AML
- but has more frequent lymphadenopathy
-hepatosplenomegaly
-more CNS involvement
- commonly causes severe bone pain
-6% of the time= sweats - 187what investigation is important in ALL (and AML) for evidence of CNS disease?- a lumbar puncture (usually performed when peripheral blasts are cleared)
- 188What might flow cytometry reveal in the case of ALL?- blasts of B cell lineage (CD10+, CD19+, CD22+)
- 20% of cases have some blasts of T-cell lineage - 189what cytogenetic finding is found in 20-25% of ALL cases (adults)?- Philadelphia chromosome
- t(9;22)
-specific therapy with imatinib - 190what other prognostic markers are there ?- t(4;11)
-t(8;14)
- hypodiploidy
- complex cytogenetics
- all have a poorer prognosis - 191what is a common finding on flow cytometry for ALL?- CD10 positivity
- 192what three phases of treatment are there for ALL?- induction
-consolidation
-maintenance - 193what kinds of drugs are used in the treatment of ALL?- chemotherapy agents with cytotoxic drugs
-steroids, vincristine, daunorubicin, asparaginase (4 drug induction)
-if the first drug doesn't work, usually the second in line will - 194what two forms of induction therapy are there in ALL?- induction (typically lasts for 3 months)
-remission induction
- different drugs exist for different parts of the induction therapy - 195what is the purpose of consolidation therapy in ALL? -how long is this?- to make sure people don't relapse
- 4 months of intensive chemotherapy and CNS prophylaxis - 196describe the maintenance phase of ALL treatment- 2 years of less intensive therapy
- normally given oral cytotoxic drugs- methotrexate and 6MP (Mercaptopurine)
-also given IV pulses of VCR (Vincristine)
-normally compatible with a fairly normal lifestyle - 197what is the percentage cure rate of ALL in a child 1-10?- >85% - best prognosis
- 198what other group of individuals have a very good prognosis?- females with low presenting WBC and no CNS disease (>90% cure rates)
- 199what is the cure rate of people on intensive treatment for ALL on national trials?- >50%
- 200name three other factors that lead to a better prognosis for ALL- low WBC count
- age < 35
- normal chromosomes
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- Flashcards on Haematology 3, created by Alexander Wolff on 28/09/2017.
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- Alexander Wolff · Sep 2017
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- May 31, 2018
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