Haematology and Blood Transfusion Flashcards
(217 cards)
1
Q
what different considerations to adults do we need to be aware of in the management of paediatric haemtological cancers?
A
blood sampling-more difficult to do
?normal reference ranges-going to change with age of the child
‘newer organs’-can tolerate more intense treatment dosing
different disease biology and evolution hence management
requirement of anaesthetic-consideration of GA for BM aspiration important when considering investigations for pt*
2
Q
what investigation is necessary before doing a BM aspiration in a child in which leukaemia is suspected?
A
CXR-as may be a mediastinal mass due to the leukaemia which is causing the child no symptoms but will cause airway compromise when the child receives a GA for BM aspiration.
3
Q
what proportion of childhood leukaemias is ALL responsible for?
A
80%
remaining 15-20%=AML
4
Q
treatment of AML in children?
A
chemotherapy for 6-8 mnths with or without a transplant
overall survival=60-70%
5
Q
when must transfusion of red cells be completed by after leaving temperature controlled storage?
A
within 4 hours
6
Q
how is a pt receiving a blood transfusion monitored?
A
observations for every unit transfused
pre-transfusion: pulse, BP, temp and RR measured not more than 60mins prior to transfusion
during: pulse, BP and temp taken at 20 mins after start of each transfusion component, if changed from baseline then measure RR.
also at 1hr into the transfusion
post transfusion pulse, BP and temp should be taken not more than 60mins after end of component.
all observations to be taken and recorded.
7
Q
what currently carries the highest blood transfusion risk?
A
incorrect blood component transfused
8
Q
what is a massive haemorrhage defined as, and what is the role of blood transfusion here?
A
50% of TBV loss in 3hrs or TBV loss in less than 24 hrs or rate of blood loss at 150mls/min
give O negative emergency blood, whilst urgent X match sent
9
Q
when is the massive haemorrhage protocol activated?
A
when 4 or more units of red cells have been transfused within an hr and similar further need is anticipated.
10
Q
what tests and processing are required on donated blood?
A
testing: HIV, Hep B, Hep C, HTLV-human T-cell lymphotropic virus, syphilis
leucodepletion
centrifugation
11
Q
importance of red cell storage in temperature controlled fridge (between 2 and 6 degrees C)?
A
if temp falls below this, cells may haemolyse
if temp goes above this, can lead to higher risk of bacteria proliferation and cause metabolic activity that may lead to deterioration in function.
12
Q
when are PLT transfusions not indicated in treatment or prevention of haemorrhage in pts with low PLTs or PLT defects?
A
thrombotic thrombocytopenic purpura-may use FFP
heparin induced thrombocytopenia
13
Q
1st sign of neutropenia?
A
sore throat (mucositis) *neutrophils required for maintaining integrity of mucosal surfaces, and prevent overwhelming bactierial infection and fever
14
Q
causes of neutropenia?
A
drugs-cytotoxics, radiotherapy, Abx-chloramphenicol, phenytoin, clozapine, carbimazole, carbamazepine
infection-espec. viral-interferon prod.-causes BM suppression
immune mediated-SLE, felty’s syndrome-splenomegaly, RA, neutropenia
BM failure-pancytopenia
physiological-afro-caribbean ancestry
hypothyrodism, hypopituitarism
15
Q
causes of neutrophilia?
A
- demargination-WBCs normally stick to b.vessel walls, can be made to mobilise-e.g. steroid treatment, post fall.
- early efflux from BM-infection-espec. pyogenic bacteria
- increased production-smoking, chronic myeloproliferative disorders-CML,polycythaemia vera, myelofibrosis
acute inflammation NOT caused by infection-surgery, infarcts e.g. MI, burns, crush injuries, RA, vasculitis
other drugs-adrenaline, G-CSF
acute haemorrhage and acute haemolysis
metabolic-DKA, gout, acute thyrotoxicosis
Ca not of haem origin e.g. carcinoma, melanoma
lymphoma
post splenectomy
16
Q
lymphopenia causes?
A
transient low count in severe infection AIDS radiotherapy chemotherapy steroid therapy
17
Q
most common cause of a reactive lymphocytosis?
A
glandular fever (infectious mononucelosis) in EBV infectious mononucleosis, the 'reactive' or atypical lymphocytes are mainly CD8+ cytotoxic T cells activated following B lymphocyte infection and their subsequent proliferation. (T cell activation to control B cell proliferation.)
18
Q
causes of lymphocytosis?
A
infection-viral-transient lymphocytosis, e.g. EBV, CMV, hepatitis, HIV in early stages. also whooping cough.
stress-MI, sickle cell crisis
trauma
adrenaline-reaction only in 1st few hrs
RA
leukaemias-CLL-mature lymphocytes, lymphomas
19
Q
causes of eosinophilia?*
A
allergy-allergic asthma, allergic rhinitis, eczema ABPA parasitic infections churg-strauss syndrome sarcoidosis SLE lymphoma drug sensitivity-penicillin idiopathic hypereosinophilic syndrome
20
Q
complications of eosinophilia?
A
restrictive cardiomyopathy and valve damage
liver disease
21
Q
how can the antigens expressed by cells be determined, and hence how can benign and malignant causes of persistent lymphocytosis, and differentiation between B and T cell subtypes be made?
A
process of flow cytometry (immunophenotyping)
can characterise cells in peripheral blood or in BM aspirate samples
fluorescence and light scatter of cells is measured, and fluorescence generated due to cell prelabelling with fluorochrome conjugated to antigen-binding Ab allows detection of specific cell surface antigens.
fluorochrome excited by argon laser.
22
Q
what condition are patients receiving immunosuppressive therapy following transplantation susceptible to as a result of loss of T cell control of EBV-infected B cells (remain infected for life)?
A
post-transplant lymphoproliferative disorder (PTLD)-B cell lymphoproliferation that may involve LNs or extranodal sites.
23
Q
importance of CMV infection in immunocompromised patients?
A
especially in post-transplant setting, is important as absence of controlling T cells can cause life threatening complications e.g. CMV pneumonitis.
24
Q
what is lymphoblastic lymphoma?
A
a malignant proliferation of lymphocyte precursors (usually T cell)
classified as a type of Non-hodkin’s lymphoma
lymphomatous equivalent of ALL, in that there is lymph node disease with little peripheral blood or bone marrow involvement.
commoner in adolescent males
frequent px with mediastinal mass
less than 20% blasts in BM (or would be ALL)
same tx protocols as ALL
25
what is CLL?
chronic lymphocytic leukaemia-malignant proliferation of B lymphocytes, characterised by accumulation of small mature lymphocytes in the blood, BM and lymphoid tissues.
26
blood film findings in CLL?
```
smear cells (disintegrated cells)-lymphocytes whose cell membrane has ruptured during slide preparation
increased numbers of small lymphocytes
```
27
name given to the transformation of CLL to a high grade large B cell lymphoma (occurs in about 3% of cases)?
Richter's transformation
28
most common presentation of CLL?
asymptomatic in 90% of cases with diagnosis following incidental finding on routine blood tests-minimum clonal B cell lymphocytosis-more than 5x10^9 lymphocytes/L
may be normochromic normocytic anaemia in advanced disease with marrow infiltration or hypersplenism.
29
clinical features of CLL?
often asymptomatic-incidental finding of lymphocytosis on routine bloods
most patients over 60 years
may be symptoms result of anaemia-fatigue, SOB
bruising and mucocutaneous bleeding/petechiae secondary to thrombocytopenia
sinusitis, bacterial pneumonia, secondary to hypogammaglobulinaemia
night sweats, fever and weight loss (B symptoms) uncommon-if severe B symptoms ?Richter's transformation to high grade diffuse large B cell lymphoma
early satiety due to mechanical obstruction by splenomegaly
o/e: lymphadenopathy, hepatosplenomegaly
30
results of investigations in CLL?
incidental finding on routine bloods-monoclonal lymphocytosis greater than 5
may be anaemia and thrombocytopenia with BM infiltration and failure
direct antiglobulin test (DAT)/Coombs test may be +ve-CLL asooc. with AI haemolytic anaemia, and also ITP
BM aspirate and trephine biopsy-extent of BM infiltration, biopsy only if intent to treat immediately
hypogammaglobulinaemia, may be monoclonal band on immunoelectrophoresis
flow cytometry-malignant lymphocyte immunophenotyping shows expression of CD5, CD19, CD20, CD23, CD79a and surface IgM, CD10 negative.
31
complications of CLL?
Richter's transformation to high grade lymphoma
B symptoms
ITP-bleeding, AI haemolytic anaemia-SOB, fatigue
BM failure-also cause of low PLTs and Hb
hepatomegaly and splenomegaly-early satiety, worseneing of anaemia
hypogammaglobulinaemia-capsulated organism infections of RT e.g. strep pneumoniae, H.influenzae, also recurrent infections e.g. HSV, VZV
secondary malignancies e.g. lung Ca, bowel Ca, ?due to immunoparesis resulting in reduction in normal tumour sureveillence by IS.
32
management of CLL?
if asymptomatic, often simple monitoring in clinic required (watchful waiting)
tment indicated if systemic symps-w.loss, sweats, fever, cytopenias. use chemotherapy regimens to prolong survival in these symptomatic patients but note not curative (cure possible exception with stem cell transplants).
33
what is the monospot test?
test for EBV infection which uses an agglutination reaction (red cell clumping to form aggregates) as EBV causes Ab development capable of agglutinating red cells of other species. test: horse rbc agglutinate on exposure to the Abs.
34
define B symptoms
these were developed for lymphoma:
weight loss more than 10% in 6 months
unexplained pyrexia spikes
night sweats
35
causes of a pancytopenia?**
acute leukaemia
aplastic anaemia
megaloblastic anaemia-severe vit B12 deficiency
36
investigations performed on a BM biopsy in investigating leukaemia?
```
flow cytometry
genetic studies (cytogenetics)
immunohistochemistry-staining
```
37
examples of myeloproliferative disorders?
polycythaemia rubra vera
CML
myelofibrosis
essential thrombocythaemia
characterised by increased proliferative activity with fairly normal maturation
38
define CML
a myeloproliferatie disorder of pluripotent haemopoietic stem cells affecting 1 or all cell lines-myeloid, erythroid and PLT.
39
what genetic abnormality do 90% of patients with CML have?
the Philadelphia chromosome:
reciprocal translocation between the long arms of chromosomes 9 and 22, with part of chromosome 9 containing ABL gene breaking off and sticking to BCR gene on chromosome 22 producing the fusion gene BCR-ABL-transcribed into an oncoprotein with tyrosine kinase activity-causes increased cell cycling and failure of apoptosis.
40
which chromosomes are involved to form the Philadelphia chromosome?
9 (ABL gene) and 22 (BCR gene)
41
complications of leukostasis in CML?
```
this occurs due to very high WCC:
priapsim-persistent and painful penile erection
lung infiltrates
amaurosis fugax
renal impairment
tinnitus
stupor
```
42
what 3 stages does CML typically progress through?
chronic phase
accelerated phase
blast crisis/blastic phase
43
describe the chronic phase of CML
this is the 1st phase in which the immune system is competent and many pts are asymptomatic for long periods
mature cells in the periphery
normal blood counts achieved with therapy
44
what is the accelerated phase of CML?
blood counts become difficult to control, increasing numbers of blast cells, 15-29% blasts in BM or blood, more than 20% basophils in blood, thromobcytosis, thrombocytopenia unrelated to therapy or clonal chromosome abnormalities in the Ph+ clone.
45
epidemiology of CML
can occur at any age but rare in children
represents 15% of all adult leukaemias
median age at diagnosis=60-65yrs
46
describe the blastic phase of CML
30% or more blasts in the peripheral blood or BM or extramedullary blastic infiltration
aggressive acute leukaemia which is usually rapidly fatal
severe constitutional symptoms due to tumour burden-weight loss, night sweats, fever, bone pain, and due to infection and bleeding and EM blastic foci.
47
how can BCR-ABL be detected in investigating CML?
can enhance with PCR then FISH
| this is quicker than testing for the Philadelphia chromosome (Ph)-shortened chromosome 22
48
lab features of CML?
FBC: anaemia, elevated WCC-often between 50 and 400, with excess neutrophils, myelocytes, basophils and metamyelocytes, blast cells in small numbers, granulocytes at all stages of development, PLT may be elevated, decreased or at normal levels
blood film-all stages of maturation seen
raised LDH, often raised uric acid
BM very hypercellular-BM aspiration and biopsy
49
what small molecule inhibitors can be used to treat CML?
imatinib-1st TK inhibitor developed for the treatment of CML, oral agent taken daily which binds to the BCR-ABL and inhibits the phosphorylation of tyrosine in protein so stops it's leukaemogenic effects of increased cell cycling and apoptosis failure.
dasatanib
nilotinib
50
overall treatment of CML?
most will respond to imatinib therapy (small molecule inhibitor of inactive conformation of tyrosine kinase, binds to BCR-ABL)
hydroxycarbamide often used in 1st few days to reduce very high WCCs
can use 2nd line TK inhibitors if pt resistant to imatinib treatment
imatinib usually provides disease control, but cannot cure the disease
allogeneic BM transplant=only known curative therapy, best carried out in chronic phase-not available to pts over 45-50yrs of age, and must find matched tissue donor-sibling or unrelated matched donor-HLA typing.
51
what important diagnostic test is used for polycythaemia rubra vera?
JAK2 mutational analysis-mutation in erythropoietin signalling pathway
52
what is polycythaemia rubra vera?
chronic clonal disorder which features excesssive proliferation of a multipotent haemopoietic stem cell causing increased rcc, markedly elevated Hb and haematocrit, and often increased WCC and PLTs.
as high Fe demand for high rcc production, MCV is low.
53
clinical features of polycythaemia vera?
insidious onset, usually px late in life
features relate to high blood viscosity due to considerable increase in rcc: dizziness, headache, can be stroke.
pruritus, part. after a hot bath
marked thrombosis tendency-mesenteric, portal, splenic vein
may also be increased likelihood of bleeding
signs: florid dusky red face-plethora
splenomegaly
hepatomegaly
erythromelalgia-increased skin temp, burning sensation and erythema, may occur in extremities.
Low Fe
54
differentials for polycythaemia vera?
secondary polycythaemia-long standing hypoxia-COPD, plus along with raised WCC-COPD infective exacerbation
raised EPO-renal cell carcinoma, PKD
apparent polycythaemia when reduction in plasma volume causes raised haematocrit e.g. diuretic tment, dehydration.
55
treatment of polycythaemia vera?
venesection
aspirin to minimise stroke risk
ruxolitunib-against jak 2
antihistamines for pruritus
30% go into myelofibrosis
10% go into AML
56
how do myeloid cells mature?
all arise from a singe multipotent common stem cell
granulocytes: myeloblast to a promyelocyte-azurophilic granules, to myelocytes, eosinophil myelocytes, neutrophil myelocytes and basophil myelocytes. neutrophil myelocytes to metamyelocytes and then neutrophils. promonocytes to monocytes.
proerythroblast to normoblast to reticulocyte to rbc
megakaryoblasts-cyctoplasmic sheddng to give megakaryocytes-to PLT.
57
most common form of acute leukaemia in adults?
AML
58
what is AML?
a malignant clonal proliferation of myeloid progenitor cells, causing BM infiltration with immature cells resulting in impaired neutrophil, rbc and PLT prod.
59
classification of malignant cell types in AML?
```
FAB classification:
undifferentiated blasts-M0
lightly granulated blasts-M1
granulated blasts often with Auer rods-M2
promyelocytic leukaemia-M3
myelomonocytic leukaemia-M4
monocytic leukaemia-M5
erythroleukaemia-M6
megakaryocytic leukaemia-M7
```
60
what genetic syndrome is assoc. with a much higher incidence of acute megakaryocytic leukaemia (M7) compared with unaffected children?
Down's syndrome-400 times higher incidence
61
what inherited mutations can predispose to AML?
those of critical haemopoietic transcription factors e.g. AML-1
62
how can AML be classified in relation to underlying molecular abnormalities?
WHO 2001 classification: 4 categories-
acute myeloblastic leukaemia with recurrent cytogenetic changes-with t(8;21), usually young pts, t(8;21) and t(15;17) assoc. with more favourable prognosis
AML with multilineage dysplasia-evolving from myelodysplastic disorder, usually older pts
AML and MDS, therapy related-alkylating agents e.g. cyclophosphamide, mitomycin C-given intravesical in pts with high risk non invasive bladder Ca, and topoisomerase II inhibitor related-anthracyclines e.g. doxorubicin. recurring abnormality of chromosome 5 and/or 7.
AML not otherwise categorised-morphologically categorised M0-M7.
63
clinical features of AML?
```
reflect BM failure:
anaemia
infections
bleeding, bruising, purpura
blast cell infiltration of other organs e.g. skin and gums-part. in monocytic leuakemia (M5), and can invade CNS
lymphadenopathy
splenomegaly
```
64
lab findings in AML?
FBC: anaemia, thrombocytopenia-BM failure, WCC-may be very high due to high numbers of circulating blasts, in over half of cases is low, in almost all pts total no. of normal circulating neutrophils is reduced.
blood film: large blast cells, may show azurophilic rod-shaped cytoplasmic inclusions (Auer rods-formed by granule fusion), espec. M2 and M3, azurophilic granules-M3-promyelocytic leukaemia.
flow cytometry-distinguish AML from ALL as treatment differs, look for expression of typical antigen profile-AML-CD13, 15, 33, stem cell marker 34. stem cell factor receptor c-kit-CD117, ALL-blast expression of B or T cell markers. note some rare leukaemias-biphenotypic, express myeloid and lymphoid antigens.
BM-aspiration and trephine biospy-BM always contains blast cells. cytogenetics-APML-translocation 15;17, blocks maturation at promyelocyte stage of development.
65
characteristics of acute promyelocytic leukaemia (M3)?
malignant cells=promyelocytes-contain abundant azurophilic granules and Auer rods. granule release may occur spontaneously or at start of cytotoxic chemo, and leads to uncontrolled activation of fibrinolytic system, causing DIC and potentially life threatening bleeding.
characterised by translocation between chromosomes 15 and 17
now most curable subtype of AML-treated with all-trans-retinoic acid (ATRA)-non chemo differentiating agent, specific for the translocation, limits DIC threat. can combine with conventional chemo e.g. anthracyclines, or with the poison arsenic trioxide.
66
AML treatment overview?
intensive chemotherapy-anthracyclines e.g. doxorubicin and cytosine arabinoside
supportive care-high risk of neutropenic sepsis following intensive chemo, often due to damaged gut mucosal surfaces allowing gram -ve bacteria to cross bowel wall into the blood, prolonged periods of neutropenia assoc. with fungal infection-aspergillus and candida.
BM transplantation-if features indicating poor risk disease or pts who have relapsed, allogeneic-myeloablative therapy to destroy patient's BM, and immunosuppression with HLA-matched donor BM to allow engrafting, procedure restricted to younger pts due to severe toxicity assoc. with the treatment, but recently the graft versus leukaemia effect of the transplant that allows eradication of chemoresistant disease can be used in older pts with reduced intensity treatment-non-myeloablative.
67
how do myelodysplastic syndromes lead to BM failure?
syndromes characterised by a clone of abnormal dysplastic haemopoietic cells that are unable to mature normally, and this block to maturation tends to worsen overtime leading to blast cell accumulation and ultimately BM failure either due to transformation to acute leukaemia or due to stem cell failure.
68
most common presentation of myelodysplastic syndromes?
symptoms of anaemia in patients over the age of 50 years.
69
what characterises Hodgkin's lymphoma?
Reed-Sternberg cells-bi or multinucleate cells with each nucleus containing 1 prominent nucleolus. type of B lymphocyte that has become malignant.
70
why is it important to do a coagulation screen in investigation of acute leukaemia?
to investigate for DIC which may be present- if acute DIC then low PLTs, prolonged PT and APTT, decrease fibrinogen, increase D-dimer and FDPs
71
what options are available for ALL treatment after achievement of remission following chemotherapy?
if complete remission achieved after induction chemo, more chemo may then be given, or may have an autologous stem cell transplant
if more than 1 induction chemo course needed for remission, a donor transplant (allogeneic) may be considered
72
what may be given alongside induction chemotherapy for ALL treatment if Ph chromosome present?
imatinib-monoclonal Ab that inhibits binds to BCR-ABL fusion protein to inhibit its tyrosine kinase activity
73
features of remission induction in ALL?
this involves chemotherapy treatment, and usually steroids, and patient has to stay in hospital for about 1 month.
74
which subtype of classical Hodgkin lymphoma has the best prognosis?
lymphocyte rich: more lymphocytes so less Reed-Sternberg tumour cells, infiltrate largely small lymphocytes, few eosinophils, reed-sternberg cells and mononuclear hodgkin's cells
75
most common subtype of classical Hodkin lymphoma?
nodular sclerosing: node divided by broad bands of CT into nodules containing mixture of reed-sternberg cells, mononuclear hodgkin's cells, lymphocytes, plasma cells, macrophages and eosinophils.
76
who is at risk of Hodkin lymphoma?
men more commonly than women
in the UK, more common in men between 20 and 24, and 75-79, and in women between 20 and 24, and 70 and 74.
suppressed IS e.g. post transplant-immunosuppressive medication, HIV, AI condition e.g. RA, SLE
EBV infection
FH of hodkin, non hodkin or CLL in 1st degree relative
smokers
obese
77
what triad of features raises the suspicion of multiple myeloma?
back pain
anaemia
raised ESR
78
most common presentation of Hodkin lymphoma?
lymphadenopathy, usually cervical and mediastinal LN enlargement
79
clinical features of Hodkin lymphoma?
cervical and mediastinal lymphadenopathy, cervical-compressive symptoms?-dyspnoea, dysphonia, dysphagia, o/e-rubbery LNs
weight loss
unexplained fever
night sweats
pruritus-cytokine mediated, often sign of relapse
alcohol induced pain in affected LNs
cough, SOB or chest pain due to extensive intrathoracic disease
80
how is definitive Hodkin lymphoma diagnosis made?
excision LN biospy (note that an excision LN biopsy is ONLY to be performed by a surgeon, so if cervical lymphadenopathy will require ENT r/f.)
81
why does LN involvement tend to be contiguous in Hodkin lymphoma?
as spread is mainly along the lymph vessels
82
how are lymphomas staged?
via the Ann-Arbor staging system using CT scanning (+BM biopsy)
83
poor prognostic factors in Hodkin lymphoma?
```
male
older patients
advanced disease
low serum albumin
anaemia
leucocytosis
```
84
treatment of early stage Hodkin lymphoma (stage IA-IIA)?
chemotherapy (2-4 cycles of ABVD therapy-adriamycin (doxorubicin), bleomycin, vinblastine, dacarbazine) and localised radiotherapy (NEVER to the mediastinum in young female)
if relapse, can often salvage with comb chemo or high dose chemo with peripheral blood stem-cell rescue (autologous BM transplant)
85
treatment of advanced Hodkin lymphoma?
6 to 8 courses of combination chemo (ABVD, also other combinations), reserve radiotherapy for residual masses or after chemo completion to areas previously involved by bulky disease.
86
complications of treatment for Hodkin lymphoma?
secondary malignancies e.g. breast Ca with radiotherapy to peripubertal breast tissue, AML with chemo e.g. alkylating agents
infertility
bleomycin-severe pulm toxicity
anthracyclines (doxorubicin)-cardiomyopathy
87
how can PET be used in Hodkin lymphoma?
may be useful to determine if active disease in residual masses after completion of treatment.
can show disease spread not apparent on CT scan so can upstage disease
often done before tment then rpted after 2 cycles in younger people to see if they are likely to respond to further treatment.
88
commonest high grade lymphoma?
Diffuse large B-cell lymphoma-type of non-hodgkin lymphoma
89
people at risk of non Hodkin lymphoma?
older people-disease commoner in later life, though can occur at all ages
men
weakened IS e.g. AI disease e.g. RA, coeliac disease-assoc. with enteropathy type T cell lymphoma-reduce risk with gluten free diet
infection-EBV-Burkitt's lymphoma, H.pylori-MALT lymphoma, human T cell lymphoma virus 1 (HTLV1), Hep C
previous Ca-leukaemia, Hodgkin lymphoma, melanoma
FH-1st degree relative-small risk
90
presentation of diffuse large B cell lymphoma?
```
night sweats
fever
weight loss
lymphadenopathy
extranodal lymphoma-GI tract, testis, brain, bone
```
91
treatment of diffuse large B cell lymphoma?
high grade so aggressive disease which may be difficult to treat but is CURABLE
combination chemo-R-CHOP-rituximab, cyclophosphamide, doxorubicin (hydroxydaunorubicin), vincristine (oncovin), prednisolone, 6 or 8 OP cycles, rituximab espec. useful for patients with low risk disease as more pronounced increase in survival.
if relapse, offer high dose chemo and peripheral blood stem cell rescue=autologous BM transplant-patient's stem cells are removed to reconstitute the BM following reinfusion after high dose chemo. stem cells collected by marrow puncture under GA or by apheresis, before which pt primed with G-CSF and chemo, then conditioning with high dose chemo, the stem cells reinfused, then supportive therapy e.g. blood products, Abx, nutritional support.
radiotherapy often to sites of bulky disease or residual masses after chemo completed.
92
disadvantages of autologous BM transplant (use of patient's own stem cells following apheresis or marrow puncture)?
potential for reinfusing malignant cells
93
what does low grade mean when referring to follicular lymphoma?
the cancer is treatable and causes few problems for the patient, but remains incurable.
there is the risk of high grade transformation to large cell lymphoma which correlates with a poor prognosis.
94
follicular lymphoma presentation?
widespread lymphadenopathy
BM infiltration
hepatosplenomegaly
extranodal features e.g. GIT, skin
95
follicular lymphoma treatment?
required when systemic symptoms, critical organ failure or bulky disease.
96
histological subtypes of classical hodgkin lymphoma?
nodular sclerosing
lymphocyte rich
mixed cellularity
lymphocyte deplete
97
what is non classical Hodgkin lymphoma?
lymphocyte predominant
| good prognosis
98
what test can be performed to investigate for AI haemolytic anaemia?
DAT (direct antiglobulin)/direct Coombs test-antibodies directed against human Ig are added to a sample of the patient's blood, if the red cells are coated in antibodies then they will agglutinate.
99
define multiple myeloma
B cell neoplasm which features a malignant proliferation of plasma cells which produce monoclonal immunoglobulins or fragments of them.
?develops from a clonal condition of plasma cells known as monoclonal gammopathy of undetermined significance-progression to myeloma at rate of 1%/year.
100
who is at risk of myeloma?
```
older population
blacks more than whites
more common in men
MGUS
IS suppression-HIV, post transplant
FH
pernicious anaemia and other AI conditions
```
101
why is myeloma assoicated with destructive osteolytic bone lesions?
Rankl dysregulation, release of IL-10, which leads to osteoclast activation
102
why are bone scans NOT useful in myeloma patients for showing osteolytic bone lesions?
lack of osteoblast activity-not allowed to proliferate
103
how can multiple myeloma involve the skin?*
as an extramedullary plasmacytoma, presenting as a red nodule or dome shaped plaque, and may ulcerate.
104
why can multiple myeloma cause SC compression?
vertebral fracture due to osteolysis as a result of rankl dysregulation
paravertebral plasmacytoma-plasma cell tumours can develop in areas other than the BM (EM plasmacytomas)
105
what problems can occur due to excess of Igs in the blood in multiple myeloma?
features of hyperviscosity syndrome-headaches, retinopathy, coma, spontaneous bleeding
raised paraprotein levels can also cause peripheral neuropathy
106
why are patients with multiple myeloma susceptible to renal failure?
amyloidosis
light chain precipitation in the renal tubules, plus chains are directly toxic to the renal tubules
hypercalcaemia
direct infiltration
infection-pts immmunosuppressed as lack normal Ig production
107
what is beta 2 microglobulin?
a component of MHC class I molecule which can be used as a tumour marker and give idea to prognosis in some blood cancers e.g. myeloma
108
how is significant hyperviscosity in multiple myeloma treated?
plasmaphoresis-blood taken, abnormal proteins removed from it by extracorporeal filtration, and blood then returned to pt via continuous circuit.
109
what is a paraprotein?
a monoclonal Ab
110
what affects outcomes in myeloma patients?
stage of disease at diagnosis-international staging system based on beta 2 microglobulin levels, duria and salmon staging system-Hb, serum Ca2+, M component, urinary monoclonal protein (Bence-Jones), bone lesion on skeletal survey
cytogenetics-helps determine initial treatment by risk stratifying patients
age
fitness
111
what does treatment of myeloma involve after patient stabilisation e.g. renal function abnormality and hypercalcaemia correction?
CHEMO-young pts (under 65yrs) treated with high dose chemo and haematopoietic stem cell transplantation, induction chemo may be thalidomide-dexamethasone.
older, frailer patients not suitable for transplant, treat with chemo e.g. lenalidomide (biological therapy) and dexamethasone, commonly used chemo=cyclophosphamide, melphalan, doxorubicin, idarubicin. steroids help chemo work better.
MPT therapy-melphalan, pred, thalidomide,
bone protection-bisphosphonates-reduce risk of pathological fractures
112
what feature are we looking for on serum electrophoresis to diagnose multiple myeloma?
an M band-discrete monoclonal band due to monoclonal Abs (paraproteins)
113
why might a pt with mutliple myeloma not test +ve for Bence Jones proteins?
in some patients no light chains are produced because the plasma cells are so defective
114
what asymptomatic phase precedes multiple myeloma?
monoclonal gammopathy of undetermined significance
115
which Ig associated in multiple myeloma with hyperviscosity?
more likely with IgA myeloma as IgA has tendency to form dimers.
116
why are myeloma patients susceptible to bacterial infections?
acquired hypogammaglobulinaemia-lack of normal Abs makes pts susceptible to infections with capsulated organisms
BM failure-neutropenia
117
what type of rbc are produced in AI haemolytic anaemia?
spherocytes
118
why should a hx from a patient who has been found to have a paraprotein include questions regarding night sweats, fevers and weight loss?
as paraproteinaemia can be the result of a lymphoma
119
how is MGUS (monoclonal gammopathy of undetermined significance) differentiated from myeloma?
MGUS lacks end organ damage and hence patients are asymptomatic
120
what 2 conditions are often associated with CLL?
AI haemolytic anaemia
| ITP
121
diagnostic criteria for myeloma?
monoclonal Ig in the serum or monoclonal light chains in the urine or both
increased proportion of plasma cells in marrow aspirates
features of end organ damage e.g. raised Ca2+, renal disease, anaemia, osteolytic bone lesions found on skeletal survey
122
what may be secreted by the malignant clone of plasma cells in myeloma?
monoclonal Ig-IgG or IgA, rarely IgD, a monoclonal light chain or both
123
what investigation is usually required for accurate diagnosis of a lymphoma?
an excision LN biopsy
124
what is myelofibrosis classed as?
a myeloproliferative neoplasm
125
how does serum protein electrophoresis work in terms of myeloma patients?*
presence of monoclonal Ab (paraprotein) will appear as a 2nd peak on the electrophoresis as proteins in the serum separated on basis of weight and charge, and albumin produces the 1st peak, then normally followed by mutliple small peaks as different sized Igs, but if all the same, as in myeloma, M band produced=single tall peak.
126
how does myelodysplastic syndrome (MDS) differ from myeloproliferative disorders?
MDS-malignant proliferation of cells which are dysplastic-poorly differentiated and poorly functioning cells, and dysmorphic, so cells destroyed by apoptosis, and therefore reduced blood cell release from the BM into the peripheral blood producing a pancytopenia.
myeloproliferative disorders-malignant proliferation of myeloid progenitor cell, and cells produced are mature functional cells, so there are increased blood cell counts.
127
why does myelodysplastic syndrome produce pancytopenia?
there is a malignant clonal proliferation of myeloid progenitor cells, with disordered growth and maturation of these cells, hence subsequent cell death and insufficient haematopoiesis among healthy marrow cells to combat this so reduced blood cells in peripheral blood.
128
how do myelodysplastic syndromes vary?
variation in degree to which each cell line is affected, and in the nature of disease severity with both low and high grade disease, with aggressive disease progressing quickly to AML.
129
what can MDS occur secondary to?
10% of MDS secondary, usually to radiotherapy or chemotherapy on average 5 years before disease onset
may be occupational exposure to radiation, benzenes or other organic solvents
worse prognosis than primary
130
MDS risk factors?
age-disease of the elderly, 80% over 60yrs
male
smoker
previous Ca therapy-radiotherapy, chemo-alkylating agents e.g. cyclophosphamide, topoismerase II inhibitors e.g. doxorubicin, GFs used to stimulate BM during chemo e.g. c-GSF (filagrastim)
environmental-benzene and other organic solvents
assoc. with other genetic diseases e.g. schwachman-diamond syndrome, fanconi's anameia, NF type 1.
131
*how do tyrosine kinases work e.g. ABL encoded protein?
phosphorylate tyrosine reuslting in activation of downstream molecules to result in protein synthesis and stimulate DNA replication and cell division.
132
presentation of MDS?
PANCYTOPENIA
anaemia-variable in severity, may be chronic anemia in older pt presenting with fatigue and exertional dyspnoea, may be worsening of pre-existing disease e.g. CHF, angina
neutropenia-recurrent/unusual infections, sepsis
thrombocytopenia-gum bleeding after brushing teeth, epistaxis, petechiae, bruising
anorexia, weight loss, sweats, fevers-occur in more advanced disease-constitutional symps
o/e: petechiae, ecchymoses-check pressure points
conjunctivae-anaemia-tachycardia, systolic flow murmur
mouth-candidiasis
splenomegaly and lymphadenopathy uncommon
133
causes of a reactive bone marrow dysplasia?
severe intercurrent illness
HIV
alcoholism
recent cytotoxic therapy
134
MDS FBC and blood film features?
FBC-normocytic or macrocytic anaemia, cytopenias
dimorphic red cells
pappenheimer bodies
dysplasia-erythrocytes with anisocytosis-varying sizes, and poikilocytosis-varying shapes
large or hypogranular PLTs
135
investigation results in patients with MDS, other than blood test and film results?
BM aspiration/trephine biopsy-often hypercellular marrow and megaloblastoid erythropoiesis, cytogenetics- often chromosomal abnormalities-part of chromosome loss, monosomy, trisomy-often chromosomes 5, 7 and 8.
136
risk classification of MDS?
WHO classification-types
IPSS-international prognostic scoring system-low risk, intermediate-1, intermediate-2, or high risk depending on % of blasts in BM and number of cytopenias.
137
treatment options for MDS?
managing symptomatic disease-anaemia-regular blood transfusion + Fe chelating therapy if required, prompt tment with BS Abx of neutropenic sepsis
low grade disease often managed without active treatment but with regular haematology clinic f/u
chemo for some patients-NICE recommends azacitidine as an option for those not eligible for allogeneic stem cell transplantation and have intermediate-2 or high risk MDS.
138
complications of MDS?
transformation to AML
myelofibrosis development increasng transfusion dependency and disease progression
transfusional Fe overload
complications of anaemia, TP and neutropenia
splenic rupture and IP haemorrhage due to splenomegaly
139
leading cause of death in MDS?
BM failure-infection and haemorrhage.
140
use of hydroxycarbamide in haematological conditions?
treatment of PRV and ET
lower WCC in leukaemia
males-must consider sperm conservation as causes azoospermia and oligospermia.
141
2 most common causes of massive splenomegaly in the UK?
myelofibrosis (myeloproliferative neoplasm)
| CML
142
what is primary myelofibrosis?
a myeloproliferative disorder in which there is a malignant clonal proliferation of myeloid stem cells and a progressive generalised reactive fibrosis of the BM, in assoc. with hamopoiesis development in the spleen and liver, causing anaemia and massive splenomegaly.
143
what does the BM fibrosis in primary myelofibrosis occur due to?
due to hyperplasia of abnormal megakaryocytes, which along with PLTs secrete PDGF and other cytokines which stimulate fibroblasts.
144
what mutation occurs in approx. 50% of patients with primary myelofibrosis?
JAK2
145
clinical features of primary myelofibrosis?
anaemia, insidious onset in older people
massive splenomegaly-abdo discomfort, early satiety, indigestion
weight loss, anorexia, fever, night sweats
in a minority-bone pain, bleeding problems, gout
146
lab findings in primary myelofibrosis?
FBC: anaemia, but normal or increased HB may be found in some pts-note some patients with similar disease features have previous PV or ET hx, and some present with clinical and lab features of both
WCC and PLTs usually high (myeloproliferative disorder), but leucopenia and thrombocytopenia common in later disease
blood film: leucoerythroblastic, red cells-'tear drop' poikilocytes
BM: trephine BIOPSY-fibrotic hypercellular marrow, often increased megakaryocytes, may be increased bone formation with increased bone density on X-ray.
JAK2 kinase mutation (non receptor tyrosine kinase)
increased but largely ineffective turnover of haematopoietic cells-causes high serum urate and LDH
transformation to AML in 10-20% of patients
147
treatment of primary myelofibrosis?
manage symptoms-anaemia-blood transfusions and regular folic acid therapy
splenomegaly-can reduce size of spleen and so help tackle weight loss due to early satiety with JAK2 inhibitors e.g.ruxolitinib
allopurinol-prevent gout and urate nephropathy
allogeneic stem cell transplant may be curative for young patients
148
causes of death in patients with myelofibrosis?
heart failure
infection
leukaemic transformation
149
what are the results of a clotting profile in antiphospholipid syndrome?
paradoxical rise in APTT (prolonged) due to reaction of lupus anticoagulant autoantibodies with phospholipids involved in the clotting cascade.
syndrome causes a predisposition to both arterial and venous thromboses, recurrent fetal loss and thrombocytopenia.
150
role of further investigations in patients with unprovoked DVT or PEs?
could be undiagnosed cancer or thrombophilia, therefore if not known to have cancer should be investigated with:
physical examination guided by patient's hx AND
CXR AND
blood tests-FBC, serum Ca, LFTs and urinalysis
if over 40yrs and 1st unprovoked DVT/PE, consider abdomino/pelvic CT scan (and mammogram for women)
for thrombophilia investigation, do not offer if going to be on lifelong warfarin
consider antiphospholipid Ab testing (anti-cardiolipin, lupus anticoagulant) if unprovoked DVT/PE
if unprovoked AND 1st degree relative had DVT/PE, consider hereditary thrombophilia testing.
151
venous thromboembolism treatment in cancer patients?
LMWH monotherapy continued for 6 months, then r/v with assessment of benefits and risks of continuing anticoagulation
LMWH preferred over Vit K antagonist for LT treatment of VTE in pt with malignancy
152
blood film for hyposplenism?
```
target cells
Howell-Jolly bodies
Pappenheimer bodies
siderotic granules
acanthocytes
```
153
what is an aplastic crisis often secondary to in sickle cell anaemia?
parvovirus infection
154
what is post thrombotic syndrome?
```
clinical complications following a DVT which result from chronic venous HTN due to venous outflow obstruction and venous insufficiency:
painful, heavy calves
pruritus
swelling
varicose veins
venous ulceration
```
155
most common inherited bleeding disorder?
von willebrand's disease
156
what complication are we trying to avoid by giving irradiated blood to patients who have/had Hodgkin's lymphoma?
transfusion associated graft versus host disease-immunocompetent cells in transfused blood (T cells) mount an immune response to the host and the host is unable to reject the immunocompetent cells in the transfused blood due to severe reduction in lymphocyte mediated IS function of the patient (severely suppressed T cell function).
157
prominent blood film feature of autoimmune haemolytic anaemia?
spherocytes
158
causes of non immune acquired haemolytic anaemia?
```
MAHA-microangiopathic haemolytic anaemia-different types
TTP-thrombotic thrombocytopenic purpura
HUS
hypersplenism
prosthetic heart valves
sepsis
malaria
PNH
drugs
secondary to liver and renal disease
paroxysmal nocturnal haemoglobinuria-acquired but red cells have an intrinsic defect.
```
159
causes of immune acquired haemolytic anaemias?
AI-warm and cold antibody types, warm-Ab reacts with red cells more strongly at 37degreesC
alloimmune-transfusion associated haemolytic reactions e.g. ABO incompatability, haemolytic disease of the newborn, allografts epec. stem cell transplantation.
160
normal rbc lifespan?
120 days
161
what happens to haem when rbc are broken down by macrophages in the spleen, liver (kupffer cells) and BM?
iron is released which is recirculated mainly to marrow erythroblasts by plasma transferrin
protoporphyrin released which is broken down to bilirubin
162
why might a CLL patient appear jaundiced?
excessive red cell breakdown with accumulation of unconjugated bilirubin in the blood due to associated AI haemolytic anaemia.
163
role of haptoglobins?
these are proteins present in normal plasma which bind free Hb and this complex is then removed from the plasma by the reticuloendothelial system hence low haptoglobin in haemolytic anaemias.
164
intravascular haemolysis plays little or no part in normal red cell destruction, true or false?
true
normal rbc breakdown is extravascular via the reticuloendothelial system which involves rbc breakdown by macrophages in the spleen, liver and BM.
165
why is the threshold for blood transfusion higher (Hb less than 80g/L) in patients with CVD?
patients more at risk of complications of low oxygen due to reduced O2 binding capacity of the blood, e.g. MI.
166
what is the likely cause of anaemia in a patient with raised unconjugated bilirubin, decreased haptoglobin, raised LDH and low folate?
haemolytic anaemia, with low folate being the result of haemolysis causing increased red cell production which is consuming folate rather than being the cause of the anaemia.
167
why might a patient with AI haemolytic anaemia have dark urine?
only if urine is left to stand as excess urobilinogen in urine due to increase in red cell breakdown increasing the amount of bilirubin being conjugated by the liver which is subsequently converted to urobilinogen which is colourless, but if urine allowed to stand is converted to urobilin which is yellow.
168
symptoms and signs of haemolytic anaemias?
features of anaemia-SOB, fatigue, headaches, dizziness, tinnitus, palpitations, tachycardia
jaundice-unconjugated hyperbilirubinaemia
dark urine-raised urobilinogen
splenomegaly
pale mucous membranes, conjunctivae, palmar creases.
169
6 components of a haemolysis screen?
bilirubin-raised
LDH-raised
haptoglobin-reduced
reticulocytes-raised
blood film-spherocytes-AIHA here is prominent feature but will be present in all causes of haemolysis, schistiocytes-intravascular Hb breakdown, polychromasia (young red cells) if BM able to respond to the anaemia
DAT-direct antiglobulin/Coombs test-detects red cells coated with auto or allo antibodies
170
what name is given to the syndrome of having both AIHA and ITP?
Evans' syndrome
171
causes of hereditary haemolytic anaemia?
red cell membrane defects-hereditary spherocytosis, elliptocytosis
red cell enzyme defects-G6PDD, PKD
abnormal Hb-sickle cell, thalassaemia
172
common indications for red cell transfusion?
acute blood loss
surgery/medical/critical care: if pt has no CVS RFs then transfuse if Hb less than 70g/L, less than 80g/L if CVD, CVS symtoms or heart failure.
severe sepsis, traumatic brain injury-transfuse if Hb less than 90.
173
why is transfusion related graft versus host disease now rare?
due to leucodepletion of blood products to be transfused.
174
3 requirements for graft versus host disease?
graft contains functioning T cells
recipient expresses antigens NOT found in the donor
recipient unable to mount immune response sufficient to eliminate transplanted cells.
the T cells in the graft respond to HLAs-class I proteins expressed on all nucleated cells, and class II mainly on haematopoietic cells e.g. B cells, dendritic cells and monocytes, expression of class II can be induced in inflammatory states.
175
presentation of acute GVHD?
skin rash-maculopapular and pruritic, may start on palms and soles but can involve whole body with scalp sparing, can cause blistering and ulceration.
GI tract-diarrhoea, also vomiting, abdo pain and anorexia, mucosal ulceration can cause massive bleeding.
liver-cholestasis and hyperbilirubinaemia
non culture positive fever
176
features of chronic GvHD-a common cause of non-relapse death after haematopoietic cell transplantation?
Diagnostic features - for example, skin poikiloderma and lichen planus, lichen-type changes on mucous membranes (such as the mouth or genitals), fasciitis and joint contractures.
Distinctive features - for example, dyspigmentation, new alopecia, nail dystrophy, xerostomia, mucoceles, ulceration of the mouth, keratoconjunctivitis sicca and myositis.
177
main part of therapy for acute GvHD
steroids-topical for skin rash, and IV methyprednisolone
| calcineurin inhibtors e.g. ciclosporin, tacrolimus
178
acute risks of blood transfusion?
acute haemolytic reaction-ABO incompatibility
anaphylaxis
minor allergic reaction-?IgA deficient patient
febrile reaction-pt driven reaction with antibodies against donor blood
circulatory overload
TRALI-anti-leucocyte Abs-within blood transfused, against HLA antigens.
179
delayed risks of blood transfusion?
infection-Hep B most common
transfusion associated GvHD-can be up to 2wks post transfusion
post-transfusion purpura-HPA antibodies against PLTs in recipient. pt previously sensitised e.g. pregnancy, or previous blood transfusions.
180
why does haemolytic reaction with ABO incompatibility with blood transfusion occur immediately where with other red cell antigen incompatibility e.g. rhesus, it is delayed?
other red cell antigen incompatibility reactions are IgG mediated
181
which blood product carries the highest risk of anaphylaxis following transfusion?
FFP-as proteins contained and anaphylactic reaction is protein mediated.
182
indications for irradiated blood products?
bone marrow transplant or peripheral blood stem cell transplant allograft recipient
autograft recipient (no TBI) less than 3mnths post transplant
Hodgkin disease patient-regardless of stage, and even if cured
due to receive or previously received intrauterine transfusion
neonate (under 6mnths) due to receive red cell exchange transfusion
congenital cellular immune deficiency state e.g. Di George Syndrome.
183
tests performed on blood sample in lab before transfusion?
ABO, rhesus D
| antibody screen
184
indications for CMV negative blood products?
pregnant
intrauterine transfusion
neonate or infant within 1st year of their life
185
causes of anaemia in a patient with CLL?
BM failure
AI haemolytic anaemia
hypersplenism
other causes to consider unrelated to their CLL-acute or chronic blood loss, Vit B12 or folate deficiency.
186
clinical indications for FFP transfusion?
- single clotting factor deficiency where no recombinant factor production
- acute DIC with bleeding and abnormal coagulation
- TTP-need plasma exchange-remove plasma with inhibitory antibodies and give plasma with the deficient protease, can give FFP until plasma exchange becomes available.
- major haemorrhage
- liver disease
187
why is complication of bacterial infection more common with transfusion of PLTs than with red cell transfusion?
PLTs are stored at room temperature whereas rbc stored in fridge.
188
how are lymphomas defined?
clonal proliferations of lymphoid cells-B and T cell neoplasms.
189
features of lymphadenoapathy in hodgkin's?
cervical and medistinal common, cervical compressive symptoms-dysphagia, dyspnoea, dysphonia
mediastinal-SOB, chest pain, cough
LNs painless usually, alcohol induced pain
can wax and wane
190
what must young women be advised about in relation to pregnancy following treatment of Hodgkin's lymphoma?
must not try and get pregnant for at least 2 years as this time period is when the pt is most at risk of disease recurrence and pregnancy represents an immunocompromised state.
191
what is marginal zone lymphoma?
low grade lymphoma that arises from marginal zone of B cell germinal follicles
classified according to site where they arise e.g. spleen, MALT or lymph node.
splenic marginal zone lymphoma usually presents as splenomegaly, may be assoc. with circulating villous lymphocytes, aetiology may relate to Hep C, splenectomy may be useful if symptomatic.
ocular marginal zone lymphoma-link to chlamydia
192
treatment of gastric MALT lymphoma (type of marginal cell lymphoma)?
initially may respond to Abx against H pylori-clarithromycin plus metronidazole or amoxicillin.
193
which haematological maligancy is part. associated with hyperviscosity?
Waldenstrom's macroglobulinaemia (lymphoplasmacytic lymphoma)- type of non-hodgkin's lymphoma, maliganant cells are mature B cells capable of secreting IgM paraprotein, high concentrations of which cause hyperviscosity-headaches, visual disturbance-papilloedema, retinal haemorrhages, and altered consciousness.
194
EBV links to lymphomas?
Hodgkins
transplant related lymphoproliferative disorder
endemic burkitt's
195
differentials for paraprotein production?
multiple myeloma
lymphoma e.g. waldenstrom's macroglobulinaemia
monoclonal gammopathy of undetermined significance
amyloidosis
196
cause of anaemia in myeloma patients?
BM failure
renal failure
plasma volume expansion secondary to paraprotein
cytotoxic drugs
197
investigation results in acute leukaemia?
FBC-normochromic normocytic anaemia
WCC-raised or low/normal
low PLTs
clotting studies, D-dimer-look for DIC-especially in acute promyelocytic leukaemia (M3)
blood film-blasts, Auer rods-AML
BM trephine biopsy-more than 20% blasts, hypercellular. Ph chromosme ALL-karyotyping of BM aspirate (cytogenetics)
flow cytometry
cytogenetics, FISH/PCR-BCR-ABL fusion gene may be present in ALL, if Ph chromosome ALL then assoc. with poor prognosis.
198
characteristic symptom of essential thrombocythaemia?
erythromelalgia- burning sensation in hands and feet, promptly relieved by aspirin.
199
characterising feature of the myeloproliferative neoplasms PV, ET and primary myelofibrosis?
JAK2 mutation
200
what name is given to the low grade non-Hodgkin lymphoma with the same morphology, cytogenetics and immunophenotype as CLL but with less than 5X10^9/L peripheral blood B cells and no cytopenias as no BM involvement?
small lymphocytic lymphoma (SLL)
| most patients elderly and often no tment required (watch and wait).
201
what tumour marker can be used as a prognostic indicator in myeloma, leukaemia and lymphoma?
beta 2 microglobulin
202
most common cause of thrombophilia?
factor V leiden (activated protein C resistance)
203
why might a negative serum protein electrophoresis be found in a patient with myeloma?
only light chain production, no heavy chains so intact monoclonal immunoglobulin that would be detected in electrophoresis is not produced.
204
light chain types that may be produced on their own in patients with myeloma?
lambda or kappa
| staining for these, along with flow cytometry, can prove the monoclonlity of the disease.
205
which investigation could you use to confirm your diagnosis in a patient with a macrocytic anaemia and blood film showing hypersegmented neutrophils?
haematinics-Vit B12 and folate
these deficiencies produce a megaloblastic macrocytic anaemia, and Vit B12 deficiency results in hypersegmeneted neutrophils on the blood film.
206
most common hereditary haemolytic anaemia in patients of northern european descent?
hereditary sperocytosis
autosomal dominant condition
diagnosis-osmotic fragility test
207
INR target in recurrent VTE?
3.5
208
indications for autologous stem cell transplantation?
lymphoma-hodgkin and non hodgkin
multiple myeloma
AML
primary amyloidosis
209
what does an autologous stem cell transplant involve?
this form of transplant involves infusing a patient with their own stem cells following their removal for harvesting
chemo and G-CSF are used to increase the numbers of haemopoietic stem cells in the blood.
the stem cells are then collected by leucophoresis during recovery phase from chemo
conditioning treatment then given before infusion of stem cells, this involves chemo sometimes in comb with whole body irradiation, to eradicate patients haemopoetic and immune system, and any malignant cells if present, can be myeloablative or non-myeloablative.
stem cells then infused, few wks of severe pancytopenia, marrow reserve remains impaired for 1-2yrs.
210
where can stem cells be collected from for transplantaion?
bone marrow
peripheral blood (PBSC)
umbilical cord
211
what specific blood test should be done initially to look for a primary immunodeficiency?
serum immunoglobulins
212
common cause of primary B cell immunodeficiency which can present at any age and results in IgG less than 5g/l?
common variable immunodeficiency (CVID): inability of B cells to mature into plasma cells, IgG less than 5g/l
increased risk of infection part. RT and ENT
most common px in patients in their 30s and 40s
tx with Ig replacement therapy, and prophylactic vaccination and Abx for chronic RT infections.
may predispose to AI disorders and lymphoma.
213
most common primary Ab deficiency?
selective IgA deficiency:
maturation defect in B cells
recurrent sinus and resp infections
assoc. with coeliac disease and may cause false -ve coeliac Ab screen
214
what is TTP? who is most susceptible?
- thrombotic thrombocytopenic purpura-thrombotic microangiopathy characterised by microangiopathic haemolysis, thrombocytopenia, neurological abnormalities, renal impairment and fever.
- due to deficiency of vWF cleaving protein
- 10-25% of cases associated with pregnancy and post-partum
- other associations-HIV, malignancy, AI disease.
215
features o/e of TTP?
- purpura
- jaundice
- splenomegaly
- pyrexia
- neurological problems
216
investigations for TTP?
- pregnancy test if indicated
- HIV, Hep B+C, autoantibody screen
- FBC-normochromic normocytic anaemia of haemolysis, low PLT
- blood film-schistocytes-microangiopathic haemolysis
- U+Es, urinalysis-microscopic haematuria and proteinuria
- clotting studies
- LDH-markedly raised
- other haemolysis screen components-bilirubin, DAT test, reticulocytes
need IV plasma exchange treatment
217
3 aims of management of CML?
- haematological remission (normal FBC and physical examination)
- cytogenetic remission (normal chromosome returns with 0% Ph+ve cells in bone marrow on karyotype or FISH)
- molecular remission (-ve PCR result for mutational BCR-ABL m-RNA)
