Heme/Onc Flashcards
(142 cards)
1
Q
Medications that increase risk of VTE
A
- combined oral contraceptive pill: esp 3rd generation
- hormone replacement therapy: the risk of VTE is higher in women taking oestrogen + progestogen preparations
- raloxifene and tamoxifen
4.antipsychotics (esp. olanzapine)
2
Q
‘tear-drop’ poikilocytes, massive splenomegaly, dry tap
A
Myelofibrosis
3
Q
What is Bombesin is a tumour marker for
A
small cell lung carcinomas
4
Q
Most common tumour causing bone metastases
A
Prostate
Breast
Lung
5
Q
Sickle cell how does acute chest syndrome present
A
dyspnoea, CP, pulmonary infiltrates on chest x-ray, low pO2
transfusion: improves oxygenation
6
Q
4 Heme disorders
A
Sideroblastic- ala synthase / vit b6
Acute intermittent porphyria - mutation porphobilinogen demainase
Lead poisoning - ala dehydratase & ferrochelarase
Porphyria cutanea tarda- decrease uroporphyinogen decarboxylase
7
Q
Ix sideroblastic anemia & rx
A
Blood letting
Deferoxamine
Severe bm or liver transplant
8
Q
Causes of lead poisoning
A
9
Q
Sx lead poisoning
A
10
Q
Dx and rx lead poisoning
A
11
Q
Cause of acute intermittent porphyria and triggeres
A
Build up of Ala & porphobilinogen
12
Q
Sx & rx of AIP
A
Raised urinary porphobilinogen (btwn attack)
Raised delta aminolaevulinic acid
13
Q
Causes of Porphyria cutanea tarda
A
14
Q
Sx & rx of PCT
A
Rx: avoid triggers. Phlebotomy, hydroxychloroquine
15
Q
Difference between PCT & AIP
A
AIP urine = raised urinary prophobiliogen
PCT= Uroporphyrinogin
16
Q
What happens when HbS is deoxygenated?
A
Sickling an polymerisation of hb
17
Q
Blood markers of hemolysis
A
Haptoglobin mop up Hema = reduced haptaglobin = unconjugated bilirubin a
18
Q
How does sickle cell affect bones
A
19
Q
How does sickle cell effect the spleen
A
Fibrosis
Sequestration of blood —> infarction
Increases susceptibility
20
Q
How does sickle cell effect kidney & penis
A
21
Q
What are the long term rx of sickle cell?
A
Hydroxyurea - increasing HbF prevents crisis
Every 5 years pneumococcal vaccine
22
Q
Explain the genetics of sickle cell
A
Glutamic acid is swapped with valine on chrom 11 = decrease HbA and increase hbs
AR
Carrier state exists
23
Q
What is the most common cause of death in Sickle cell
A
acute chest syndrome
24
Q
A
25
What causes increased HbA2
Target cells & anisopoikilocytosis ?
26
Why does parvovirus cause aplastic anemia in beta thalassmia and sickle cell
Suppresses rbc production = crisis
27
What is the main difference btwn Acute & Chronic Leukemias
**acute leukemias**,-cells don’t mature at all, =“blast” form; tend to progress rapidly.
**chronic leukemias**-caused by the increased proliferation of immature leukocytes,
Progress slowly; CLL,CML,HCL
28
Where do abnormal Leukemias cells deposit?
- liver and spleen = hepatosplenomegaly,
- lymph nodes = lymphadenopathy,
- skin causing purple or flesh colored plaques or nodules = leukemia cutis.
29
Lymphomas vs Leukemias typically form
Lymphomas solid - tumors in lymphatic tissue such as lymph nodes, thymus, or spleen.
Leukemias - bone marrow or blood.
30
What are the differences in translocations in AML & ALL
ALL - children- need to not sent to school @ 9:22 or picked up 12;21
AML - adults pick up at 15:17
31
What can cause acute leukaemias
Translocation
Both Ass w/ - RAD
Only AML
32
Most common type of AML
What is its translocation
What is rx
APL 15;17
Vit A & arsenic
33
I’m ALL what cells are abnormal?
Can be
Bcells in 80% of cases
Or
T cells
34
Which leukaemias are ass with Philadelphia chrom?
9:22 ALL & CML
35
In CML what does the fusion of 9(abl) & 22 (BCR) cause ?
What is rx for cml
BCR-ABL = continuous cell division = blast crisis
BCL- ABL inhibitors
36
CCL
Cell type
Ix of choice
Labs
Blood flim
Rx
B-cells
Immunophenotyping
Smudge cells
ITP + autoimmune haemolytic anemia
FCR : fludarabine, cyclophosphamide, rituximab
37
What chronic leukaemia is ass w/ BRAF gene
What effect does this have on the bone
Hairy cell
Bm fibrosis = pancytopenia + severe spleenomegally
38
How can you differentiate CML to a leukamoid rnx & what is leukaemoid rnx
Leukaemiod rnx is the presence of immature cell in the peripheral blood because push out of the bone marrow.
Which can happen in infections, hemolysis, hemorrhage, ca often indicated by a neutrophilia
**CML will have Low Alkaline phosphatase score**
39
CML ix
Cytogenetics - Philadelphia chrom
Lukocyte alkaline phosphatase - low (differs from other myeloproliferative disorders
BM aspiration- to qualify blast & fibrosis
40
How can you differentiate aml from ALL as on BM aspiration shows >20% blast cell (bm or peripheral bl)
Myloblasts have aura rods
Immunophenotyping
41
Dx Hairy cell
42
Rx ALL
vincristine, corticosteroids, and anthracycline (daunorubicin, doxorubicin, rubidazone, idarubicin), with or without cyclophosphamide or cytarabine
Maintenance : daily 6-mercaptopurine and weekly methotrexate
43
Poor prognosis in ALL
FAB L3 type
* T or B cell surface markers
* Philadelphia translocation, t(9;22)
* age < 2 years or > 10 years
* male sex
* CNS involvement
* high initial WBC (e.g. > 100 * 109/l)
44
most valuable test to confirm CLL
Immunophenotyping - shows circulating clonal B lymphocytes expressing particular antigens (CD5, CD19, CD20 and CD23).
45
Compare IX of choice in CLL & CML
CLL - Immunophenotyping + Smudge cells more likely to have Lymphadenopathy
CML-
**Cytogenetics** - Ph chromosome; **BM aspiration & biopsy** - material for cytogenetic. Also to quantify the % of blasts & degree of fibrosis
**leukocyte alkaline phosphatase test ** LOW
More likely to have hepatosplenomegaly
46
Compare IX of choice in Acute Luekimas
Both classification requires 20% or greater amount of blasts in BM or peripheral blood
AML - will have aura rods esp in PML
ALL- glycogen granules, Immunophenotyping for B vs T cells
47
Poor prognosis CLL
Poor prognostic factors (median survival 3-5 years)
- male sex
- age > 70 years
- lymphocyte count > 50
- prolymphocytes comprising more than 10% of blood lymphocytes
- lymphocyte doubling time < 12 months
- raised LDH
- CD38 expression positive
- TP53 mutation
(del 17p) are seen in around 5-10% of patients =poor prognosis
48
Leukimas that causes enlarged thymus
TALL
ALL
49
1. What is it call when a leukaemia cells enter the lymph node and change into a high-grade, fast-growing non-Hodgkin's lymphoma.
2. Which leukaemia does this happen
Richter's transformation
Ass w/ CLL
50
Rx CLL
Rx: fludarabine, cyclophosphamide and rituximab
51
Compare HL to NHL
Cells
Spread
Extra nodal
Age
**Hodgkin lymphoma**
-Reed-Sternberg
- arise from B-cells and
- spread in a contiguous manner,
-rarely involve extranodal sites.
-Bimodal age distribution-20 y.o > 60 years of age.
*Think: Older wiser owl cells(Reed-Sternberg) orderly (contiguous ) and quite (Not extra nodal)*
NHL
No Reed-Sternberg cells
- sometimes spread non-contiguously,
- Can involve extranodal sites: skin, GI & brain.
-children and adults
52
Name the 5 B-cell subtypes in NHL
1. **Follicular** -BCL2 gene t(14;18), waxing and weaning neck swelling. Prevent cell death
2. **Diffuse large B-cell**- (most common in adults) aggressive, most common BCL 2&6
3. **Burkitt** -myc – ass EBV, extra Nodal (ileocecal or jaw ) , starry sky appearance;
4. **Mantel**- Aggressive more common in male, translocation bcl1
5. **Marginal zone lymphoma** :Malt- extra nodal,
6. **lymphoplasmacytic lymphoma**- leads to Waldenstrom macroglobulinemia
53
Dx CLL
54
2 main subtypes of HL
Classical has CS 15 & CD 30 expressed
55
In HL what are the 4 subtypes of classical HL
Which has the best or worst prognosis
Which 2 are ass with Immcompromised
56
Which HL is ass with popcorn cells ?
Nodular lymphocytic predominant HL
57
How is NHL divided?
B cell & T cell
58
Name the two T cell NHLs
Adult T cell
Mycosis fungoides
59
Which T cell NHL causes sezary syndrome what is it ?
60
Useful prognostic indicator in lymphoma
ESR
61
How are NHL B & T differ
B cells have CS 20 expressed
62
NHL B-cell: Follicular lymphoma
Translocation causes over express of what gene
Think afternoon give follicles/ zits
63
NHL B-cell: most common & aggressive in adults
diffuse large cell lymphoma
BCL 2&6
64
NHL B-cell lymphoma: burkitts
Ass w/ virus
Translocation &gene
African presentation outside Africa
Starry skys in New York
65
NHL B-cell: mantle cell
Translocation & gene
Think pic should be mantle of els Brith
66
NHL B-cell: marginal zone lymphoma associated with
67
Which b cell lymphoma is ass with Waldenstorm macroglobinemia ?
68
Which NHL Tcell lymphoma is ass with HTLV ?
69
Ix of choice for lymphoma?
Excisional lumph node biopsy
70
Describe staging of NHL lymphoma
Ann Arbor system.
Stage 1 - One node affected
Stage 2 - More than one node affected on the same side of the diaphragm
Stage 3 - Nodes affected on both sides of the diaphragm
Stage 4 - Extra-nodal involvement e.g. Spleen, bone marrow or CNS
The stage is combined with the letter A or B to indicate the presence of 'B' symptoms. With the letter A indicating no B symptoms present and B indicating any of the beta symptoms present. For example, a patient with a single node affected and no 'B' symptoms would be stage 1A.
71
Name the 3 plasma cell disorders and what do they all produce ?
1. multiple myeloma,
2. monoclonal gammopathy of unknown significance or MGUS(em-gus),
3. Waldenström’s macroglobulinemia.
Each of them produce a monoclonal or M-protein,
72
Discuss lymphoma
73
Discuss lymphoma
74
Sx of MM
75
What M protein is produced in MM
most common IgG, followed by IgA, and these immunoglobulins have both a heavy and light chain.
Rarely, the myeloma cells can only make the **kappa or lambda light chain** of the immunoglobulin=the Bence-Jones protein.
76
what is Bence-Jones protein
kappa or lambda light chain** of the immunoglobulin
77
Ix MM
BM aspiration
Peripheral smear
Type of amemia
Serum & protein electrophoresis
78
Ix MM
BM aspiration
Peripheral smear
Type of amemia
Serum & protein electrophoresis
79
How does MGUs an MM differ
80
How does MM, Mgus and Waldenström’s macroglobulinemia differ
Serum Electrophoresis
skeletal survey
BM
**MM**
Sx CRABBI SPEP
**Serum Electrophoresis:** IgG /IgA OR NEG But urine = Bence-Jones protein.
**skeletal survey** - lytic lesions.
**BM:** >10% lymphoplasmacytic cells
**MGUS**- asymptomatic
**Serum Electrophoresis:** IgG
No lytic lesions
BM: <10% lymphoplasmacytic cells
**Waldenström’s macroglobulinemia**:
Sx hyperviscosity or autoantibodies
**Serum Electrophoresis:** IgM
BM: >10% lymphoplasmacytic cells.
81
SX of Waldenström’s macroglobulinemia
May be Asymptomatic
Hyperviscosity syndrome, = mucosal bleeding from the nose &gums.
Eyes-distension of retinal veins = retinopathy or blurring and loss of vision.
Raynaud
IgMs can also inappropriately act as autoantibodies against
RBC = autoimmune hemolytic anemi
Or attack sheaths of nerves = peripheral neuropathy.
lymphadenopathy, splenomegaly, and hepatomegaly
82
Rx MM
lenalidomide in combination with dexamethasone, and bortezomib either alone or in combination with pegylated doxorubicin
83
Rx tumour lysis syndrome
Rasburicase (a recombinant version of urate oxidase, an enzyme which catalyses the conversion of uric acid to allantoin*)
84
What is tumour lysis sx
hyperkalaemia, hyperphosphataemia, hyperuricaemia, hypocalcaemia & AKI
85
Age distribution in Leukaemia
ALL -children
CML- Middle age
AML - Older Middle age
CLL- old age
86
Tumour maker: Carcinoembryonic antigen (CEA)
Colorectal cancer
87
Tumour maker: S-100
Melanoma, schwannomas
88
Tumour maker :Alpha-feto protein (AFP)
Hepatocellular carcinoma, teratoma
89
Tumour maker CA125
Ovarian
90
Carcinogen Aflatoxin (produced by Aspergillus)
Liver - (hepatocellular carcinoma)
91
Carcinogen Aniline dyes
Bladder (transitional cell carcinoma)
92
Carcinogen Nitrosamines
Oesophageal and gastric cancer
93
Carcinogen Vinyl chloride
Hepatic angiosarcoma
94
t(15;17)
* seen in acute promyelocytic leukaemia (M3)
* fusion of PML and RAR-alpha genes
* Good prognositic Acute myeloid leukaemia
95
Oncovirus Epstein-Barr virus causes
(4)
Burkitt's lymphoma
Hodgkin's lymphoma
Post transplant lymphoma
Nasopharyngeal carcinoma
96
Oncovirus Human papillomavirus 16/18
Cervical cancer
Anal cancer
Penile cancer
Vulval cancer
Oropharyngeal cancer
97
Oncovirus Human herpes virus 8
Kaposi's sarcoma
98
Oncogenes ABL
Chronic myeloid leukaemia
99
Oncogenes BCL-2
Follicular lymphoma t(14;18)
100
Oncogenes RET
Multiple endocrine neoplasia (types II and III)
101
Oncogenes RAS
Many cancers especially pancreatic
102
Oncogenes n-MYC
Neuroblastoma
103
Oncogenes
gain of function results in an increased risk of cancer
104
Tumor suppressor genes
loss of function results in an increased risk of cancer
105
RX HL
**ABVD** (doxorubicin, bleomycin, vinblastine, and dacarbazine): considered the standard regime
BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone): alternative regime with better remission rates but higher toxicity
106
pentad of fever, neuro signs, thrombocytopenia, haemolytic anaemia and renal failure
TTP
ADAMTS13
107
Rx Methaemoglobinaemia
NADH methaemoglobinaemia reductase deficiency: **ascorbic acid**
acquired: IV **methylthioninium chloride (methylene blue)**
108
Rx cyanide poisoning
Dicobalt edetate & hydroxocobalamin
109
leukaemia that often presents as DIC
AML
Acute promyelocytic leukaemia
110
HbAS indicates
sickle cell trait
111
Hb SC indicates
is a milder form of sickle disease
112
Protein C deficiency + warfarin
=skin necrosis
113
deletions of part of the short arm of chromosome 17 (del 17p) in which leukaemia is associated with a poor prognosis
CLL
114
Low haptoglobin indicates
haemolytic anaemias
115
most common inherited thrombophilia
Activated protein C resistance (Factor V Leiden)
116
Haemolytic anaemias:
Intravascular haemolysis: causes
mismatched blood transfusion
G6PD deficiency*
red cell fragmentation: heart valves, TTP, DIC, HUS
paroxysmal nocturnal haemoglobinuria
cold autoimmune haemolytic anaemia
*stay inside as it a cold night for a meditarainin*
117
Extravascular haemolysis causes
haemoglobinopathies: sickle cell, thalassaemia
hereditary spherocytosis
haemolytic disease of newborn
warm autoimmune haemolytic anaemia
118
Hereditary angioedema screening
C4 are low
119
Hereditary angioedema to confirm the diagnosis
serum C1-INH levels
120
aromatase inhibitors Example and function & SE
Anastrozole and letrozole
reduces peripheral oestrogen synthesis
**Adverse effects**
osteoporosis
hot flushes
arthralgia, myalgia
insomnia
121
Hereditary spherocytosis what is it
genetic inheritance
decent
Triggers
Blood film
Choice Ix
G6PD deficiency
- Male (X-linked recessive
-**Descent** African + Mediterranean
**Triggers** : Infection/drugs
**Blood film**Heinz bodies
**Ix:** enzyme activity of G6PD
Hereditary spherocytosis (AD)- Male + female
- Northern European
**Trigger:** infection
**Film** Spherocytes (round, lack of central pallor)
**Ix:** EMA binding test
122
ECOG score performance status' scale
0 Fully active, able to carry on all pre-disease performance without restriction
1 Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work
2 Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours
3 Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours
4 Completely disabled; cannot carry on any selfcare; totally confined to bed or chair
5 Dead
123
good response to a single dose of adrenaline & complete resolution of symptoms
Resus Council UK recommend how long before discharge
2 Hours
124
Resus Council UK recommend how long before discharge :
2 doses of IM adrenaline needed, or
previous biphasic reaction
6 hours
125
Resus Council UK recommend how long before discharge :
severe rnx requiring > 2 doses of IM adrenaline
- pt has severe asthma
possibility of an ongoing reaction (e.g. slow-release medication)
Pt presents late at night
pt in areas litmited access to care may
minimum 12 hours after symptom resolution
126
How do you distinguish between
transfusion related lung injury (TRALI ) &
transfusion associated circulatory overload (TACO)
TACO presents with **HYPERtension** often without F and leukopenia,
127
What causes
recurrent bacterial infections (e.g. Chest)
eczema
thrombocytopaenia
low IgM levels
Wiskott-Aldrich syndrome
X-linked recessive
127
What are Irradiated blood products and what are they used for
depleted of T-lymphocytes and used to avoid transfusion-associated graft versus host disease (TA-GVHD)
✓ Bone marrow / stem cell transplants
✓ Immunocompromised (chemo/congenital)
✓Pts with/previous Hodgkin lymphoma
✓ Granulocyte transfusions
✓ Intra-uterine transfusions
✓ Neonates
128
Polycythaemia rubra vera can progress to
myelofibrosis or AML
129
Rx vitamin B12 deficiency no neuro sx and no folate deficiency
1 mg of IM hydroxocobalamin 3 times each week for 2 weeks, then once every 3 months
if a pt is also deficient in folic acid then it is important to treat the B12 deficiency first to avoid precipitating subacute combined degeneration of the cord
130
most common cause of neutropenic sepsis
Coagulase-negative, Gram-positive bacteria such as Staphylococcus epidermidis
131
low neutrophils, splenomegaly and rheumatoid arthritis
Felty's syndrome
131
rx smoldering multiple myeloma
watch and wait
132
What is the underlying problem in methaemoglobinaemia
oxidation of Fe2+ in haemoglobin to Fe3+
normally regulated by NADH methaemoglobin reductase
Rx NADH methaemoglobinaemia reductase deficiency: ascorbic acid
IV methylthioninium chloride (methylene blue) if acquired
133
most common inherited thrombophilia
Activated protein C resistance (Factor V Leiden) i
134
Organomegaly with no bone lesions
Waldenstrom's macroglobulinaemia
135
Irinotecan MAO
inhibits topoisomerase I which prevents relaxation of supercoiled DNA
Doesn't iron it out
136
Hodgkin's lymphoma - best prognosis =
lymphocyte predominant
137
CLL Indications for Rx
BM failure:- worsening of anaemia and/or thrombocytopenia
lymphadenopathy massive (>10 cm)/ progressive
splenomegaly massive (>6 cm) or progressive
progressive lymphocytosis: > 50% increase over 2 months or lymphocyte doubling time < 6 months
systemic symptoms:
- weight loss > 10% Over 6 mo,
-F >38ºC for > 2 weeks,
extreme fatigue, night sweats
autoimmune cytopaenias e.g. ITP
138
RX CLL
fludarabine, cyclophosphamide and rituximab (FCR)
139
best diagnostic test for paroxysmal nocturnal
Flow cytometry for CD59 and CD55 is the gold standard test for paroxysmal nocturnal haemoglobinuria
140
What is Rasburicase
recombinant version of urate oxidase, an enzyme that metabolizes uric acid to allantoin
