Heme/Onc Flashcards
Medications that increase risk of VTE
- 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)
‘tear-drop’ poikilocytes, massive splenomegaly, dry tap
Myelofibrosis
What is Bombesin is a tumour marker for
small cell lung carcinomas
Most common tumour causing bone metastases
Prostate
Breast
Lung
Sickle cell how does acute chest syndrome present
dyspnoea, CP, pulmonary infiltrates on chest x-ray, low pO2
transfusion: improves oxygenation
4 Heme disorders
Sideroblastic- ala synthase / vit b6
Acute intermittent porphyria - mutation porphobilinogen demainase
Lead poisoning - ala dehydratase & ferrochelarase
Porphyria cutanea tarda- decrease uroporphyinogen decarboxylase
Ix sideroblastic anemia & rx
Blood letting
Deferoxamine
Severe bm or liver transplant
Causes of lead poisoning
Sx lead poisoning
Dx and rx lead poisoning
Cause of acute intermittent porphyria and triggeres
Build up of Ala & porphobilinogen
Sx & rx of AIP
Raised urinary porphobilinogen (btwn attack)
Raised delta aminolaevulinic acid
Causes of Porphyria cutanea tarda
Sx & rx of PCT
Rx: avoid triggers. Phlebotomy, hydroxychloroquine
Difference between PCT & AIP
AIP urine = raised urinary prophobiliogen
PCT= Uroporphyrinogin
What happens when HbS is deoxygenated?
Sickling an polymerisation of hb
Blood markers of hemolysis
Haptoglobin mop up Hema = reduced haptaglobin = unconjugated bilirubin a
How does sickle cell affect bones
How does sickle cell effect the spleen
Fibrosis
Sequestration of blood —> infarction
Increases susceptibility
How does sickle cell effect kidney & penis
What are the long term rx of sickle cell?
Hydroxyurea - increasing HbF prevents crisis
Every 5 years pneumococcal vaccine
Explain the genetics of sickle cell
Glutamic acid is swapped with valine on chrom 11 = decrease HbA and increase hbs
AR
Carrier state exists
What is the most common cause of death in Sickle cell
acute chest syndrome
What causes increased HbA2
Target cells & anisopoikilocytosis ?
Why does parvovirus cause aplastic anemia in beta thalassmia and sickle cell
Suppresses rbc production = crisis
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
Where do abnormal Leukemias cells deposit?
- liver and spleen = hepatosplenomegaly,
- lymph nodes = lymphadenopathy,
- skin causing purple or flesh colored plaques or nodules = leukemia cutis.
Lymphomas vs Leukemias typically form
Lymphomas solid - tumors in lymphatic tissue such as lymph nodes, thymus, or spleen.
Leukemias - bone marrow or blood.
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
What can cause acute leukaemias
Translocation
Both Ass w/ - RAD
Only AML
Most common type of AML
What is its translocation
What is rx
APL 15;17
Vit A & arsenic
I’m ALL what cells are abnormal?
Can be
Bcells in 80% of cases
Or
T cells
Which leukaemias are ass with Philadelphia chrom?
9:22 ALL & CML
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
CCL
Cell type
Ix of choice
Labs
Blood flim
Rx
B-cells
Immunophenotyping
Smudge cells
ITP + autoimmune haemolytic anemia
FCR : fludarabine, cyclophosphamide, rituximab
What chronic leukaemia is ass w/ BRAF gene
What effect does this have on the bone
Hairy cell
Bm fibrosis = pancytopenia + severe spleenomegally
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
CML ix
Cytogenetics - Philadelphia chrom
Lukocyte alkaline phosphatase - low (differs from other myeloproliferative disorders
BM aspiration- to qualify blast & fibrosis
How can you differentiate aml from ALL as on BM aspiration shows >20% blast cell (bm or peripheral bl)
Myloblasts have aura rods
Immunophenotyping
Dx Hairy cell
Rx ALL
vincristine, corticosteroids, and anthracycline (daunorubicin, doxorubicin, rubidazone, idarubicin), with or without cyclophosphamide or cytarabine
Maintenance : daily 6-mercaptopurine and weekly methotrexate
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)
most valuable test to confirm CLL
Immunophenotyping - shows circulating clonal B lymphocytes expressing particular antigens (CD5, CD19, CD20 and CD23).
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
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
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
Leukimas that causes enlarged thymus
TALL
ALL
- What is it call when a leukaemia cells enter the lymph node and change into a high-grade, fast-growing non-Hodgkin’s lymphoma.
- Which leukaemia does this happen
Richter’s transformation
Ass w/ CLL
Rx CLL
Rx: fludarabine, cyclophosphamide and rituximab
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
Name the 5 B-cell subtypes in NHL
- Follicular -BCL2 gene t(14;18), waxing and weaning neck swelling. Prevent cell death
- Diffuse large B-cell- (most common in adults) aggressive, most common BCL 2&6
- Burkitt -myc – ass EBV, extra Nodal (ileocecal or jaw ) , starry sky appearance;
- Mantel- Aggressive more common in male, translocation bcl1
- Marginal zone lymphoma :Malt- extra nodal,
- lymphoplasmacytic lymphoma- leads to Waldenstrom macroglobulinemia
Dx CLL
2 main subtypes of HL
Classical has CS 15 & CD 30 expressed
In HL what are the 4 subtypes of classical HL
Which has the best or worst prognosis
Which 2 are ass with Immcompromised
Which HL is ass with popcorn cells ?
Nodular lymphocytic predominant HL
How is NHL divided?
B cell & T cell
Name the two T cell NHLs
Adult T cell
Mycosis fungoides
Which T cell NHL causes sezary syndrome what is it ?
Useful prognostic indicator in lymphoma
ESR
How are NHL B & T differ
B cells have CS 20 expressed
NHL B-cell: Follicular lymphoma
Translocation causes over express of what gene
Think afternoon give follicles/ zits
NHL B-cell: most common & aggressive in adults
diffuse large cell lymphoma
BCL 2&6
NHL B-cell lymphoma: burkitts
Ass w/ virus
Translocation &gene
African presentation outside Africa
Starry skys in New York
NHL B-cell: mantle cell
Translocation & gene
Think pic should be mantle of els Brith
NHL B-cell: marginal zone lymphoma associated with
Which b cell lymphoma is ass with Waldenstorm macroglobinemia ?
Which NHL Tcell lymphoma is ass with HTLV ?
Ix of choice for lymphoma?
Excisional lumph node biopsy
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.
Name the 3 plasma cell disorders and what do they all produce ?
- multiple myeloma,
- monoclonal gammopathy of unknown significance or MGUS(em-gus),
- Waldenström’s macroglobulinemia.
Each of them produce a monoclonal or M-protein,
Discuss lymphoma
Discuss lymphoma
Sx of MM
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.
what is Bence-Jones protein
kappa or lambda light chain** of the immunoglobulin
Ix MM
BM aspiration
Peripheral smear
Type of amemia
Serum & protein electrophoresis
Ix MM
BM aspiration
Peripheral smear
Type of amemia
Serum & protein electrophoresis
How does MGUs an MM differ
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.
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
Rx MM
lenalidomide in combination with dexamethasone, and bortezomib either alone or in combination with pegylated doxorubicin
Rx tumour lysis syndrome
Rasburicase (a recombinant version of urate oxidase, an enzyme which catalyses the conversion of uric acid to allantoin*)
What is tumour lysis sx
hyperkalaemia, hyperphosphataemia, hyperuricaemia, hypocalcaemia & AKI
Age distribution in Leukaemia
ALL -children
CML- Middle age
AML - Older Middle age
CLL- old age
Tumour maker: Carcinoembryonic antigen (CEA)
Colorectal cancer
Tumour maker: S-100
Melanoma, schwannomas
Tumour maker :Alpha-feto protein (AFP)
Hepatocellular carcinoma, teratoma
Tumour maker CA125
Ovarian
Carcinogen Aflatoxin (produced by Aspergillus)
Liver - (hepatocellular carcinoma)
Carcinogen Aniline dyes
Bladder (transitional cell carcinoma)
Carcinogen Nitrosamines
Oesophageal and gastric cancer
Carcinogen Vinyl chloride
Hepatic angiosarcoma
t(15;17)
- seen in acute promyelocytic leukaemia (M3)
- fusion of PML and RAR-alpha genes
- Good prognositic Acute myeloid leukaemia
Oncovirus Epstein-Barr virus causes
(4)
Burkitt’s lymphoma
Hodgkin’s lymphoma
Post transplant lymphoma
Nasopharyngeal carcinoma
Oncovirus Human papillomavirus 16/18
Cervical cancer
Anal cancer
Penile cancer
Vulval cancer
Oropharyngeal cancer
Oncovirus Human herpes virus 8
Kaposi’s sarcoma
Oncogenes ABL
Chronic myeloid leukaemia
Oncogenes BCL-2
Follicular lymphoma t(14;18)
Oncogenes RET
Multiple endocrine neoplasia (types II and III)
Oncogenes RAS
Many cancers especially pancreatic
Oncogenes n-MYC
Neuroblastoma
Oncogenes
gain of function results in an increased risk of cancer
Tumor suppressor genes
loss of function results in an increased risk of cancer
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
pentad of fever, neuro signs, thrombocytopenia, haemolytic anaemia and renal failure
TTP
ADAMTS13
Rx Methaemoglobinaemia
NADH methaemoglobinaemia reductase deficiency: ascorbic acid
acquired: IV methylthioninium chloride (methylene blue)
Rx cyanide poisoning
Dicobalt edetate & hydroxocobalamin
leukaemia that often presents as DIC
AML
Acute promyelocytic leukaemia
HbAS indicates
sickle cell trait
Hb SC indicates
is a milder form of sickle disease
Protein C deficiency + warfarin
=skin necrosis
deletions of part of the short arm of chromosome 17 (del 17p) in which leukaemia is associated with a poor prognosis
CLL
Low haptoglobin indicates
haemolytic anaemias
most common inherited thrombophilia
Activated protein C resistance (Factor V Leiden)
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
Extravascular haemolysis causes
haemoglobinopathies: sickle cell, thalassaemia
hereditary spherocytosis
haemolytic disease of newborn
warm autoimmune haemolytic anaemia
Hereditary angioedema screening
C4 are low
Hereditary angioedema to confirm the diagnosis
serum C1-INH levels
aromatase inhibitors Example and function & SE
Anastrozole and letrozole
reduces peripheral oestrogen synthesis
Adverse effects
osteoporosis
hot flushes
arthralgia, myalgia
insomnia
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 filmHeinz 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
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
good response to a single dose of adrenaline & complete resolution of symptoms
Resus Council UK recommend how long before discharge
2 Hours
Resus Council UK recommend how long before discharge :
2 doses of IM adrenaline needed, or
previous biphasic reaction
6 hours
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
How do you distinguish between
transfusion related lung injury (TRALI ) &
transfusion associated circulatory overload (TACO)
TACO presents with HYPERtension often without F and leukopenia,
What causes
recurrent bacterial infections (e.g. Chest)
eczema
thrombocytopaenia
low IgM levels
Wiskott-Aldrich syndrome
X-linked recessive
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
Polycythaemia rubra vera can progress to
myelofibrosis or AML
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
most common cause of neutropenic sepsis
Coagulase-negative, Gram-positive bacteria such as Staphylococcus epidermidis
low neutrophils, splenomegaly and rheumatoid arthritis
Felty’s syndrome
rx smoldering multiple myeloma
watch and wait
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
most common inherited thrombophilia
Activated protein C resistance (Factor V Leiden) i
Organomegaly with no bone lesions
Waldenstrom’s macroglobulinaemia
Irinotecan MAO
inhibits topoisomerase I which prevents relaxation of supercoiled DNA
Doesn’t iron it out
Hodgkin’s lymphoma - best prognosis =
lymphocyte predominant
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
RX CLL
fludarabine, cyclophosphamide and rituximab (FCR)
best diagnostic test for paroxysmal nocturnal
Flow cytometry for CD59 and CD55 is the gold standard test for paroxysmal nocturnal haemoglobinuria
What is Rasburicase
recombinant version of urate oxidase, an enzyme that metabolizes uric acid to allantoin
