Haematology and Oncology Flashcards
Blood Film Findings in Hyposplenism
Howell Jolly Bodies
Lemiere’s Sydrome
= thrombophelbitis of internal jugular vein
Usually occurs as secondary to throat infection
Disproportionate Microcytosis in Anaemia
Thalassaemia Trait
Mild Haemophilia A
- Needs procedure e.g. dental work - what is given?
Desmopressin
= promotes endogenous factor VIII and vWF factor production to avoid need for exogenous
Management of benefit in acute chest crisis
Transfusion threshold
Incentive spirometry
Usually >100 aiming for Hb - haematologist decision
Myelofibrosis blood film finding
Tear drop poikilocytes
- shedding a tear because fear of myelofibrosis
CD marker found on Reed Sternberg cells
CD 15
Leukaemoid reaction
Left shift neutrophils
= bone marrow reaction to stress or infection
Management of Acute Promyelocytic Leukaemia
All-trans retinoic acid (ATRA)
Pathogenesis of TTP
Failure to cleave vWF normally
- deficiency of ADAMTS13 protein which usually does the cleaving
What is LAP?
High LAP
Low LAP
LAP = leukocyte alkaline phosphatase
Found within mature WBC
High = mature WBC pathology e.g. myelofibrosis
Low = immature WBC pathology e.g. CML
What is associated with a poor prognosis in lymphoma?
B symptoms
Mechanism of action of LMWH heparin
Activation of antithrombin III
Inhibits factor Xa only
(LMWH is low-key, activates AT3)
Mechanism of action of standard heparin
Inhibits factors inc Xa, IXa, Xia, XIIa
Mechanism of action of DOAC
Direct Xa inhibition
Complication of plasma exchange
- why?
Hypocalcaemia
Contains sodium citrate which chelates calcium
Citrate used as anticoagulant
Test for hereditary spherocytosis
EMA binding test
- has replaced osmolality fragility test
Types of Hb
A - adult (a+b chains)
A2
Foetal (a+gamma chains)
Iron found in
- haemoglobin
- myoglobin
- Methahaemoglobin
Hb = Fe2+
Myo = Fe2+
Metha = Fe3+
Oxygen Dissociation Curve
- shift to the right =
- shift to the left =
Right = reduced affinity for oxygen, releases O2 at tissues better
Left = increased affinity for oxygen, doesn’t release as easily (sticky)
Factors which shift the Hb curve to the left (5)
= increased affinity for O2
LOW pCO2
LOW H+ (alkali)
LOW temp
HIGH carbon monoxide
Foetal haemoglobin
Factors which shift the Hb curve to the right (3)
= decreased affinity for O2
HIGH H+ (acid)
HIGH temp
HIGH pCO2
Pathophysiology of sickle cell anaemia
- Homozygous
- Heterozygous
Amino acid substitution on B chain
Can only make A2 and F haemoglobin if homozygous
Can make HbA if heterozygous
Why is haptoglobin low in haemolytic anaemia?
Haptoglobin binds to free Hb and clears it
= consumed in haemolytic anaemia
= low
What is the cause of factor V leiden?
Activated protein C resistance
(HOT TO GO)
In ITP what are the antibodies directed against?
Glycoprotein
Herceptin =
Trastuzumab
Used in HER2 positive breast cancer`
Pathophysiology of CLL
= monoclonal B cell proliferation
(vs myeloma which is plasma cell clones)
Positive diagnosis of anti-phospholipid syndrome
Antibodies
e.g. anti-cardiolipin, glycoprotein B2
on at least 2 occasions, 12 weeks apart
AA vs AL amyloid `
AA = inflammatory conditions e.g. rheumatoid arthritis, renal presentation most common
AL = more common, 2y to malignancy
Chromosome associated with alpha thalassaemia
Ch 16
(almost 16 letters)
Why do you give desmopressin in vWF
Desmopressin encourages release of vWF from the endothelial cells
(similar mechanism to use in haemophilia)
t11:14 association
Mantle cell lymphoma
What is the mechanism of action in Heparin induced thrombocytopaenia?
Antibodies against complexes of platelet factor and heparin
What is used as prophylaxis in sickle cell disease?
Hydroxyurea
Gene mutation in hairy cell leukaemia
BRAF
Mastocytosis VS Mast cell leukaemia
No blasts on blood film
Why is INF-a useful in hairy cell leukaemia?
INFa = anti-viral action
Useful in malignancies associated with viruses
e.g. kaposi’s sarcoma, hairy cell leukaemia
Presentation of hairy cell leukaemia (4)
Splenomegaly
Weight loss
Lymphocytosis
Cells with broad based projections
Vincristine
- mechanism
- side effect
Inhibits mitosis
S/E: peripheral neuropathy
Cyclophosphamide
- mechanism
- side effect
Promotes cross linking of DNA
S/E: haemorrhagic cystitis
Doxorubicin
- mechanism
- side effect
Stabilises DNA topoisomerase which inhibits DNA/RNA synthesis
S/E: cardiomyopathy
Bleomycin
- mechanism
- side effect
Degrades DNA
S/E: lung fibrosis - lower zones
Cisplatin
- side effects (4)
Nephrotoxic
Ototoxic
Peripheral neuropathy
Hypomagnesaemia
Causes of intravascular haemolysis (5)
Acute haemolytic transfusion reaction
G6PD deficiency
Cold AIHA
Paroxysmal nocturnal haemoglobinuria
Red cell fragmentation
Extravascular causes of haemolysis (4)
Sickle cell disease
Thalassaemia
Haemolytic disease of the newborn
Warm AIHA
What is the cause of a positive Schumm test?
Intravascular haemolysis
Causes of cold AIHA (3)
Mycoplasma
EBV
Lymphoma
Causes of warm AIHA (4)
Penicillin
Cephalosporins
Lymphoma
SLE
Ch responsible for alpha chain in Hb
Ch 16
Genetic issue in sickle cell disease
Amino acid substitution
Glutamate substitutes for valine at codon 6
Ch responsible for beta chain Hb
Ch 11
Lead poisoning
- microscope finding
- defect
Basophilic stippling
Defect in ferrochelatase ALA dehydratase
Defect in sideroblastic anaemia
- finding
Delta aminolevulinate synthase 2
Sideroblasts
What is the role of G6PD?
Promotes production of NADPH which promotes generation of gluthianone which protects RBC from oxidative damage
Pathophysiology of paroxysmal nocturnal haemoglobinuria
Pig A mutation
Reduced GPI
Reduced DAF - results in unregulated complement damage and intravascular AIHA
Investigation of paroxysmal nocturnal haemoglobinuria
Flow cytometry - see a lack of CD59/CD55
What is the indirect coomb’s test used for?
Detects free and unbound antibodies against specific antigens
Worst prognosis of Hodgkin’s lymphoma
Lymphocyte depleted
What is the Schumm test?
When haptoglobin becomes saturated the Hb binds to albumin = methemalbumin
What is the most common subtype of Hodgkin’s Lymphoma?
Nodular sclerosing
Genetic mutation associated with Burkitt’s lymphoma
c-myc
8:14 translocation
What is a stage 3 Hodgkin’s lymphoma?
= positive lymph nodes either side of the diaphragm
What is JAK2?
It is a non-receptor tyrosine kinase which stimulates growth
Percentage with myelodysplasia which progress to AML?
30%
Why do you get splenomegaly in myelofibrosis?
- investigation finding
Bone marrow fibrosis means there is extramedullary haematopoiesis
Tear drop poikilocytes
Primary polycythaemia =
= polycythaemia rubra vera
Investigation findings in PRV (4)
Low ESR
High leukocyte ALP
High Hb
Low epo
Management of essential thrombocytosis
Hydroxyurea
Features suggestive of poor prognosis in AML (2)
<60 years
Deletions at Ch 5 or 7
Investigation findings in AML (3)
Auer rods
>30% blasts in BM
15:17 in APML
Induction chemotherapy in AML
Cytarabine + anthracycline
(then consolidation)
Management of CML (2)
Imatinib
Hydroxyurea
Investigation findings in CML (3)
Ch 9: 22 - philadelphia chromosome
= BCR-ABL proto-oncogene
Low leukocyte ALP
Poor prognostic markers in CLL (2)
Association with CLL
TP53
CD38
Warm AIHA
Richter’s transformation ?
Transformation of CLL to high grade NHL
Management of CLL
- chemotherapy regimen
RT usually
Chemo = FCR
Fludarabine, Cyclophosphamide, Rituximab
Good prognosis in CLL
13q14 deletion
Poor prognostic markers in ALL (2)
4:11 translocation
Philadelphia chromosome
Features of hyposplenism on blood film (3)
Howell Jolly bodies
Target cells
Pappenheimer bodies
Features of IDA on blood film (2)
Target cells
Pencil poikilocytes
Feature of megaloblastic anaemia on blood film
Hypersegmented neutrophils
What is hairy cell leukaemia?
A subset of CLL
Association of AL amyloidosis
Malignancy - MGUS, waldenstrom’s, myeloma
Association of AA amyloid (3)
Chronic infection
SLE
TB
What is Waldenstrom’s macroglobulinaemia associated with?
Cryoglobulinaemia I (monoclonal proliferation)
mGUS vs myeloma investigation finding
mGUS = normal B2 microglobulin
Causes of acquired Haemophilia A (6)
- mechanism
Psoriasis
Malignancy
Pemphigus
IBD
Phenytoin
RA
= IgG antibodies with factor VIII
Mechanism of action of TXA
Inhibits plasminogen conversion to plasmin
Investigation findings in vWF (2)
Slightly raised APTT
Reduced factor VII
Primary haemostasis
- 3 steps
Platelet adhesion - via GP1b receptors and vWF
Platelet activation - release of ADP to GP2b/3a receptors and release of TA2 resulting in chemotaxis
Platelet aggregation = platelet plug
Problem in methahaemaglobinaemia
Fe2+ oxidised to Fe3+
= reduced capacity for O2 carrying, high affinity for oxygen, poor release of O2 at tissues
Investigation finding in methahaemoglobinaemia
Management
ABG - normal PaO2 but low SaO2
Methylene blue
What is the mechanism in ITP?
IgG antibodies against GP2b3a
What is Evan’s syndrome?
ITP + AIHA
Features of systemic mastocytosis (3)
Urticaria
Flushing
Darrier’s sign = wheals appearing on rubbing the skin
Management of HIT?
Stop heparin
Do not give warfarin - can trigger necrosis skin reaction
Genetic change in haemochromatosis
HFE gene on chromosome 6
What can you reverse in haemochromatosis with treatment?
Skin pigmentation
DCM
What do you need to do prior to elective splenectomy?
Vaccinations 2/52 before
Pneumococcus
Haemophilus influenza
Men A/C
Influenza
Investigation findings in haemochromatosis (3)
Raised transferrin
Raised ferritin
Chondrocalcinosis
