Haematology and Oncology Flashcards
What is the single most important test in determining the prognosis in acute myeloid leukemia?
Cytogenetic analysis is the most important prognostic factor in acute myeloid leukaemia (AML).
Specific chromosomal abnormalities are strongly associated with treatment outcomes and survival rates. For example, t(8;21), inv(16), and t(15;17) are associated with favourable prognosis, while complex karyotype, monosomy 5 or 7, and 11q23 abnormalities indicate poor prognosis. This information directly influences treatment decisions and helps predict response to therapy.
What are some features of lead poisoning?
Features
abdominal pain
peripheral neuropathy (mainly motor)
neuropsychiatric features
fatigue
constipation
blue lines on gum margin (only 20% of adult patients, very rare in children)
What are the investigations for lead poisoning?
1) Lead levels in bloods greater than 10 mcg/dl are considered significant
2) FBC: microcytic anaemia. Blood film shows red cell abnormalities including basophilic stippling and clover-leaf morphology
3) Raised serum and urine levels of delta aminolaevulinic acid may be seen (making it sometimes difficult to differentiate from acute intermittent porphyria)
4) Urine coproporphyrin is also increased (urinary porphobilinogen and uroporphyrin levels are normal to slightly increased). In children, lead can accumulate in the metaphysis of the bones although x-rays are not part of the standard work-up
How is lead poisoning managed?
Management
various chelating agents are currently used:
dimercaptosuccinic acid (DMSA)
D-penicillamine
EDTA
dimercaprol
How does acute intermittent porphyria typically present?
The classical presentation is a combination of abdominal, neurological and psychiatric symptoms:
abdominal: abdominal pain, vomiting
neurological: motor neuropathy
psychiatric: e.g. depression
hypertension and tachycardia common
What can you measure in someone who is having an acute intermittent porphyria attack?
Urinary porphobilinogen
What is the pathophysiology of acute intermittent porphyria?
Acute intermittent porphyria (AIP) is a rare autosomal dominant condition caused by a defect in porphobilinogen deaminase, an enzyme involved in the biosynthesis of haem. The results in the toxic accumulation of delta aminolaevulinic acid and porphobilinogen. It characteristically presents with abdominal and neuropsychiatric symptoms in 20-40-year-olds. AIP is more common in females (5:1)
How can you diagnose acute intermittent pophyria?
classically urine turns deep red on standing
raised urinary porphobilinogen (elevated between attacks and to a greater extent during acute attacks)
assay of red cells for porphobilinogen deaminase
raised serum levels of delta aminolaevulinic acid and porphobilinogen
How is immune thrombocytopenia managed?
First line treatment for ITP is oral prednisolone
pooled normal human immunoglobulin (IVIG) may also be used
it raises the platelet count quicker than steroids, therefore may be used if active bleeding or an urgent invasive procedure is required
splenectomy is now less commonly use
How do you manage acute intermittent pophyria?
1) avoiding triggers
2) acute attacks:
IV haematin/haem arginate
IV glucose should be used if haematin/haem arginate is not immediately available
Name the medications which may cause drug-induce pancytopenia
Drug causes of pancytopaenia:
- cytotoxics
- antibiotics: trimethoprim, chloramphenicol
- anti-rheumatoid: gold, penicillamine
carbimazole*
- anti-epileptics: carbamazepine
- sulphonylureas: tolbutamide
Which antibodies are typically seen in immune thrombocytopenia?
Antibodies are directed against the glycoprotein IIb/IIIa or Ib-V-IX complex.
What is Evan’s syndrome?
ITP in association with autoimmune haemolytic anaemia (AIHA)
How does cyclophosphamide work?
Cyclophosphamide is an alkylating agent which causes cross-linking in DNA
What are some adverse effects of cyclophosphamide?
Adverse effects include: haemorrhagic cystitis, myelosuppression, transitional cell carcinoma
How do these cytotoxic antibiotics work?
1) Bleomycin
2) Anthracyclins
Bleomycin: degrades preformed DNA
Anthracyclins e.g. doxorubicin: stabilises DNA-topoisomerase II complex inhibits DNA & RNA synthesis
What is meant by the ‘leukaemoid reaction’?
The leukaemoid reaction describes the presence of immature cells such as myeloblasts, promyelocytes and nucleated red cells in the peripheral blood. This may be due to infiltration of the bone marrow causing the immature cells to be ‘pushed out’ or sudden demand for new cells
Causes
severe infection
severe haemolysis
massive haemorrhage
metastatic cancer with bone marrow infiltration
How can you distinguish between a leukaemoid reaction and chronic myeloid leukaemia?
Leukaemoid reaction
high leucocyte alkaline phosphatase score
toxic granulation (Dohle bodies) in the white cells
‘left shift’ of neutrophils i.e. three or fewer segments of the nucleus
Chronic myeloid leukaemia
low leucocyte alkaline phosphatase score
What is the universal donor of fresh frozen plasma?
AB RhD negative blood
What are the adverse effects of cytotoxic agents?
1) Bleomycin
2) Anthracyclines
1) Bleomycin - haemorrhagic cystitis
2) Anthracyclines - cardiomyopathy
What is the pathophysiology of G6PD deficiency?
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the commonest red blood cell enzyme defect. It is more common in people from the Mediterranean and Africa and is inherited in an X-linked recessive fashion. Many drugs can precipitate a crisis as well as infections and broad (fava) beans
What are some features of G6PD?
1) neonatal jaundice is often seen
2) intravascular haemolysis
3) gallstones are common
4) splenomegaly may be present
5) Heinz bodies on blood films. Bite and blister cells may also be seen
What are some medications which may cause haemolysis in G6PD?
Some drugs causing haemolysis
anti-malarials: primaquine
ciprofloxacin
sulph- group drugs: sulphonamides, sulphasalazine, sulfonylureas
What is the inheritance pattern of hereditary spherocytosis?
Autosomal dominant
How does the blood film for someone with G6PD differ from a patient with hereditary spherocytosis?
G6PD: Heinz bodies
HS: Spherocytes (round, lack of central pallor)
How do you diagnose G6PD and hereditary spherocytosis?
G6PD: measure enzyme activity of G6PD
HS: EMA binding
How is chronic lymphocytic leukaemia managed?
Indications for treatment
progressive marrow failure: the development or worsening of anaemia and/or thrombocytopenia
massive (>10 cm) or progressive lymphadenopathy
massive (>6 cm) or progressive splenomegaly
progressive lymphocytosis: > 50% increase over 2 months or lymphocyte doubling time < 6 months
systemic symptoms: weight loss > 10% in previous 6 months, fever >38ºC for > 2 weeks, extreme fatigue, night sweats
autoimmune cytopaenias e.g. ITP
Management
1) patients who have no indications for treatment are monitored with regular blood counts
2) fludarabine, cyclophosphamide and rituximab (FCR) has now emerged as the initial treatment of choice for the majority of patients (for fit patients with intact TP53 and with mutated IGHV)
3) ibrutinib may be used in patients who have failed a previous therapy
Which type of acute myeloid leukaemia has a good prognosis?
t(15;17) - a fusion of PML and RAR-alpha genes. It generally presents younger than other types of AML and has a much better prognosis.
What would you see on the blood film for someone with acute myeloid leukaemia?
Auer rods (seen with myeloperoxidase stain)
What are the conditions that cause combined B- and T-cell disorders?
Combined B- and T-cell disorders: SCID WAS ataxic (SCID, Wiskott-Aldrich syndrome, ataxic telangiectasia)
Which conditions are typically associated with thymomas?
Associated with
myasthenia gravis (30-40% of patients with thymoma)
red cell aplasia
dermatomyositis
also : SLE, SIADH
Which cancers is Bombesin raised in?
Small cell lung carcinoma, gastric cancer, neuroblastoma
How do you differentiate between MGUS and myeloma?
Differentiating features from myeloma
- normal immune function
- normal beta-2 microglobulin levels
- lower level of paraproteinaemia than myeloma (e.g. < 30g/l IgG, or < 20g/l IgA)
- stable level of paraproteinaemia
- no clinical features of myeloma (e.g. lytic lesions on x-rays or renal disease)
How are the subtypes of monoclonal gammopathy of undetermined significance (MGUS, also known as benign paraproteinaemia and monoclonal gammopathy)?
Subtypes:
Non-IgM MGUS
most common
may progress to multiple myeloma or AL amyloidosis
IgM MGUS
may progress to Waldenström macroglobulinaemia or lymphoma
Light chain MGUS
increased risk of renal disease or AL amyloidosis
What is the most common inherited thrombophilia?
Factor V Leiden is the commonest inherited thrombophilia
What are some investigation results which would be suggestive of myelofibrosis?
anaemia
high WBC and platelet count early in the disease
‘tear-drop’ poikilocytes on blood film
unobtainable bone marrow biopsy - ‘dry tap’ therefore trephine biopsy needed
high urate and LDH (reflect increased cell turnover)
dry tap
What is the pathogenesis of thrombotic thrombocytopenic purpura (TTP)?
1) abnormally large and sticky multimers of von Willebrand’s factor cause platelets to clump within vessels
2) in TTP there is a deficiency of ADAMTS13 (a metalloprotease enzyme) which breakdowns (‘cleaves’) large multimers of von Willebrand’s factor
overlaps with haemolytic uraemic syndrome (HUS)
What are the causes of thrombotic thrombocytopenic purpura (TTP)?
1) post-infection e.g. urinary, gastrointestinal
2) pregnancy
3) drugs: ciclosporin, oral contraceptive pill, penicillin, clopidogrel, aciclovir
4) tumours
5) SLE
6) HIV
What is associated most with a poor prognosis in acute myeloid leukaemia?
Poor prognosis: deletion of chromosome 5 or 7
What is the most common organism causing neutropenic sepsis?
Coagulase-negative, Gram-positive bacteria such as Staphylococcus epidermidis are the most common cause of neutropenic sepsis
How can TRAILI be differentiated from TACO?
TRALI is differentiated from TACO by the presence of hypotension in TRALI vs hypertension in TACO
What are the features of autoimmune haemolytic anaema?
anaemia
reticulocytosis
low haptoglobin
raised lactate dehydrogenase (LDH) and indirect bilirubin
blood film: spherocytes and reticulocytes
What medications are prescribed for antiphospholipid syndrome in pregnancy?
Antiphospholipid syndrome in pregnancy: aspirin + LMWH
What is the gold standard test for paroxysmal nocturnal haemoglobinuria?
Flow cytometry for CD59 and CD55 is the gold standard test for paroxysmal nocturnal haemoglobinuria
What is the pathophysiology of paroxysmal nocturnal haemoglobinuria?
Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired disorder leading to haemolysis (mainly intravascular) of haematological cells. It is thought to be caused by increased sensitivity of cell membranes to complement (see below) due to a lack of glycoprotein glycosyl-phosphatidylinositol (GPI). Patients are more prone to venous thrombosis.
What would be the outcome of a Coomb’s test in autoimmune haemolytic anaemia?
positive direct antiglobulin test (Coombs’ test).
What are the causes of warm haemolytic anaemia?
Warm is the most common type of AIHA. In warm AIHA the antibody (usually IgG) causes haemolysis best at body temperature and haemolysis tends to occur in extravascular sites, for example the spleen.
Causes of warm AIHA
idiopathic
autoimmune disease: e.g. systemic lupus erythematosus*
neoplasia
lymphoma
chronic lymphocytic leukaemia
drugs: e.g. methyldopa
How do you manage warm haemolytic anaemia
Treatment of any underlying disorder
steroids (+/- rituximab) are generally used first-line
What are the causes of cold haemolytic anaemia?
The antibody in cold AIHA is usually IgM and causes haemolysis best at 4 deg C. Haemolysis is mediated by complement and is more commonly intravascular. Features may include symptoms of Raynaud’s and acrocynaosis. Patients respond less well to steroids
Causes of cold AIHA
neoplasia: e.g. lymphoma
infections: e.g. mycoplasma, EBV
What is a thrombotic sickle cell crisis precipitated by?
Thrombotic, ‘vaso-occlusive’, ‘painful crises’: precipitated by infection, deoxygenation and dehydration
What is acute chest syndrome in sickle cell crisis?
Acute chest syndrome: vaso-occulusion within pulmonary microvasculature, lung parenchyma infarction, dyspnoea, chest paink, pulmonary infiltrates on CXR, low PO2, mx: pain relief, resp support, transfusion, most common cause of death after childhood
What is sequestration in a sickle cell crisis?
Sickling of organs such as spleen or lungs, pooling of blood with worsening anaemia, associated with increased retiuclocyte count
What are the most common tumour causing bone metastases?
Most common tumour causing bone metastases (in descending order)
prostate
breast
lung
How do you treat acute promyelocytic leukaemia with a t(15;17) translocation?
APML is treated with all-trans retinoic acid (ATRA) to force immature granulocytes into maturation to resolve a blast crisis prior to more definitive chemotherapy
What is the pathophysiology of Methaemoglobinaemia?
Methaemoglobinaemia describes haemoglobin which has been oxidised from Fe2+ to Fe3+. This is normally regulated by NADH methaemoglobin reductase, which transfers electrons from NADH to methaemoglobin resulting in the reduction of methaemoglobin to haemoglobin. There is tissue hypoxia as Fe3+ cannot bind oxygen, and hence the oxidation dissociation curve is moved to the left
What are the congenital and acquired causes of methaemoglobinaemia?
Congenital causes
haemoglobin chain variants: HbM, HbH
NADH methaemoglobin reductase deficiency
Acquired causes
drugs: sulphonamides, nitrates (including recreational nitrates e.g. amyl nitrite ‘poppers’), dapsone, sodium nitroprusside, primaquine
chemicals: aniline dyes
What are the features ofmethaemoglobinaemia?
‘chocolate’ cyanosis
dyspnoea, anxiety, headache
severe: acidosis, arrhythmias, seizures, coma
normal pO2 but decreased oxygen saturation
How do you manage methaemoglobinaemia?
NADH methaemoglobinaemia reductase deficiency: ascorbic acid
IV methylthioninium chloride (methylene blue) if acquired
