Clinical haematology & oncology Flashcards
haemophilia
- types? what are they def in? which is more common
- inheritance?
- fts on blood tests
A: lack of factor 8 (90% of haemophilia)
B: lack of factor 9
Long APTT w normal bleeding time/thrombin time/PT
X-linked recessive
tear drop poikilocytes
myelofibrosis
TTP
- pathology?
- causes?
- features?
Most common cause of TTP: acquired inhibition of ADAMTS13 (usually cleaves vWF multimers)
NOTES Features: • Fever • Fluctuating neuro signs (microemboli) • MAHA • Low plts • Renal failure
Causes:
- Post-infection (UTI, GI etc) - Pregnancy - Drugs: COCP, cyclosporin, penicillin, clopidogrel, aciclovir - Tumours - SLE - HIV
Pathology
• abnormally large and sticky multimers of vWF cause platelets to clump within vessels
• deficiency of ADAMTS13 (a metalloprotease enzyme) which breakdowns (‘cleaves’) large multimers of von Willebrand’s factor
overlaps with haemolytic uraemic syndrome (HUS)
hereditary angioedema
- pathology?
- screening?
- tx?
- features
· C1-INH deficiency (C1 inhibitor)
· C4 = screening (low)
NOTES · AD Ix · During an attack: low C1-INH · Always: low C2 & low C4
Symptoms
· attacks may be proceeded by painful macular rash
· painless, non-pruritic swelling of subcutaneous/submucosal tissues
○ may affect upper airways, skin or abdominal organs
○ (can occasionally present as abdominal pain due to visceral oedema)
· urticaria is NOT usually a feature
Management
• acute
1. IV C1-inhibitor concentrate
2. If not available: FFP
• prophylaxis: anabolic steroid Danazol may help
cryoglobulinaemia
- symptoms
- bloods
- type 1?
- type 2?
- type 3?
symptoms: • Raynaud’s = type I
• cutaneous: vascular purpura, distal ulceration, ulceration
• arthralgia
• renal involvement (diffuse glomerulonephritis)
Bloods: low complement (esp C4), high ESR
tx: immunosuppression, plasmapharesis
type 1: raynauds ass. IgG or IgM. ass w MM/waldenstrom’s
2: mixed mono&polyclonal. usually RF. hep C, RA, Sjogren’s, lymphoma
3: polyclonal w RF. RA, sjogren’s
cryoglobulinaemia
- symptoms
- bloods
- type 1?
- type 2?
- type 3?
symptoms: • Raynaud’s = type I
• cutaneous: vascular purpura, distal ulceration, ulceration
• arthralgia
• renal involvement (diffuse glomerulonephritis)
Bloods: low complement (esp C4), high ESR
tx: immunosuppression, plasmapharesis
type 1: raynauds ass. IgG or IgM. ass w MM/waldenstrom’s
2: mixed mono&polyclonal. usually RF. hep C, RA, Sjogren’s, lymphoma
3: polyclonal w RF. RA, sjogren’s
sideroblastic anaemia
- causes?
- diagnostic feature?
- bloods?
· Acquired causes: alcohol, lead, anti-TB meds, myelodysplasia
· Dx: ring sideroblasts in BM iron/prussian blue stain
more
• FBC: hypochromic microcytic anaemia (more so in congenital)
• iron studies
○ high ferritin
○ high iron
○ high transferrin saturation
• blood film: basophilic stippling of red blood cells
spherocytes - ddx (3)
AI haemolysis, transfusion reactions & hereditary spherocytosis
If direct coombs test negative = not AI
hereditary spherocytosis
- inheritance?
- dx?
- fts
AD
Dx: EMA binding test
Presentation • FTT • jaundice, gallstones • splenomegaly • aplastic crisis precipitated by parvovirus infection • degree of haemolysis variable • MCHC elevated
Diagnosis
- FHx, typical clinical fts, lab Ix (spherocytes, high MCHC, high reticulocytes): no further tests needed - Equivocal dx: EMA binding test, cryohaemolysis test - Atypical presentation: electrophoresis analysis of erythrocyte membranes
what can PRV progress to?
myelofibrosis
AML
key difference between TACO and TRALI
TRALI: hypotension. TACO: hypertension
causes of haemolysis
- intravascular
- extravascular
Intravascular haemolysis: causes • mismatched blood transfusion • G6PD deficiency • red cell fragmentation: heart valves, TTP, DIC, HUS • paroxysmal nocturnal haemoglobinuria • cold autoimmune haemolytic anaemia
Extravascular haemolysis: causes • haemoglobinopathies: sickle cell, thalassaemia • hereditary spherocytosis • haemolytic disease of newborn warm autoimmune haemolytic anaemia
most common inherited thrombophilia
activated protein C resistance (factor V leiden)
most common inherited thrombophilia
activated protein C resistance (factor V leiden)
irradiated blood products
- key change to them?
- used to avoid what complication
- used in what situs
Depleted in T-lymphocytes
- used to avoid transfusion-ass graft versus host disease (TA-GVHD) caused by engraftment of viable donor T lymphocytes.
used in intra-uterine, neonates up to 28ds post-delivery, BM/stem cell transplant, immunocomp, previous or current hodgkin’s
gene mutations/translocations seen in
- CML
- burkitt’s lymphoma
- acute promyelinocytic leukaemia
- T(9;22): philadelphia chr (BCR-ABL gene) = CML
- T(15;17): PML and RAR-alpha fused = acute promyelocytic leukaemia (M3)
- T(8;14): MYC = burkitt’s lymphoma
- T(14;18): follicular lymphoma (increased BCL-2)
- T(11;14): mantle cell lymphoma (BCL-1/cyclin D1 gene deregulated)
most common inherited bleeding disorder
von willebrand’s
VwD
- inheritance
- presentation
- mx?
- bloods?
- what does vwf do?
AD
Like a platelet disorder: nose bleeds, menorrhagia, bruising without trauma
Mx:
- Mild bleeding: tranexamic acid - Desmopressin: induces release of VwF from endothelial cells - Factor 8 (VIII) concentrate
Ix:
- Long bleeding time - Can have long APTT - Can be low Factor VIII
Vwf: carrier molecule for factor 8, promotes plt adhesion to damaged endothelium
80% type 1 vwd = partial reduction in vwf
anaphylaxis: do you ever give adrenaline IV?
no - always IM
neoplastic spinal cord compression
- lesions above L1: signs?
- lesions below?
neuro signs dep on the level of the lesion.
- Lesions above L1: UMN signs in the legs and a sensory level.
- Lesions below L1 usually cause LMN signs in the legs and perianal numbness.
- Tendon reflexes tend to be increased below the level of the lesion and absent at the level of the lesion
Features
• back pain
○ the earliest and most common symptom
○ may be worse on lying down and coughing
• LL weakness
• sensory changes: sensory loss and numbness
li-fraumeni - what mutation?
germline mutations to p53 (tumour suppressor)
BRCA 1 and 2 - risks of what cancers
• Chr 17 (BRCA 1) and Chr 13 (BRCA 2)
• Breast cancer (60%) risk.
• Risk of ovarian cancer (55% with BRCA 1 and 25% with BRCA 2).
BRCA2: prostate cancer in men
lynch syndrome: inheritance, what cancers
- AD
- colon and endometrial cancer at young age
- 80% of affected individuals will get colonic and/ or endometrial cancer
- High risk individuals may be identified using the Amsterdam criteria
Amsterdam criteria
- Three or more family members with a confirmed diagnosis of colorectal cancer, one of whom is a first degree (parent, child, sibling) relative of the other two. - Two successive affected generations. - One or more colon cancers diagnosed under age 50 years. - Familial adenomatous polyposis (FAP) has been excluded.
gardners syndrome
what is it
features
what mutation
• AD familial colorectal polyposis
• Multiple colonic polyps
• Extra colonic diseases include: skull osteoma, thyroid cancer and epidermoid cysts
• Desmoid tumours are seen in 15%
• Mutation of APC gene located on chromosome 5
• Due to colonic polyps most patients will undergo colectomy to reduce risk of colorectal cancer
Now considered a variant of FAP
ITP mx
Life or organ threatening bleeding: plt transfusion, IV methylpred + IVIg
Plts >30: observe
Asym and <30: oral pred
plt transfusion threshold is 30
most common clotting disorder
factor V leiden (activated protein C resistance)
philadelphia chromosome
- what is it
- good prognosis in?
- bad prog in?
t(9;22) - good prognosis in CML, poor prognosis in AML + ALL
paroxysmal nocturnal hamoglobinuria
- dx?
- features?
- pathology?
· Gold standard dx: flow cytometry for CD59 and CD55
NOTES
Features
· haemolytic anaemia
· Can get pancytopenia (as RBC, WBC, plts or stem cells can be affected)
· haemoglobinuria: dark urine in AM (or throughout the day)
· VTE e.g. Budd-Chiari syndrome
· aplastic anaemia may develop in some patients
DETAILS
· acquired disorder
·»_space;> haemolysis (mainly intravascular) of haematological cells.
· Theory: increased sensitivity of cell membranes to complement due to a lack of glycoprotein glycosyl-phosphatidylinositol (GPI)
what cancers are they ass with - ebv - htlv-1 - HIV 1 - helicobacter pylori malaria
Viruses:
- EBV: Hodgkin’s and Burkitt’s lymphoma, nasopharyngeal carcinoma
- HTLV-1: Adult T-cell leukaemia/lymphoma
- HIV-1: High-grade B-cell lymphoma
Bacteria - Helicobacter pylori: gastric lymphoma (MALT)
Protozoa - malaria: Burkitt’s lymphoma
neutropenic sepsis
- most common bacteria?
- mx?
Most common bac: gram +ve cocci (staph epidermis)
If likely to end up neutropenic: offer fluoroquinolone prophylaxis
If suspect, start abx immediately (don’t wait for WBC): Tazocin
positive DAT/coombs means?
warm - what Ab, causes?
cold - what Ab, causes?
autoimmune haemolytic anaemia
warm: IgG
- SLE, lymphoma, CLL, methyldopa
cold: lymphoma, mycoplasma, EBV. IgM
what type of haemolysis is haptoglobin low in?
intravascular
causes mismatched blood transfusion G6PD deficiency* red cell fragmentation: heart valves, TTP, DIC, HUS paroxysmal nocturnal haemoglobinuria cold autoimmune haemolytic anaemia
universal donor of FFP?
FFP: AB RhD negative blood
- produce neither anti-A or anti-B so compatible with all
RBC: O neg
burkitt’s lymphoma
- what cell?
- gene , microscopy, mx?
- C-myc gene translocation
- Microscopy: starry sky
- Mx: chemotx (risk of tumour lysis syndrome)
high-grade B-cell neoplasm
cisplatin elec abnormality
low Mg
anastrozole/letrozole - mechanism?
aromatase inhibitors that reduces peripheral oestrogen synthesis
tamoxifen
- what does it do?
use?
SERM = selective oestrogen receptor modulator
- acts as an oestrogen receptor antagonist and partial agonist
use: mx of oestrogen receptor-positive breast cancer.
initial mx of suspected neoplastic SC compression
high dose dex
then urgent whole spine MRI
systemic sclerosis - most common cause of death
resp involvement and ultimately failure (due to ILD and pulm arterial hypertension)
acute intermittent porphyria - inheritance - cause - fts dx
AD
Cause: defect in porphobilinogen deaminase (enz in biosynth of haem)
-»_space; toxic accumulation of delta aminolaevulinic acid and porphobilinogen
PC: abdo + neuropsych syms in 20-40 year olds
- 5x more in women
PC: combo of abdo, neuro and psych symptoms: • abdo: abdominal pain, vomiting • motor neuropathy • psych: e.g. depression • hypertension and tachycardia common
DX
• 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
when do you use cryoprecipitate in bleeding pt
low fibrinogen level
