Haematology Flashcards
1
Q
Burkitt’s lymphoma pathology
A
c-myc gene
t8;14 translocation
Starry sky appearance: lymphocyte sheets, macrophages containing apoptotic tumour cells
EBV in African mandibular subtype
ileo-caecal / abdominal subtype is sporadic
2
Q
Complication of Burkitt’s lymphoma treatment
A
Tumour lysis syndrome - give rasburicase
3
Q
Chronic myeloid leukaemia
A
T9:22 - 9 ABL (oncogene - an aberrant tyrosine kinase) + 22 B cell receptor
4
Q
Acute pro-myelocytic leukaemia
A
T15:17 - 15 Promyelocytic gene + 17 Retinoid acid receptor alpha (Fusion protein binds retinoid acid receptor and promotes transcription).
AUER RODS (also in AML)
Bilobed / multilobed granulocytes (immature)
Clinical features: splenomegaly, pancytopenia, can present as DIC
Mx: all-trans retinoic acid
5
Q
Follicular Lymphoma
A
T14:18 - 14 Ig heavy constant region + 18 Bcl2 (anti-apoptotic gene)
6
Q
Mantle Cell Lymphoma
A
T11:14 - 11 - Cyclin D (oncogene) + 14 Ig heavy constant region
7
Q
Diabetes monitoring with abnormal haemoglobin
A
HbA1c does not work
Use total glycated haemoglobin or glycosylated fructosamine
8
Q
Heinz bodies
A
Denatured haemoglobin inclusions in RBCs e.g. exposure to oxidative stress
G6PD
9
Q
Acanthocytes
A
spiculated RBCs
hyposplenism, abetalipoproteinaemia
10
Q
Basophilic stippling
A
lead poisoning, megaloblastic anaemia, thalassaemia, myelodysplasia
11
Q
Burr cells
A
Irregularly shaped cells
Stomach cancer
12
Q
Howell-Jolly bodies
A
nuclear remnant (purple spot) in RBC
hyposplenism: post-splenectomy, sickle cell, coeliac, UC/crohn’s
megaloblastic anaemia
hereditary spherocytosis
13
Q
Leucoerythroblastic anaemia
A
marrow infiltration -> nucleated RBCs and immature WBCs in blood
Myelofibrosis, malignancy with marrow infiltration
14
Q
Polychromasia
A
Reticulocytosis
15
Q
Rouleaux foramation
A
chronic inflammation, parapropteinaemia, myeloma
16
Q
schistocytes
A
Fragmentation haemolysis is occurring
- DIC
- HELLP syndrome
- mechanical valve turbulence
- TTP / HUS
17
Q
Spherocytes
A
hereditary spherocytosis
Autoimmune haemolytic anaemia
18
Q
Target cells
A
Increased cell membrane:cell volume size
- IDA
- thalassaemia
- hyposplenism
- liver disease
19
Q
Hypersegmented neutrophil
A
megaloblastic anaemia - e.g. b12/folate defiency
20
Q
Tear drop cells
A
extramedullary haemopoiesis e.g. myelodysplasia, myelofibrosis, thalassaemia
21
Q
Poikilocytosis
A
Varied RBC shape
22
Q
Anisocytosis
A
varied RBC size
23
Q
Hyposplenism (and post splenectomy) blood film
A
target cells Howell-Jolly bodies Pappenheimer bodies siderotic granules acanthocytes
24
Q
IDA blood fbc / film / haematinics
A
FBC
- RDW increases early
- microcytosis later (but more specific)
Blood film
- target cells
- ‘pencil’ poikilocytes
Haematinics
- low ferritin
- raised transferrin (compensatory)
- reduced TIBC
25
Myelofibrosis
'tear-drop' poikilocytes
JAK2 mutation
Dry tap bone marrow
26
Indications for CLL treatment
>6cm splenomegaly
>10cm lymphadenopathy
B symptoms (weight loss, fever)
progressive lymphocytosis (>50% in 2 months, doubling time <6months)
progressive marrow failure (anaemia, thrombocytopenia)
27
CLL mx
FCR: fludarabine, cyclophosphamide, rituximab
- prophylactic co-trimoxazole (fludarabine)
Chlorambucil if not fit for FCR
Ibrutinib if fail to respond to the above
28
Unprovoked DVT ix
For over 40s...
1) CXR, bloods, urinalysis including PSA and dip
2) CT AP and mammogram
3) Consider antiphospholipid antibodies (do on younger patients)
4) hereditary thrombophilia screen only if 1st degree relative (or young?)
29
Beta thalassaemia major
```
Severe microcytic anaemia
Target cells
Transfusion dependent
HbA2 > 5%
HbF up to 95%
No HbA
```
30
Beta thalassaemia intermedia
Mod microcytic anaemia
Not transfusion dependent
HbA2 >4%
HbF up to 50%
31
Beta thalassaemia minor
Mild microcytic anaemia
HbA2 >4%
HbF up to 5%
32
Alpha thalassaemia major
```
Either hydrops faetalis in utero
OR
HbH disease
- HbH up to 30%
- HbA2 up to 4%
- moderate microcytic anaemia
```
33
Alpha thalassaemia minor
```
Mild microcytic anaemia
Hb Barts (3 to 8%, only in the newborn period)
```
34
IgA deficiency features
Respiratory tract infections
Associated with atopy
Risk of severe transfusion reactions
35
Myelofibrosis mx
1) Allogenic stem cell transplant
| 2) Ruxolitinib, fedratinib, hydroxyurea
36
Cryoglobulinaemia features
- Raynaud's only seen in type I
- cutaneous: vascular purpura, distal ulceration
- arthralgia
- renal involvement (diffuse glomerulonephritis)
- peripheral neuropathy
37
Type 1 cryoglobulinaemia aetiology
Monoclonal IgM or IgG responsible
Causes: myeloma, waldenstrom macroglobulinaemia
Specific features: raynaud's
38
Type 2 (mixed) cryoglobulinaemia aetiology
- Mixed poly and monoclonal Ig
- RF positive usually
Causes: hep C, HIV, rheumatoid arthritis, sjogren's, lymhpoma
Mx: treat the cause, steroids / rituxumab
plasma exchange if hyperviscosity
39
Type 3 cryoglobulinaemia
Polyclonal Ig
| Rheumatoid arthritis or Sjogren's
40
Causes of paraprotein bands
MGUS
- IgM / M protein < 3g/dL
- < 10% lymphoplasmocytic / plasma cells on BM
- abnormal kappa: lambda free light chain ratio
- absence of end organ damage
Waldenstrom's macroglobulinaemia
- IgM gammopathy of any size
- >10% lymphoplasmocytic cells on BM
- hyperviscosity, splenomegaly common (more than MM)
Multiple myeloma
- more commonly IgG gammopathy
- >10% plasma cells on BM
- evidence of end organ damage
Smouldering multiple myeloma
- 10-60% plasma cells
- absence of end organ damage
41
Acute (pro)myelocytic complications
(DIC), anaemia, thrombocytopenia, hyperviscosity
42
Hereditary angioedema - acute mx and prophylaxis
Acute: IV C1-inhibitory concentrate OR FFP
Prophylaxis: tranexamic acid, danazol
43
Mx polycythaemia rubra vera
Venesection aim hct < 0.45
Low dose aspirin
Hydroxyurea if >60 years old or hx of thrombosis
44
Neurovisceral only porphyrias
Acute intermittent porphyria
| Aminolaevulinic acid dehydrogenase porphyria
45
Photosensitive only porphyrias
Porphyria cutanea tarda
Congenital erythropoietic porphyria
Erythropoietic protoporphyria
46
Mixed neurovisceral / photosensitive porphyria
Hereditary coproporphyria
| Variegate porphyria
47
Stroke in vaso-occlusive sickle cell crisis
Exchange transfusion
48
Haemophilia A & B coagulation
- normal PT / INR
- raised APTT (decreases with mixing)
- normal bleeding time
49
von Willebrand coagulation and ix
- normal PT / INR
- raised APTT
- raised bleeding time
- reduced vWF activity (ristocetin cofactor)
- reduced factor VIII
50
DIC
- all raised with thrombocytopenia
- raised d-dimer
- reduced fibrinogen (but can be normal or raised in early disease)
51
vitamin K deficiency
- raised PT / INR
- raised APTT
- normal bleeding time
52
Acute intermittent porphyria investigations
Raised urinary porphobilogen acutely
Raised serum porphobilogen, delta aminolaevulinic acid
porphobilogen deaminase defect in RBCs
53
Paroxysmal nocturnal haemoglobinuria features
- acquired mutation in haematopoietic stem cell lineage: de novo or aplastic anaemia / myelofibrosis / myelodysplasia
- haemolytic anaemia
- Thrombosis e.g. DVT, budd-chiari
- haemoglobinuria
54
Paroxysmal nocturnal haemoglobinuria ix
Positive Ham's test
Flow cytometry CD59 and CD55
low haptoglobin, raised ldh
55
Paroxysmal nocturnal haemoglobinuria mx
blood products
anticoagulation
eculizumab - give meningitis vaccines
stem cell transplant
56
Indications for irradiated blood products include:
Immunocompromised marrow or organ transplant recipients
Patients with haematological disorders who will be undergoing allogeneic marrow transplantation imminently
Intrauterine transfusions
Patients with Hodgkin's disease
Patients treated with purine analogue drugs (e.g. fludarabine)
57
Glanzmann's thrombasthenia
Autosomal recessive defect GIIb/IIIa -> thrombocytopenia and purpura -> excessive bleeding e.g. menorrhagia
58
Poor prognostic features in multiple myelom
Raised B2 microglobulin
| Low albumin
59
AML blood film
Auer rods - needle shaped cytoplasmic inclusions (in myeloblasts)
60
CLL prognostic factors
Poor
- 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
- deletions short arm chromosome 17 (del 17p)
Good
- deletions long arm of chromosome 13 (del 13q)
61
Exchange transfusion target in sickle cell
HbS < 30%
62
CML management
1) imatinib
2) allogenic stem cell transplant - if young, chronic phase and not responding to imatinib OR blast phase
3) other agents: cytarabine, hydroxyurea
63
Methaemoglobinaemia features
- State of abnormally increased haem iron oxidation to Fe3+ impairing oxygen delivery to tissues
- Usual range 1-3% HbMet
- Respiratory and metabolic acidosis
- Normal sats / PaO2 on ABG but reduced on sats probe
64
Methaemoglobinaemia causes
Congenital
- NADH methaemoglobin reductase deficiency
- HbH or HbM haemoglobin chain variants
Acquired
- poppers (alkyl nitrates)
- dapsone
- nitrates
- sodium nitroprusside
- primaquine
65
Methaemoglobinaemia treatment
NADH methaemoglobin reductase deficiency
- ascorbic acid
Acquired causes
- IV methylthioninium chloride / methylene blue
- exchange transfusion
66
Causes of splenomegaly
Massive splenomegaly
- haem: CML, myelofibrosis
- infection: visceral leishmaniasis, malaria
- metabolic: Gaucher's syndrome (AR lysosomal storage)
Other
- haem: CLL, Hodgkin's, haemolytic anaemia, thalassaemia, early sickle, polycythaemia rubra vera
- infection: endocarditis, hepatitis, glandular fever
- gastro: portal hypertension
- rheum: Felty's syndrome
67
Paroxysmal cold haemoglobinuria pathogenesis
- Type of autoimmune haemolytic anaemia
| - antibodies bind to RBCs in the cold -> fix complement -> intravascular haemolysis -> spherocytes
68
Paroxysmal cold haemoglobinuria causes
Acquired causes
- Secondary or tertiary syphilis
- Post-viral infection (eg, varicella, measles, mumps, EBV, CMV)
- Post-bacterial infection (eg, mycoplasma, Klebsiella, Escherichia coli, Haemophilus influenzae)
- Post-measles vaccine
- Autoimmune disorders
- Lymphoma or CLL
69
Paroxysmal cold haemoglobinuria features
Haemoglobinuria after cold exposure, jaundice, anaemia, raynaud's, urticaria
Ix: DAT / Coomb's +ve, urinary haemosiderin
70
TTP features
- fever
- fluctuating neurological signs
- AKI
- thrombocytopenia
- microangiopathic haemolytic anaemia (schistocytes AND Coomb's/DAT negative)
71
TTP causes
Hereditary - AR deficiency ADAMTS13 gene
Acquired autoantibody vs ADAMTS13
- pregnancy / post partum, COCP
- drugs
- SLE
- infections inc. HIV, E Coli
72
TTP management
1) plasma exchange for all
| 2) seroids +/- rituximab / caplacizumab (depending on severity e.g. neuro)
73
CMV negative blood product indications
- granulocyte transfusions
- intrauterine transfusions
- neonates up to 28 days adjusted
- maternal transfusions during pregnancy
74
Pain in lymph nodes when drinking alcohol
Hodgkin's lymphoma
75
Acute intermittent porphyria mx
Acute: glucose, hematin / heme arginate
Reduce frequency of attacks: prophylactic heme arginate, givosiran, liver transplant
76
Causes of platelet transfusion failure to increment (<10)
splenomegaly
new HLA abs (repeated transfusions)
DIC
Sepsis
77
HLH / MAS features
Fever
Splenomegaly
Mimics infection: encephalitis, hepatitis, PUO
```
Cytopenias
Deranged LFTs
Raised ferritin
Hypertryglyceridaemia
Haemophagocytosis on BM biopsy
```
78
HLH / MAS treatment
Treat the cause
If critically unwell
- etoposide & dexamethasone
- intrathecal hydrocortisone & methotrexate if CNS features
79
Acute promyelocytic leukaemia
- emergency treatment
- indications
- all transretinoic acid (ATRA)
| - blast crisis with severe anaemia, sepsis, DIC
80
Hairy cell leukaemia features
Rare malignant proliferation of B cells
BRAF mutation
Males 4:1
- pancytopenia
- splenomegaly
- skin vasculitis in 1/3 patients
- 'dry tap' despite bone marrow hypercellularity
- cells have 'fried egg' appearance
- tartrate resistant acid phosphotase (TRAP) stain positive
81
Hairy cell leukaemia management
1) chemotherapy: cladribine, pentostatin
| 2) immunotherapy: rituximab, interferon-alpha
82
Germline TP53 mutation
Li Fraumeni syndrome
- AD
- sarcomas, sarcomas, breast carcinoma, glioblastoma, lymphoma and leukaemia.
83
Hereditary spherocytosis mx
1) Folate replacement
| 2) Splenectomy if recurrent anaemia
84
ITP pathogenesis
Acquired abs vs platelet antigens
Primary ITP - no cause / trigger found
Secondary ITP - infection / rheumatological conditions / alemtuzumab as trigger
85
ITP features
Thrombocytopenia
- other cell lines completely normal
Bleeding
Petechiae (which coalesce into purpura)
86
ITP management
Treat bleeding
Steroids if no bleeding
IVIG if bleeding or as second line treatment
87
HUS vs TTP
- less neuro signs
- more significant renal failure
- Shiga toxin as trigger - bloody diarrhoea
88
Lead poisoning clinical features
- fatigue
- neuropsychiatric
- peripheral neuropathy (motor predominant)
- GI upset
- blue lines on gums
89
Lead poisoning ix
- microcytic anaemia with basophilic stippling
- raised urinary coproporphyrin
- raised blood lead levels
90
Lead poisoning mx
Chelating agents
- dimercaptosuccinic acid (DMSA)
- D-penicillamine
- EDTA
- dimercaprol
91
Acute chest syndrome mx
- IV fluids, oxygen, analgesia
- IV antibiotics (if infective precipitant)
- Transfuse to aim Hb >100 in mild cases
- In more severe cases: exchange transfusion aim Hbs <30%
92
Rivaroxaban drug withhold pre-op
1 day if normal egfr
93
How long to stop apixaban pre-op
1-2 days if normal egfr
94
How long to stop UFH pre-op
6 hours if IV
| 12 hours if SC
95
LMWH
12 hours prophylactic
| 24 hours treatment dose
96
Heparin induced thrombocytopenia
>50% reduction in platelets (5-10 days onset)
HIT screen, serotonin release assay
Mx options
- bivalirudin
- lepirudin
- danaparoid
- fondaparinux
97
Management of autoimmune haemolytic anaemia (e.g. secondary to CLL)
1) Steroids
2) Rituximab
3) Splenectomy
98
Factor deficiencies leading to PT prolongation alone
VII
99
Factor deficiencies leading to APTT prolongation alone
VIII, IX, XI, XII
100
Factor deficiencies prolonging both PT ant APTT
II, V and X
101
Role of 50:50 mixing studies
Simple factor deficiencies, coag corrects. If inhibitors are present e.g. lupus anticoagulant, these do not correct
102
Acquired factor VIII deficiency
```
- occurs in elderly
Causes
- psoriasis
- pemphigus
- cephalosporins, penicillins
```
103
Myelodysplasia
- occurs in elderly with anaemia / pancytopenia
- no splenomegaly (vs CML)
- precursor to AML (30% transform)
- give chemo if elevated WCC
104
Delayed transfusion reactions
- pyrexia, jaundice, icteric, drop in hb
- urine: urobilogen raised
- blood film: spherocytosis
- diagnosis: DAT / Coombs'
105
INR target metal aortic valve
2-3
106
INR target metal mitral valve
2.5-3.5
107
Clotting in antiphospholipid
Raised APTT
| Does not correct with mixing
108
DIC acquired cause in elderly men
Prostate cancer invading marrow
109
Dx primary polycythaemia
Maj
- hb >185 OR >165 (women)
- JAK2 mutation
Min
- BM bx hypercelullarity
- low serum EPO
Other
- raised LAP score
110
Cause of TRALI
donor blood anti-granulocyte antibodies
111
Non-hodgkin's lymphoma treatment
R-CHOP
112
C1 esterase deficiency
AD hereditary angioedema
- mx: C1 inhibitory concentrate OR FFB
- prophylaxis: tranexamic acid
113
Anaphylaxis after RBC transfusion
IgA deficiency
114
Antiphospholipid syndrome mx in pregnancy
Aspirin + LMWH
115
Multiple myeloma mx
Good functional status?
- induction chemotherapy (proteasome inhibitor e.g. bortezomib + dexamethasone) -> autologous stem cell transplantation
Poor functional status?
- thalidomide + melphalan (alkylating agent) + dexamethasone
116
How to reduce frequency of sickle cell crisis
Hydroxyurea (increases HbF production)
117
von willebrand disease features and mx
- inherited disease
- M=F
- bleeding gums, menorrhagia
Mx
1) tranexamic acid
2) desmopressin
3) factor VIII concentrate
118
Homocystinuria features and mx
- short-sightedness
- marfanoid
- ligamentous laxity
- lens dislocation
- thromboembolic events
- neuropsych features
- livedo reticularis
Ix: urinary homocysteine
Mx: pyridoxine / folic acid
119
Causes of pure red cell aplasia
- idiopathic / autoimmune
- initial presentation of myelodysplastic syndrome
- CLL
- RA, SLE
- EPO
- phenytoin
- co-trimoxazole
- zidovudine
- MMF
- parvovirus B19
- HIV
- EBV
- viral hepatitis
120
Absolute and relative contraindications to thrombolysis
Absolute
- previous ICH
- intracranial neoplasm
- seizure at stroke onset
- stroke / TBI in last 3 months
- LP last 7 days
- GI bleed last 3 weeks
- oesophageal varices
- active bleeding
- pregnancy
- uncontrolled hypertension >200/120
Relative
- INR >1.7
- active diabetic haemorrhagic retinopathy
- intracardiac thrombus
- major surgery <2 weeks
