Haematology Flashcards
Burkitt’s lymphoma pathology
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
Complication of Burkitt’s lymphoma treatment
Tumour lysis syndrome - give rasburicase
Chronic myeloid leukaemia
T9:22 - 9 ABL (oncogene - an aberrant tyrosine kinase) + 22 B cell receptor
Acute pro-myelocytic leukaemia
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
Follicular Lymphoma
T14:18 - 14 Ig heavy constant region + 18 Bcl2 (anti-apoptotic gene)
Mantle Cell Lymphoma
T11:14 - 11 - Cyclin D (oncogene) + 14 Ig heavy constant region
Diabetes monitoring with abnormal haemoglobin
HbA1c does not work
Use total glycated haemoglobin or glycosylated fructosamine
Heinz bodies
Denatured haemoglobin inclusions in RBCs e.g. exposure to oxidative stress
G6PD
Acanthocytes
spiculated RBCs
hyposplenism, abetalipoproteinaemia
Basophilic stippling
lead poisoning, megaloblastic anaemia, thalassaemia, myelodysplasia
Burr cells
Irregularly shaped cells
Stomach cancer
Howell-Jolly bodies
nuclear remnant (purple spot) in RBC
hyposplenism: post-splenectomy, sickle cell, coeliac, UC/crohn’s
megaloblastic anaemia
hereditary spherocytosis
Leucoerythroblastic anaemia
marrow infiltration -> nucleated RBCs and immature WBCs in blood
Myelofibrosis, malignancy with marrow infiltration
Polychromasia
Reticulocytosis
Rouleaux foramation
chronic inflammation, parapropteinaemia, myeloma
schistocytes
Fragmentation haemolysis is occurring
- DIC
- HELLP syndrome
- mechanical valve turbulence
- TTP / HUS
Spherocytes
hereditary spherocytosis
Autoimmune haemolytic anaemia
Target cells
Increased cell membrane:cell volume size
- IDA
- thalassaemia
- hyposplenism
- liver disease
Hypersegmented neutrophil
megaloblastic anaemia - e.g. b12/folate defiency
Tear drop cells
extramedullary haemopoiesis e.g. myelodysplasia, myelofibrosis, thalassaemia
Poikilocytosis
Varied RBC shape
Anisocytosis
varied RBC size
Hyposplenism (and post splenectomy) blood film
target cells Howell-Jolly bodies Pappenheimer bodies siderotic granules acanthocytes
IDA blood fbc / film / haematinics
FBC
- RDW increases early
- microcytosis later (but more specific)
Blood film
- target cells
- ‘pencil’ poikilocytes
Haematinics
- low ferritin
- raised transferrin (compensatory)
- reduced TIBC
Myelofibrosis
‘tear-drop’ poikilocytes
JAK2 mutation
Dry tap bone marrow
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)
CLL mx
FCR: fludarabine, cyclophosphamide, rituximab
- prophylactic co-trimoxazole (fludarabine)
Chlorambucil if not fit for FCR
Ibrutinib if fail to respond to the above
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?)
Beta thalassaemia major
Severe microcytic anaemia Target cells Transfusion dependent HbA2 > 5% HbF up to 95% No HbA
Beta thalassaemia intermedia
Mod microcytic anaemia
Not transfusion dependent
HbA2 >4%
HbF up to 50%
Beta thalassaemia minor
Mild microcytic anaemia
HbA2 >4%
HbF up to 5%
Alpha thalassaemia major
Either hydrops faetalis in utero OR HbH disease - HbH up to 30% - HbA2 up to 4% - moderate microcytic anaemia
Alpha thalassaemia minor
Mild microcytic anaemia Hb Barts (3 to 8%, only in the newborn period)
IgA deficiency features
Respiratory tract infections
Associated with atopy
Risk of severe transfusion reactions
Myelofibrosis mx
1) Allogenic stem cell transplant
2) Ruxolitinib, fedratinib, hydroxyurea
Cryoglobulinaemia features
- Raynaud’s only seen in type I
- cutaneous: vascular purpura, distal ulceration
- arthralgia
- renal involvement (diffuse glomerulonephritis)
- peripheral neuropathy
Type 1 cryoglobulinaemia aetiology
Monoclonal IgM or IgG responsible
Causes: myeloma, waldenstrom macroglobulinaemia
Specific features: raynaud’s
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
Type 3 cryoglobulinaemia
Polyclonal Ig
Rheumatoid arthritis or Sjogren’s
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
Acute (pro)myelocytic complications
(DIC), anaemia, thrombocytopenia, hyperviscosity
Hereditary angioedema - acute mx and prophylaxis
Acute: IV C1-inhibitory concentrate OR FFP
Prophylaxis: tranexamic acid, danazol
Mx polycythaemia rubra vera
Venesection aim hct < 0.45
Low dose aspirin
Hydroxyurea if >60 years old or hx of thrombosis
Neurovisceral only porphyrias
Acute intermittent porphyria
Aminolaevulinic acid dehydrogenase porphyria
Photosensitive only porphyrias
Porphyria cutanea tarda
Congenital erythropoietic porphyria
Erythropoietic protoporphyria
Mixed neurovisceral / photosensitive porphyria
Hereditary coproporphyria
Variegate porphyria
Stroke in vaso-occlusive sickle cell crisis
Exchange transfusion
Haemophilia A & B coagulation
- normal PT / INR
- raised APTT (decreases with mixing)
- normal bleeding time
von Willebrand coagulation and ix
- normal PT / INR
- raised APTT
- raised bleeding time
- reduced vWF activity (ristocetin cofactor)
- reduced factor VIII
DIC
- all raised with thrombocytopenia
- raised d-dimer
- reduced fibrinogen (but can be normal or raised in early disease)
vitamin K deficiency
- raised PT / INR
- raised APTT
- normal bleeding time
Acute intermittent porphyria investigations
Raised urinary porphobilogen acutely
Raised serum porphobilogen, delta aminolaevulinic acid
porphobilogen deaminase defect in RBCs
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
Paroxysmal nocturnal haemoglobinuria ix
Positive Ham’s test
Flow cytometry CD59 and CD55
low haptoglobin, raised ldh
Paroxysmal nocturnal haemoglobinuria mx
blood products
anticoagulation
eculizumab - give meningitis vaccines
stem cell transplant
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)
Glanzmann’s thrombasthenia
Autosomal recessive defect GIIb/IIIa -> thrombocytopenia and purpura -> excessive bleeding e.g. menorrhagia
Poor prognostic features in multiple myelom
Raised B2 microglobulin
Low albumin
AML blood film
Auer rods - needle shaped cytoplasmic inclusions (in myeloblasts)
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)
Exchange transfusion target in sickle cell
HbS < 30%
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
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
Methaemoglobinaemia causes
Congenital
- NADH methaemoglobin reductase deficiency
- HbH or HbM haemoglobin chain variants
Acquired
- poppers (alkyl nitrates)
- dapsone
- nitrates
- sodium nitroprusside
- primaquine
Methaemoglobinaemia treatment
NADH methaemoglobin reductase deficiency
- ascorbic acid
Acquired causes
- IV methylthioninium chloride / methylene blue
- exchange transfusion
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
Paroxysmal cold haemoglobinuria pathogenesis
- Type of autoimmune haemolytic anaemia
- antibodies bind to RBCs in the cold -> fix complement -> intravascular haemolysis -> spherocytes
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
Paroxysmal cold haemoglobinuria features
Haemoglobinuria after cold exposure, jaundice, anaemia, raynaud’s, urticaria
Ix: DAT / Coomb’s +ve, urinary haemosiderin
TTP features
- fever
- fluctuating neurological signs
- AKI
- thrombocytopenia
- microangiopathic haemolytic anaemia (schistocytes AND Coomb’s/DAT negative)
TTP causes
Hereditary - AR deficiency ADAMTS13 gene
Acquired autoantibody vs ADAMTS13
- pregnancy / post partum, COCP
- drugs
- SLE
- infections inc. HIV, E Coli
TTP management
1) plasma exchange for all
2) seroids +/- rituximab / caplacizumab (depending on severity e.g. neuro)
CMV negative blood product indications
- granulocyte transfusions
- intrauterine transfusions
- neonates up to 28 days adjusted
- maternal transfusions during pregnancy
Pain in lymph nodes when drinking alcohol
Hodgkin’s lymphoma
Acute intermittent porphyria mx
Acute: glucose, hematin / heme arginate
Reduce frequency of attacks: prophylactic heme arginate, givosiran, liver transplant
Causes of platelet transfusion failure to increment (<10)
splenomegaly
new HLA abs (repeated transfusions)
DIC
Sepsis
HLH / MAS features
Fever
Splenomegaly
Mimics infection: encephalitis, hepatitis, PUO
Cytopenias Deranged LFTs Raised ferritin Hypertryglyceridaemia Haemophagocytosis on BM biopsy
HLH / MAS treatment
Treat the cause
If critically unwell
- etoposide & dexamethasone
- intrathecal hydrocortisone & methotrexate if CNS features
Acute promyelocytic leukaemia
- emergency treatment
- indications
- all transretinoic acid (ATRA)
- blast crisis with severe anaemia, sepsis, DIC
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
Hairy cell leukaemia management
1) chemotherapy: cladribine, pentostatin
2) immunotherapy: rituximab, interferon-alpha
Germline TP53 mutation
Li Fraumeni syndrome
- AD
- sarcomas, sarcomas, breast carcinoma, glioblastoma, lymphoma and leukaemia.
Hereditary spherocytosis mx
1) Folate replacement
2) Splenectomy if recurrent anaemia
ITP pathogenesis
Acquired abs vs platelet antigens
Primary ITP - no cause / trigger found
Secondary ITP - infection / rheumatological conditions / alemtuzumab as trigger
ITP features
Thrombocytopenia
- other cell lines completely normal
Bleeding
Petechiae (which coalesce into purpura)
ITP management
Treat bleeding
Steroids if no bleeding
IVIG if bleeding or as second line treatment
HUS vs TTP
- less neuro signs
- more significant renal failure
- Shiga toxin as trigger - bloody diarrhoea
Lead poisoning clinical features
- fatigue
- neuropsychiatric
- peripheral neuropathy (motor predominant)
- GI upset
- blue lines on gums
Lead poisoning ix
- microcytic anaemia with basophilic stippling
- raised urinary coproporphyrin
- raised blood lead levels
Lead poisoning mx
Chelating agents
- dimercaptosuccinic acid (DMSA)
- D-penicillamine
- EDTA
- dimercaprol
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%
Rivaroxaban drug withhold pre-op
1 day if normal egfr
How long to stop apixaban pre-op
1-2 days if normal egfr
How long to stop UFH pre-op
6 hours if IV
12 hours if SC
LMWH
12 hours prophylactic
24 hours treatment dose
Heparin induced thrombocytopenia
> 50% reduction in platelets (5-10 days onset)
HIT screen, serotonin release assay
Mx options
- bivalirudin
- lepirudin
- danaparoid
- fondaparinux
Management of autoimmune haemolytic anaemia (e.g. secondary to CLL)
1) Steroids
2) Rituximab
3) Splenectomy
Factor deficiencies leading to PT prolongation alone
VII
Factor deficiencies leading to APTT prolongation alone
VIII, IX, XI, XII
Factor deficiencies prolonging both PT ant APTT
II, V and X
Role of 50:50 mixing studies
Simple factor deficiencies, coag corrects. If inhibitors are present e.g. lupus anticoagulant, these do not correct
Acquired factor VIII deficiency
- occurs in elderly Causes - psoriasis - pemphigus - cephalosporins, penicillins
Myelodysplasia
- occurs in elderly with anaemia / pancytopenia
- no splenomegaly (vs CML)
- precursor to AML (30% transform)
- give chemo if elevated WCC
Delayed transfusion reactions
- pyrexia, jaundice, icteric, drop in hb
- urine: urobilogen raised
- blood film: spherocytosis
- diagnosis: DAT / Coombs’
INR target metal aortic valve
2-3
INR target metal mitral valve
2.5-3.5
Clotting in antiphospholipid
Raised APTT
Does not correct with mixing
DIC acquired cause in elderly men
Prostate cancer invading marrow
Dx primary polycythaemia
Maj
- hb >185 OR >165 (women)
- JAK2 mutation
Min
- BM bx hypercelullarity
- low serum EPO
Other
- raised LAP score
Cause of TRALI
donor blood anti-granulocyte antibodies
Non-hodgkin’s lymphoma treatment
R-CHOP
C1 esterase deficiency
AD hereditary angioedema
- mx: C1 inhibitory concentrate OR FFB
- prophylaxis: tranexamic acid
Anaphylaxis after RBC transfusion
IgA deficiency
Antiphospholipid syndrome mx in pregnancy
Aspirin + LMWH
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
How to reduce frequency of sickle cell crisis
Hydroxyurea (increases HbF production)
von willebrand disease features and mx
- inherited disease
- M=F
- bleeding gums, menorrhagia
Mx
1) tranexamic acid
2) desmopressin
3) factor VIII concentrate
Homocystinuria features and mx
- short-sightedness
- marfanoid
- ligamentous laxity
- lens dislocation
- thromboembolic events
- neuropsych features
- livedo reticularis
Ix: urinary homocysteine
Mx: pyridoxine / folic acid
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
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
