Haematology Flashcards
What is myelodysplasia and what is the risk?
Ineffective blood cell production due to bone marrow failure, from fibrosis or lymphocytic infiltration of the marrow.
30% transform to become Acute Myeloid Leukaemia
Elderly lady at her GP is found to have a high white blood cell count, not acutely unwell, what is the likely cause?
Chronic lymphocytic leukaemia
Auer rods are characteristic of which blood cancer?
Auer rods? My rods
CML
Carbot rings occur in the blood film of people who have suffered poisoning from what?
Lead poisoning, Carbot rings may be microtubules gone awry
Which virus triggers an aplastic crisis in sickle cell patients, and what happens when this occurs?
Parvovirus B19
Reduction in RBCs
Drug causes of spherocytosis (Coombs +ve)?
MNOPQ
Methyldopa NSAIDs Oh IFN! Penicillin Quinine
Low Hb, raised bilirubin
Blood film shows: Spherocytosis, Coombs +ve
Not worsened by cold
What could be the cause and Rx?
Warm haemolytic anaemia, spherocytes = spherical cells
Coombs = autoimmune, Warm = IgG
Idiopathic
CLL, Lymphoma
Autoimmune, SLE
High dose prednisolone
Infectious causes of Coombs +ve cold autoimmune haemolytic anaemia (what type of Ig mediates it?)
IgM- mycoplasma pneumoniae, EBV
A patient has been on holiday and over the last few days has had rigors, developed jaundice and reports black urine.
FBC shows progressive anaemia. Cause? Rx?
Blackwater fever (malaria) due to massive intravascular haemolysis, possibly from autoimmune reaction. Rx: antimalarials
Things someone with Glucose 6 Phosphate Dehydrogenase should avoid and disease inheritance?
X linked, G6PD is an enzyme protecting from oxidative stress
Aspirin, sulphonamides
Broad beans
Henna, dapsone (coeliac rash)
Cause of severe haemolytic uraemic syndrome? Possible complications?
E Coli 0157, produces Shiga toxin that stimulates cytokines promoting clot formation and inactivates ADAMTS13 protease (needed to cleave vWF to prevent multimers + clots)
Kidney failure, due to clots in small vessels + bloody diarrhoea
In someone with von willebrand’s disease, what FBC and clotting studies would be expected?
vWF binds factor 8 (intrinsic cascade) to carry it, promoting adhesion of platelets to damaged endothelium.
Reduction in levels leads to prolonged bleeding time
APTT may be prolonged (as less factor 8 carried)
Hb or MCV may be low if bleeding leads to iron deficiency
How do platelet disorders and coagulation disorders present differently in regards to symptoms?
Platelet disorders (which includes vWF disease) = epistaxis and menorrhagia Coagulation disorders are more severe = haemoarthrosis and muscle haematomas
68 year old patient has splenomegaly, lymphadenopathy and IgM paraprotein level of 40g/L. Normal calcium and creatinine.
Likely diagnosis?
Waldenstrom’s macroglobulinaemia
IgM paraprotein raise= less likely to be multiple myeloma (IgG, IgD would be more likely)
And other findings are not suggestive
Monoglonal gammopathy requires paraprotein of no more than 30g
Those with polycythaemia vera typically get intense itching when? What other conditions are associated?
When warm or humid (ie getting out the shower, due to histamine release by the RBCs)
Gout and DVTs
What findings indicate tumour lysis syndrome, how can you prevent it?
Hyperkalaemia (cell breakdown)
Hyperuricaemia (purine breakdown)
Hyperphosphataemia (nucleotide breakdown)
Allopurinol
Mutation causing polycythaemia rubra vera?
JAK2 (in 90%)
RBCs are more responsive to GFs like erythropoietin and do not apoptose if EPO is absent
Cause of polycythaemia?
Primary- JAK2 mutation (= rubra vera)
Secondary, hypoxia- altitude, COPD, cyanotic heart disease, smoking
Secondary, too high EPO- renal or hepatocellular carcinoma
Which infections are associated with non-hodgkins lymphomas?
EBV- Burkitts
HTLV- T cell
HCV, HHV8- Castleman’s
H Pylori- MALT
What are the diagnostic criteria of multiple myeloma?
Name 4 things
- Serum/urine electrophoresis- monoclonal band
- Marrow biopsy- more plasma cells
- End organ damage: hypercalcaemia, renal insufficiency, anaemia
- Bone lesions via xray or PET
What is the pathogenesis of primary amyloidosis?
Myeloma- proliferation of plasma cell clone
> Amyloidogenic monoclonal Ig
> Extracellular fibrillar light chain deposits
> Resistant to degradation
> Organ failure
What are the different types of amyloidosis?
AL amyloid (primary) due to Ig chains from myeloma
AA amyloid due to acute phase protein from chronic inflammation
Familial due to mutations in ‘prealbumin’
IHx for amyloidosis?
Biopsy and Congo Red stain: birefringent light makes it apple green
Which blood clotting test does haemophilia effect?
Prolonged aPTT
As haemophilia A (F 8) and haemophilia B (F 9) both affect the intrinsic pathway (factors 12, 11, 9 and 8)
Haemophilia A and haemophilia B have what kind of inheritance, and which clotting factor is affected?
Haemophilia A- factor 8
Haemophilia B- factor 9
Acquired haemophilia- antibodies against factor 8
Which clotting factors are vitamin K dependent?
2, 7, 9, 10
2 (prothrombin) + 10 = aPTT + PT
7 = PT
9 = aPTT
What agents are added to plasma samples to test PT, aPTT and thrombin time?
PT- thromboplastin
aPTT- Kaolin
Thrombin time- thrombin
How does Warfarin work?
Inhibits the reductase enzyme needed to regenerate vit K to make clotting factors 2, 7, 9 and 10
(And also some anti-coagulation factors, hence why warfarin has an initial pro-thrombotic effect and should be covered with heparin until day 5)
Target INR when someone has prosthetic heart valves?
3-4
Target INR with DVT or AF?
2-3
Can give aspirin if falls risk is high, but is less effective
Once a patient has had a DVT, how long should you continue anticoagulation?
If cause has gone away
6 weeks for below knee DVT
3 months for above knee DVT or PE
6 months if no cause found
Indefinitely if cause is enduring, ie thrombophilia
When should you stop Warfarin? (What PC or INR?)
When should you give vit K?
Stop Warfarin when INR is above 6
Give Vit K if INR above 8 + RFs for bleeding
Give vit K and prothrombin complex concentrate if major bleed
Which conditions are made worse by steroids?
DiTCH OP
Diabetes TB Chickenpox Hypertension Osteoporosis Peptic Ulcers
What medication works via an opposing mechanism to azathioprine?
Allopurinol inhibits xanthine oxidase
Azathioprine metabolised to mercaptopurine, broken down by xanthine oxidase (so leads to toxicity if given with allopurinol)
11 year old in last few hours has noted petechiae and purpura coming out along legs and trunk.
FBC: low platelets only
What tests would be prudent?
Idiopathic thrombocytopenic purpura
IHx: film to ensure no other abnormalities
Rx: consider steroids or Ig
Life-threatening bleed = platelet transfusion
Management of chronic ITP in children?
Splenectomy stops sequestration of antibody coated platelets in spleen
Rituximab and anti-D may reduce need for splenectomy
What features present with purpura make ITP less likely?
Abnormalities on blood film (aside from low platelets) Mucosal bleeding Lymphadenopathy Hepatosplenomegaly Pancytopenia
Way to remember Rx for hODgkINs?
BleOmycin
Daunorubicin
Decarbazine
VINcristINe
Which blood test indicates activity level of lupus?
Complement levels
What blood test is important to do if investigating anaemia aside from FBC? And what does it indicate?
Reticulocyte count
If low in the context of anaemia = underproduction of RBCs
If high = haemorrhage, haemolysis etc
How does the spleen indicate whether an anaemia is acute or chronic haemolysis?
Large spleen = chronic
Why does G6PD deficiency cause a haemolysis?
RBCs need some housekeeping enzymes to survive for 3 months, if it lacks G6PD (X linked) then increased oxidative stress from drugs or infection or fava beans (broad beans which have a little fungus on them) will cause rapid death to RBCs
(IHx: Heinz bodies due to Hb precipitating in RBC )
Why do Heinz bodies form in G6PD deficiency attack?
Without G6PD, the RBC can’t deal with oxidative stress and prevent the Hb becoming oxidised into mecaptohaemaglobin, which forms precipitating lumps visible as ‘golf ball’ patterned Heinz bodies
What is the difference between HbA, HbA2 and HbF?
HbA = a2b2 HbF = a2y2 (gamma) HbA2 = a2d2 (delta)
In thalassaemia, if there chains are not being used (due to a mutation in the matching a or b chains) how does the precipitation of these unpaired globin cause symptoms?
If precipitating in RBCs = haemolysis
If precipitating in bone marrow = ineffective erythropoetis
= anaemia = erythopoetin = bone marrow expansion, iron and skeleton deformities
What do children with beta-thalassaemia major die from?
Iron overload
Require chelation
Mother comes in for her antenatal results where they did FBC, which showed normal Hb but microcytic. What could the cause be?
Thalassaemia
Antenatal screening test includes Hb electrophoresis so would pick this up hopefully
What is the pathology of damage caused by iron overload?
Iron exceeds the transferrin ability to bind it, so it travels free in the blood, is selectively uptaken by organs and promotes hydroxyl free radical production = damage
(Heart failure, endocrine failure)
When chelating iron in iron overload (ie in blood transfusion Rx) what is the target ferritin?
Below 1000
The chelators have some bad side effects, neurotoxicity etc so can’t go mad with them
Why does a RBC with sickle mutation sickle?
HbS polymerise into crystals in low O2 sats, causing characteristic shape.
Why does hydroxyurea help prevent vaso-occlusive crises in children with sickle cell?
It increases levels of HbF
What is the chromosome translocation in Burkitt’s lymphoma
8,14
Occurs in HIV + Africans
Which type of myelocytic lymphoma is associated with bleeding problems, what therapy can be given?
Acute Promyelocytic Myeloid Leukaemia
Ie get DIC
What chromosome translocation occurs in acute promyelocytic leukaemia?
15, 17
Responsive to all-transretinoic acid
Multiple myeloma diagnoses require 1 major and 1 minor criteria, or 3 minor criteria.
What are the major criteria?
Major criteria:
Plasmacytoma- biopsy specimen (mass of abnormal plasma cells)
30% plasma cells on bone marrow biopsy
Serum or urine electrophoresis- elevated levels of Monoclonal protein
For multiple myeloma diagnoses, 1 major + 1 minor criteria needs fulfilling or 3 minor. What are the minor criteria?
Minor criteria:
Bone marrow sample- 10% to 30% plasma cells
Plasma/urine electrophoresis- minor elevations in the level of M protein
Osteolytic lesions on imaging (xrays of chest, spine, pelvis + skull)
Low levels of other types of antibodies
Which diseases are worsened by steroids?
Increase monitoring:
TB, chickenpox
Hypertension, diabetes
Osteoporosis
Which medications reduce prednisolone concentration?
Anti-epileptics
Rifampicin (TB)
What steps might reduce adrenal suppression if giving steroids?
Giving steroids alternate days
Giving steroids in the morning
Use lowest efficacious dose
3 golden rules if on long term steroids:
- Carry a steroid card or bracelet
- Increase doses when sick
- Increase doses when stressed
What dose of prednisolone warrants gradual withdrawal (due to adrenal suppression) rather than abrupt stopping?
Assuming the patient has been taking them > 3 weeks
7.5mg a day
When would gradual weaning off steroids be needed if it’s a a short term treatment? (Under 3 weeks in length)
PMH: previous adrenal suppression
DHx: repeated courses of steroids
doses at night
>40mg dose
What dose of steroids warrants gradual weaning even if given as a short term course? (Ie under 3 weeks)
> 40mg dose prednisolone
PMH: previous adrenal suppression
DHx: repeated courses of steroids
doses at night
A patient is taking ciclosporin (calcineurin inhibitor) for transplant immunosupression. What is the main SE to worry about?
Dose-dependent nephrotoxicity
Other SEs: raised BP, oedema
Confusion, seizures
Gum hypertrophy, skin cancer
Patient has had a transplant and is complaining of gum overgrowth (hypertrophy), what might the cause be?
Ciclosporin (calcineurin inhibitor)
What blood test monitoring is needed for patients taking ciclosporin (calcineurin inhibitor used in transplant immunosuppression)?
U+Es and creatinine every 2 weeks for 3 months
(As nephrotoxicity is the main SE)
Also LFTs as hepatotoxicity can occur
What change in creatinine warrants a dose reduction in a patient taking ciclosporin for Immunosuppression?
Increase of 30%, even if within the normal range
What blood test is worth doing if a patient is taking cyclophosphamide?
(Given for R-CHOP in Non-Hodgkins, or for CLL)
Cyclophosphamide = alkylating agent
Causes marrow suppression - do FBC
Patient is taking R-CHOP for Non Hodgkins lymphoma, suddenly starts peeing blood and has increased urinary frequency, what could be the cause?
Haemorrhagic cystitis: from cyclophosphamide (alkylating agent) of the R-CHOP
Name the 4 commonest inherited causes of thrombophilia
- Deficiency in protein S or C (breaks down factor 5 and 7)
- Activated Protein C Resistance/ Factor 5 Leiden (factor 5 resists protein C breakdown)
- Prothrombin mutation (increases levels available to convert to thrombin)
- Antithrombin deficiency (inhibits thrombin)
Which disease is associated with anti-phospholipid syndrome?
SLE
When is testing for inherited causes of thrombophilia warranted?
In those with unprovoked DVT or PE if unsure whether to stop anticoagulation
May not be any great benefit to doing so, especially if patient will be on lifelong anticoagulation anyway
Patient has a swollen red leg, had a resection of their bladder tumour a few days ago. What are the two next steps?
DVT might have occurred
Do a Wells score- 2 or more = likely
As cancer and recent surgery, they will have a high score
Do a proximal leg ultrasound if available within next 4 hours
Patient is suspected of DVT, has a Wells score of 2. The hospital has no ultrasound technicians available for at least 8 hours. What test and Rx should be commenced?
A D-dimer and a parenteral anticoagulant
USS should be done within 24 hours
Patient is suspected of a DVT, has a Wells score of 1. What IHx should be performed?
D dimer
If positive do USS within 4 hours or within 24 hours with an anticoagulant given
Patient is suspected of DVT Wells score is 2 d dimer +ve Leg USS -ve What further management is needed?
Repeat leg ultrasound at 1 week incase of early but propagating DVT
Patient has an unprovoked DVT and you want to rule out a underlying malignancy, what simple tests should you do?
Urine dip (bladder) FBC LFTs Ca (myeloma) CXR (lung) ± CT abdo pelvis, mammogram
A patient is deemed at risk of DVT due to increased immobility from her neck of femur fracture. Why might TED stockings be unsuitable?
Evidence of ischaemia
Absent posterior tibial or pedal pulses
Shiny skin or loss of hair
3 causes of slow flow retinopathy- ‘feels like looking through a watery car windscreen’
- Hyperviscosity syndrome (high RBCs, WBCs, Igs-myeloma)
May have confusion, abdo pain, lethargy also - Carotid disease
- Takayasu’s disease (aorta arteritis, thrombosis, aneurysm)
A patient has known multiple myeloma and reports reduced vision and a curtain falling over their sight. Aside from a stroke what might be the cause?
Hyperviscosity syndrome- high level of plasma componants
Causes of massive splenomegaly:
My mate chrissy looks grouchy
Myelofibrosis Malaria CML Leishmaniasis Gaucher's (genetic enzyme defect causing lipid storage dysfunction)
What 3 features differentiate the spleen from an enlarged kidney if there is a mass in the left upper quadrant?
- It moves down on inspiration (kidney is retro-peritoneal)
- You may feel the medial notch
- ‘You can’t get above it’- top margin disappears under the ribs
What characteristic blood film is seen in someone post-splenectomy?
Normally the spleen removes them:
Howell-Jolly bodies (residual nuclear fragments)
Pappenheimer cells (iron granules)
Target cells
What types of bacteria tend to be a problem in splenectomy patients?
Encapsulated ones:
Strep pneumo
Haemophilus influenzae
Neisseria meningitidis
