Haemotology Flashcards
What is Hairy cell leukaemia?
A rare malignant proliferation disorder of B cells
features of Hairy cell leukaemia
pancytopenia, splenomegaly, skin vasculitis in 1/3 patients, and tartrate resistant acid phosphotase (TRAP) stain positive
what is diagnosis if tartrate resistant acid phosphotase (TRAP) stain positive and pancytopenic?
hairy cell leukaemia (b cell malignant prolif)
Patient with high platelets and burning sensation in hands
Essential thrombocytosis… JAK2 mutation is found in around 50% of patients
It’s a myeloproliferative disorders which overlaps with chronic myeloid leukaemia, polycythaemia rubra vera and myelofibrosis.
Essential thrombocytosis
Myeloproliferative disorder which overlaps with CML, polycythemia rubra Vera, myelofibrosis
Treatment of essential thrombocytosis
hydroxyurea (hydroxycarbamide)
Or interferon-alpha in younger pt
low dose aspirin may be used
Philadelphia chromosome
Present in 95% of patients with chronic myeloid leukemia
Sometimes found in acute lymphoblastic leukaemia and is bad prognostic
Sickle cell genetics
Autosomal recessive
Features of Acute promyelocytic leukaemia
Presents younger than other AML (25yr)
And presents with DIC
good prognosis
T(15:17), Auer rods (seen with myeloperoxidase stain)
Most common type of Hodgkin’s lymphoma
Nodular Sclerosing
Good prognosis
Associated with lacunar cells
Features of lead poisoning
Abdominal pain, unusual taste in mouth, parasthesia of extremities, blue lines on gum in 20%, fatigue, constipation
Microcytic anaemia,
Features of thrombotic thrombocytopenic purpura (TTP)
Thrombotic thrombocytopenic purpura (TTP) is classically characterised as a pentad of: thrombocytopenia, microvascular haemolysis, fluctuating neurological signs, renal impairment and fever…
treat with plasma exchange
Liver biopsy of haemochromatosis
Perl’s stain
Genetic mutations in haemochromatosis
C282Y and H63D
Testing family members: HFE mutation on chromosome 6
General screen with transferrin saturation
What bloods determine if venesection is needed for haemochromatosis
Transferrin saturation and ferritin
What histology is associated with DIC
DIC is associated with schistocytes due to microangiopathic haemolytic anaemia
Medication to treat neutropenia
Filgrastim
- Recombinant human granulocyte-colony stimulating factor (rhG-CSF) stimulates the production of neutrophils
17 year old bleeding excessively after tooth extraction, most likely factor deficiency
Haemophilia A accounts for 90% of haemophilias and is due to a deficiency of factor VIII
haemophilia B (Christmas disease) there is a lack of factor IX
Diagnosis if schistocytes present on blood film
Aka helmet cells
Intravascular haemolysis (TTP) Mechanical heart valve Disseminated intravascular coagulation
Diagnosis of Haemochromatosis
Transferrin saturation…then confirm with molecular genetic testing for the C282Y and H63D mutations
autosomal recessive disorder of iron absorption and metabolism resulting in iron accumulation
HFE gene chromosome 6
most common inheritied bleeding disorder
Von Willebrand’s
Prolonged bleeding
APTT may be prolonged
Immune thrombocytopenia. Antibodies directed to…
Glycoprotein II b / III a complex
Treatment if DVT and cancer
Even though it’s provoked, you still carry on for 6months of warfarin
Hyperviscosity , weight loss, hepatosplenomegaly… IgM monoclonal paraproteinemia
Waldenstroms macro globulinaemis
Antibodies for warm Vs cool coombs test in haemolytic anaemias
IgM cold
IgG warm
Haemolytic anaenia normal wcc
Lymphoma has normal WCC. Can be warm (IgG) or cold (IgM)
Leukaemia is raised
which blood product has highest risk of bacterial contamination
platelets
Features of myeloma
C - hypercalcaemia
R - renal failure
A - anaemia (from thrombocytopenia)
B - bone features /lytic lesions
Blood tests for antiphospholipid syndrome
paradoxical rise in the APTT and reduced platelets
which immunoglobulin can cross placenta?
IgG
predominantly IgA in breast milk
management of Vitamin b12 deficiency with neuro involvement
Urgent haem referral
Hydroxocobalamin 1mg IM every other day until there is no further improvement
diagnosis of vit d resistant rickets
high urinary phosphate (it is a x-linked dom condition whiich causes impaired phosphate resorption in renal tubules)
causes of decreased iron absorption
PPI (needs gastric acid to absorb)
Tetracycline
Tannin (in tea)
gastric achlorhydria
increased absorp with Vit C
management if isolated rise in transferrin
could be due to dietary iron so repeat a fasting sample
if persistently raised then molecular genetic testing for the C282Y and H63D mutations
how long before iron testing should you have stopped iron replacement?
four weeks.
can cause raised transferrin
ferritin or transferrin saturation in iron deficiency diagnosis?
both would be low but transferrin saturation is not specific - low in pregnancy, contraceptive pill and chronic illness
remember transferrin rises in iron def to maximise utilisation of iron stores
what is a useful prognostic marker in Myeloma?
B2 Microglobin (if > 5.5 mg/l median survival is 29m)
Afro-caribbean gentleman is found to have neutrophil 0.8. Otherwise asymp. Probable diagnosis?
Benign ethnic neutropenia
Patient with sickle cell presents with bone pain, sudden drop in Hb and reticulopenia…diagnosis
Aplastic crisis
Commonly parvovirus b19
Recurrence is rare due to immunity
What is the treatment for idiopathic thrombocytopenic purpura
High dose prednisolone
Platelet transfusion isn’t that helpful because of the autoantibodies destroying it again
What is the result of bone marrow biopsy for idiopathic thrombocytopenic purpura?
increased megakaryocytes
Distinguish between Haemolytic uraemic syndrome and thrombotic thrombocytopenic purpura?
HUS or TTP? Neuro signs point towards TTP
renal failure, pyrexia and thrombocytopaenia
Which immunoglobulin is associated with warm and cold autoimmuneHaemolytic anaemias respectively
IgG warm (G for Ghana) extra vascular.....SLE IgM cold (M for Manchester) intra vascular (in UK)..ebv
What drug can precipitate haemolytic anaemia in patient with G6PD?
Primaquine,
Ciprofloxacin
sulphonamides, sulphasalazine, sulfonylureas
Patient with petechial skin rash and mildly reduced factor VIII (87%) presents with bleeding. Diagnosis
VWB
Haemophilia A would have 5-30% VIII even in mild
Most common and most specific antibodies in pernicious anemia, respectively
90% anti gastric parietal cell antibodies
Only 50% anti IF antibodies, but very specific
Describe antibodies in heparin induced thrombocytopenia
antibodies form against complexes of platelet factor 4 (PF4) and heparin
Management of thrombotic thrombocytopenic purpura
Plasma exchange
Abx can make it worse
Features of thrombotic thrombocytopenic purpura
Typically adult females Fever Fluctuating neuro signs due to micro emboli Thrombocytopenia Renal failure
Assx with pregnancy Post infection (urine, gastro) Cyclosporine, penicillin, clopi, oral contraceptive, aciclovir SLE HIV
What is the pathophysiology of TTP?
Failure to cleave Von willebrand factor normally so unusually large number in plaama
Features of Wiskott-Aldrich syndrome
WATER - WASP mutation , Thrombocytopenia , Eczema , Recurrent infection/ Recessive X linked
Haemophilia A prophylaxis pre dental surgery
Desmopressin
BCR-ACL
associated mostly with chronic myeloid leukaemia
It is the result of the Philadelphia chromosome
Imatinib is an nhibitor of the tyrosine kinase associated with the BCR-ABL defect
Which blood cancer has granulocytes at different stages of maturation
Cml
lymphocyte predominant hodgkin’s lymphoma prognosis
Best prog
Lymphocyte depleted worst prog,
B symps worse prog
Old, male, low Hb/alb, high WCC
Reed-Sternberg cells
Mixed cellularity Hodgkin’s lymphoma
Good prog
lacunar cells
Nodular sclerosing Hodgkin’s lymphoma
Most common (around 70%)
Good prognosis
Gen women
Smear cells aka smudge cells
CML
Why do CLL need irradiated blood
Depletion of doner White cells
Management of HUS
Supportive
Can do plasma exchange in severe cases without diarrhoea
Common complication of plasma exchange
Hypocalcaemia (due to citrate, which is an anticoagulant)
Metabolic alkalosis
Coag factor and immunoglobulin depletion
Removal of systemic medications
Haemolytic anaemia related to pneumonia
Mycoplasma pneumoniae may cause cold agglutins (IgM) haemolytic anaemia, thrombocytopenia
Prognosis of ITP
Acute ITP - more commonly children (either gender), usually self limiting after 1-2/52
Chronic - young/middle aged women, tends to be relapsing remitting
Evans syndrome is assx with autoimmune haemolytic anaemia
JAK2 mutation
95% of pt w Polycythaemia Vera
50% essential thrombocytosis
Prognosis of monoclonal gammopathy of undetermined significance
10% develop myeloma in 10yr
50% at 15yr
Differentiating myeloma and monoclonal gammopathy of undetermined signif
No bone pain or risk of infections
Normal beta 2 microglobulin
Both have raised paraproteinaemia but MGUS would be<20
If IgM it might be Waldenstrom’s macroglobulinaemia
Commonest inherited thrombophilia
Factor V Leiden (activated factor V is unactivated more slowly by activated protein C resistance) ~5% of population
Heterozygous have 5 X risk
Homo have 10x risk
What features suggest leukemoid reaction over CML?
HIGH leucocyte alkaline phosphatase score
Toxic granulation (Dohle bodies) in white cells
Left shift of neutrophils (immature)
Investigation for CLL
Smudge cells aka smear cells in blood film
Immunophenotyping
Smudge cells
CLL
Auer rods
AML
Thrombophilia screening
Don’t usually do if patient will be on lifelong warfarin as will treat anyway
Consider screening for anti phospholipid if unprovoked DVT or pe
G6PD Vs Hereditary spherocytosis
Both have gallstones
G is X linked (so male only) African/ Med descent Intravasc haem Precipitates by drugs Heinz bodies
HS is auto dom
Northern Europe descent
Extravasc haemolysis
Leucocyte alkaline phosphatase
In CML
Low in less mature cells… Like CML, pernicious anaemia
Raised
Leucocyte alkaline phosphatase
Low in less mature cells… Like CML, pernicious anaemia, infectious mono, paroxysmal nocturnal hemoglobinuria
Raised in leukomoid reaction, Polycythaemia, infections (except mono), steroids, preg
Philadelphia chromosome
Present in 95% of patients with chronic myeloid leukemia
Sometimes found in acute lymphoblastic leukaemia and is bad prognostic
t9;22
