Alfred Haem 2 Flashcards
why is haptoglobin low in haemolysis
made by the liver and binds to free Hb
what condition would cause a low haptoglobin without haemolysis
liver disease (made by the liver)
does intravascualr or extravascular haemolysis cause lower haptoglobin
intravascular
what type of haemolysis have positive urinary haemosiderin
intravascular haemolysis
classiicaiton of intravascular haemolysis
- Red cell fragmentation
- PNH
- PCH
haemolysis + schistocytes/red cell fragments diagnosis
MAHA
what cell membrane surgace proteins protects the RBC from complement mediated lysis
CD 55 and CD 59 (implicated in PNH)
gold standard for diagnosis of PNH
flow cytometry - loss of expresison of GPI linke proteins on neutrophils or RBC in peripheral blood
what mAb is used for the management of PNH
eculizuman (humanized chimeric MoAb anti-C5)
mechanism of warm AIHA
IgG+/- C3d
causes of warm AIHA
SLE, CLL/lumphoma, drugs, idiopathic
diagnosis of warm AIHA
DAT (coomb’s test)
what class of antibodies cause cold AIHA
IgM
which AIHA is amendable to steroids
warm AIHA
steroids doesn’t work for cold AIHA
G6PD deficiency blood film
intravascular haemolysis
bites and blisters on film
self limiting
diagnosis of G6PD deficiency
enzyme assay when well (as false negative with reticulocytosis)
medications/foods that increase oxidative stress ( and can exacerbate G6PD
antimalarials
sulphur containins drugs
aspirin
vit K analogues
moth balls
probenecid
fava beans
when does haemoglobin switch occur?
12-18 months (often when beta thalassaemia manifest)
diagnosis of alpha thalassaemia
genetic studies because there is decrease in all the haemoglobins so might not show on gel electrophoresis
what haemoglobins are produced as a result of decreased alpha chain synthesis in alpha thalasseamia
tetrameters:
- Hb H (Betax4)
- Hb Bart’s (gamma4) - hydrops fetalis has Hb Bart’s only
what genotype of the parents will produce hydrops (thalassamia)
–/aa x –/aa or other combinations where both parents have a –/__
diagnosis of beta thalassaemia
haemoglobin electrophoresis - increased A2 and F
need to exclude Fe deficiency because Fe def can reduce beta globin production
sickle cell trait clinical characteristics
heterozygous
sickling may be precipitated by right shift in oxygen dissociation curve (fever, hypoxia, acidosis, general anaesthesia)
generally asymptomatic
management of sickle cell disease
chronic exchange therapy program
hydroxyurea - increases HbF levels and prevents crisis
folic acid
avoid triggers (note gen anaesthesia)
crizanlizumab
P-selectin antibody to prevent vaso-occlusion in sickle cell disease
are secondary or treatment related AML better or worse prognosis
worse
good risk cytogenetics
t(15:17) - APML
t(8:21)
inv16
bad risk cytogenetics (2)
monosomy 7
complex cytogenetics (asso with therapy AML)
bad risk molecular risk
FLT3 +ve
cKIT gene
good risk AML molecular studies
NPM +ve
CEBPA +ve
what TKI inhibits FLT3
midostaurin
general CML TKI SE
pleural effusions/oedema, muscle aches, nausea
EPO in polycythemia
low
management of ET
aspirin +/- cytoreduction (hydrea) in high risk (age >60, plt >1000, Hx thrombosis)
interferon for cytoreduction in pregnancy
5q minus syndrome clinical features
- middle aged or older females
- refractory anaemia
- well preserved or even elevated platelet counts
- good responses to lenalidomide
- low rate of progression to AML
- mortality from complications of iron overload
causes of acquired vWD
lymphoproliferative disorders
myeloproliferative disorders
aortic stenosis
why is chromosome 14 implicated in lymphoma
heavy chain promotor - translocation results in juxtaposition with oncogene
what virus is implicated in the pathogeneis of splenic marginal zone lymphoma
Hep C
where are Reed-Sternberg cells found
Hodgkin’s lymphoma
But these cells only make up a small amount of tumour bulk with the remaining tumour made up of supporting cells
what cells express CD30+
(i) classical Hodgkin’s lymphoma (originally identified on Reed-Sternberg cells)
(ii) anaplastic large cell lymphomas (ALCL)
(iii) primary cutaneous CD30+ T-cell lymphoproliferative disorders
adverse effects of ibrutinib
bleeding (platelet inhibition) and AF
what types of CLL would FCR (Fludarabine, Cyclophosphamide, Rituximab) have no effect in
del(17p) or p53mut
imaging for diagnosis of bone lesions in MM
whole body myeloma CT scan
bone disease multiple myeloma supportive therapy
IV zoledronic acid for 2 years
most common cause of mortality following autograft SCT
relapse of disease
which leukaemia has the highest risk of transplant after HSCT
ALL >AML > CML
What mutation is Budd Chiari syndrome associated with
JAK2
What are features of the MCV:Hb ratio in iron deficiency anaemia vs thalassaemia?
IDA has similarlly reduced Hb and MCV where as in thalassaemia, the MCV is a lot more reduced than the Hb
What does hepcidin do to ferroportin?
Hepcidin causes ferroportin to be internalised and trapped in enterocytes and less system absorbtion of iron
What condition is associated with pencil cells on blood film?
Iron deficiency anaemia
What is the best screening test for haemochromatosis?
Transferrin saturation
Where is transferrin produced?
In the liver
How to delinate for IDA in anaemia of chronic disease?
Ferritin >100 unlikely to be iron deficiency anaemia
Ferritin <100 - look at soluble transferrin receptors
Soluble transferrin receptors are soluble fragments of transferrin receptors which are upregulated in low iron states
What is functional B12 bound to?
transcobalamin II
What is the best test for folate deficiency?
red cell folate
What is the most specific for pernicious anaemia?
Parietal cell antibodies
What are some causes of secondary cold agglutinin disease?
What pathway is affected in G6PD deficiency?
Hexose-monophosphate pathway: pentose phosphate pathway
Involved in produxxtion of NADPH for protection of cell against oxidative stress and oxidation of G6P (into pentose 5-P)
What is the inheritance of G6PD deficiency?
What causes thorney apple cells on blood film?
Pyruvate kinase deficiency (another RBC membrane problem)
Dx by enzyme assay
What does HPLC and electrophoresis show for -a/-a or –/aa?
How to manage beta thal major?
Transfuse to Hb 9-10g/L to suppress X-medullary haematopoiesis
Iron chelation aim for ferritin <1000: desferrioxamine (subcut)
What is the amino acid substitution in sickle cell disease?
ATRA syndrome
Management of PRV
Low risk (<60 and no PHx thrombosis) - phlebotomy for Hct <45%; low dose aspirin
High risk (\>60yo or PHx thrombosis) - as per low risk group AND cytoreductive therapy (hydroxyurea)
What lymphomas are EBV associated with?
Burkitt’s, Hodgkins lymphoma, HIV assoc lymphoma, PTLD
What is the most common cause of SVC obstruction in young adults?
Hodgkin’s lymphoma
What are bad cytogenetics in CLL?
17p del, trisomy 12, 11q
What is the MOA of venetoclax?
BH3 mimetic that inhibits function of BCL2
Bcl2 is usually located on the outer membrane of the mitochondria to inhibit pro-apoptotic proteins thus promoting cell survival
What prophylaxis does bortezimib require?
Aciclovir for HSV prophylaxis
What gender is a major risk factor for the development of GVHD
Female
