Haem 2 Flashcards
haemaglobinopathies are generally what
autosomal recessive
commonest monogenic disorders
thallasaemias
increase in thallasaemia where
malaria endemic areas
where are people with thallasaemia from
SEA
ME
medditirean
alpha thal trait
what it be mistaken for
1 or 2 missing
iron defic but ferritin normal and RBC count is high
HbH disease
alpha chain production
what kind of anaemia
only 1 alpha chain left
<30% or normal
anaemia with low MCV and MCH
what are HbH bodies
excess beta chains that form tetramers that can’t carry oxygen
red cell inclusions (HbH bodies) can be seen with some stains
Hb barts hydrops fetalis is what
what forms are seen at birth
minimal or no alpha chain production. HbA can't be made Hb barts (gamma4) and hbh at birth
what with hydrops fetalis is seen in peripheral blood
what happens to most babies with this
nucleated RBC
most die in utero
in beta thallasamei what kind of hb is affected
only HbA
genetic for beta thallasaemias
point mutations
beta thallasmaie trait is what
what kind of anaemia
reduced amount in one or none in one
mild or no anaemia
beta thal intermediate
symp and rx
both low or ones got none and the other low
mod severity requiring occasional transfusion
beta thal major
treatment
none in both
life logn transfusion
blood film of beta thal major
macrocytosis
hypochromia
anispokilocytosis and target cells
HPLC of beta thal major
mainly HbF present
small amounts of HbA
treatment for beta thal major
regular transfusion to maintain hb 95-150
transfusion cx
iron over load hepB/C alloautoantibodies TRs bacterial sepsis
how much iron in a unit of red cells
200-250mg
iron overload leads to what endocrine
cardiac
liver
endo - impaired growth, DM, osteoporosis
cardiac - cardiomyopathy, arrhythmias
liver - cirrhosis, hepatocellular cancer
what can be given to treat iron overload
desferrioxamine - chelatops bind to iron and secreted in urine/stool
increase in HbA2 seen on HPLC
beta that trait
can HPLC diagnose alpha thal trait
no normal in it
need DNA testing to confirm
sickle cell genetics
point mutation on chromosome 6 of the beta globin gene that substitutes glutamine to valine production Bs
HBS polymerase
changes shape if exposed to low levels of oxygen fro a prolonged period of time
sickle trait
HbS
one normal one betas
HbS<50%
what can happen in sickle trait
can sickle in severe hypoxia - high amplitude, under anaesthesia
sickle cell anaemia genetic
HbS HbA
episodes of what
autosomal recessive
HbS>80% no HbA
episodes of tissue infarction due to vascular occlusion
effects of sickle cell anaemia
chronic haemolysis
hyposplenism
sickle cell crisis
shortened RBC life spac
due to repeated splenic infarcts
hypoxia, dehydration, infection, cold exposure, stress/fatigue
treatment of sickle cell crisis
opiate analgesia, hydration, rest, oxygen, ABs, transfusion
life long treatment
hyposplenism and others
prophylactic penicillin. pneumococcal, meningococcal and haemophilus influenza vaccines yearly
folic acid supplementation
hydroxycarbamide - induce HbF production
HbS/beta thal
mild if b+ severe if b0
HbSC dx
milder but increased risk of thrombosis
lysine replaces glutamic acid in position 6
activation of complement cascade in haemolytic TR
c3a and c5a
powerful anaphylaxotoxins, increase vascular permeability, dilate blood vessels, release serotonin and histamine
formation of MAC - rupture of transfused RBCs
activation of coagulation in haemolytic TR
DIC
activation of kinin system in haemolytic TR
activated by factor 7, formation of bradykinin:
arteriolar dilatation
vascular permeability - hypotension - release of catecholamines - vasoconstriction in kidneys and in other organs
delayed TR when
5-10 d after
what can be found in a delayed HTR
spherocytic red cells on film
increase in bilirubin and LDH
positive DAGT and/- RC alloautoantibodies
may be degree of renal failure present
what kind of transfusions for febrile TRs happen in
2% of RC 20% of platelet
symp of febrile TR
1-2 degrees rapid rise
preventionof febrile TR
prevention - antipyretics, leucodepleted blood components
whats found in febrile TR
ABs to contaminating white blood cells - release of cytokine and vasoactive substances from white cells during storage
urticarial reactions why
symp
rx
mast cells - IgE to infused plasma proteins
rash and wheals within mins
slow transfusion.
circulatory TR who what
elderly px with CCF
pulmonary oedema
bacterial infection organisms in RC
platelets
psuodomonas, yersinina
staph, strep, serrritla, salmonella
viral infections HIV
HBC
HCV
1/6mil
1/1.6mil
1/2.6mil
transferrin >50%
risk of iron overload
dx of iron overload
males ferritin >300
females >200
liver biopsy if uncertain or to assess organ damage
treatment of primary haemochromatosis
weekly phlebotomy 450-500ml (200-250mg of iron)
get ferritin to <20 then keep it under 10ug/L
treatment for secondary iron overload
why is venesection not an option
not an option in already anaemic px
deferoxamine SC or IV, deferipone PO, deferasirox PO
what happens to anaemia in chronic disease
inflam macrophages iron block -> iron supply to marrow erythroblasts impaired -> hypochronic red cells
why are red cells more prone to damage
biconcave shape
limited metabolic reserve
can’t generate new proteins - no nucleus
consequences of haemolysis
erythroid hyperplasia
excess RC breakdown
extravascular haemolysis what happens
what grows
release of what
taken up by reticuloendothelial system (spleen and liver predom)
hepatosplenomegaly
release of protoporphyrian: unconjugated bilirubin - jaundice, gall stones, urobiliuria
intravascular what happens
ix kind of
RC destroyed within circulation spilling contents
haemglobinaemia
methalmalbinaemia
haemoglobinuria - pink urine turns black on standing
haemisderinuria
increased hb and increased haemsiderin
intravascular
which kind of haemolysis is most common
extrvacular
what causes intravascular haemolysis
haemolytic TR
GP6D
black water fever
PNH/PCH
film showing spherocytes
red cell fragments
heinz bodies
HbS
membrane damage
mechanical damage
oxidative stress
sickle cell
test for auto immune haemolysis
direct coombs test
AI haemolsysi types IgG
IgM
idiopathic. commonest. SLE, CLL, penicillins, infections
idiopathic. EBV. mycoplasma. CLL
alloimmune haemolyiss
immune response
passive transfer
AB produced
haemolytic disease of the newborn IgG
immune transfer is what
immediate
delayed
haemolytic TR
immediate IgM intravascular
immediate IgG extravascular
mechanical destruction of Rbc causes
DIC haemolytic uraemia syndrome EColi 0157 leaving heart valve - MAHA TTP infection - malaria burns - microspeheres
abnormal cell membrane liver
liver disease - zieves syndrome
haemolysis, alcoholic liver disease, hyerlipidaemia
other causes of abnormal cell membrane
vit E defic, paroxysmal nocturnal haemaglobinemia
hereditary pherocytosis
paroxysmal nocturnal haemaglobinemia
hams test
urine dark only at night and morning
abnormal cell metabolism
GP6D defic - genetic
dapsone - haemolytic anaemia
myeloma direct tumour effects
bone lesions, increased calcium, bone pain, marrow failure
myeloma paraprotein mediated effects
renal failure, immune depression, hyperviscosity, amyloid
malignant melanoma cell shift balance of bone production
increase in osteoclasts
decrease in osteoblasts
treatment of myeloma
corticosteroids, alkylating agent - cyclophosphamide, thalidomide, lenlamide
what can be used to monitor myeloma
paraprotein
monoclonal gamapathy of uncertain significance
paraprotein <30
monoclonal protein in blood
bona marrow plasma cells <10%
no evidence of myeloma and organ damage
AL amyloidosis is what
where is mutation
poor prognosis if
symp
small cells plasma clone
mutation in light chain
poor prognosis esp if cardiac failure
kidneys: nephrotic syndrome, neuropathy, GI - malabsorption, heart - cardiomyopathy, liver disease
AL amyliodosis ix
congo red stain
green birefringence
rectal or fat biopsy
walderstroms macroglobinaemia what Ig
IgM - pentameric
lymphaplasmacytoid neoplasm is what
clonal disease of cells intermediate between lymphocytes and plasma cells
tumour effects of walderstroms
lymphadenopathy
splenomegaly
marrow failure
paraprotein effects of walderstorms
hyper viscosity - fatigue, visual disturbances, confusion, bleeding CF
neuropathy
night sweats, weight loss
treatment for walderstorms
chemo
plasmapheresis
