haem Flashcards
what are the sites of haemoposiesis:
- embryo
- at birth
- adult
embryo - yolk sace then liver then marrow
at birth- mostly marrow
adult- bone restirted to skull, rib sternum, pelvis and prox femur
what do erythroid precursors develop into
platelets and RBCS
what do monocyte precursors develop into
macrophages, and granulocytes eg neut, baso,eosino
whta cells are also know as polymorphs
neutrophils
what graulocyte has a bi-lobes nucelus
eosinophil
what does the nucleus of a neutrophil look like
multi-loculated
describe the makeup of a haemoglobin molecule
2 alpha chanins
2 bets chains
haem group (FE2+) in porphyrin ring in each chain
bilirubin is created from the breakdown of what group
porphyrin ring
what is glbin recycled to
amino acids
how do red cells creat energy
only via glycolysis - 2 ATP generated
what type of iron can oxygen bind to
Fe2+ not Fe3+
how is FE2+ converted back to FE3+ in the RBC
via NADP - redox reaction - gain electron
function of G6PD enxyme
prevents oxidtive stress in RBC
how is G6PD deficiency inherited
X-linked recessive
how is carbon dioxide trasnported in the blood
- 10% dissolved
30% - bound to Hb as carbimo - Hb
60% as bicarb
what shifts bohr effect curve to the right
increased CO2, increased H+ (low pH)
2-3 BPG
does macro or microcytic anaemia casue hypochromia
microcytic
causes of microcytic anaemia
T- thalaaseami
A- anaemia of chronic disease
I -iron deficiency
L- lead poisioning
S- sideroblastic
in microcytic anaemia pathologically where does the defect ccur
in heamoglobin production - haem or globin deficiency
therefore cytoplasmic defect
condition that causes a globin deficiency
thalassaemia
what is circulating iron bound to
trasnferrin
trasnports iron to marrow
what is iron stored as and where
ferritin in liver mainly - and macrophages
what would transferrin saturations be in anaemia of Cd and iron deficiency
reduced
where is iron absorved
jejunum
cutanoeous features of iron deifciency anaemia
itchy rash
koiionychia
angular chelitis
smooth tongue
treatment of iRon deficiency anaemia and expected response
ferrous fumurate - shoud rise about 10 g/L a week
how to differetiate between a megaloblastic anaemia and non- megaloblastic anaemai
the presence of hypersegmented neutrophils (>5) indicates megaloblastic i.e impaired DNA synthesisi
how to dsitinguish between B12 and folated deficiency
methymalonic acid - increased in b12
causes of megalblastic anaemia
b12 deficency
folate deficiency
DNA affetign drugs- methotrexate, azathioprine , sulfa derivatives eg salufasalazine and trimepthoprim , phenytoin and 5-fluorouracil
causes of b12 deficiency
vegans
pernicious anaemia
causes of folate deficiency
diet malabsorption
excessive utilisation eg, pregnancy, haemlysis, anti-convulsants
where is B12 absorbed and how long is it stored for
ileum and 2-4 years
where is folate absorbed and how long is it stroed for
duodenum/jejunum and 4 months
Symptoms of b12 and folate deficiency
signs of anaemia and fatigue
weight loss, diarrhoea, inferitlity
sore tongue- burning mouth and jaundice
neuro symptoms
what would be seen on blood film in megaloblastic anaemia
hypersegmented neutrophils
macro-ovalocytes
causes of non -megaloblastic anaemia
alcohol
preganncy
liver disease
hypothyroid
marrow failure- eg myledysplasia, myeloma and aplastic anaemia
causes of normocytic anaemia
anaemia of chronic disease
chronic kidney disease
aplastic anaemia
haemolytic anaemia
acute blood loss
what types of cells would be seen on blood film in iron deficiency anaemia
anisopoikilocytosis (red blood cells of different sizes and shapes) ,
target cells,
‘pencil’ poikilocytes
what age demographic has the highest incidence of iron deficiency anameia
pre-school children due to preiods of rapid growth- high iron demand
what chromosome is the ABO blood grouping found on
chromosome 9
what antigen and antibody does blood group A have
A antigen and Antibody B
what antigens does blood group O have
neither - has both antibodies
what Ig are blod group antibodies
IgM
what HB levels indicate trasnfusion
70g/l
80 in ACS
a platelet count of what in active bleedign would indicated plateelt trasnfusion
<30 if grade 2 eg haematemesisi
<100 if critical sites eg CNS
what type of blood product transfusion has the higehst level of bacterial infection
plateleet
does ahigh or low INR increase blleding rise
high - higher the thinner
when should FFP be given
if PT or APTT>1.5
what is the universal doner of FFP
AB as lacks antibodies
what is found in FFp
clotting factors, albumin and immunoglobulin.
what is irradiated blood missign
depleted of t-cell lymphocytes
What does the use of irradiated blood products avoid
transfusion assoc grafte versus host disease
describe the 3 main forms of haemoglobin
HbA - 2aplha 2 beta
HbA2 - 2 alpha and 2 delta
HbF - 2 alpha 2 gamma
alpha globin chains are found on what chromosome and how many copies
chromo 16
2 alpha genes per chromo
4 in total
beta globin genes are found on what chromosome and how many copies
chromo 11
one copy per chromo
when are adult level beta chains reached
6-12 months
what is difference between thalassaemi and sickle cell
thala - decreased rate of globin synthesis - normal chains
sickle - norm rate - abnorm chains
in alpha thalassaemia if only 1 or 2 copies are missing hwo would this present
thalassaemia trait - microcytic, hypochromic red cells but norm Hb - asymp carrier
if 3 copies of alpha globin allele affected in alpha thalassaemia whta is this called and how would it present
HbH -
jaundice splenomegaly growth retardation
hypochromic microcytic anaemia
if all 4 alpha globin genes affected what thalassaemia would this cause
Hb bart/ hydrops fetalis - death in utero
in Hb H disease what is seen on blood film and why
golf ball cells - excess beta chain form tetramers
hypochromic microcytic anaemia
what type of mutation casues alpha thalassaemia
deleteion
what type of mutation causes beta thalassaemia
point mutation
how are teh thalassaemia inherited
auto recessive
raised what is diagnostic of beta -thalassaemia trait and why
HbA2 - 2 alh , 2 delta chians
how does beta thalassaemi amajor present
presents in the first year of life with failure to thrive and hepatosplenomegaly
extramedullary haematopoesisi casues :
- hepatosplenomegaly
- skeletal changes
- organ damage
what would be seen on Hb analysis in beta-thalassaemia major
HbF and HbA2 raised
NO HBA
management of beta-thalassaemia major
repeated transfusion- 95-105
this leads to iron overload → organ failure
iron chelation therapy is therefore important (e.g. desferrioxamine)
genetic mutation in sickle cell
point mutation in codon 6 of B globin gene
turns glutamine into valine
therefore HbS
what is sickle cells trait
one abnormal sick cell gene one normals
aymp carrier unless in crisis
inheritance patter on sickle cell
auto recessive
who tends to get sickle cell and why
afrocarribean - protective against malaria
what age does sickle cell anaemia present and why
4-6 months when HbF stops
inbestigation for sickle cell
plasmaphoresis
precipitants of sickle cell crisi
cold, infection. dehydration , deoxygenation
how is a sickle cell thrombotic crisis diagnosed
clinically
what casues an aplastic crisis in sickle cell and what is seen
parvovirus
sudden fall in Hb and reduced retic count
management of sickle cells anaemia
penicillin if hypospelinism
hydroxycarbamide/hydroxyurae - induce HBF production
pneumo vaccine every 5 years
treatment of a Non-haemolytic febrile reaction to transfusion
slow rate
monitor
paracetamol
cause of transfusion reaction anaphylaxis and tx
patients with IgA deficiency who have anti-IgA antibodies
Stop the transfusion
IM adrenaline
ABC support
oxygen
fluids
pathophysiology of acute heamolytic trasnfusion reaction
red blood cell destruction by IgM-type antibodies.
do reticulocytes have a nucleus
no only RNA not DNA
what conditions cause MAHA
DIC
HUS
TTP
what antibodies are involves in RBC destruction in paroxysmal cold haemoglobinuria and paroxysmal nocturnal haemoglobinuria
IgG
examples of immune mediated intravasculaar haemlysis
cold haemoglobinuria
what type of haemolysis is osmotic lysis
intravascular - hypotonic Iv solution causes RBCs to burst
what is produced in liver if high iron stroes to down regulate absorption
hepcidin- also produced in anaemia of chronic disease
primary vs secondary haemostasis
primary - platelet plug
secondary - coagulation cascade
in primary haemostasis endothelial damaage causes exposure of what factors
collage and VW factor
Pt and APTT what one is intrinsic pathway and what one is extrinsic
intrinsic - PT
extrinsic - PATT
what would cause multiple clotting factor deficiency
DIC And liver failure
vitamin k dependent clotting factors
2,7,9 and 10
what do warfarin adn heparin affect with regards to PT and APTT
warfarin - PT time
heparin - APTT
broad cateogries of casues of failure of platelet plug and what they include
VASCULAR - collagen deficiency eg marfans
vasculitis- HSP
scurvy - vit c
PLATELETS - thrombocytopenia
hereditary vs acquires
eg dic, ITP (autoimmune), hypersepnism
VW deficiency
casues of failure of secondary haemostasis - fibrin clot
clottin gfactor deficiency
multiple- DIC , liver disease
single - haemophilia
how might pbstructive jaundice casue clotting factor deficiency
bile needed to absorb vit k
treatment of ITP in adults
steroids
inheritance pattern of haemophilia
x-linked recessive
difference between haemophilia A and B
A - VIII deficiency
B - IX deficiency (christmas disease)
PT and APTT in haemophilia
PT - norm
APTT - prolonged
what breaks dwon the fibrin clot
plasmin
role of tpa in body
tissue plasminogen actovator converts plasminogen to plasmin - this breaks dwon fibrin clot
what are the naturally occuring anti-coagulatns
antithrombin,
protein C and S
examples of inherited thrombophilias
factor V leiden
protein s deficiency
preotein c deficiency
anti thrombin deficicency
prothrombin 20210 mutation
example of an acquired thrombophili
anti-phospholipid syndrome
features of anti phospholipid
arterial and venous thrombosis
fetal loss
mild thrombocytopenia
what is seen with Pt and APTT in anti-phospholipid
normal PT
prolonged APTT
antibodies seen in anti-phospholipid
anticardiolipin antibodies
anti-beta2 glycoprotein I (anti-beta2GPI) antibodies
lupus anticoagulant
management of anti-phospholipid
prophylaxis - asprin
after first event - warfarin
MOA of heparin
potentiate anti thrombin
diff between unfractioned and LMWH MOA’s
unfraction- anti-thrombin binds with thrombin
LMWH - anti thrombin binds with factor Xa
what form of heparin requires monitoring adn how
unfractionated via APTT
heparin reversal agent
protamine sulphate
side effects of heparin
osteoporosis
trombocytopenia
bleeding
hyperkalaemia
side effects of heparin induced thrombocytopenia
pro-thrombotic
what juice is avoided with warfarin
cranberry
why is heparin used alongside warfarin in the first 5 days
to avoid skin necrosis
when warfarin is first started biosynthesis of protein C is reduced- this results in a temporary procoagulant state after initially starting warfarin,
what is required for vitamin K absorption
bile
why are newborns given vitamin K
to avoid haemorrhagic disease of the newborn
lifespan of plateele
7-10 days
