Haem Flashcards
give the range
-normal neutrophils
- neutropenia
normal: 1.7 - 6.5 x109/L
neutropenia <1 x109/L
severe neutropenia <0.5 x10*9/L
causes of neutrophilia
- acute bacterial infection.
- conditions of severe stress (trauma, surgery, necrosis, burns, haemorrhage and seizures)
- inflammation ( polyarteritis nodosa, myocardial infarction, and disseminated malignancy)
- corticosteroid use ( - may also causes lymphopenia
- myeloproliferative disease ( CML, polycythaemia vera, and essential thrombocythaemia)
A 63 yo alcoholic w/ acute upper GI bleed & shock is Adx onto ED.
Exam: Soft abdomen, liver not palpable, Spleen is moderately enlarged, no rashes.
FBC
- Hb of 68 g/L
- low grade leukocytosis
- thrombocytopenia.
What is the likely cause of this patient’s presentation?
Oesophageal varices
think varices in 1. Hx alcoholism, 2 splenomegaly w/ thrombocytopenia
plt count helps differentiate betwen variceal / non-variceal bleeding ( portal HTN –> splenomegally & hyperfunction –> plt sequestration
What is the MCV
The mean cell volume (MCV) - size of the red blood cell
Give the male and female normal ranges for
- Hb
- MCV
Hb male 140-180 g/L
Female 115-165 g/l
MCV (both ) 80-100 femolitres
Give the 5 causes of microcytic anaemia
TAILS
Thalassemia
Apanemia of chronic disease (mostly w/ CKD)
Iron deficiency
Lead Poisoning
Sideroblastic anaemia - bone marrow produced ringed sideroblasts, not healthy RBCs
Causes if normocyric anaemia
AAAHH
A – Acute blood loss
A – Anaemia of chronic disease
A – Aplastic anaemia
H – Haemolytic anaemia
H – Hypothyroidism
What are the types if macrocytic anaemia
What are the causes of both types
Megaloblastic anaemia : impaired DNA synthesis–>preventing normal cell division –> grow into large, abnormal cells.
Megaloblastic anaemia:
B12/folate deficiency
Normoblastic macrocytic anaemia:
Alcohol
Reticulocytosis (usually from haemolytic anaemia or blood loss)
Hypothyroidism
Liver disease
Drugs, such as azathioprine
1st line Mx in vWD
2nd line/ 1st line in type III von Willebrand disease
Desmopression - releases stored vWF and FVIII into blood –> homeostasis
VWF/FVIII concentrate
How would acute chest syndrome in Sickle cell Anaemia present
Pain, fever, resp Sx ( tachypnoea, Wheeze, cough)
CXR - pulmonary infiltrates ( the cause of Sx), involving whole lung segments
Acute chest syndrome management
Oxygen, analgesia, empirical Abx
How would sequestration crisis in Sickle cell Anaemia present
Shock (low BP, high HR)
Severe anaemia
Cause: blood pooling in spleen
Is the lifespan of neutrophils longer or shorter than that of platelets
Shoeter
Neutrophils: 4days
Platelets: 7-10 days
A pt with Hx of fatigues blood results are as follows:
WCC normal
Hb 103 g/L
MCV 119 fL
Plt low
Blood fill : megalobasts
Serum folate: normal
What is the most suitable tx and route
IV hydroxycobalamin (B12)
This is B12 deficiency anaemia - a megaloblastic macrocytic anaemia
How does vaso-occlusive crisis in Sickle cell Anaemia present
Sudden onset of pain
No abnormalities on exam
No sig drop in Hb
Hx common trigger: cold, dehydration, infection, hypoxia
Typical locations of pain
Toddlers: hands and feet
Others: anywhere
what is the genetic inheritance of Haemochromatosis
autosomal recessive
mutation in what gene causes haemochromatosis and on what chromosome is it located
HFE gene
Chromosome 6
at what age do the Sx of haemochormatosis appear
> 40
(post menopausal in women, as menstrual period heps rulate iron storage)
Give 8 Sx of haemochromatosis
chronic tiredness
joint pain
pigmentation ( bornze skin)
mles - testicular atrophy & erectile dysfunction
female - amenorrhoea ( absence of periods)
cognitive: memory & mood disturbance
hepatomegaly
what is the initial Ix in suspected haemochromatosis
serum ferritin
also raised in infections (acute phase reactant), chronic alcoholism, NAFLD, hepatitis, cancer
what marker can help distinguish between high ferritin caused by iron overload or other causes
transferrin saturation
- high: iron overload
- normal: other cause
what stain is used on a liver biopsy to establish the iron conc of the liver
Peri’s stain
Mx in haemochromatosis (x3)
venesection (2nd line iron chelation if regular venesection not tolerated
monitoring serum ferritin
monitoring and Tx complications
in anaemia of chronic disease,
is TIBC
ferritin
raised, normal or low
TIBC - reduced
ferritin normal/raised
Describe the 2 types of autoimmune hepatitis
Type 1
Females aged 40/50s
presents: fatigue, features of liver disease
Type 2
female young children/adolescents
acute
high transaminases & jaundice
Give 5 findings in autoimmune hepatitis type 1
high transaminases (ALT & AST)
Autoantibodies:
* Anti-nuclear antibodies (ANa)
* Anti-smooth muscle antibodies (anti-actin)
* Anti-soluble liver antigen (ani-SLA/LP
what is Richters transformation?
when CLL transforms to high-grade lymphoma ( non-hodgkins)
around 75% of which haematological cancer is found in those <6oyo
ALL
give 4 complications of CLL
anaemia
hypogammaglobulinaememia ( which causes recurrent infections )
warm autoimmune haemolytic anaemia
transformation to hihg-grade lymphoma ( Richter’s transformation
how does Richter’s transformation present?
pt with CLL with acute ( 1 of these symptoms suffices)
lymph node swelling
fever without infection
weight loss
night sweats
nausea
abdo pain
difference in
leukaemia
lymphoma
myeloma
leukaemia - cancer of stem celll line in bone marrow
lymphoma - cancer of lymphocytes and in lymphatic system (causes lymphadenopathy )
Myeloma - cancer of plasma cells in bone marrow ( B lymphocytes)
which leukaemia is associated with down syndrome
ALL
ALL is most associated with children & down syndrome
which Leukaemia shows smear/smudge cells on blood film?
CLL is associated with
* richters transformation
* smudge cells ( fragile cells rupture while preparing blood film)
* warm haemolytic anaemia
Which Leukaemia is associaed with philadeplhia chromosomes
CML
CML has 3 phases, and is associated with the Philadelphia chromosome ( translocation from chromosome 9 to 22, affecting chromosome 22)
The leukaemia which may from from a myeloproliferative disorder is associated with which finding on blood film
Auer rods
AML may develop from a myeloproliferative disorder
it is associated with Auer rods
what cells are formed from the myeloid line?
WBCS
RBCs
Thrombocytes
describe the Sx in the3 3 phase of CML
Chronic - asymptomatic , dx incidentally. takes years to progress
accelerated - high proportion of abnormal blast cells (10-20%). More symptomatic, with anaemia, thrombocytopenia and immunodeficiency.
Blast - >20% blast cells. Sx severe, pancytopenia fatal
what cells are formed from the lymphoid line ( accumulate in ALL)?
lymphocytes ( T&B0
leukaemia is typically treated with Chemo & targeted therapy (@ radiotherapy, bone marrow transplant and surgery are other options). give 2 examples for targeted theraapies
ibrutinib , Rituximab
- Tyrosine kinase inhibitors (e.g., ibrutinib/ imatinib)
- Monoclonal antibodies (e.g., rituximab, which targets B-cells)
what proliferative disorders may precede AML
Primary myelofibrosis
Polycythaemia vera
Essential thrombocythaemia
there are multiple chemo complications, one of which is tumour lysis syndrome.
what changes occur to teh blood concentrations of: uric acid, potassium, phosphate and calcium)
high: uric acid, potassium, phosphate)
low: calcium
all increase as cell lysis releases them into the body
calcium decreases due to high phosphate
what drugs can be used to supress the high uric acid levels caused by tumour lysis syndrome?
Allopurinol/ Rasburicase
otherwise good hydration & urine output is required prechemo as prophylaxis
what is the name of the genes affected in the translocation which is found in chronic myeloid leukaemia
BCR-ABL
translocation between the long arm of chromosome 9 and 22 - t(9:22)(q34; q11).
Part of the ABL proto-oncogene from chromosome 9 fuses with the BCR gene from chromosome 22. The resulting BCR-ABL gene
an elderly pt presents with abdo discomfort. Splenomegaly is found on examination
the bloods show an increase in granulocytes at different stages of maturation +/- thrombocytosis. what leukaemia does this indicate?
chronic myeloid leukaemia
raised granulocytes at diff stages of maturation: e.g. monoblasts ( macrophage precursor) high, neutrophils high, plts high
so in increased granulocytes at different stages of maturation +/- thrombocytosis
= CML
(pts typically 60-70 yo)
what type of cells would largely be found in AML ( maturity)
blasts - immature cells
(think acute, so rushing, doesn’t wait for differentiation –> precursors proliferate)
what type of cells would largely be found in ALL ( maturity)
blasts - immature cells
(think acute, so rushing, doesn’t wait for differentiation –> precursors proliferate)
a normal thrombocyte range is
(140-400 x 109/l)
this may be raised e.g. to 420 x 109/l in CML
from which point is essential thrombocytosis considered?
typically >450 * 109/l (much higher)
Platelet counts below 10 x 10*9/L are at high risk of what types of bleeds
spontaneous bleeding.
Particularly:
* Intracranial haemorrhage
* Gastrointestinal bleeding
<50 is where e.g. bleeding gums, haematuria,
what is the 1st line Tx in ITP
Oral prednisolone
(ITP = antiobodies against platelets)
others:
* Prednisolone (steroids)
* IV immunoglobulins - raises plt count quicker than steroids, so used in active bleed/ urgent procedure
* Thrombopoietin receptor agonists (e.g., avatrombopag)
* Rituximab (a monoclonal antibody that targets B cells)
* Splenectomy
what is the cut off for tx in ITP
plts <30x10*9/L
or slightly higher if poroloned bleeding/ reduced QOL/ injury prone profession
what is the most suitable investigation in suspected autoimmune haemolytic anaemia
Direct coombs’ test
if positive: positive direct antiglobulin test
do reticulocytes increase, decrease or stay the same in autoimmune haemolytic anaemia
increase
(bone marrow responds by increasing reticulocyte synthesis)
rituximab is one of the medications used in ITP. how does it work
Abs produced by B cells
Rituximab ( monoclonal antibody) targets CD20 proteins on surface of B cells
so reduction of Bcells = reduction of Aba
describe TTP
thrombotic thrombocytopenic purpura - thrombi develop in small vessels
causes: thrombocytopenia, .purpura, ischaemia & end organ damage
deficiency in what protein leads to TTP
ADAMTS13
normally
- inactivates vWF
- reduces platelet adhesion to vessel walls
- reduces clot formation
Mx of TTP - haematologists
what causes Heparin-induced thrombocytopenia ( HIT)
platelet antibodies develop in response to heparin –> bind to plts –> activate clotting cascade –> hypercoagulable sgtate
typical pt: low plt count, abnormal blood clots, recently started heparin
5-10 days post starting heparin
in HIT, heparin is stoppped, what alternatives can be used
fondaparinux/ argatroban
give the 5 causes of microcytic anaemia
TAILS
* T – Thalassaemia
* A – Anaemia of chronic disease
* I – Iron deficiency anaemia
* L – Lead poisoning
* S – Sideroblastic anaemia
Give 5 causes of normocytic anaemia
3As,2Hs
- A – Acute blood loss
- A – Anaemia of chronic disease
- A – Aplastic anaemia
- H – Haemolytic anaemia
- H – Hypothyroidism
what is the management in anaemia of chronic disease caused by CKD
erythropoietin
anaemia of chronic disease typically occurs with CKD –> lack of erythropoietin by kidneys
anaemia of chronic disease= the A in tAils ( microcytic anaemia)
what are the 7 causes of macrocytic anaemia
megaloblastic macrocytic anaemia: B12/Folate deficiency
Normoblastic macrocytic anaemia ( HARD-L)
Hypothyroid (also causes normocytic anaemia)
Alcohol
Reticulocytosis ( high conc. retiiculocytes from haemolytic anaemia/blood loss)
Drugs ( azathioprine)
L liver disease
give 2 sx of anaemia specific to IDA
pica
hair loss
which forms of anaemia are specific to these signs & symptoms
- Koilonychia
- Angular cheilitis
- Atrophic glossitis
- Brittle hair and nails
- Jaundice
- Bone deformities
- Oedema
- Koilonychia (spoon-shaped nails) - IDA
- Angular cheilitis - IDA
- Atrophic glossitis (smooth tongue due to atrophy of the papillae) -IDA
- Brittle hair and nails - IDA
- Jaundice - haemolytic anaemia
- Bone deformities - thalassaemia
- Oedema, hypertension and excoriations on the skin - chronic kidney disease (anaemia of chronic disease )
what antibodies found in the blood indicte pernicious anaemia
intrinsic factor
following bloods, what tests should be done for unexplained anaemia
Exclude GI cancer s source of bleeding in unexplained IDA: colonoscopy/ oesophagogastroduodenoscopy
Unexplained anaemia/ possible malignancy - bone marrow biopsy
which form of anaemia presents as a microcytic hypochromic anaemia
IDA (hypochromic as its pale due to reduced haemoglobin concentration)
most common cause of iron deficiency anaemia in
- children
- adults
children - dietary insufficiency
adults - bleed (inc. IBD, angiodysplasia)
what parts of the bowel is iron mainly absorbed in
duodenum and jejunum
(acid from stomach maintains stable Fe2+ , less acid –> unstable Fe3+ so PPIs may reduce absorption)
why do coeliac and crohns disease reduce iron absorption
cause inflammation of the duodenum +/ jejunum
what protein is bound to iron and transports it
transferrin
what does
low ferritin
normal ferritin
raised ferritin
indicate
low - highly suggestive of IDA
normal - does not exclude iron deficiency
high could be raised in : inflammtaion, liver disease, iron supplements, haemochromatosis
ferritin is typically stored in cells, its an acute-phase reactant
what does the marker Total iron-binding capacity indicate?
the amount of transferrin in the blood
TIBC and transferrin increase with iron deficiency and decrease with iron overload
what does transferrin saturation indicate
total iron in body
less iron - less saturated
fasting sample is the most accurate as transferrin can temporarily increase post meal/ supplement
give 3 causes of iron overload
haemochromatosis
iron supplements
acute liver damage ( liver contains lots of iron)
iron overload will show raised: serum iron ferritin and transferrin saturation ( normal should be 15-50%)
TIBC will not be raised
what is the Ix in IDA without clear underlying cause ( e.g. menstruation)
colonoscopy & oesophagogastroduodenscopy
check for malignancy
what are the 3 options for tx IDA
Oral iron ( ferrous sulphate/ ferrous fumarate) - slow increase
iron infusion ( IV) - fast increase
blodd transfusion ( severe)
what are the risks/ side effects in Mx IDA with oral iron
common:
constipation
black stools
what are the risks/ side effects in Mx IDA with IV CosmoFer ( iron infusion)
small risk: allergic reaction/anaphylaxis
do not use in infection - bacteria can “feed” on it
Give 3 causes of low B12
Pernicious anaemia
low intake (vegan diet)
meds that reduce absorption ( PPIs metformin
