nm5266: we're going to er start off er by talking about er venous thrombosis 
this evening er the er you won't be able to read the er slide up up there but 
it says er didn't you tell sister that you're only just visiting and er we do 
need to be clear sometimes why we're here and what we're actually doing and er 
we're going to talk about er pulmonary embolism and venous thromboembolic 
disease i think the first thing to say is that er venous thromboembolic disease 
is not necessarily an acute problem it's better really to think of it as a 
chronic condition because many patients having had an acute episode of venous 
thrombosis have a further event and some of the long term sequelae of er having 
a venous thrombosis can be long lasting and effect patients throughout their 
life clearly the thing that we're concerned about is patients who have an 
extensive deep vein thrombosis embolising and that clot ending up in the lungs 
causing a pulmonary embolism er pulmonary embolism clinical presentation you 
may have seen but er er for a significant percentage of patients it may just be 
that er the only they have is that they have an acute fatality and that is one 
of the presentations more commonly of course they present with pleuritic chest 
pain or hemoptysis or just simply increasing breathlessness and er it is part 
of the disease of er venous thromboembolic disease if you actually look in 
patients who've had a deep vein thrombosis for evidence of a er pulmonary 
embolism then you will find if you look hard enough and use enough radiological 
techniques that the majority of them do have some evidence of pulmonary 
embolism so er we need to remember that er venous thromboembolism is a serious 
problem and er it can present without signs and symptoms er it's also a common 
problem in hospital because many patients are obviously immobile and once you 
put people to bed and er keep them in hospital for significant periods of time 
then their risk of developing developing a pulmonary embolism increases er the 
good thing to say about it is that most patients er most cases of pulmonary 
embolism are preventable and er with the use of prophylactic measures for 
patients particularly in the post-operative period but also acutely ill medical 
patients er should be receiving some form of thromboprophylaxis to prevent them 
having er a pulmonary embolism so most events are preventable and venous 
thromboembolic disease is a chronic problem alright we have lots and lots of 
patients nowadays who are put on anticoagulant treatment and you do need to 
know quite a bit about anticoagulant management because when you're a houseman 
one of the things that you're guaranteed you're going to have to do is to 
manage patients in terms of their anticoagulant therapy in terms of er the 
numbers of patients on oral anticoagulants well the numbers increase year-by-
year large numbers of patients are now put on oral anticoagulants because of 
atrial fibrillation patients with venous thromboembolic disease are in general 
kept on longer and longer periods of anticoagulation compared with even a 
matter of a few years ago and we will go through that now er this a picture of 
the mother-in-law and it's probably her most appealing er aspect er but the 
problems that you get with acute venous thrombotic events do become chronic and 
here you can see the typical lady who has bilateral swollen er legs with 
chronic venous congestion these legs are at risk of ulceration and er it leg 
ulcers account for an incredible amount of morbidity and if you actually er 
cost out the amount of money that the N-H-S spends on leg ulcers from people 
who've got chronic venous problems it is a major major problem and it's 
something which you don't really see unless you're in er primary care because 
you see the patients who come in with an acute venous thrombosis they're 
treated you think that's all fine they've gone away but in fact there are lots 
of problems with chronic post-phlebitic syndrome and chronic venous congestion 
right the other thing to say is that there are certain clinical states that are 
associated with an increased risk of venous thrombosis and clearly a number of 
these will be well known to you but pregnancy particularly in the post-partum 
period er throughout pregnancy there is a slight increase risk of er venous 
thrombosis but that increase increases particularly after thirty weeks and is 
at the highest in the six weeks in the post-partum period so when we give 
prophylaxis in pregnancy er inevitably we're going to use anticogulate patients 
in the six week's post-partum and then depending on other factors whether we 
would do it antenataly or not the thing we don't do nowadays er is put patients 
to bed because we're worried about the clot moving er it used to be er the 
situation whereby people and particularly some of the older nursing staff would 
be terrified that patients if they moved would end up throwing a bit of clot 
off and in point of fact all that did was help extend the clot er so it's 
important that patients are mobilised at the earliest opportunity however 
extensive their clot is so don't think that a little bit of clot that's moving 
around er is going to be more at risk by mobilising people it's much worse if 
you leave them and let them just sit so venous thrombosis is a problem that's 
particularly associated following trauma to the legs particularly associated 
with er post-surgical period particularly associated with orthopoedic surgery 
well how do we actually er sc-, screen and examine for a start patients with er 
suspected venous thrombosis well there are a number of clinical screening tests 
that you need to be aware of and depending on what the er system is in the 
local hospital it could be any combination of some of these but perhaps one of 
the commonest practices is to perform a clinical probability score in other 
words i'll go through that but it means actually carrying out a proper clinical 
examination and actually scoring the patient er as to whether they would be at 
high moderate or low risk er sometimes er ultrasonography is used as a 
screening test there's impedence plethysmography er and although less commonly 
used venometry is less commonly used now whereby you inject a dye into the leg 
it's certainly not used very commonly as a screening test but may be used as a 
diagnostic test commonly used is the D-Dimer test now the D-Dimer is a fragment 
of cross-linked fibrin and is raised in probably ninety-nine per cent patients 
who've got evidence of venous thromboembolic disease it is however not specific 
for venous thrombosis and can be raised in a variety of other acute medical 
problems so in acute infection it's raised almost inevitably in pregnancy so 
just having a raised D-Dimer is not a reason to investigate someone further for 
venous thromboembolic disease unless you have some clinical probability score 
to go with it so we don't want you ordering a D-Dimer on anybody who comes in 
with chest pain just because it's next to the box where you tick cardiac 
enzymes if somebody comes in with a myocardial infarction the D-Dimer's almost 
inevitably going to be raised as well what it's detecting is the presence of 
new clot formation a negative D-Dimer however is helpful because if you've got 
a negative result then it really is unlikely that you've got evidence of venous 
thrombotic disease so you need to be careful how you interpret it so it has a 
very good negative predictive value it has a low positive predictive value er 
just to go through some of the diagnostic techniques used in er the diagnosis 
of er deep vein thrombosis historically venography has been the gold standard 
that er has been used whereby you inject a dye into the dorsal er venous arch 
and er you look for evidence of filling defects the other thing you have to 
remember with venography is that a small percentage of patients if you inject a 
dye into their leg will develop a D-V-T as a result of it impedence 
plethysmography i won't spend any time on but it's a useful screeing test the 
ultrasound is much more commonly used and doppler ultrasound er is perhaps the 
most commonly used er screening technique er and diagnostic technique now er in 
the United Kingdom certainly diagnostic technique the disadvantage of using an 
ultrasound is that clots below the calf are often not apparent on ultrasound 
now you may argue that that isn't that important because it's clots that are 
above the knee are the one's which extend particularly and embolise but if you 
carry out serial doppler scans of calf vein thrombosis then a substantial 
number of them will actually extend above the knee so overall we would 
recommend that patients who have calf vein thrombosis also receive 
anticoagulant treatment now when you're assessing these patients you need to do 
a clinical pre-test probability and as i've said there are major minor scoring 
systems so this is sort of a a scheme that you might adopt if you've got 
somebody with a suspected er deep vein thrombosis you would carry out the 
probability score er you would carry out a D-Dimer measurement if the D-Dimer 
is raised if you have a high clinical probability score then these patients er 
should have some further diagnostic technique such as a venous compression 
ultrasonography for patients in whom er the ultrasound is negative and you have 
a still have a high clinical probability then you may go on and look at other 
techniques in particular perhaps then venography so these are some of the 
clinical criteria for major scores for deep vein thrombosis and really er when 
you're clerking these patients in it'd be important to have this score in front 
of you so most hospitals would have some pathway with these sort of scoring 
systems on them as you'll see if patients have cancer they're at significantly 
higher risk of having a deep vein thrombosis sixteen per cent of all patients 
with deep vein thrombosis have cancer have known cancer at the time of 
presentation obviously if patients are paralysed or immobilised for substantial 
periods of time that's an important factor if they're bedridden and had recent 
surgery if they have clinical signs of localised tenderness if they have 
measurable differences in the diameters measured at the calf or at the thigh 
then that's a significant factor also if they have a strong family history of 
venous thrombosis or if they've got previous venous thrombotic events 
themselves then clearly they're that much more at risk and then there are some 
minor points which are less important er er mild erythema if they've been 
hospitalised within the previous six months so there are some minor scores 
there which have some slight relevance and basically using these sort of 
clinical er algorithm you can come to some conclusion as to the probability of 
whether they're got a venous thrombosis this is very useful it's very important 
that if you're going to use a D-Dimer score that you do this in conjunction 
with it right well there are different methods of measuring D-Dimer's some of 
which you can do at the bedside there are some near patient tests that you can 
er use there's a test called a simply red score and this test er could be used 
in primary care it doesn't actually give any specific quantitation it just 
gives a positive or negative result there are more specific techniques in the 
laboratory whereby you can measure the er D-Dimer which are better in many 
respects but they do take longer to perform i won't spend too much time on the 
rest of that okay so there are a number of factors in terms of managing v-, 
venous thrombosis er it's important that if you've got a patient with suspected 
venous thrombosis that er these patients are commenced on the low molecular 
weight heparin er there may be time some delay sometimes in getting er 
diagnostic procedures performed but if you've done a clinical probability and a 
D-Dimer score there and then you're pretty well on the way to making a a 
reasonable conclusion we would normally suggest you use low molecular weight 
heparin er unfractionated heparin is dangerous if it were had came to the 
situation now where it had to be approved by the F-D-A i don't think 
unfractionated heparin would actually get a license it's difficult to monitor 
and invariably you never get it right so it's much easier to use low molecular 
weight heparin it's given on a weight adjusted basis doesn't require monitoring 
there are factors which clearly affect er patients er how long they're actually 
er in hospital or how they're treatments going to be man-, monitored er 
depending on the patients age mobility and er concurrent medical illness the 
vast majority of patients i would think well over ninety per cent of our 
patients in South Warwickshire don't actually get admitted to hospital they 
actually are treated on an outpatient basis alright well i think that's 
probably as much as i want to say about the management of er venous thrombosis 
at present er other than to reiterate it's a chronic problem and this is the 
sort of chronic mess that patients can get into here you can see some really 
gross venous congestion in a lady who's got a history of recurrent venous 
thrombosis i think the only other thing to say is how long do you actually 
anticoagulate somebody for if it's a first venous thrombotic event then for 
patients who've got clots certainly above the calf i think a minimum of six 
months anticoagulation for a new case of venous thrombosis and for pulmonary 
embolism again a minimum of six months anticoagulant treatment there is 
increasing evidence however that er because the recurrence rate is something 
like six to seven per cent per annum so in other words by five years thirty per 
cent of patients would have had a further venous thrombotic event that many of 
these patients may require longer periods of treatment and what we need to do 
is somehow to be able to identify those patients that are at greater risk of 
recurrence patients who have persistently high D-Dimer levels at the end of the 
period of anticoagulation would appear to be those among those who are at 
increased risk of er re-, recurrent thrombosis those who on repeat scanning 
have evidence of persistent clot also would appear to be at increased risk and 
it may well be in the not too distant future that the first venous thrombotic 
event may be required to be treated for longer than six months and certainly 
we'll have a better idea soon as to which of the patients who require longer 
term anticoagulant treatment and are at more risk of thrombosis just to finally 
say that if present with a deep vein thrombosis you're much more likely to have 
a further deep vein thrombosis if you present with a pulmonary embolism and you 
have a recurrence it's much more likely that there'll be a pulmonary embolism 
these legs break down and as i said venous thromboembolic disease is a chronic 
problem here's a chronic venous ulcer this could take anything up to twelve 
months to heal if it ever heals at all er so just to re-emphasise it is a 
medical problem that needs to be addressed properly thank you any questions 
quickly before we move on all seen lots of D-V-T's and patients with pulmonary 
emboli if you the best people to get hold of in your hospitals are to see the D-
V-T nurses because you know they would see several patients er in a week with 
venous thrombosis and it's probably worth spending a day with them and seeing 
how they actually manage these patients because you might not actually see too 
many of them actually being admitted to the hospitals because they're mainly 
managed as outpatients right no questions fine well we're going to now talk 
about er thrombocytopoenia and er i'll hand over 
sm5268: hello there hiya good afternoon er today i'm going to be talking about 
purpura and er Emma's supposed to be doing it with me but she's sitting down at 
the moment so no it's cool okay firstly to d-, define purpura it's defined as a 
skin rash resulting from bleeding into the skin from small blood vessels and 
the individual small spots that we can see are known as petechaie i hope i've 
pronounced that right er they're part of the bleeding disorders they result 
they are a result of er blood vessel defect platelet defect or defect in the 
coagulation pathway and they can be classified as part of one of these groups 
now blood vessel defects can either be hereditary or acquired er the hereditary 
one's include hereditary haemorrhagic telangiectasia which is pretty rare and 
er other connective tissue disorders such as Ehlers-Danlos Marfan's syndrome 
and er osteogenesis imperfecta er the acqui-, acquired er blood vessel defec-, 
defects are due to severe infections such as meningococcal and typhoid er drugs 
such as steroids er allergic reactions such as Henoch-Schonlein purpura which 
occurs mainly in children and it's a type three hypersensitivity reaction er 
others include scurvy senile purpura and easy bruising syndrome now er another 
part of the classification is a pla-, platelet defect thrombocytopoenia er er 
decreased platelet number or decreased function that's one that we're going to 
be er focussing mainly on today and the third lot is a coagulation defect again 
that can be hereditary or ac-acquired the hereditary is haemophilia A or B or 
von von Willibrand's disease and the acquired is er via anticoagulant treatment 
liver disease or D-I-C er our current case presentation we saw Mr C he's a 
fifty-five year old he c-, was saw his G-P for bleeding gums he had a four-day 
history of bleeding gums and on further questioning he also said that he had a 
rash on his lower legs for many months but he he didn't you know take much 
notice of it he'd recently being taking diclofenac for back pain as well er 
he's asthmatic and has type two diabetes which he says is controlled mainly by 
diet and he also has a family history of type two diabetes er the drugs that 
he's on he's on er beclomethasone dipropionate for his asthma and salbutamol 
disc inhaler again er for his asthma he was taking diclofenac for back pain and 
er erythomycin he wasn't sure why he was put on them but i'm sure he had some 
kind of infection er social history he lives at home with his wife and he looks 
after the speedway track at Coventry he smokes er ten cigarettes per day and he 
has been doing for thirty years so he's got a fifteen pack year history of 
smoking and er he drinks sixteen units of alcohol per week on examination for a 
markedly obese gentleman er he had widespread petechiae on arms trunks and legs 
on his trunk and legs he had active gum bleeding er no lymphadenopathy or 
hepatosp-, splenomegaly however abdominal er examination was difficult and er B-
P was one sixty over a hundred investigations er a full blood count showed a 
very low platelet count er er four times ten to the nine er it's usually above 
a hundred and fifty to four hundred er white cell count was normal and 
haemoglobin was normal er bone marrow examination showed normal cellularity and 
megakaryocytes which are precursors to the platelets they were normal as well 
er therefore based on these two tests there's more likely to it's more likely 
to be a peripheral destruction of the platelets er so we thought it w-, er the 
patient had chronic autoimmune thrombocytopenic purpura and er the consultant 
thought it was secondary to him taking diclofenac er treatment of this er er 
the first line of treatment is to give prednisolone sixty milligrams er once 
daily and he also prescribed lansoprazo-, lansoprazole for to protect the 
stomach and er thought it'd good to monitor his blood sugar levels as the 
steroids can have an effect on these er a follow-up one week later the bleeding 
had stopped and platelet count had increased to eighteen but it's not er it's 
not really a significant increase but we could see that the blood glucose was 
out of control it's fifteen millimols and er so the consultant decided to 
reduce the prednisolone gradually and add danazol which is a non-virulizing 
androgen er two weeks later platelet count again had risen to eighty-eight 
times ten to the nine and the haemoglobin was thirteen point five but as the 
blood sugars were still high er the the er consultant decided to add a 
hypoglycaemic agent for adequate control of this er Emma will carry on and talk 
a bit more about what will you talk about autoimmune thrombocytopenic purpura 
there we go 
sf5269: okay er yes i'm going to talk about autoimmune idiopathic 
thrombocytopenic purpura it's er A-I-T-P which as the name suggests is an 
autoimmune disease er in which the platelets are destroyed by immune complexes 
er it's characterised by spontaneous bruising and er there's two clinical 
presentations which are the acute presentation and the chronic presentation er 
acute A-I-T-P er is usually seen in children er often after a viral infection 
er and it's thought that er destruction is due to the immune complex d-, 
deposition onto the platelets er but the er development of platelet auto 
antibodies is er responsible for the shortened lifespan er of the platelets er 
in chronic A-I-T-P er adult women are usually er affected er and it may occur 
in association with other autoimmune diseases such as lupus and thyroid 
diseases er but it may occur after viral infections particularly er those 
infected with the H-I-V virus er auto antibodies for the glycoproteins on the 
cell membrane of the platelets are found in sixty to seventy per cent of people 
er but it's thought that er in the remaining thirty to forty per cent there are 
actually auto antibodies they're just er not detected er the clinical features 
er include major haemorrhage although this is extremely rare and really only 
occurs in people er that have severe er thrombocytopenia er purpura easy 
bruising epistaxis and menorrhagia also can occur along with splenomegaly but 
er again that's er quite rare er for investigations er the only abnormality on 
the full blood count would be thrombocytopenia and er you could expect a 
platelet count of between thirty and a hundred er in people with er mild to 
moderate thrombocytopenia er a bone aspirate may reveal normal or increased er 
megaka-, megakaryocytes and of course er the auto antibodies to the 
glycoproteins on the platelet cell membrane er may be present er for the 
treatment er acute A-I-T-P er fortunately er usually it remits spontaneously er 
but this isn't the case for chronic A-I-T-P and er it's usually treated with 
prednisolone er which works by reducing the production of the auto antibodies 
er and it also removes antibody coated platelets from the system er with twenty 
per cent of people who er undergo prednisolone treatment er it's a they have a 
complete response and they don't require any other other er form of treatment 
er sixty per cent er have a partial response and have of these er may not 
require a treatment or if they do they have a maintenance dose of prednisolone 
about five to fifteen milligrams daily er the remaining half er may require a 
splenectomy er and ninety per cent of people who undergo a splenectomy have er 
a successful remission er some of the remainder may also respond to er other 
immunosuppresive drugs such as cyclophosphamide or danazol which er our patient 
Mr C was on er there's also a er high dose infusion of immunoglobulin which has 
the effect of blocking F-C receptors on the macrophages in the spleen er and er 
therefore there's a er transient increase in platelet count er and this can be 
used for people who have er had a recent haemorrhage or in preparation for 
surgery that's it
nm5266: fine so we're going to talk about er thrombocytopenia and particularly 
er immune mediated thrombocytopenia er in terms of your differential diagnosis 
er when a child in particular turns up with increased bruising and purpura 
usually the parents have already made a diagnosis in that they already think 
that they've got a child who's got leukaemia and er you do need to be er 
careful as to er what you actually say to these patients and to the relatives 
bearing in mind that immune thrombocytopenic purpura is much more common than 
leukaemia and er it is a not uncommon er problem that er paediatricians have to 
manage the usual clue of course is that in these patients they usually have a 
normal haemoglobin and they have a normal white count with quite a marked 
reduction in platelet count where as in leukaemias you usually have 
abnormalities in several of the cell lines so the patient is usually anaemic 
and thrombocytopenic the white count might be low or it might be significantly 
raised so er just by looking at the blood count you can get a pretty good idea 
so an isolated thrombocytopenia in a child who's otherwise pretty well and has 
a normal haemoglobin and white count would very much be in er make the 
diagnosis of er I-T-P er for the majority of children if that was the blood 
picture you got you probably wouldn't feel justified in doing a bone marrow i 
think you would only feel justified in doing a bone marrow in a child in this 
situation if you felt you had to treat the child in other words you were going 
to give them steroids and the reason that you would need to do a bone marrow in 
that situation is that if you did have an acute leukaemia the common type of 
childhood leukaemia of course does respond to steroids and you might er make 
the diagnosis extremely difficult and er the child might go into a temporary 
remission and of course it'd be that much worse when they relapsed a few weeks 
later so as long as you haven't got er other abnormalities in the blood count i 
think you can be fairly confident you've just got an isolated thrombocytopenia 
that that's the most likely cause of thrombocytopenia in a child there is one 
other condition you need to be aware of in children and in these children they 
have a prodromal illness of bloody diarrhoea er and they have a haemolytic 
anaemia with fragmented red cells and they have a degree of renal impairment 
together with thrombocytopenia and who can tell me what that is well the 
condition is called the haemolytic uremic syndrome and if you think of Mr Barr 
you know Mr Barr in Scotland who sold dodgy pasties to his clientele and er 
several of the clientele went down with food poisoning with diarrhoea bloody 
diarrhoea a number of these patients went on to develop chronic renal problems 
and this is due to ingestion of e-coli and a pers-, specific serotype of e-coli 
O-H-one-five-seven and this serotype of O-H-one-five-seven produced an exotoxin 
called verocytotoxin and it's the verocytotoxin in conjunction with cytokine 
release that causes the haemolytic uremic syndrome that is a much more 
significant and it is important to be part of your differential diagnosis in a 
child so a child with thrombocytopenia and bloody diarrhoea you do not just 
assume it's I-T-P a child with an abnormality in the haemoglobin or white count 
you do not assume it's I-T-P those'd be the common presentations of 
thrombocytopenia in in childhood er it does spontaneously remit in children in 
the majority of cases so often time just tells er a very small percentage do go 
on and get chronic I-T-P the adult situation as we've heard already is 
different because the majority of adults who develop I-T-P it is a chronic 
problem er and really a differential diagnosis in a adult with a particularly 
low platelet count is is it due to increased platelet consumption as we've 
heard with I-T-P where by the antibodies sorry the platelets are covering in 
antibody and the spleen removes the antibody coated platelets more quickly than 
normal or is it due to a problem in terms of marrow production so er you're 
more likely to end up doing a bone marrow in adult patients with er suspected 
chronic I-T-P and as we've heard the management is difficult in that there is 
no really er simple and easy way of improving the platelet count can you do 
with steroids but you don't want to put young patients on steroids for the next 
twenty thirty years of their life er and some of these patients would come to 
splenectomy splenectomy would result in round about eighty per cent of patients 
being cured with round about twenty per cent still having chronic problems and 
as we've heard patients coming in bleeding with significant clinical problems 
and I-T-P you would give them an immunoglobulin infusion because that would the 
quickest way of actually in getting the platelet count up okay right we're 
going to move on now to er anaemias unless anybody's got any desperate 
questions that they want to ask 
sm5267: oh how do i get it up on the screen okay great er okay Rena and i are 
going to present two patients with anaemia and er anaemia's defined as low 
haemoglobin concentration it's normally characterised or er put into three 
different groups microcytic normocytic and macrocytic and those terms refer to 
the actual volume of the red cell so in microcytic anaemia the the volume of 
the average red blood cell is reduced w-, along with the haemoglobin in 
normocytic er anaemia the volume of the red blood cells stay the same and in 
macrocytic anaemia the volume of the red blood cell increases even though the 
haemoglobin concentration has come down which is the definition of anaemia er 
just add a bit of tangential thinking into this talk er the aim is that you try 
and work out the association between the city in the background and microcytic 
anaemia and there is a link and there's just going to be two clues and the 
first clue is that the fountain is the tallest fountain in the world the one 
that you can see there so going to present a eighty-one year old female M-L who 
is a former shop assistant we saw her in the haematology clinic in the 
outpatient clinic and she presented with shortness of breath fatigue and 
headache which er had been going on for two days two days prior to her 
presentation at the clinic she'd been venous sected er for a condition known as 
hereditary haemochromotosis and i'll mention that in a in a minute after the 
venous section she had collapsed in the clinic but she hadn't lost 
consciousness since that time after she'd gone home she had been constantly 
short of breath she felt very tired and had had a persistent headache that 
normal analgesia hadn't done anything about and exactly the same er pattern of 
of events had occurred three months earlier when she had previously been for 
her venous section treatment er hereditary haemochromotosis it's er an 
inherited disorder of increased iron absorption and it leads to deposition of 
iron in lots of different organs and it's worth knowing something about because 
it's the commonest recessive autosomal er condition in Northern Europe so it 
does present quite frequently in Ireland the U-K Scandinavia and Germany the 
treatment is venous section which basically means that the person goes along to 
the clinic and er they're bled they're bled er a unit of of blood or one to two 
units of blood she also er had osteoporosis she'd had her both her hips 
replaced in nineteen-eighty-eight but there was no other significant history of 
of illness or operations from systems review her only medication she was on 
taking calcium tablets aspirin and she didn't have any allergies her family 
history wasn't particularly significant her father died at fifty-seven from an 
M-I her mother had died in her eighties from old age and er her brother also 
had this condition hereditary haemochromotosis she lives with her husband she 
has good support from her three children and she doesn't have any significant 
smoking or alcohol history examination on the whole was unremarkable er she did 
have pallor in the conjunctivi and her shortness of breath was very evident er 
when she was moving around in in the room and as she was actually walking in 
into the room where we saw her significant negative findings related to anaemia 
there was no koilonychia nail spooning which is associated with iron deficiency 
er anaemia no glossitis a swelling of the tongue another sign to look out for 
in anaemia normally in microcytic anaemia it's painless but in macrocytic 
anaemia it's normally painful that's glossitis er no angular sto-, stomatitis 
that's ulceration in the mouth normally beginning on the corners of the mouth 
and also no telangiectasia er the small dilated capillaries that occur in 
little red spots and in some people in this condition hereditary haemorrhagic 
telangiectasia they can occur in the mouth and bleed leading to anaemia so it's 
worth looking out for those particular signs but they weren't found in her er 
examination of her cardiovascular system respiratory system and abdomen were 
all unremarkable we next er took a look at er some of her blood values and 
these showed us that her haemoglobin level was down which wasn't surprising i 
mean we'd we had thought initially about anaemia shortness of breath headache 
are quite common presenting complaints associated with anaemia her urethra 
sites were down as well her mean m-, er corpuscular volume that's the M-C-V 
that's the actual volume of the red blood cell and that's what differ-, 
differentiates anaemia into microcytic normocytic or macrocytic that was 
reduced indicating a microcytic anaemia the two er last er parameters the mean 
corpuscular haemoglobin is the average amount of haemoglobin in the average red 
blood cell it's in picograms that was reduced and the mean corpuscular 
haemoglobin concentration the concentration of haemoglobin in in a known er er 
conce-, in a known volume of blood that was also reduced as well because of her 
er reduced M-C-V or mean corpuscular volume which is indicative of a microcytic 
anaemia we looked at her iron levels because iron deficiency is the c-, one of 
the commonest causes if not the commonest cause of microcytic anaemia we saw 
that her serum iron was reduced her serum ferritin which is one of the er er 
proteins that's which er stores which is er bound to iron which stores iron 
that was reduced but the actual capacity to er bind iron was increased so we've 
got here a lady who presented with shortness of breath headache we we noticed 
that she had pallor in in her conjuctivi we know that her er haemoglobin is 
definitely reduced and it looks like a microcytic anaemia and as i said for 
that reason we looked at the iron er levels so as i said they're the common 
presenting features of anaemia shortness of breath tiredness headache there was 
nothing else really in the history or examination that indicated a 
cardiovascular or pulmonary er cause the onset of the symptoms had been related 
we they were related to this venous section that had occurred two days prior to 
her presentation and er the haemotological investigations indicate that it was 
a microcytic anaemia what i'd like to do now just go through the main causes of 
microcytic anaemia with the reduced M-C-V the first one as i said is iron 
deficiency that's the most common cause alpha and beta thalassemias and the 
traits of those that also can cause microcytic anaemia and something called 
congenital sideroblastic anaemia Rena's going to mention another form of that 
but that's very rare indeed because of her reduced iron levels we were looking 
more towards her anaemia being caused by er iron deficiency which if you think 
about it is kind of paradoxical given that she's got this hereditary 
haemochromotosis which is iron overloading you have to remember that the whole 
point of venous secting somebody for hereditary haemochromotosis is actually to 
make somebody slightly iron deficient because they've got this iron overload 
but you don't want them to necessarily become anaemic the main causes of iron 
deficiency anaemia the first one is blood loss most common certainly er in 
women that are menstruating in menorrhagia G-I bleeding particularly be aware 
of occult G-I bleeding the second clue to the er the tangential thinking by the 
way is that hookworm globally is the commonest cause of er iron deficiency 
anaemia due to the bleeding that it causes the G-I bleeding but in this case it 
seemed it is was quite an unusual presentation because it seemed that the 
lady's venous section treatment was almost like an iatrogenic anaemia it had 
actually been caused by her venous section the other causes of er iron 
deficiency are decreased absorption for example in celiac disease and also in 
partial and total gastrectomies and also er poor diet poor iron intake and 
that's especially in children so the er diagnosis of of this patient which 
isn't particularly common but it's worth bearing in mind is that although she 
was iron overloaded she went for treatment to reduce the iron by venous section 
and paradoxically became so iron deficient that she ended up with a microcytic 
anaemia and er that's the end of the talk oh yeah does anybody know what the 
connection is
su: Cairo
sm5267: sorry
su: is it Cairo
sm5267: no it's not Cairo
su: is it Cape Town
sm5267: not Cape Town it's got the tallest fountain in the world a hundred and 
eight metres er well i'll put you out of your misery it's er it's Geneva in 
Switzerland and er Geneva is the seat of the World Health Organisation which 
spear heads the campaign to control and manage iron deficiency anaemia due to 
hookworm in the developing world sorry
nm5266: i i i think if anybody had actually worked out that connection they 
should leave the room actually because er they're obviously er mentally 
unstable so er it's important really to be aware of the common conditions that 
cause er iron deficiency and er we've had a very good presentation to tell us 
about those er haemochromotosis is is an interesting condition as we've heard 
the gene frequency is really quite high and really er these patients can go on 
and develop quite severe liver problems er and many of the patients will 
present at a time when er it's all a bit too late so patients anybody 
presenting with liver disease liver failure er unexplained jaundice er is 
somebody who you would actually er look for the presence of iron overload and 
many of these patients at presentation will have ferritin levels of several 
thousand er so they'll have very high ferritin levels and er the iron can get 
deposited in a variety of different organs not only just the liver it can get 
deposited in the in the myocardium and can get deposited in a variety of 
endocrine organism-, organs so that they can present with er hypopituitarism 
they can present with er er problems that are er secondary to the er pancreas 
as well okay any questions about er iron deficiency for a start remember common 
things are common as we've heard children don't eat very much vegans don't eat 
very much iron take very much iron er there's a lot of iron in red meat if you 
don't take red meat er be suspicious that er there may be a dietary cause and 
of course the commonest reason in females relates to menorrhagia so you do need 
to be aware of that older patients er you do need to be aware that a male let's 
say in their forties presenting with iron deficiency anaemia without other 
obvious reason you would be suspicious of some pathology within their G-I tract 
and that would clearly be an indication to investigate them for a variety of 
conditions and in particular to exclude the presence of a neoplasm in the bowel 
okay right thank you very much we'll er move on and er we're now going to have 
something on macrocytic anaemias
sf5270: how is everybody alright okay er thanks Mike er i'm going to talk about 
anaemia er and that's just a picture of Victoria where i live i just thought 
i'd add to the entertainment today er right i saw P-K it's a sixty year old 
year old female er in the haematology clinic and she presented actually to her 
G-P with shortness of breath she was feeling tired and was lacking in energy 
for the past few months er so bas-, and then the other symptoms that she didn't 
have which are tend to be associated with anaemia since this is a talk on 
anaemia are dizziness er palpitations and headache which are the cardiac 
response to lack of oxygen er ringing in the ear anorexia dyspepsia bowel 
disturbance and sometimes in elderly patients you can get angina and 
intermittent and confusion but she didn't have any of those er the past medical 
history er there was nothing really relevant er she had er venous surgery D-V-
T's er no history of er blood loss or iron deficiency er nothing relevant in 
her drug history or family history she was a non-smoker and a non-drinker on 
examination er it was actually a follow-up appointment but there are no 
specific signs were found actually er her cardiovascular and respiratory and 
abdomen er examinations were all normal er yeah er signs that you might see in 
an anaemic patient are pallor of the mucous membranes hyperdynamic circulation 
which is er tachycardia bounding pulse cardiomegaly systolic flow murmur and 
congestive heart failure and there's also specific signs that you can find with 
different types of anaemia er for example the first one that i've mentioned 
there the spooning nails painless glossitis and the sto-, stomatitis as with 
iron deficiency that's what Mike spoke about you can get jaundice with 
haemolitic or meglobas-, megloblastic anaemia and with sickle cell or other 
haemolitic anaemias you can get leg ulcers and er sometimes with thalassemia 
and er haemolitic anaemia you can get bone deformities and you might also see 
hepatosplenomegaly and those are pictures out of Epstein right so this patient 
er the blood results were actually done at their G-P's and as you can see the 
patient is clearly anaemic er with low haemoglobin and if you look at the M-C-V 
er she's got a macrocytic anaemia so what are we thinking macrocytic anaemia 
differential diagnosis er B-twelve or folic deficiency it could be caused by 
alcohol or liver disease er cyotoxic drugs such as er hydroxyurea er 
myodysplastic syndromes infiltrations haemolysis and er other drugs it can also 
be caused by hypothyroidism haemolysis and aplastic er conditions but that's 
also sometimes shows in normocytic anaemia so that's why it's starred so 
further investigations that were done in this patient er serum B-twelve was 
fine serum folic was fine antibodies to gastric parietal cells and intrinsic 
factor were negative so that rules out your er B-twelve or folic deficiency 
LFT's were normal E-S-R was fine and thyroid function tests were normal so what 
do we do next do a bone marrow biopsy bone marrow biopsy's can show four things 
it can show that you can have a megaloblastic anaemia a normoblastic 
erythropoiesis increased erythropoiesis or an abnormal erythropoiesis and in 
this patient the patient was found to have sideroblastic anaemia from the bone 
marrow biopsy right what is b-, er sideroblastic anaemia it is characterised by 
the in-, incorporation of iron into you get iron overloading and you get ring 
sideroblasts causes it's a bit confusing here because the congenital type you 
actually get a microcytic anaemia but the acquired type which is what this 
patient has is a is a macrocytic anaemia and those can be caused by myeloid 
stem cell disorders toxic toxins drugs alcohol and sometimes it can be 
idiopathic features that you can see in sideroblastic anaemia it tends to occur 
in older adults it's a progressive anaemia and you get hepatosplenomegaly 
sometimes you can get neutropenia and thrombocy-, cytopoenia may develop and er 
the bone marrow that you might see is that ninety per cent of red cell 
precursors are destroyed and you get a high rate of erythropoiesis and you'll 
see ring sideroblasts and ring sideroblasts are red cell precursors with iron 
deposits around the nucleus and they look that that so you see the little ring 
yeah alright er so management it's okay Gavin er is to remove the precipitating 
factor so if it's caused by alcohol or something or drugs that a patient's 
taking stop those er treat the underlying disorder if there is one and 
supportive care so blood transfusions antibiotics and iron chelation for the 
iron overloading er because that can have effects as well back to this patient 
er this patient has a mild dysplastic condition so there's no way to improve 
the anaemia they are considering to do thalidomide and erythropoietin 
injections to help that but it's not sure if whether that will work she's been 
prescribed folic acid because the bone marrow's in hyperdrive so you want to 
make sure that you have enough nutrients and she's been given two units of 
blood and at this point the patient's just going to be given supportive care so 
just treat the symptoms as they come so and that's Victoria as well so
nm5266: right so if you've got somebody with a macrocytic er anaemia to start 
with er perhaps the commonest cause er that you would er find in this country 
probably relates to alcohol alcohol er more often than not will produce a 
macrocytosis it doesn't always produce an anaemia unless you've got one or two 
other features to go with it but if you had folate deficiency which you can 
have in association with er alcoholic liver disease or if you had a big spleen 
and hypersplenism so that the cells are being gobbled up in your spleen that 
also could be associated with an anaemia er but er an elderly lady presenting 
with a macrocytic anaemia without a history of er increased alcohol intake i 
think your first thought would really be does this lady have pernicious anaemia 
and pernicious anaemia as er we've heard er is an disease whereby you have er 
an absence of production of intrinsic factor or reduced production of intrinsic 
factor and as you remember er intrinsic factor is produced in the s-, 
nm5266: stomach yes where in the stomach
su: parietials
nm5266: parietal cells good that's excellent somebody's awake and alive good er 
so you need intrinsic factor to bind to vitamin B-twelve before it's absorbed 
and it's absorbed where again
su: terminal ileum
nm5266: terminal ileum excellent good okay so er bound B-twelve will be 
absorbed now in pernicious anaemia you get er often antibodies to intrinsic 
factor or a failure of an-, intrinsic factor production and er the er test that 
you can do are to measure the intrinsic factor antibodies and gastric parietal 
cell antibodies now gastric parietal cell antibodies are not particularly 
specific so round about eighty to eight round about about eighty per cent of 
patients with pernicious anaemia would have gastric parietal cell antibodies 
intrinsic factor antibodies are much more specific but round about only fifty 
per cent of patients with er pernicious anaemia would have intrinsic factor 
antibodies so there's still a significant number of patients who've got 
pernicious anaemia who would have negative intrinsic factor antibodies and in 
these patients you would probably wish to carry on further investigation and i 
wonder if anybody can tell me what further investigation you might wish to do 
so you've got somebody with a low B-twelve and they've got er no intrinsic 
factor antibodies and you want to know whether they've got pernicious anaemia
nm5266: a schilling test right excellent now can anybody tell me about the 
schilling test
nm5266: it is good excellent so basically what you do is you have a label of 
radioactive B-twelve which you take orally and measure the radioactive 
radioactivity in the urine following the subsequent twenty-four hour collection 
er and you can repeat this in the presence of intrinsic factor to see if it 
actually corrects and that's probably the best diagnostic test in terms of er 
er confirming er the diagnosis of pernicious anaemia it's one of the very few 
things in medicine that you can actually treat of course most things in general 
medicine you can't you can look at and er they can have chronic problems but 
it's very treatable and you treat them with hydroxocobalamin injections perhaps 
if they have five injections over a period of a fortnight and then go onto a 
three-monthly er long term er replacement injection there's one group of 
patients that sometimes get lost particularly the surgeons manage to lose that 
end up with B-twelve deficiency i wonder if you could just remind me which 
group of patients they are
su: ileum
nm5266: yes well certainly if you've had any surgery to the terminal ileum that 
would certainly put you at risk and what other surgery a bit further up
su: gastrectomy
nm5266: gastrectomy yes it's very easy to er forget that these patients will 
develop er B-twelve deficiency and er it's something that er needs to be 
identified and they need to go onto some maintenance B-twelve support again on 
a long term basis okay you can anybody tell me the let's have something a 
little bit on the clinical presentation of somebody with pernicious anaemia er 
if you have what would make you let's say clinically consider that the patient 
has pernicious anaemia you're in your surgery and a little old lady comes in
su: her poos are black
nm5266: if her poos are black well er i i think i'd be more concerned that 
she's bleeding if she's got black poos if she got melena er so er good effort 
but er nil points yeah okay
nm5266: well er with iron deficiency er you could er er as i say if you've got 
blood loss you would certainly look to see if they've got black stools er 
common causes of iron deficiency in females are clearly if they've got 
menorrhagia er once you get over a certain age however you don't er have 
periods a little old lady pernicious anaemia well there is an association with 
er blue eyes white hair they often have a lemon tinge because there is a mild 
degree of haemolysis that will accompany the presence of pernicious anaemia and 
the other thing to be er wary is that patients with pernicious anaemia don't 
necessarily just have an anaemia they can also sometimes have a pancytopenia so 
it will actually effect also the white cell production and the platelet 
production so anybody with a pancytopenia really and a macrocytosis should also 
have a B-twelve and a folate checked right any questions that er anybody's got 
on anything to do with anaemias anything to do with venous thrombosis anything 
to do with iron overload all happy i think just that just the final thing to 
say is that for patients with thrombocytopoenia we didn't say or i didn't 
mention is that you need to be careful what drugs you give them so don't go 
round giving them anti-platelet agents or if they're on anti-platelet agents 
and they've got thrombocytopoenia then do stop them the first case that we had 
we had somebody with diclofenac which is a non-steroidal anti-inflammatory 
agent and it would clearly be sensible that that was stopped rarely diclofenac 
can cause thrombocytopoenia but it's much more likely that cause additional 
bleeding in anybody with thrombocytopoenia because er of it's er a-, anti-
platelet activity so aspirin in particular clopidogrel er and all the other 
anti-, non-steroidal anti-inflammatory agents you need to really think about 
stopping if you've got somebody with severe thrombocytopoenia right okay well 
i'd like to thank all our speakers er who've all given us a very good talk and 
er thank you very much for your attention