29 June 2011 (Wednesday) - Just the Hb... (!)

This morning a midwife phoned for the result of a blood count. “Just the Hb” she chirpily announced.

GREEN, TERESA                                   AB+      Queue
DOB  25/09/1987 Sex F Pat No 123456       Received  09:40
Address   IN A TENT                                 29/06/2011
Specimen No : AW268935F    (Haematology)      

24/06/2011 00:00  EDTA
  Haemoglobin               10.9           g/dl         (    11 to 15    )
  White Blood Cells         8.7            10^9/l       (     4 to 11    )
  Platelets                 412            10^9/l       (   150 to 400   )
  Red Blood Cells           4.97           10^12/l      (   3.8 to 4.8   )
  Haematocrit               0.370          ratio        (  0.36 to 0.46  )
  Mean Cell Volume          73.4           fl           (    80 to 100   )
  Mean Cell Haemoglobin     21.9           pg           (    27 to 32    )
  Mean Cell Haemoglobin Con 29.9           g/dl         (    32 to 36    )
  Neutrophils               6.3            10^9/l       (     2 to 7.5   )
  Lymphocytes               1.9            10^9/l       (   1.5 to 4     )
  Monocytes                 0.4            10^9/l       (   0.2 to 1     )
  Eosinophils               0.1            10^9/l       (  0.02 to 0.5   )
  Basophils                 0.0            10^9/l       (     0 to 0.1   )
  XE FLAG1                  Iron deficiency ?                             
  XE FLAG2                  ^A blood film has been reviewed               

A haemoglobin of 10.9 isn’t entirely unexpected in an ante-natal case. But an MCV of 73.4 is indicative of incipient iron deficiency. So I gave her the Hb and the MCV. I could tell from the tone of voice that she had no idea why I’d read out the MCV. So I explained. “But the Hb’s normal” she said. So I explained (briefly) about iron metabolism.
So many people still feel that haemoglobin level and iron status are synonymous. They are not. I can remember having a similar conversation with a midwife when my son (now aged twenty three) was at the ante-natal stage. It would seem that some things never change.
It’s just as well that there’s the likes of me available to advise…..

28 June 2011 (Tuesday) - Burkitt's Lymphoma

Another on-line case study: “A 54 year old man presents to the hospital with a two week history of a sore throat and flu like symptoms.  He has previously been entirely well.  His General Practitioner has treated him with antibiotics but this has not led to any improvement in his symptoms.  On examination he appears quite well but he does have enlarged lymph glands in the neck.  A number of blood tests are performed including a blood count and blood film.  His biochemical screen shows mild renal failure and a very elevated lactate dehydrogenase  level

My gut feeling was that this was adult acute lymphoblastic leukaemia, or (bearing in mind the lymph node involvement) a lymphoma of some sort.
On submitting my answer I was told that although I’d got all the cell identification and morphology stuff right, the expert opinion was that this is a case of Burkitt’s lymphoma.

However the expert opinion did go on to say that “no definitive diagnosis will be possible from the blood film morphology alone”. It then mentioned “…rapidly proceed with more discriminatory investigations.  This must include bone marrow aspiration and trephine biopsy with performance of immunophenotyping and cytogenetics”; none of which were available for the purposes of this exercise.

I must admit I’m getting a tad fed up with these exercises: if a diagnosis is going to depend on a certain test then that test result should be available. Presenting me with horse dung and hoof prints and then saying “zebra!!” is a bit unfair…..

26 June 2011 (Sunday) - Hate Mail

This blog received its first bit of hate mail today. A couple of weeks ago (17 June), I wrote a few lines about short bowel syndrome. It’s a particularly nasty condition in which sufferers have all sorts of nutritional problems, and there is a serious mortality problem.
I ended my article with the observation that having evolved as carnivores, but having become herbivores, Pandas all have the problems of short bowel syndrome. There are several references on-line to this fact. Here’s one. Here’s another. And another. And another. This isn’t insulting in any way to people who suffer from short bowel syndrome, merely a statement of fact.
Disease isn’t confined purely to humans. Cats get leukaemia. Dogs get diabetes. A lot can be learned about disease processes by examining the bigger picture. A very good friend of mine died a few years ago from Cushing’s disease. Should I put a turd in the post to my mate who’s Yorkshire Terrier has dared to contract the same malady?

There was nothing personal or insulting intended in my observation about Pandas: I was merely expressing my amazement that a serious medical condition isn’t exclusively confined to humans.
Was what I wrote offensive? I’ve re-read it a few times and I can’t see it.

However this morning at 6.20am (my time) someone in the Chicago area, whilst browsing the Internet using Internet Explorer 7 on Windows Vista came across what I had written. They didn’t like it and sent me an anonymous message saying “my son has short gut syndrome and comparing it to a panda i want to slap your face”.

Obviously capitalisation and punctuation isn’t this anonymous poster’s strong point. It’s a shame they didn’t have the courage to put their name to their post, but who needs names when you have an IP address (which is every bit as good).
I have reported this episode to their Internet provider (Cricket Communications).
I doubt anything will come of it, but it never hurts to remind keyboard warriors that the Internet isn’t as anonymous a place as they might think it is.

23 June 2011 (Thursday) - A Screening Programme

A day in the wicked city. I was up with the lark at at the railway station far earlier than was sensible. After waiting for our train to pull off for twenty minutes there was an announcement. The train manager was trying to find a train driver. As soon as one became available we’d be on our way. That filled me with confidence, and after five minutes a big fat man in train driver costume was seen running along the platform. We got going soon after that, and were only five minutes late for our day’s outing.
I say “five minutes late” – we’d been told that the NHS National Sickle Cell and Thalassaemia Screening Programme’s Laboratory Training Day started at 9.30am. Having run from St Pancras to Russell Square we found that registration and coffee was from 9.30am, and lectures started at 10am. I got some coffee, and spent fifteen minutes getting my breath back.

We started with an update on what the programme had been up to for the last year. This lecture was the worst of the day. Lacking any structure, it was not so much a lecture as a disjointed rambling in which the speaker leapt from one topic to the next (and back again) at random, seemingly contradicting herself at regular intervals.
The second talk was more interesting; covering screening programs and the management of risk in haemoglobinopathy screening. It’s actually a fascinating subject; the science behind it is something which I personally find the most interesting part of my job. And there’s some serious ethical dilemmas. Thalassaemia major is one of the most serious genetic conditions there is – babies with it can die before birth, and many of those that do survive can only live because of life long blood transfusions. But screening of parents can avoid such children being born. In the UK parents are screened early in pregnancy. In other parts of the world people are screened before conception takes place. In some parts of the world (where marriage is still de rigueur) priests won’t marry unscreened couples. Effectively these people require a licence to breed. There’s a can of worms….

The third lecture was interesting covering serious incidents and lessons learned. Like everything and anything, the screening programme is not perfect, and has had some failures. Lessons have been learned and the service has improved, but what does anyone do  when a couple decide to breed, having been told of the risk of conceiving a child who will be born to suffer?
After a tea break was the best part of the day – a lecture from Professor Bain, who is a world-renown expert on the subject of haemoglobinopathies. And then dinner - very nice. Perhaps too nice...?
After dinner I slept through a session on data interpretation. I knew the session was going to be bad: over the years I’ve formed a serious distrust of anyone who refers to a blood-testing machine as an ”instrument”. I could feel myself nodding after only a couple of minutes, and was soon sound asleep. I awoke with a start and the thought “F@!! - I’m in a lecture” ran though my mind as the speaker asked “did everyone find that helpful?

After another cuppa the day closed with some fascinating case studies. For all that I find the haemoglobinopathies to be fascinating, they are not common conditions. In fact I often describe then to my students as being as abundant as rocking horse poo. And this last session gave some seriously obscure tales, involving sickle cell trait with a duplicated normal beta gene, and the discovery of the unstable Hb Kingsbury.

All things considered it was a good day out, but I did have a couple of criticisms. The projector screen was too small – I could hardly see the presentations.
And the venue: has anyone realised that the country is in financal queer street? Surely the Imperial Hotel in Russell Square isn’t the most cost effective place to hold such a meeting. Heaven only knows what the place cost to book, but I did see that the lunchtime menu was seventeen quid a head. With about forty of us on the course, I expect the total cost of the day would have been about a thousand pounds.
Whilst I realise that a London venue is central for all participants, surely there are church halls, scout halls, YMCAs, community centres that could have done the day at a fraction of the cost?

22 June 2011 (Wednesday) - Kliehauers

The Kliehauer test is the standard method of measuring fetal-maternal hemorrhage (FMH). It takes advantage of the differential resistance of foetal haemoglobin to acid as compared to adult haemoglobin.

A standard blood smear is prepared from the mother's blood, and exposed to an acid bath. This removes adult haemoglobin, but not foetal haemoglobin, from the red blood cells. Subsequent staining makes foetal cells (containing foetal haemoglobin) appear rose-pink in colour, while adult red blood cells are only seen as 'ghosts'.

All of which has very little application to my daily round, but today the people in blood bank found a good example of a positive result. And using our digital camera that I obtained cheaply we were able to record the image for training purposes. So I’ll chalk up another success of my forty-quid result!

21 June 2011 (Tuesday) - Portfolio Success

Another portfolio assessment - another success. That's now twenty one students whose training I've overseen to HPC registration.
I can't help but feel that the pre reg portfolio website I've created has helped all of us in the more recent successes. And with two more students doing their portfolios perhaps I should spend a little more time working on that website...

20 June 2011 (Monday) - Some Sums

I’ve been looking at formulae which distinguish between the microcytic anemia of iron deficiency from that of thalassemia minor. Bearing in mind that these formulas may not be applicable:

  • if the patient has been treated with iron;
  • if the patient has been treated with blood transfusions;
  • if both iron deficiency and thalassemia minor coexist in the same patient
  • in some patients with polycythemia vera who develop iron deficiency (England-Fraser formula)

here’s some formulae:

Mentzer Formula

Mentzer value =  ((MCV) / (red blood cell count))

Iron deficiency is indicated by a value  > 13.
Thalassemia minor is indicated by a value  < 13.

England-Fraser Formula

England-Fraser formula = ((MCV) - ((5 * (hemoglobin)) + (RBC) + K))

 K = 3.4 if the hematocrit is corrected for plasma trapping (usual situation) or 8.4 if it is not. 

no differentiation: formula > 0 (positive)
thalassemia minor: formula < 0 (negative)

The England-Fraser formula may provide only poor discrimination between thalassemia and non-thalassemic causes of microcytosis.
In patients with polycythemia vera who develop iron deficiency, a negative value for the England-Fraser formula may result. 
The validity of the discriminant function may depend on the relative proportions of patients with iron-deficiency anemia and thalassemia in the population being examined.

 M / H Ratio

In thalassemia microcytes exceed hypochromic cells. In iron deficiency, hypochromic cells exceed microcytes. The ratio of microcytes (M) to hypochromic cells (H) can help distinguish thalassemia from iron deficiency anemia.

Patient selection: presence of hypochromic anemia

Parameters (as originally determined on the Techinicon H*1 automated analyzer):
(1) M = percentage of cells that are microcytes (erythrocytes with volume less than 60 femtoliters)
(2) H = percentage of cells that are hypochromic (erythrocytes with hemoglobin less than 28 g/dL MCHC)

ratio = M / H

 A ratio  < 0.9 indicates iron deficiency.
 A ratio  > 0.9 indicates thalassemia minor.
 A ratio = 0.9 is indeterminate. 

Mixed thalassemia minor and iron deficiency is relatively common. 

Algorithm of Mulherin et al for the Diagnosis of Iron Deficiency Anemia vs Anemia of Chronic Disease in a Patient with Rheumatoid Arthritis

Serum ferritin levels may be elevated in patients who have both iron deficiency and chronic inflammation, making the distinction between iron deficiency anemia and the anemia of chronic disease difficult. Mulherin et al developed a simple algorithm based on simple laboratory measures to help diagnose anemia in patients with rheumatoid arthritis. The authors are from Dublin, Ireland.

Step 1: Does the patient have rheumatoid arthritis? (If "yes" proceed, else stop).
Step 2: Is the patient anemic? (for males, hemoglobin < 11 g/dL; for women, hemoglobin < 10.5 g/dL)
Step 3: Is the serum ferritin < g/L? (If "no", proceed to Step 4; if "yes", iron deficiency.) 40
Step 4: Is the MCV > 85 fL? (If "no", proceed to Step 5; if "yes", anemia of chronic disease).
Step 5: Is the percent iron saturation < 7%? (If "no", anemia of chronic disease; if "yes", iron deficiency.)

(1) The algorithm should be applicable to other patients with autoimmune disease.
(2) The age range for the patients was 20 to 80 years.
(3) The study involved 45 patients. I would be interested to see the algorithm validated in a larger group, and to see whether any of the patients classified as anemia of chronic disease responded to iron therapy.

Green and King Formula

The Green and King formula uses red cell indices to help identify the cause of microcytosis.

formula of Green and King = ((((MCV)^2) * (RDW)) / ((Hb) * 100))

 iron deficiency:  > 72
 thalassemia minor:  < 72

MCH / RBC Ratio

The MCH-to-RBC ratio is another calculation using red cell indices to help identify the possible cause of microcytosis.

MCH-to-RBC ratio =
= (MCH) / (red blood cell count)

 iron deficiency:  >4.4
 thalassemia minor:  < 4.4


The product of RDW times HDW can be used with automated red cell analyzers to help identify patients who may have thalassemia.

product of RDW and HDW =
= (RDW) * (HDW)

 iron deficiency: formula  > 530
 thalassemia minor: formula  < 530

RDW / RBC Ratio

The RDW-to-RBC ratio is another calculation using red cell indices to help identify the possible cause of microcytosis.

RDW-to-RBC ratio= (RDW) / (RBC)

 iron deficiency:  > 3.3
 thalassemia minor:  < 3.3

Shine-Lal Formula

This is a screening tool for differentiating heterozygous beta-thalassemia from healthy subjects. It cannot discriminate between beta-thalassemia and iron deficiency.

Shine-Lal formula = (((MCV)^2) * (MCH)) / 100
 thalassemia minor:  < 1530.

Trouble is none of them seem to have a better than 95% success rate. I want six sigma good…..

17 June 2011 (Friday) - Short Bowel Syndrome

Another diagnosis I'd not heard of before:
Short bowel syndrome is a malabsorption disorder usually caused by the small intestine being of unusually short length. Usually as a result of surgery, or more rarely due to the complete dysfunction of a large segment of bowel. The syndrome does not manifest unless more than two thirds of the small intestine have been removed or are absent.

Most cases are acquired (obviously!): short bowel syndrome caused by the surgical removal of a portion of the bowel may be a temporary condition, due to the adaptive property of the small intestine. Physiological changes to the remaining portion of the small intestine occur to increase its absorptive capacity. These changes include:

  • Enlargement and lengthening of the villi
  • Increase in the diameter of the small intestine
  • Slow down in peristalsis through the small intestine
Some children are born with a congenital short bowel. In these cases the 4-year survival rate on parenteral nutrition is approximately 70%. In newborn infants with less than 10% of expected intestinal length, 5 year survival is approximately 20%.
Some studies suggest that much of the mortality is due to a complication of the TPN, especially chronic liver disease.
Although promising, small intestine transplant has a mixed success rate, with postoperative mortality rate of up to 30%. One-year and 4-year survival rate are 90% and 60%, respectively.

On further research I found that Giant Pandas effectively all have short bowel syndrome: having the gut of a carnivore and the diet of a herbivore....
Of professional relevance to me are the various nutritional anaemias that are far more likely to develop in SBS than in the average person, but personally I'm intrigued by the pandas...

16 June 2011 (Thursday) - Xanthelasma

A diagnosis I'd not heard before:

A xanthelasma is a sharply demarcated yellowish collection of cholesterol underneath the skin, usually on or around the eyelids. Strictly, a xanthelasma is a distinct condition, only being called a xanthoma when becoming larger and nodular, assuming tumorous proportions, however it is often classified simply as a subtype of xanthoma.

Xanthoma is a deposition of yellowish cholesterol-rich material in tendons or other body parts in various disease states. They are cutaneous manifestations of lipidosis in which there is an accumulation of lipids in large foam cells within the skin.

They are associated with hyperlipidemias, both primary and secondary types. Tendon Xanthoma are associated with Type II hyperlipidaemia and chronic biliary obstruction.Palmar xanthomata and tuboeruptive xanthomata (over knees and elbows) occur in Type III hyperlipidaemia

8 June 2011 (Wednesday) - CPD Seminars

No lunchtime seminar today – we’ve reached the end of the program for this academic year. This is the fourth year I’ve organised a program of CPD talks, and on reflection it’s been a success. We’ve had over thirty talks covering subjects as diverse as modernising scientific careers, glandular fever, cardiolipins and meningitis. We’ve had case presentations, and speakers have ranged from health care assistants to consultant physicians. This year’s sessions have been far better than last year’s which I gave up with after three months.

We’ve increased the popularity of the seminars amongst the staff by securing permission for staff to eat in the seminar room. However, for all that this was touted as a major reason why people did not attend seminars last year; so far I’ve yet to see anyone actually eat their lunch during a seminar.
We still have the problem that the laptop we use is old, and cannot use .pptx files, and that we cannot access the internet during seminars. But so far these have not been insuperable problems.
I produce certificates for all attendees: I’m not sure that people find these useful. I might review that for the next series of talks.

I’ve got some speakers for the next round of talks I’m planning for September. If only I could persuade everyone in the workplace to do a talk, we’d only have to do one each every two or three years….

7 June 2011 (Tuesday) - At An Angle...?

Whilst unpacking some ESR pipettes I discovered a strange plastic object. I wondered what it was, but noticed that on the sides it was marked with angles of 45o and 60o. It’s a rack for doing ESRs at strange angles. I always thought they should be vertical.

Here's an interesting article http://www.nrcresearchpress.com/doi/abs/10.1139/y73-104?journalCode=cjpp 
As a trainee I remember my chief at the time telling me that he'd heard that by angling a tube at 45o, one could obtain the result of an hour's ESR in ten minutes. However he did give the proviso tat the relationship only held in health, in disease states this was not always the case.
We've been looking at running automated ESRs for thirty minutes rather than an hour lately, but have found poor correlation between results over thirty minutes and an hour. Highs are still high, and normals are still normals, but there would seem to be very different ranges. Which is what one would expect from what are effectively different tests.

Personally if we are going to change method I'd forget about thirty minute ESRs and go straight for ten minute ones. Both will necessitate a change in the reference range, but one is much quicker. I wonder if 10 minute ones can be automated.....?

6 June 2011 (Monday) - Iron Deficiency

The nice people over at Medical Laboratory And EQAS News run a survey every Sunday. Yesterday’s was a blood film (pictured above) from “44 years old male from Murmansk, North Russia has been feeling very weak and tired during last two months. He is working as timberjack, but has been unemployed lately.

WBC: 5.5
RBC: 4.28 (Low)
HGB: 9.7 (Low)
HCT: 29.9 (Low)
MCV: 69.7 (Low)
MCH: 22.6 (Low)
MCHC: 32.4 (Low)
RDW: 18.4 (High)
PLT: 331

What is your suggestion for diagnosis? And what (one) further test should be performed?

I got the correct answer for the first section: Severe iron deficiency anaemia. Severe hypochromasia, microcytosis, pencil-shaped cells, low haemoglobin, low haematocrit and high RDW are typical for iron deficiency anaemia.

This was relatively straight forward. There was really only one possible diagnosis – iron deficiency. Bearing in mind the patient leads a very active life as a timberjack and has only recently become ill, the only other possible cause of this blood count (thalassaemia with blood loss) is unlikely as thalassaemia is a life long malady.
The further testing wasn’t quite so straight forward. Obviously to confirm the iron deficiency, it would be a good idea to check body iron store. Low ferritin and high TIBC support the iron deficiency. However only being given one choice of test made it difficult. Ferritin or TIBC? Personally I went for ferritin, which was the majority decision.

But it wasn’t much of a majority. Only 31% plumped for this. More people wanted to assess B12 & folate levels than wanted to measure the TIBC. What on Earth were they thinking of? And interestingly 9% of the respondents thought the case was thalassaemia major. (!??!?!?!)

The expert opinion given went on to say that “Sometimes blood cell count and smear findings can be quite similar in thalassemia minor. If the findings are unclear, haemoglobin electrophoresis would be relevant to exclude thalassemia minor.” I’ll grant that microcytosis is common between iron deficiency and thalassemia minor. But iron deficiency causes an anaemia, thalassemia minor does not. In fact an erythrocytosis is a more common finding in thalassemia minor. The pencil cells evident in iron deficiency are not seen in thalassemia minor; target cells are. And how does haemoglobin electrophoresis ‎exclude thalassaemia? A haemoglobinopathy would certainly be excluded, but not a thalassaemia.

June 1, 2011 (Wednesday) - Moh's Procedure

A lunchtime seminar. Mohs surgery, created by a general surgeon, Dr. Frederic E. Mohs, is microscopically controlled surgery used to treat common types of skin cancer. It is one of the many methods of obtaining complete margin control during removal of a skin cancer using frozen section histology.
Mohs surgery allows for the removal of a skin cancer with very narrow surgical margin and a high cure rate, and involves near patient testing for biomedical scientists with a histological bent.

There’s no denying that in the past I have often looked down on histologists as being glorified bacon slicers. And back when I worked in histology (spring 1982), histology was rather dull. But having had an insight on what they get up to these days, it would seem that I was wrong. Times have changed.
Here’s hoping that today’s session marks the start of an involvement of the histologists into our ongoing CPD program. If today was anything to go by, I for one will get a lot from it…