Wednesday, 24 November 2010

Until Today - 24th November 2010

Where has the time gone - been so busy busy busy! Currently stepped up into an acting Transfusion senior role. So far, so good. Have made a few new changes and my acting chief is doing a grand job - long may it last!

Was luckily enough to get to another meeting yesterday, a joint BBTS and NEQAS meeting at Gatwick. A lot of the morning session focused on anti-D, immune or prophylactic? Anti-D for prophylaxis is manufactured from hyper immunised patients, it is therefore human derived and can not be distinguished from immune anti-D.

Under normal circumstances prophylactic anti-D poses no risk of HDFN (levels are too low), however, one case did occur in a patient where, following 1500iu for RAADP, had multiple pv bleeds where further 1500iu doses were repeatedly given (remotely held anti-D - no lab involvement). The patient ended up with an anti-D quantification of 25iu/mL and the baby had HDFN. A lot of SHOT incidents involved remotely held anti-D stocks where anti-D was not issued on a named patient basis, maternity staff were able to access and administer the anti-D.

When assessing if anti-D is immune or prophylactic the following should be considered:- dose of prophylactic anti-D given, how long ago it was given, how strong the reactions are and the in vivo decay that occurs only with prophylactic anti-D (levels drop if anti-D prophylactic, they will remain constant or rise if immune).

1500iu anti-D given intramuscularly (IM) can be detected serologically within 4 hours of administration (this however, does depend on patient size). A maximum anti-D plasma concentration is reached after 2-4 days after which, levels decline. Distribution kinetics between the plasma and tissues is complex. Uptake rates are thought to range between 14-33%  of injected dose at 3-4 days.

5000iu was administered to 3 male volunteers and the levels monitored, uptake was similar for all three. A rapid drop in levels was observed and the half life measured at approx. 23 days (3 weeks).

Routine iu/mL levels of prophylactic anti-D will not exceed 0.1 iu/mL which equates to a 1 - 2+ reaction. After 6 weeks, only a very weak reaction is detectable. If a 3-5+ reaction is measured then immune anti-D is present.

Assume 40mL of plasma/kg body rate. If 60kg = average body weight  = approx. 2.5L plasma volume. 1500iu anti-D in 2.5L plasma = 0.6iu/mL. If uptake approx. 40% = approx. 0.2-0.3 iu/mL after approx. 4 days. Level should decline about half every 4 weeks. 500iu is too low for reliable quantification.
Question - should body weight be considered in anti-D administration? ie. if large body weight, should a higher dose be administered?

Strong reactions can not be ignored. If prophylactic suspected but can not be proven, it may be sufficient to monitor in-house by IAT titre - monitor once or twice at 4 weekly intervals. If level rises, alert the obstetric team.

Weak reactions was the next subject and how we should approach them:-  check for reagent failures, dispensing failures, incubation failures. Are the weak reactions reproducible? Causes of false positives: contaminated reagents, sensitised red cells (DAT+) - the inclusion/interpretation of an inert control can detect false positives. Reasons for 'true' weak reactions: weak antigen expression (babies etc.), ABO subgroups, D weak, mixed populations (tx or BMT), low concentration antibody, low avidity antibody.

Expansion of D weak. D weak can be a qualitative and quantitative variant. There are more than 40 recognised D weak genotypes. Some can form allo anti-D (4,11 & 15). Common weak D types (1, 2 & 3) generally don't make anti-D. Weakest D weak = DEL. Can stimulate the production of anti-D when transfused to a D negative recipient but can not themselves be alloimmunised by normal D. Genotyping can classify D weak and partial phenotypes however, getting results takes time.
It is important to ensure D compatible red cells are transfused. D negative stocks should be conserved and not given to patients unnecessarily (7% of blood donors are D-, 10% of recipients are D-).
Is D gp > predetermined cut off? If yes, report as D+, if no; is patient female <60yrs, if yes, confirm D genotype, if no; will patient require chronic tx support? if yes, confirm genotype, if no, report and treat as D+.

Titration's are a deliberate induction of a weak reaction. Many different factors can influence titre levels - best practise to titre previous sample along side current sample - standardises variables. Automation for reading titration endpoints would provide standardisation.

Afternoon sessions explored differences between MHRA CAPA (corrective and preventative action) and CPA CAPA. Reasons behind the need for good documentation - what paperwork is necessary and why - just think having to justify / evidence your actions in court! But be sensible - why am I recording this, does it add value?? Must put a name to work. National Collaborative recommendations along with crosstraining chemists in the transfusion laboratory. All very relevant and interesting topics.

As a result, I have raised issues with regards to weak D patients, anti-D prophylactic issues (managing anti-D exposure to a single batch during pregnancy - is it possible??) and titre practises. I intend to disseminate this knowledge to my colleagues at the next transfusion team meeting.

Should D weak antenatal patients receive RAADP? If a D- mother has a D weak baby, should anti-D be given??

Tuesday, 26 October 2010

19th Oct - 20th Oct

Went to the NEQAS Haematology meeting in Birmingham. It was a really good meeting. On Tuesday 19th, I went to a session about new NEQAS schemes. It was a discussion session and we talked about n-RBC's, ESR's, MPV, RDW and iron deficiency indicators. NEQAS are piloting an n-RBC scheme at the moment and are trying to create their own in-house material. Our Sysmex XE analysers are capable of n-RBC counts. At the moment, we only perform counts on neonatal samples. If any adult specimens contain n-RBC's, the analysers produce a NRBC flag and a film is looked at. We informed NEQAS that it was more important that the n-RBC material was able to generate an NRBC flag, which we cold then go on and quantitate.

The value of the ESR was discussed, a couple of laboratories no longer perform an ESR but conduct plasma viscosity testing instead. It was felt that despite the ESR being a non-specific test, GPs and A&E staff find it a good indicator of disease status and as a monitoring tool. Despite the vast number of years over which the ESR test has been performed, there is still no external quality assurance scheme available. NEQAS are trying to produce an ESR scheme. Most laboratories did use internal QC material for automated ESR's.

The Mean Platelet Volume was introduced as a new parameter. Very few laboratories reported the MPV. The science is that MPV can be an indicator of risk of thrombosis. The larger the MPV, the greater the risk. The room ws asked why the MPV was not being reported. One answer was that there was no room on the printed report. One answer to this was to stop reporting the MCHC as this, although a useful parameter in the laboratory for assessing sample integrity, was of no clinical value. It' space on the report could be taken by the MPV. Most laboratories stated that they were not reporting the MPV as clinicians were not requesting it. This led to a debate on who's responsibility it was to educate the clinicians about new parameters available from the laboratory. Some felt it was the responsibility of biomedical scientists to educate their consultants and to try an get the word to the hospital doctors via the grand rounds. My feeling is that until a guideline is written, we are unlikely to begin reporting this parameter. Many laboratories said that they do report the RDW. Currently, the laboratory I work in does not report this parameter. The use of the percentage hypochromia, and some others, were also mentioned as a new parameters for iron deficiency.. Again, many laboratories had analysers that can measure this parameter but very few reported it.

On Wednesday 20th, we had a talk about harmonisation in haematology. This talk was about Carter; moving services closer to the patient, exploring new ways of working, consolidation/networks, innovation in workforce and technology etc. We were then given a talk about trying to harmonise reference ranges across the UK, Wales have achieved this to a certain extent. As ideal as this would be, different analysers using different reagents require different reference ranges. All laboratories were urged to at least report their parameters in harmonised units ie Hb in g/dL not g/L. NEQAS schemes are helping to achieve this by requesting results back to them in specified units. The use of comments was also approached. Comments should be standardised, meaningful, consistent, add value and be evidenced based.

A talk was then given about the Haematinic's NEQAS scheme and the problems experienced with specific analysers. The measurement of Holotranscolabumin (active B12) was mentioned.

A funny talk was given about the naming of cells. Check out the website similes.

An overview of the Tuesday afternoon session was given and also for the other session about Digital Morpohology. NEQAS run a digital morphology scheme that biomedical scientists can sign up to for CPD.

Overall, it was a really good meeting.

Monday, 11 October 2010

4th Oct - 8th Oct

This week was spent working on re-writing the 'Procedure with Incompatible Crossmatch' SOP. Almost there!

I also managed to get an audit done. I did a comparative audit between the result interpretations that we submitted with our NEQAS Haematinics results and the consensus results. The results suggested that a revision of the normal range in use for Folates should be considered. Hope to get some feedback.

Placed an order for some neonatal group A- platelets from our NHSBT centre. We were called to say that no group A neonatal platelets were avaliable, would group O be OK? Intitially I agreed to the group O platelets but felt uneasy at doing so and therefore sort advice from a more senior collegue. He called the blood centre and asked if they could check whether group A neonatal platelets were avaliable at the next closest blood centre, there was a unit of A+ neonatal platelets which we requested. My senior advised me to write to our local blood centre to ask why the stock at the next nearest blood centre was not checked before we were contacted to say no group A units were avaliable. I await a response.

Our TP finished off a new prophylactic anti-D request and combined traceability form that myself and a collegue helped her to design. This is in response to a couple of recent incidents where the layout of the anti-D request form was a contributary factor to (i) the incorrect dose of anti-D being issued and (ii) anti-D not being issued for the patient's appoinment resulting in an appoinment reshedule. We were also not conforming to traceibilty protocols for anti-D being sent to satelitte antenatal clinics, we therefore chose to combine the redesign of the request form with a new traceability form. It needs to go for consultation but hopefully will be in use in the not too distant future.

Monday, 27 September 2010

My week of CPD - 21st - 25th Sept 2010

During this week I was reading the BCSH transfusion guidelines for neonates and older children as part of the study for my BBTS certificate. I became a little confused when the guidelines told me that if RhD positive FFP was given to an RhD negative girl, prophylactic anti-D would have to be given as there was sufficent red cell stroma in the FFP to provoke RhD sensitization. This advice contradicted the advice in the adult FFP BCSH guidelines that state the red cel stroma left in FFP following the freeze/thawing processes was not immunogenic and therefore RhD positive FFP could be given to a RhD negative female of child bearing age without the risk of sensitization and therefore prophylactic anti-D immunoglobulin was not required.

I e-mailed BC about it and he felt that the neonatal guidelines were incorrect. We discussed it the following day and I showed him the relevant paragraphs in each of the guidelines. He approached GE with the evidence and her feelings were that the neonatal guidelines were wrong. Both guidelines were written in 2004. BC is now to take the matter higher! Surely I can't be the only one to have picked up on this ?error. BC will feed back to me on what he finds out.

This week, we were proving blood for a 16 year old acute lymphobastic leukaemia (ALL) patient who is shared care with Kings College Hospital in London. With the first unit of blood she was transfused, she developed a rash up her arm, spreading from the blood infusion site. The transfusion was stopped and she was investigated for a ? transfusion reaction. No serelogical evidence of Tx reaction could be demonstrated. She then proceeded to be transfused with a second unit of blood, again, she suffered a reaction to the transfused unit and again the transfusion was stopped. The transfsuion practitioner reviewed her case and contacted the consultant at NHSBT for advice. The concern was that this patient was suffering allergic reactions to the transfusion and that they may develop into severe anaphylactic reactions. I learnt that these reactions can happen when the patient has antibodies to 'foreign' white blood cells in the transfused unit, or, if the patient does not produce their own IgA antibodies, they can produce anti-IgA antibodies.

A reaction to white cells in a unit of packed red cells is rare as all packs of red cells are leucodepleted i.e. the majority of white cells have been removed. Individuals who do not produce their own IgA antibodies are also extreemly rare. Patient specimens were referred to NSHBT to determine if our patient had white cell or anti-IgA antibodies. In the mean time, the NHSBT consultant advised that any further transfusions would require washed red cells. It fell to me to order two units of washed red cells, a task I had never under taken before. The units can be ordered using a non-standard blood product request form. I requested two units of group specific washed red cells and had to specify the requirement for them to be K- CMV-. I contacted Tooting, who advised that the red cells would be washed at Brentwood and sent directly to us. When red cells are washed, the blood pack is opened and the cells are washed in saline. Because the pack has been opened, it is no longer sterile and there is a high risk of bacterial contamination. The shelf life of the units is therefore reduced to 24 hours from the time of washing. The washing had to be arranged to take place as late in the day as possible, so that they could be transported from Brentwood to Ashford, be crossmatched and ready for transfusion early the following morning, to give the ward staff sufficent time to complete the transfusion before expiry of the units. Communication with NHSBT and Padua ward was key.

All went smoothly, the transfusion was completed within the 24 hour timeframe and the patient suffered no adverse reactions to the washed red cells. The results from her blood tests showed no white cell or anti-IgA antibodies were present so a cause for the reactions remains unknown.

Thursday, 23 September 2010