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??

No comments:

Post a comment