Tuesday, September 3, 2013

Contaminated Platelets - A Major Risk at +22~

Since the advent of blood component therapy in the 1960s and its popularization in the 1970s, one of the gravest problems facing blood transfusion has been the transmission of bacterial and viral diseases through the use of blood.
The viral illnesses that are transmitted via blood transfusion seem to not be much affected by storage conditions, however, the same cannot be said for bacterial and protozoal pathogens. Dangerous bacteria in particular, can thrive and multiply in blood.
We do screen each donated unit to try to detect and then eliminate any disease carrying blood from the supply. The TTI testing has grown in sophistication, sensitivity and specificity to such an extent that very few TTIs actually take place. The concentration in TTI testing is to detect anything commonly pathogenic that is already present in a detectable quantity at the time of donation.
However, what happens to pathogens that are present in the blood and for which we do not routinely do TTI testing, and what happens to the few pathogens that may have entered the blood at the point of donation and then multiply on storage to dangerous levels? The different blood components are stored in different ways. For example, RBCs store well at +4C and this temperature does not encourage most bacterial pathogens to proliferate and so the storage temperature itself does lessen the risk quite a bit for this component. The same is true of FFP as it is commonly stored at -30C or below.
While at first PLT too were stored at +4C, at that temperature they had a shelf life of only 24 hours. The numbers of PLT that we had to discard daily because of this short expiry was mind boggling, and there were also frequent shortages of PLT. However, from the late 1970s onwards, it was recognized that PLT do better when kept at room temperature (20 to 24C). At first, due to limitations of the plastics available, these room temp platelets were discarded after 3 days. However, as our storage technology improved, it was found that PLT could well survive and be useful in transfusion for up to 7 days.
Soon, though, we had to pull back from this 7 day storage as quite a number of PLT units were then found with heavy bacterial contamination. The risks of transfusing such contaminated PLT units should be very obvious, and many deaths and serious illnesses were associated with PLT transfusions. The storage period was therefore limited to 5 days as this somewhat mitigates the ability of bacterial contaminants to proliferate to the very dangerous levels seen in 7 day-old PLT.
Since it was soon recognized that many of the contaminated units were growing skin comensals, we knew that the point of donation, when the phlebotomy needle pierces the skin, was a very probable source for these contaminants. Therefore, most blood banks now take extra care to completely clean the site and surroundings of the venipuncture before starting the bleed (see our earlier blog post on donor prep and see the LinkedIn Blood Components Group discussion here). Another useful practice is to sequester the first few milliliters of blood drawn as that probably contains the 'skin plug' that enters the bore of the phlebotomy needle. This practice is also very useful at reducing the amount of contaminated PLT. In spite of these measures, unfortunately, PLT bacterial contamination continues to be a very major source of transfusion related morbidity and even mortality.
One would think that spotting a unit of PLT that has been heavily contaminated would be easy, but it is not so. There are mostly few, if any, signs that there could be something wrong with the PLT unit.

Furthermore, we have to be able to do any testing with the blood samples drawn at the time of donation or within the closed system itself and this limitation has made practical testing difficult. Very recently we have seen a few tests that can be done at the time of issue or even POC before starting the PLT transfusion. There's a beautiful and detailed PPT on "Enhancement of Bacterial Testing in Platelets" by Mark Edmunds, MD, (Blood Centers of the Pacific) that clearly summarizes the current scene.
Of course, further testing does add to the cost, but compared to the very serious risks involved, we should certainly encourage the development of better and quicker tests for contamination. It's very good to see that some companies have introduced workable tests and that they have also started getting approval in the US (FDA) and in Europe for these tests.
One factor that will help mitigate the additional costs will be the savings of being able to store and issue PLT for the full 7 day period. One would hope that safer PLT can also be made available in developing countries with special pricing and with the encouragement of local entrepreneurs/scientists to help bring the costs down.
Another promising technique that is being explored is to neutralize any pathogens inside the blood unit, and some of these techniques have been introduced and are proving promising, see our LI Group  Discussion on this started by Dr. Rashmi Sood.
One would also hope that all PLT units are well enough tested before release from the blood bank that we stop seeing cases of contaminated PLT altogether!

Here are a few online references:
http://www.cdc.gov/bloodsafety/bbp/bacterial-contamination-of-platelets.html
http://www.veraxbiomedical.com/products/platelet-pgd-test.asp https://www.lstream.org/Files/Edmunds.pdf http://www.psbc.org/news/pdf/2012_September_Platelet_Bacterial_Safety.pdf
http://www.youtube.com/watch?v=4uOhFXb4KOk http://www.aabb.org/events/misc/Pages/public-conference.aspx
http://www.cap.org/apps/cap.portal?_nfpb=true&cntvwrPtlt_actionOverride=%2Fportlets%2FcontentViewer%2Fshow&_windowLabel=cntvwrPtlt&cntvwrPtlt{actionForm.contentReference}=cap_today%2Ffeature_stories%2F0905Platelet.html&_state=maximized&_pageLabel=cntvwr
http://www.cap.org/apps/docs/committees/0412_are_those_platelets_safe.pdf
http://www.fenwalinc.com/PressReleases/Pages/News/Verax-Platelet-PGD-Test-Cited-As-Important-Safety-Measure.aspx

Abbreviations:
FFP - Fresh Frozen Plasma
PLT - Platelet Concentrate
POC -  Point of Care
RBC - Red Blood Cells (packed red blood cells, packed cells)
TTI - Transfusion Transmitted Diseases, testing