Thursday, April 09, 2009

"Boogie Woogie Bugle Boy Of Company B" - Back to the future!

Transfusion medicine colleagues - get ready for a sea change:
The tide has finally turned. All the griping heard over the years about ineffective and costly measures to protect the blood supply will soon bear fruition. Something will finally triumph over the impossible desire for zero risk and the associated measures that were implemented and fueled by the HIV and HCV tragedies of the 1980s and '90s.

How do I know?

The April issue of Transfusion has no less than 5 papers that discuss
  • tests that have outlived their usefulness
  • ineffective donor deferrals
  • proposed measures that are over-kill
These papers continue the drum beat of two papers discussed in earlier blogs:
(i) "The Rapa Nui caveat" in the Feb. 2009 issue of Transfusion, which argued for a more flexible approach to the precautionary principle, an approach that did not defer and turn off younger donors who could spread their discontent via social networking, and called for a national workshop to review donor restrictions.
(ii) "Cost-effectiveness analysis: what it really means for transfusion medicine decision making" in the Jan. 2009 issue of Transfusion Medicine Reviews, which proposed using cost effectiveness as a key driver of decisions on donor safety measures.
This blog will briefly and selectively review the growing drum beats for modified blood donor screening in the April Transfusion. I call it, "Boogie Woogie Bugle Boy Of Company B - Back to the future!" The blog presents musings on scrapping several blood donor screening tests and policies.
Obtaining a complete understanding of each paper's nuanced content will require reading the originals, which are rich in details not presented here.
Reader Challenge - Identify the Real 'Perp'
As you read, determine what you believe is the 'something' that is primarily responsible for the current increasing calls for a major shift in donor screening, namely scrapping several existing tests and policies. Why is there a push on now? Potential answers are sprinkled throughout the papers, much like clues and red herrings in a mystery novel.
Paper #1 (Research paper)

Goldman M, Xi G, Yi Q-L, Fan W, F. O'Brien SF. Reassessment of deferrals for tattooing and piercing. Transfusion 2009;49(4):648-54.
Today, tattoos and piercing are increasingly frequent in donors. After Canada decreased its deferral period for tattoos from 12 to 6 months in 2005, Goldman, et al. conducted a study to determine the prevalence of tattoos and piercings in donors, the impact of the decreased deferral on viral marker rates, and changes in blood availability.
They found the following donor rates (% performed in the past 6 mths):
  • Tattoos - 14% (0.4%)
  • Pierced ears - 54% (0.7%)
  • Piercings of other body parts - 10% (0.3%)
Transmissible disease test results were unchanged (21.6 versus 19.2 per 100,000 before and after). The number of tattoo- and piercing-related deferrals declined by 21% and 32%, respectively.
Their conclusions:
  • Data suggest that donor deferral for recent tattoo or piercing contributes little to blood safety in Canada, since decreasing the deferral period did not change the TD marker rate.
  • The value of other temporary deferrals should similarly be reassessed.
Paper #2 (Research paper)
The authors used the American Red Cross (ARC) database to demonstrate that a confirmed positive serologic test for syphilis (STS) would have detected zero new HBV, HCV, or HTLV infections among more than 3 million fully tested repeat donors during 2006 - 2007. They estimate that STS might identify approximately 0.1 HIV 'window-period' (w-p) donations every 2 years among ARC donors.
Conclusion - the current surrogate value of the syphilis test appears to be negligible.
Paper #3 (Editorial)
  • Katz LM. A test that won't die: the serologic test for syphilis. Transfusion 2009; 49(4): 617-9.
This editorial reviews the long history of screening donors using an STS. Introduced in the 1950s, STS has survived as a surrogate test for other transfusion-transmitted diseases, despite the multitude of additional tests and policies that identify T. pallidum infection in donors.
Katz reviews the many reasons why the continued use of STS as a surrogate test makes little sense. He also contends that surrogacy is no longer the driver for continued STS donor screening. Rather the test remains entrenched due the TM community's inability to prove a negative, namely that transfusion-transmitted syphilis will not occur if the test is removed.
Moreover, although the direct cost of donor STS screening is trivial, the cost of the test's non-specificity is substantial, resulting in needless destruction of 1000s of blood components annually. Other approaches that he sees as similarly wasteful include
  • Deferral of tens of 1000s of US donors for tourist travel to Mexico for a tiny malaria risk
  • Year-round WNV testing
  • Opting for near universal testing for infection with T. cruzi
Paper #4 (Review)
The authors review human prion disorders, the etiology of vCJD, vCJD cases in transfusion recipients, the precautions taken to reduce that risk, potential future safety precautions such as filters and a test, and all the uncertainties therein.
Some of their interesting assertions:
  • Study of transfusion-transmitted (TT) vCJD is difficult given that it requires transfusion traceability of 10-30 years, perhaps almost as long as the human life span.
  • Even if TT vCJD becomes a certainty, transfusion benefits greatly outweigh any risk.
  • Never before have so many measures been taken in transfusion medicine to counteract a risk that is numerically so low, some taken even before the first case of TT vCJD had been reported.
  • The precautionary principle has not just gone into the law: it has also penetrated the senses.
Paper #5 (Editorial)
  • Menitove JE. Accepting donors with tattoos and other in-favor changes. Most of the change we think we see in life is due to truths being in and out of favour. (The Black Cottage—Robert Frost 1914). Transfusion 2009; 49(4):615-6.
Menitove's editorial initially comments on Goldman's tattoo / piercing study but then discusses the broader issue of scientific truths being in and out of favour.
Three arguments are particularly instructive:
  • Patient and donor safety remain priorities but since 2008 it is unquestionably "in favor" to use dollars wisely. The USA should adopt selective testing strategies. i.e., test donors only once for T. cruzi rather that test every donation, discontinue syphilis testing, and investigate selective testing for HTLV antibodies.
  • Tension between evidence-based decisions and those based on the precautionary principle, both are in vogue and seemingly diametrically opposed, confound the discussion. Perhaps the emerging change in [USA] national politics to pragmatism and empiricism will reengage efforts to resolve this disconnect and permit acceptance of some risk.
  • Patient and donor care are primary concerns, but indifference to economics will stifle growth and discourage investment. Dialogue with emerging suppliers must emphasize long-term opportunities in transfusion medicine and cellular therapies.
Conclusion: Today's challenging climate presents an opportunity to bring about significant change and accept more risk. Sufficient future donors and dollars will not meet patient needs unless we reevaluate and revise truths longing to be in favor.


A few random musings on these papers:
#1. Today, tattoos and piercing are increasingly frequent in donors and constitute a significant cause of deferrals among young blood donors, who are desperately needed to keep the system sustainable. Goldman and colleagues provide evidence for safely decreasing the time deferral on tattoos and body piercings.
Note that tattoo parlors still present a potential risk of transmitting infectious diseases:
#2. Zou et al. provide evidence that syphilis testing, retained mainly as a surrogate for other infections, has little value as a surrogate for HBV, HCV, or HTLV infections, although in the USA it could perhaps detect 1 HIV w-p unit every 20 years.
So many syphilis studies, so little action, and as Katz notes in his editorial:
  • It's impossible to prove a negative, i.e., no STS, no transfusion-transmitted syphilis, which perpetuates inefficient tests and policies.
Lumping in other tests and policies such as malaria deferral for travel to Mexico, screening for WNV year-round, and near universal T. cruzi testing as similarly ineffective and costly seems almost anecdotal, given that the author did not provide much, if any, evidence to support these contentions.
#3. Lefrère and Hewitt bemoan the example of safety precautions for TT vCJD, claiming that "never before have so many measures been taken in transfusion to counteract a risk that is numerically so low."
I am reminded of Churchill's words about RAF fighter pilots during the Battle of Britain in WWII:
  • Never in the field of human conflict was so much owed by so many to so few.
As applied to TT vCJD, this would perhaps become,
  • Never in the field of transfusion medicine was so much owed by so few to so many.
Lefrère and Hewitt's point is that vCJD precautions are over-kill given the rarity of the condition.
It's worth recalling that the once orthodox position of TM experts was that the human form of "mad cow disease" was not transmitted via transfusion, that is until the discovery of vCJD in 1996 and the first transfusion-associated case of vCJD reported in 2003.
For a superb examination of the complex issues involved in implementing a test for vCJD, see:
#4. Menitove's editorial initially comments on the tattoo / piercing study of Goldman, et al. but then discusses the broader issue of scientific truths being in and out of favour.
In a way, Menitove is talking about the concept of scientific paradigm shifts as first postulated by Thomas Kuhn in The Structure of Scientific Revolutions, but on a much smaller, even minuscule, scale.Okay, it's a stretch, but I've been wanting to get the cliche paradigm shift into one of these blogs for a long time.
The fact that today hepatitis C is no longer significantly associated with tattoos is not so much a truth that has fallen out of favour as a truth that is no longer valid. Truths change when enough evidence points to their fallacy. Truths being in and out of favour implies that they are still valid but no longer popular with the scientific community.
The precautionary principle (PP), evidence-based medicine (EBM), and cost-effective analysis can be in and out of favour, but truth, not so much.
PP vs EBM?
Menitove also sees the PP and EBM as diametrically opposed competitors for making decisions. To me, the conflict is not as extreme.
First, there is not much in transfusion medicine that is evidence-based. Many of our practices reflect historical precedent, physician beliefs and preferences based on their teachers, and happenstance.
To protest strongly that a particular donor deferral policy or screening test is not evidence-based is disingenuous, given that hardly any transfusion practices are. And it's not as if needless transfusions do not cause significant harm and cost vast sums of money. That said, two wrongs do not make a right.
Second, the PP does require some evidence, just not higher level evidence. The principle implies that there is a responsibility to protect the public from harm if research discovers a plausible risk, especially if it is a severe risk. But the proof of harm need not be certain, and cause and effect do not need to be fully established. Indeed, for serious threats, lack of scientific certainty should not be a reason to postpone preventative interventions.
Many transfusion risks constitute plausible and serious risks worthy of applying the PP. Surely we are obligated ethically to apply interventions that help prevent transmission of serious diseases.
Third, often unstated in the PP are the notions that interventions should be
  • effective
  • not make things worse, e.g., not dry up the supply of available donors to the point where patient lives are at risk
  • not cost so much time and money that other equally or more important safety measures are threatened
As they say in the law, res ipsa loquitur - the thing speaks for itself.
Unfortunately, the devil is always in the details.That's where EBM studies help. They do not so much compete with the PP for which test or policy should be implemented, but rather act to
  • Identify if a particular threat is indeed plausible and serious and thereby worthy of applying the PP AND then
  • Identify which intervention options are effective and do not cause harm
EBM supports the validity of PP-motivated interventions. Treating EBM and PP as mutually exclusive opposites is easy to do (I have done it myself) but it only serves to undermine the basic goodness of the PP.
I have not read anywhere that the PP is meant to implement ineffective, costly, harmful safety measures. But neither do PP-motivated measures need to be perfectly effective and cheap. That's a standard not applied to other interventions.
Also, I noticed that Menitove used, "Patient and donor safety remain priorities / are primary concerns, but..." twice. This reminds me of Queen Gertrude in Hamlet saying, "The lady doth protest too much, methinks."
Lastly, Menitove presented an argument that I have not seen used before, at least not directly - that indifference to economics will stifle growth and discourage investment.and that suppliers need to be told about long-term opportunities in TM. In other words, TM health professionals need to help grow the biotechnology sector, so that it will be there when needed for emerging threats.
In particular, those involved on the blood centre side of the business need to nurture suppliers so that the commercial infrastructure is in place for 'shovel-ready' projects should they be urgently needed. Otherwise the industry may migrate to more profitable ventures in the transfusion service and other sectors.
The tide has turned and it's back to the future. Who knows what year we will be beamed back to. When syphilis testing is dropped, as it inevitably will be, it will be early days, indeed:
The Real 'Perp'
So, what do you believe is the 'something' that is primarily responsible for the current increasing calls for a major shift in donor screening policies - a shift that involves scrapping several existing policies and tests? Why have the drum beats increased now?
What is the real 'perp' and what are the red herrings?
  • Dedication to patient safety?
  • Belief in evidence-based medicine?
  • Need to save money?
Of course, the above choices may not include the most plausible explanation. It's possible that the real key driver is something else.

Tattooing & piercing in Canada (2004 backgrounder)

Alter HJ. Pathogen reduction: a precautionary principle paradigm. Transfus Med Rev. 2008 Apr;22(2):97-102.

And do not forget this paper - it spells out just how complex blood safety policy decisions are:
Mapping out the consequences of screening blood donations for PrPSc (UK DOH)
Earlier related blogs:
Comments are most welcome BUT, due to excessive spam,  please e-mail me personally or use the address in the newsletter notice. 

No comments: