Showing posts with label cryoprecipitate. Show all posts
Showing posts with label cryoprecipitate. Show all posts

Sunday, March 16, 2014

Hey Jude (Musings on why paid plasma makes it worse, not better)

Last updated: 29 May 2014 
This months blog is a two-fer. The title is a take-off on the best Beatles song ever, Hey Jude.

The blog was motivated by the recent decision of the Ontario government to introduce legislation to ban paid plasma. (Yikes! In the first version, I forgot the lead. Unforgivable. See BBTS blog's advice.)

#1. BBTS BLOG
I'm delighted and honoured to be a guest blogger for the BBTS:
Born to be Wild? (Musings on how to blog for transfusion professionals)

The BBTS blog is about how to blog as a transfusion medicine professional. Take a peek. The advice can be applied to e-mail messages too.

#2. MARCH BLOG
However, this month I cannot resist blogging on a recent development in Canada involving paid plasma clinics.

On March 14, 2014 one of Canada's provincial governments, Ontario, decided to ban paying for plasma (and all blood donations), as had already been done in Quebec (see Further Reading).

Humour me with a few simple thought experiments. Probably best to think of them as 'What If' games.

'What If' Game #1
What if I represented Canadian experts who told you that surrogate tests for non-A, non-B hepatitis used in the USA were scientifically unsound.

The tests had poor sensitivity (missed many true positives) and poor specificity (detected many false positives) and would threaten the blood supply by preventing many perfectly safe blood donors from donating. Plus the testing was expensive.

Then I asked for a vote on doing surrogate testing on all blood donations or not. Based on expert opinion, you'd probably vote not to do it, right?
Game #1 Outcome Turns out that because Canada's TM experts prevailed, thousands of Canadian recipients of blood donations were needlessly infected with what we now call hepatitis C. Despite the flawed surrogate tests, they would have prevented many HCV cases in transfusion recipients. See
'What If' Game #2
What if I told you that concentrated Factor VIII to treat hemophilia had several advantages over the existing treatment, cryoprecipitate, including a known quantity of Factor VIII and more convenient storage. Doctors touted it as 'latest and greatest' advancement.

Then I asked for a vote on using cryo or Factor VIII conc. Based on expert opinion, you'd probably vote for using only Factor VIIII concentrate, right?
Game #2 Outcome Turns out that Factor VIII concentrate was made from the plasma of 10s of thousands of blood donors and it only took one donor to be infected with the then unknown human immunodeficiency virus (HIV), that causes AIDS. The saviour of patients with hemophilia turned out to be a death sentence for many.
'What If' Game #3
What if I told you that Factor VIII concentrate transmits several deadly diseases but, when heat-treated Factor VIII became available, and was shown not to transmit HIV, we should still give the unheated product to hemophiliacs.

After all, experts contend that most hemophilia patients are likely already infected and we have mega-bucks worth of product in storage. As well, if we don't give the unheated product to them, many would suffer life-threatening hemorrhages.

Then I asked for a vote on transfusing the existing stock of Factor VIII concentrate to likely already-infected hemophilia patients. Based on expert opinion, you'd probably vote for using unheated Factor VIII concentrate, right? We have the stock, it'll save money, and they're already infected.
Game #3 Outcome Turns out that this expert decision cost the lives of many hemophiliacs who were NOT already infected. How the experts reasoned will never be known.
Unlike US President Nixon, minutes of key meetings by decision makers (Can. Red Cross physicians and their provincial paymasters) were destroyed. I kid you not. 
To their credit, a few Canadian physicians opted for using single-donor cryoprecipitate, thereby protecting their hemophilia patients from HIV.
LEARNING POINTS
We decide based on what we know at the time and rely heavily on perceived experts.But we only know what we know. We don't know what we don't know.

And experts can be oh so wrong, as expertly detailed by Canada's Krever Commission (see below) and, more superficially, in my What If games above. Which is why I'm not onside with our TM experts on Canada's further venture into paid plasma.

Of course, you can also make an ethical case that Canada should not go down the path of paying for plasma.

ONTARIO UPDATE (Added 17 Mar. 2014)
Canadian Plasma Resources is a private company in Ontario whose sole purpose is to pay for and collect plasma for further manufacturing.

In Canada the safety of the blood supply is a federal responsibility that falls to Health Canada but whether plasma donors can be compensated rests with provincial and territorial governments.

On March 14, 2014, the government of Ontario issued this press release:
Among other things, it plans to introduce legislation to ban paying for blood in Ontario (as Quebec does now). Canadian Plasma Resources has plans to open plasma clinics in Toronto and nearby Hamilton, Ontario.
See Further Reading for news items on the announcement and background info on the issues. I'll update with more news items as they become available.
The case against paying for plasma is discussed on Impact Ethics: Making a difference in bioethics:
The authors are from Dalhousie University, Halifax, NS, Canada:
  • Matthew Herder, Asst Professor, Faculties of Medicine and Law
  • Francoise Baylis, Professor and Canada Research Chair in Bioethics and Philosophy
Included in the article is a copy of their submission to Health Canada, which is well worth a read too:
Of course, the issue in Ontario is far from settled:
  • First, after wide consultation, the legislation has to pass in Ontario's legislature. 
  • Second, Ontario has a minority government with an election required by Oct. 1, 2015, with strong polling support for three parties. 
  • Third, there will be blowback from vested interests.
REPLY TO COMMENT(Added 18 Mar. 2014)
This is in reply to the comment below from 'Anonymous', a hemophiliac who contracted HIV and HCV in the 1980s. He ended by predicting that 'the smoking gun will be IVIG for our next round.' Please see my reply to him below, which I'll expand upon here.

 I'll briefly comment on the safety and ethics of paid plasma, which is fractionated into plasma derivatives such as IVIG. 

Safety
First SAFETY. In a commentary that CBS CEO Graham Sher authored in the Toronto Star in March 2013 ('Prohibiting pay-for-plasma would harm patients'), Dr. Sher wrote (summarized by me):
  • Manufacturers must be licensed and meet stringent quality and safety standards.
  • Safety procedures built into fractionation are extensive, and include donor screening and testing, plasma quarantine, technology that inactivates viruses, and purification steps. 
  • These products are extraordinarily safe. 
  • Many studies show plasma products from paid donors are as safe as those manufactured from volunteer donors.
All medical experts stress that plasma derivatives such as IVIG are extremely safe when it comes to transfusion-transmitted infectious agents. They stop just short of claiming they are 100% safe, because such a claim could come back to haunt them.
No one wants to be in Dr. Noel Buskard's shoes when on behalf of the Canadian Red Cross he denied a link between AIDS and blood products. (2 min. CBC video. Sorry for the 45 seconds of ads).  
Dr. Buskard quit the Red Cross in 1991 saying that it had developed a “fortress mentality” when confronted with the tragedy. He became a noted whistleblower, who in 2001 was awarded the 'Whistleblower Award' from the B.C. Freedom of Information and Privacy Association. (Source: A tribute on his death in 2011)
Ethics
Because plasma derivatives are relatively safe, some against paying for plasma say it's best to concentrate on the ETHICS of paid plasma. I'm not going to regurgitate the many complex rationales for and against paying for plasma. For one thing, it's above my pay grade and expertise.

 To quote CBS CEO Sher, the ethical case for paying is that the derived products are 'extraordinarily safe' and patient lives would be threatened without paid plasma: 
  • The reality is that thousands of patients depend on these life-saving fractionated products, and without those produced using plasma from paid donors we would not be able to meet patients’ needs...When lives are at risk, that’s simply not an option.  
The ethical case against paying for plasma includes the reality that 
  • Commercial plasma collectors exist to make money. 
  • Exploiting the poor and vulnerable and selling to the highest bidder are what drives for-profit enterprises. 
  • Witness Canadian Plasma Resources building a clinic next to a homeless shelter. 
Is this really a path Canadians want to take? Matters not what happens in the USA or elsewhere. That's not us.

 Hypocritical?
Some call this position hypocritical since we use products made from paid plasma in other countries. Perhaps. 

 But is it any more hypocritical than CBS closing a Canadian plasma collection centre saying demand for 'plasma for transfusion' was down, and at the same time outsourcing plasma collection to the USA because it was cheaper? Then having its CEO claim that lives are at risk if we don't use paid plasma?

 CBS Annual Report 2007-2008 (p.22): 
This year, we also re-introduced the collection of source plasma at our existing plasmapheresis sites ...laying the foundation for CBS to improve our plasma sufficiency - one of the basic principles of the blood supply as outlined in Justice Krever's report.
CBS Announces closure of Thunder Bay Plasma Centre (29 Mar. 2012)
Over the past two years, new replacement products and a decline in hospital demand have led to a decrease in the need for plasma for transfusion. 
CBS Financial Report March 2011 (p.32)
In 2010/11 CBS started a pilot program to purchase surplus recovered plasma from the United States (collected by organizations with an FDA licence) which will continue in 2011/2012.
Report to Canadians 2012/2013, Management Analysis (p.43)
As self-sufficiency is not operationally or economically feasible in a volunteer, non-remunerated model, CBS strives to maintain a sufficiency of 30% for Ig. The demand for Ig continues to rise in Canada and internationally, and to meet our needs CBS purchases surplus recovered plasma (from voluntary donations) from the United States for fractionation, which increased by 4,572 litres or 17.0% in 2012/2013 over 2011/2012.  
'Don't let the perfect be the enemy of the good.'
So, yes, hypocrisy abounds on all fronts. It would be preferable (perfect) if we didn't need to use plasma derivatives sourced from paid plasma anywhere, but to me, banning paid plasma clinics in Canada is preferable (good). Not PEFECT, but GOOD.

 To return to the comments made by Anonymous below, I've discussed the IVIG safety issue and that history shows we can never be certain about blood safety. About his introduction: I am a hemophiliac that got HIV and HCV in the 80's, I'd like to end with
  • The tragedy of Factor VIII Concentrate (19 min. CBC video you won't soon forget. Take time to watch it sometime. As transfusion professionals we owe it to Canada's hemophiliacs and to ourselves.)
Added 29 May 2014: 'Must read' on paid plasma: 
'FOR FUN'
Hey Jude is a 1968 song by Paul McCartney, with an interesting origin.

Regardless, Hey Jude is about trying to make something that is bad better. Paying for body organs and tissue, including plasma, is a bad idea.
  • Hey Jude (Paul McCartney, Live in Red Square)
Hey Jude, don't make it bad. Take a sad song and make it better...
As always, the ideas are mine and mine alone. See comments below. More comments are most welcome.

Also, don't forget Born to be Wild? (my first blog for the BBTS)

Further Reading
Posted by Blut at 7:36 PM 8 comments
Labels: , , , , , , , , , , ,

Sunday, October 12, 2008

Responsibility - what's that?

The October issue of Transfusion has many interesting papers.

Two items caught my eye and got me to thinking how we view responsibility when colleagues fail to provide optimal care. We seldom get upset. Is it because we value calm, reasoned reactions over emotional responses? Because a quality system promotes a blame-free approach and focuses on systemic problems? Because we believe, "Let he who is without sin cast the first stone"?

This blog is about how we as a profession responsible for the safety of the blood system deal with physicians who order inappropriate transfusions and how that process compares with how we deal with other health professionals who do not follow established best practices. Besides the Transfusion papers, an Australian report featured the same problem:
The two Transfusion papers that caught my eye were
The first paper was a magnet - who can resist the notion of an immaculate transfusion? The authors describe the immaculate transfusion as issuing blood for transfusion when no order to transfuse exists.

After their transfusion service began to require a photocopy of a physician's order to transfuse blood before issuing products for transfusion (except when the need for rapid issue was more important than full compatibility testing), they audited blood requests for compliance to having a written physician order. As would be expected, they found various inappropriate blood requests, including some immaculate transfusions.

My guess is that they mean a virginal transfusion, since immaculate conception is a doctrine that believes that Mary, biblical mother of Jesus, was born without original sin. But immaculate transfusion has a nice ring to it.

The second paper initially jumped out because of its Canadian authors, two of whom I know. But more significantly, I have always been interested in cryo, a wonderful discovery by Judith Pool in 1965 that gave new life to people with hemophilia. See this reminiscence by Dr. Martin Inwood:
Cryo's downfall?
Cryo became associated with the tainted blood scandal of the1980s and its legitimate uses became fewer with the development of safer alternatives (e.g., recombinant Factor VIII and desmopressin, aka DDAVP). Over time, it seemed that cryoprecipitate and its association with the AIDS tragedy had become an outcast, a black sheep of the blood component family, admittedly nothing like the association of FVIII concentrate prepared from huge plasma pools of tens of 1000s of potentially infected donors.

Somewhat surprisingly, cryo continues to be used extensively, and inappropriately in many cases, as has been documented in this large Canadian study. To keep with a biblical analogy, (I know it's a stretch), it is almost as if cryo was a prodigal son , a product that behaved badly yet was somehow rehabilitated.
  • If you like music, listen for the prodigal son reference as the Dubliner's sing Wild Irish Rover.
The study in the October 2008 issue of Transfusion involved a 2 month audit of cryoprecipitate use in 25 major Canadian hospitals. Cryoprecipitate transfusions were designated
  • appropriate if a fibrinogen level (taken 6 hr before/after transfusion) was not more than 1.0 g/ L
  • inappropriate if the pretransfusion fibrinogen level was more than 1.0 g/L and posttransfusion fibrinogen level was more than 1.0 g/L or not performed
4370 units of cryoprecipitate were transfused in 603 events to 453 patients representing 62% of cryoprecipitate issued to Canadian hospitals during the study.

Allowing that current recommendations for appropriate cryo transfusion are based on the opinion of TM experts, since no randomized controlled clinical trials have been done, the authors use the criterion of bleeding and significant hypofibrinogenemia (fibrinogen 0.8-1.0 g/L), which is generally considered appropriate.

Results. Using a fibrinogen level of at or below 1.0 g/L as "appropriate," (and ignoring whether patients were bleeding):
  • 24% of cryoprecipitate transfusions were considered appropriate
  • 34% were inappropriate
  • 42% - appropriateness could not be determined
The authors conclude that "A 2-month audit of cryoprecipitate use in Canada revealed that most cryoprecipitate use in Canada is not in accordance with published guidelines." They note that, "During the period of our audit, up to 72 percent of patient exposures likely only carried risk, with no perceivable benefit."

What are inappropriate transfusions?
These papers discuss unauthorized transfusions and inappropriate transfusions. If unauthorized transfusions are immaculate conceptions, what analogies apply to inappropriate transfusions? Inappropriate transfusions include
  • transfusing the wrong blood component (e.g., transfusing plasma as a blood volume expander instead of non-blood products such as saline, pentastarch, et al., which also need to be transfused appropriately but carry no infectious risks)
  • infusing the wrong dose (e.g., transfusing 4 RBC when 2 would achieve the desired clinical effect)
  • transfusing a blood component or product when transfusion is not clinically indicated
Why should we care?
Why should we care about transfusions that result in no immediate adverse event or in adverse events that are hard to document? Inappropriate transfusion implies that the treatment may
  • not do what it is supposed to do, namely improve the patient's condition or prevent further deterioration
  • potentially harm patients by exposing them to infectious disease risks and other adverse events
  • needlessly increase the cost of health care by wasting scarce blood products
According to this BMJ paper, reasons to reduce blood exposure include
  • Immunological complications
  • Red cell alloantibodies: haemolytic transfusion reaction
  • HLA antibodies: refractoriness
  • Transfusion related acute lung injury, post-transfusion purpura, transfusion associated graft versus host disease, etc.
  • Errors and "wrong blood" episodes
  • Infections (bacterial, viral, and possibly prion)
  • Immunomodulation (risk of infection or malignancy)
  • Litigation
  • Limited resource
At their worst, inappropriate transfusions constitute an unneeded treatment that is forced upon an unsuspecting victim who may or may not be harmed. At their best, who knows? Even if all they do is waste money, that is money that could be spent more effectively elsewhere.

Frankly, if I were to be transfused inappropriately with any blood product and contacted a transmissible disease (admittedly a low risk, but not zero) or suffer any adverse event, I would not think kindly on the physician who prescribed the transfusion. Even without any harm being done, I would resent the needless exposure to potential risks. Is this reasonable accountability? I would also wonder about how the inappropriate order got through the transfusion system, which presumably has processes to monitor and prevent inappropriate transfusions (more on this later).

Is this playing a non-productive blame game? Should I just say, "What the heck. My doctors were doing what they thought best, even though they were ignorant of good transfusion practice." Is ignorance a valid excuse?

How to detect, identify, and prevent inappropriate transfusion
The first step in prevention is to detect problems and classify them. With transfusion-associated adverse events, this is accomplished by hemovigilance systems.
With inappropriate transfusions, identification is harder. Such transfusions may not result in immediate harm or may result in adverse events that are difficult to link directly to transfusion as a significant cause. As well, the harm may be impossible to identify except by large studies, which, even then, cannot prove causation definitively.

With inappropriate transfusions, the identification process is usually done by developing standards against which ordering behavior is measured, then auditing performance for compliance with defined best practices and standards.

All of this takes resources and expertise, both of which are increasingly scarce.

We are in the infancy stage but have developed several tools.

Clinical indications
One tool is to include clinical indications on the transfusion request form, along with relevant hematogic and related criteria. Some examples:
  • RBC: Hb less than 70g/L or Hct. less than 21%
  • Platelets: less than 20 x 109/L
  • Cryoprecipitate: Bleeding and fibrinogen less than 1.0 g/L
Presumably, the inclusion of such guidelines on the form gives clinicians the clue that these are accepted indications for transfusion of a particular product and that they should carefully consider transfusion if their patient's situation falls outside the guidelines, realizing that a patient's overall clinical condition is paramount in decisions to transfuse.

MSBOS
Another blood utilization tool is the maximum surgical blood order schedule (MSBOS), which has been around for more than 30 years. See this example.

Transfusion service as gatekeeper
Transfusion service clinical laboratory scientists/technologists are expected to act as gatekeepers when clinical indications and data are not completed on forms or seem inappropriate, or when orders exceed the MSBOS. This puts them in an awkward position, for physicians generally do not like their decisions questioned by anyone, especially by non-physicians. TM labs generally contact the medical director or designate and have them deal with clinicians on a peer-to-peer basis.

However, sometimes circumstances dictate direct contact with clinicians. Ask any experienced technologist or nurse who has ever questioned a physician's order, usually indirectly, in the most respectful, even subservient manner, what the experience is like. In many cases, the experience is not pleasant, and sometimes down-right abusive.

From my experience surveying technologists across Canada who work in transfusion service laboratories about what happens when clinicians order questionable or clearly inappropriate transfusions, there are several possibilities:
  • Nothing at all happens. The inappropriateness may go unnoticed, may be ignored because staff are too busy, or may be ignored because a culture of questioning a doctor's orders is not encouraged.
  • If the blood order is drastically inappropriate and would clearly cause immediate harm, the TS medical director is contacted, intervenes, and manages to protect patient safety.
  • If the blood order does not correspond to current best practices and is inappropriate according to the TS's criteria for clinical use of a particular product, the TS medical director may or may not intervene.
The bottom line is that, if the clinician persists, the technologist is often told,
  • "Just give the blood."
Presumably, this happens because ultimate responsibility for patient treatment, including transfusion, rests with the attending physician AND, as would be expected, TS staff do not like having a policing role.

Other tools
Many other strategies and tools exist to promote safe and effective blood utilization but are beyond the scope of this blog. They include hospital transfusion committees, targeted education by Transfusion Safety Officers, hospital grand rounds, educational conferences, wallet cards with reminders of transfusion guidelines, websites with transfusion guidelines, etc.

EDUCATION
Clinician education on appropriate blood use remains a significant challenge. An earlier blog a year ago focused on this topic:
The blog discusses a paper (Dzik S. Use of a computer-assisted system for blood utilization review. Transfusion 2007;47(s2): 142S) dealing with computerized physician order entry and computer-assisted blood utilization review and feedback.

In brief, the educational intervention in the paper is as follows:
  • A TM physician reviews daily reports of transfusion orders and clinicians who made questionable decisions to transfuse are targeted for education.
  • A non-judgmental e-mail is sent to the clinician within 24 hours of the decision to transfuse.The e-mail displays the pre- and post-transfusion lab data; provides the criteria for the review process; and links to an in-house educational site.
  • On the website, for each blood component the physiology of blood use is summarized and articles on the clinical use of blood are listed. Each article is linked to a summary of the paper's findings and to the published paper.
  • The e-mail invites the physician to reply if there are questions or concerns.
The author's innovative strategy uses a non-judgmental approach to educating physicians, which fits with the quality systems approach of being non-punitive and staying away from the blame game.

Other studies have shown varying degrees of effectiveness of educational interventions:
RESPONSIBILITY
What is the responsibility of the TS medical director in preventing inappropriate and potentially harmful transfusions? What is the responsibility of ordering physicians? What is the responsibility of lab technologists and nurses who may notice that a doctor's transfusion order seems questionable?

The fact is that we all have varying degrees of responsibility.

My experience is that transfusion services have dedicated professionals who fight the good fight and achieve steady nano-progress with educating clinicians who order transfusions. Most clinicians have little transfusion education in their undergraduate programs - sometimes it amounts to only a few hours. This leaves a huge gap for transfusion services AND the physician to bridge.

What happens to physicians personally when they order inappropriate transfusions? In the absence of immediate patient harm, apparently, not much. The current approach is to improve a clinician's transfusion practice through gentle face-saving educational interventions designed to motivate voluntary changes in behavior. Maybe this is all that can be expected.

But how much responsibility do clinicians share for being knowledgeable about a treatment they provide? Decisions about transfusing patients are difficult and often made under stressful conditions. That said, a hallmark of educated professionals is to know what they do not know, to actively pursue continuing education, and to seek help when needed.

If technologists and nurses were to consistently break accepted best practices, and such behavior put patients at risk, what would happen? Would they receive nothing but educational interventions? Perhaps. For how long would repeated deviations be tolerated? In some regards, technologists and nurses are in a different position, because best practices and guidelines are often documented in written SOPs used in the training of new staff and these SOPs must be followed.

Indeed, blood safety standards specify that blood transfusion training is mandatory for all staff involved in transfusion practice. But apparently such training is not mandatory for physicians who prescribe blood transfusion.

Are physicians treated differently because of their status in the health care system or are they treated the same as other professions? Other than offering multiple voluntary educational opportunities and providing gentle education after the fact for those who order inappropriate transfusions, what strategies and tactics can improve physician transfusion practices? These are questions to ponder.

Is the current situation - ongoing inappropriate transfusions for multiple blood components and products - the natural result of what happens when there are no consequences for inappropriate behavior? Transfusions have the ability to do much good and to save lives but carry risks.

BALANCE

Money
Today, blood utilization tends to focus on cost control of expensive plasma protein products such as albumin and IVIG. For example, in Canada for the year ending Mar. 31, 2008, IVIG was the largest single expense at $137.4 million, almost 16% of the total budget that neared $900 million.
See utilization management for some of the projects that have been done in this area.

Cost control is essential to sustain the entire blood system, but how can the focus on the most expensive products be better balanced with an overall utilization strategy? One idea is to use a variation of the original Pareto Principle (80-20 rule that 80% of the wealth was owned by 20% of the population) - namely, that 80% of consequences stem from 20% of the causes.

Should we try to prioritize? To identify the 10, 15, or 20% of the physicians or medical services that cause most (60, 70, or 80%?) of the inappropriate transfusions, regardless of cost, and target education at them?

Responsibility
We also need to balance the need for blame-free interventions with processes that better motivate clinicians to assume responsibility for becoming knowledgeable about transfusion practice. Assigning blame causes resentment and anger; it tends to drive people underground and undermine error prevention strategies.

However, should not blaming people equate with having no consequences, especially where patient safety is involved? This issue has been examined in
The author writes:
  • In my experience as both a regulator and safety exponent, systems issues usually accompany breaches of professional responsibility (weak regulations, reporting requirements, or inadequate training). It depends how you look and where.
  • A root cause analysis would nearly always identify systems problems and rarely individuals. Systems failures may also mitigate the level of responsibility for the individuals.
  • Where and how professional responsibility fits into the ‘‘no blame’’ culture is unclear. How can we make it clearer?
BOTTOM LINE
Whether immaculate, virginal, or something more "sinful," inappropriate transfusions remain an ongoing challenge around the globe.

One of the key issues is responsibility.

Take a peek at this rendition of Responsibility by the punk band MxPx. All docs ordering transfusions - Tx Rx? - should take note of their behavior, as in the MxPx lyrics:
  • Responsibility? What's that?
  • Responsibility? Not quite yet.
  • Responsibility? What's that?
  • I don't want to think about it; we'd be better off without it...
Comments are most welcome BUT, due to excessive spam,  please e-mail me personally or use the address in the newsletter notice. .

Posted by Blut at 8:35 PM 0 comments
Labels: , , , , ,
Subscribe to: Posts (Atom)