Nitric Oxide in transfused red cells

[Mabel Adams]

Since the Nitric Oxide issue has hit the lay press has anyone got a lead on a good resource for answering patient's and clinician's questions?

[jmatt]

I've just started my search and any help would be appreciated. Apparently, my PR department has been contacted for a press story and will be expecting a statement.

[heathervaught]

I found these quotes:

"This is an important observation and it needs to be followed up," said Dr. Louis Katz, a past president of America's Blood Centers, which provides about half the nation's blood.

"If you are going to store red cells, is there a way to make sure appropriate nitric oxide levels are maintained?" said Katz, who was not part of the research teams.

It is possible that these findings may make the public concerned about transfusions, Katz said: "There is no doubt, if you are bleeding to death from a trauma" you need a transfusion.

Stamler agreed that "physicians need to be able to give blood if people are bleeding profusely."

Overall, Katz said: "This is neat research. It needs to be proven that it's clinically relevant."

Stamler agreed on the need for clinical trials

The "Stamler" is Dr. Jonathan Stamler of Duke University, leader of one of the research groups.

I think (for what it's worth) that it is always safe to say to a patient or physician that Transfusion Medicine is a continuously evolving field, and we are always looking for ways to make blood transfusions safer and better. Just like we are always adding more infectious disease tests to our donated blood, scientists are also looking for other things that can be done to improve the safety, purity, and efficacy of transfused blood products. I would also add that transfusing blood in its current state is currently the safest thing that we can do until controled clinical trials on human subjects. There will always be risks, but as an industry we do everything that we can to mitigate and control those risks.

[Mabel Adams]

http://www.dukemednews.duke.edu/news/article.php?id=38

This link is from 2001 but has some good background info.

[Mabel Adams]

http://www.wtop.com/?nid=106&sid=1263417

Here is the source in the lay press in case you missed it.

There was also an article in Transfusion a few years ago on the function of Nitric Oxide, that stayed on my nightstand for 2 years hoping I would eventually understand it.

[bbbirder]

If I remember right, anesthesiologists are also very interested in nitric oxide effects. It is used to treat pulmonary hypertension. (?) I don't know if they add it routinely when doing surgery, or if inhaled NO can impact transfused RBCs.

[galvania]

Interesting thread! I'm only guessing, but I would imagine that many gases would disappear from stored blood quite quickly? But wouldn't the NO in the patient's own blood compensate for its lack in the stored product? After all, from a purely empirical standpoint, most of the blood transfusions that have been given in the past have worked, despite the lack of NO. Mabel - do you have the reference for the article in transfusion. I'd like to read it. thanks

[rcurrie]

I have been waiting for the other shoe to drop for years, just like Mabel. I suspect that a lot of research $$$ will now be redirected toward NO research. I always try to help physicians who request more info, but those who demand "this and that" research results are simply told that I am offering my product for their use as is, and it is up to them to decide how and when to use it. In other words, do your own research. That may sound cold, but the colder reality is that when a patient dies and blood transfusion is implicated, the physician will try to pass the buck by pointing to the blood bank. I have seen this happen, and been on the receiving end. It won't happen again. I don't refute any research. When one of our cardiovascular surgeons showed us some research that said that redo CABG patients needing transfusion were less likely to survive unless given fresh blood <7 days old, I didn't say "rubbish." I said that we can support one patient a week with a requirement to provide blood <7 days old. With that limitation, suddenly it wasn't the issue it was before. I have had physicians demand products we don't offer. My answer is we have what we have- this is our menu. Our blood cooks follow recipes from which they cannot deviate. Dallas is 150 miles up the road. I can certainly recommend a good blood restaurant up there if you absolutely have to have such-and-such. (The proper wine to serve with blood is a nice Merlot.)

I can see one direction this may go. In the future, we may issue a nitric acid popper with each unit of blood. "Okay, Mr. Jones, I am starting the transfusion now. If you feel any tightness in your chest, pop this ampule, wait 2 seconds, then inhale the white smoke deeply twice and hit your call button."

BC

[Mabel Adams]

John R. Pawloski, Jonathan S. Stamler (2002)

Nitric oxide in RBCs

Transfusion 42 (12), 1603–1609.

doi:10.1046/j.1537-2995.2002.00278.x

[heathervaught]

It seems to me that the lay press has sensationalized the risk of heart attack or stroke associated with blood transfusion. Does anyone know the actual rate? The http://www.time.com/time/health/article/0,8599,1669438,00.html?cnn=yes article on this just keeps referring to "many"...

i.e. "...for many of the five million patients who receive blood transfusions every year"

and "...many get sicker"

How many of the five million? 10? 1,000? 1,000,000? If you use my rule of thumb, a couple = 2; a few = 3-4; several = 5-7; many = 8 or more.

[galvania]

Thanks for the reference Mabel - I will read that one. I had another thought. Smoking is known to change the NO concentration in your blood..............

[sgoertzen]

I was forwarded this link this morning by one of our hematology specialty technologists asking me what I thought about all this. I'm not sure what to tell him.

http://www.medpagetoday.com/HematologyOncology/Hematology/tb2/6918

[rcurrie]

I would tell him that studies often lead to improvements in products, but clinical trials must come first, and when the trials prove that the proposed change is more beneficial than it is harmful, and the cost to benefit ratio is on the side of benefit, then we may see changes in the way we store blood. Until then, the menu is still the same.

BC

[Yanxia]

This is a interesting finding, I think it will open a new era of blood transfusion.

Before adding NO , we need know what is the proper quantity of NO in red cells, avoid dilate the vessel too much, result in haemorrhage or other bad case.

[Yanxia]

This few days I read some papers about Nitric Oxide ,I have a question about whether the acting Nitric Oxide is in red cells or in plasma. I think it maybe in red cells. It is such a pity that I can't get the original article about Nitric Oxide's function in blood transfusion, I don't know they test what part of NO. This kind of gas in body can produced by endothelium and other cells, and lots of factor can stimulate body to produce it, especially in trauma and infection so why the transfused cells can't absorb it in circulation if they can easily diffuse to cells in pre-transfusion charge?

[Mabel Adams]

Scientists discover a new chemical process conducted by hemoglobin.

Science Daily (11/6) reports that researchers have "discovered a previously undetected chemical process within the oxygen-carrying molecule hemoglobin," according to a study published in Nature Chemical Biology. Investigators discerned "how hemoglobin, through a catalytic reaction that does not change its own chemical properties, converts nitrite salt to the vasodilator nitric oxide." They also noted "how the nitric oxide activity harnessed by hemoglobin escapes the red blood cell to regulate blood flow and how the process...relies on the oxidized...form of hemoglobin, previously associated only with diseased states." Previously, researchers knew that "n the bloodstream, iron-rich hemoglobin consumes, on contact, any free nitric oxide released by the blood vessels, so the idea that hemoglobin participates in forming nitric oxide had seemed implausible."

There is quite a lot of information on Hemoglobin research to be found at the Science Daily site. http://www.sciencedaily.com/releases/2007/11/071105091931.htm

[labgirl153]

It's been >3 years since Stamler's 2007 paper on nitric oxide (and youtube video). He's no longer at Duke (transferred to Ohio I believe). Since then, have been digging through to find out how far along in the research the trials are, and if one day we'll be popping units with NO capsules just prior to transfusion. Anyone here of late read more on this subject?

[Mary**]

Where is "isle of misfits"???

[goodchild]

off the top of my head i seem to recall that the isle of misfits is the place where all the unwanted toys go, in the claymation christmas classic with the santa's helper elf who wanted to be a dentist.

[Mabel Adams]

Rudolph the Red Nosed Reindeer. Is claymation really that old? Wow.

[ybunch]

PBS ran a nice clip--www.pbs.org under What You Need to Know show--Transfusions. On going studies are in progress. Perhaps, they will help the transfusion industry to learn a better way to preserve cells. Also, The Bleeding Edge has information. "An airline accident is almost always the end result of a causal chain of events. If any one link was different the outcome may have been different Almost no accident was the result of just one ."•

ØCapt. Chesley “Sully†Sullenberger

in “Highest Dutyâ€

Nitric Oxide is just one link. We must learn from the aviation industry. And, just as we don't stop flying when a problem comes up, as the consumer, we want there to be an investigation. There are certain instances that blood transfusion may be medically indicated such as in an active bleed. Yet, at the same time we need to promote blood conservation that starts at the beginning of pre-operative planning.

[Mabel Adams]

That reminds me of this quote from Transfusion on Blood Bank errors:

“Some years ago, we at the Edinburgh & S. E. Scotland Blood Transfusion Service did a forensically detailed analysis of documents and interviewed staff members who had been involved in or witnessed incidents in which patients were given red cells that were intended for a different patient. In most cases, it emerged that there had been a sequence of errors or failures to perform a required procedure step, and it seemed that each error prepared the ground in some way for the next. Where errors had occurred up the line, the unit of blood reaching the patient’s bedside became an accident waiting to happen. In an early survey of blood banks in the United Kingdom (UK), respondents often reported on such a contribution of sequential errors to the error that finally lead (sic) to detection.” Treating a Sick Process, Transfusion, Vol 38, Nov/Dec 1998

[ybunch]

Stale blood linked to dangerous infections

Alison Branley

November 24, 2010

• 
  

AUSTRALIAN patients may be at risk of developing blood infections as a result of being given transfusions of stale blood, scientists have found.

The research is expected to have a major impact on the way blood donations are handled.

Researchers have recommended an immediate ban on all blood products older than 35 days to the NSW chief health officer, Kerry Chant, after a 10-year Hunter New England Health study of more than 20,000 blood transfusions.

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The study, the largest of its kind in the world, found patients who receive blood more than 14 days old are up to four times more likely to develop potentially lethal blood poisoning.

Dr Chant is expected to take the issue to the National Blood Authority.

Under world health guidelines, blood donations can be stored for up to 42 days.

Hunter New England Health has instituted an embargo on blood older than 35 days and is trying to reduce this to 28 days.

Researchers emphasised the findings should not be a reason for people to stop donating blood but, rather, an encouragement to do so more regularly.

The older blood is not infected but because it starts to break down over time, older blood weakens the immune system and makes patients more vulnerable to hospital infections.

The lead author, Stephen O'Mara, said patients should not refuse blood transfusions but should question the age of the blood age and whether the procedure is necessary.

''Fresh blood less than 14 days of age is completely safe.''

Dr O'Mara said the use of old blood was a bigger safety issue than HIV-AIDS or ''mad cow'' disease. The findings meant surgeons would need to be more frugal with transfusions.

In the 1990s a new preservative increased the storage age of blood to 42 days but it is only in the last three years researchers have questioned its use.

''There were no safety data published to determine if this older blood was safe,'' Dr O'Mara said.

''If this was a new drug it would never have been 'registered' to be given to humans.''

Blood poisoning is treatable but one in five affected patients die - about half from the blood poisoning and others from associated illnesses. Nationally, it is estimated there are 12,000 hospital-acquired septicaemia (blood poisoning) cases each year and up to 400 deaths.

The study mainly involved patients receiving blood after general surgery, kidney disease, obstetrics and other medical admissions.

[carolyn swickard]

It will be very intereseting to see the results in Australia after an article like the previous one. I have also wondered where we were going with NO. It was made to seem like such an "easy fix" in the early articles, but no one had any suggestions or procedures for the "fix", nor was there any discussion (for the US) of how the FDA would react to adding anything to a blood unit. Not so "easy" after all, but it still sounds like it will be something to watch for progress on. Meanwhile - we will just have to do the best we can on blood inventory management and make sure the oldest units are used first and not left to get "stale" (why ever did they decide to use that word!!).