Transfusing Older Blood

Transfusion of red blood cells after prolonged storage produces
harmful effects that are mediated by iron and inflammation.
Blood. 2010 Mar 18.
Hod EA, Zhang N, Sokol SA, Wojczyk BS, Francis RO, Ansaldi D,
Francis KP, Della-Latta P, Whittier S, Sheth S, Hendrickson JE,
Zimring JC, Brittenham GM, Spitalnik SL.
Department of Pathology and Cell Biology, Columbia University College
of Physicians and Surgeons, New York, NY, United States;


Although red blood cell (RBC) transfusions can be lifesaving, they
are not without risk.
In critically ill patients, RBC transfusions are associated with
increased morbidity and mortality, which may increase with prolonged
RBC storage before transfusion.
The mechanisms responsible remain unknown.
We hypothesized that acute clearance of a subset of damaged, stored
RBCs delivers large amounts of iron to the monocyte/macrophage
system,
inducing inflammation.
To test this in a well-controlled setting, we used a murine RBC
storage
and transfusion model to show that the transfusion of stored RBCs, or
washed stored RBCs, increases plasma non-transferrin bound iron
(NTBI),
produces acute tissue iron deposition, and initiates inflammation.
In contrast, the transfusion of fresh RBCs, or the infusion of stored
RBC-derived supernatant, ghosts, or stroma-free lysate, does not
produce
these effects.
Furthermore, the insult induced by stored RBC transfusions synergizes
with sub-clinical endotoxinemia producing clinically overt signs and
symptoms.
The increased plasma NTBI also enhances bacterial growth in vitro.
Taken together, these results suggest that, in a mouse model, the
cellular
component of leukoreduced, stored RBC units contributes to the
harmful
effects of RBC transfusion that occur after prolonged storage.
Nonetheless, these findings must be confirmed by prospective human
studies.


PMID: 20299509
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I have been trying to explain THAT for a number of years.
Their hypothesis is nothing new to me.
This "hemolysis in blood donor bags" we discussed and one guy with a bit of experience ventured .. "add arginine to offset the hemolysis".
With a bit of research it added up and look at the study below.
One might wonder WHETHER adding arginine to the blood bag MIGHT make a big difference ?
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Arginine Butyrate Heals Sickle Cell Leg Ulcers

Jane Salodof MacNeil

Dec. 10, 2002 (Philadelphia) — Researchers working with an
experimental drug for sickle cell anemia noticed an unexpected side
effect: the incidental healing of debilitating leg ulcers in seven
patients.

That serendipitous observation led to a 25-patient phase II study in
which treatment with the compound, arginine butyrate, healed 17 of 37
leg ulcers. In contrast, among 24 ulcers that received standard local
care for wounds, complete healing was documented for one ulcer.

Several of the participants had suffered with large open sores for
decades, according to investigator Susan Perrine, MD, of Boston
University School of Medicine in Massachusetts. One woman had leg
ulcers for 30 years, Dr. Perrine reported in a presentation here at
the American Society of Hematology annual meeting.

The investigator showed dramatic before and after photographs of legs
from several patients who benefited from the treatment. The mean
initial area of ulcers in the arginine butyrate arm of the study was
50.8 cm2 — nearly twice the 26.4 cm2 in the control group.

Within three months of treatment, the area had been reduced by 53% in
patients who received arginine butyrate, but the area was reduced by
9% in the control arm. Dr. Perrine said the researchers don't know why
the compound heals these ulcers.

H. Grant Prentice, MD, of the London Clinic in the U.K., called the
study "extremely important." The former head of hematology at the
Royal Free Hospital in London, Dr. Prentice said the most common
therapy for leg ulcers associated with sickle cell disease is
hydroxyurea. "It's not very effective, and the patients don't like to
take it," he told Medscape.

About 25% of sickle cell patients suffer from leg ulcers, according to
an earlier study of 2,000 patients that Dr. Perrine cited at the start
of her talk. In the United States, she said, the typical sickle cell
ulcer lasts as long as three years; in the Caribbean more than nine
years is common. Even if they are cured, between a quarter and a half
of these ulcers will recur.

Despite their prevalence, the ulcers are not well known, even in the
sickle cell community, according to Dr. Perrine. They tend to occur in
adults, she said, explaining she had little experience with them
because she works in pediatrics.

Patients in the treatment arm of the trial received 500 mg/kg of
arginine butyrate six hours a day three days a week for twelve weeks.
Although hydroxyurea is used, she said there is no standard regimen
for these sores. The control group was treated aggressively according
to local standards for wound healing, but no particular protocol was
used in the six-center study.

Although the study ended after three months, patients were allowed to
continue for 16 weeks if their ulcers were closing with arginine
butryate. Within five to seven months, a 10-fold increase in wound
healing was reported.

Dr. Perrine said the investigators plan to seek funds for a phase III
trial. The pilot study was conducted with support from the U.S. Food
and Drug Administration's orphan drug program, she said. Arginine
butryate is an experimental compound and is not yet commercially
available.

ASH 44th Annual Meeting: Abstract 26. Presented Dec. 8, 2002.

Reviewed by Gary D. Vogin, MD

Jane Salodof MacNeil is a freelance writer for Medscape.
Conference Coverage
44th Annual Meeting of the American Society of Hematology

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This is interesting and fits with a previous discussion about adding nitric oxide to blood, so that it has more value when transfused.

http://www.thalassemiapatientsandfriends.com/index.php?topic=1261.msg10011#msg10011

Nitric oxide is necessary for blood vessels to open, and stored blood rapidly loses the NO content. Arginine is a key to NO production. It seems blood transfusion could be much more efficient with some attention to these facts.