Bad blood

Blood transfusions may induce infections and harm the recipient's body.

INCE it was first introduced into hospitals during the World War 11, blood transfusion has been popular among surgeons as a way of helping patients recover more quickly by replacing the blood they might lose during an operation. Although initially developed for emergency situations where patients suffer massive blood loss from traumatic injuries, events and accidents,surgeons soon began using donated blood in routine surgery.

But it seems that in many non-life-threat-ening cases, this blood could be doing unnecessary harm to patients, and some surgeons are increasingly reluctant to give transfusions except in emergencies. It appears that blood transfusions are linked to higher death rates and post-operative illness in patients than those who do not receive donated blood.

The cause of these problems is not the much-publicised risk of blood-borne infections that may be missed in screening, or
even the use of the wrong blood type. In fact, the latest evidence suggests that chemical changes in donated blood harm the recipient's body, increasing the risk of heart attacks, strokes and organ damage. Many surgeons are now opting to carry out routine surgery without blood transfusions.

"There has never been a clinical trial on whether blood transfusions during surgery are actually beneficial," said Dr Gavin Murphy, a consultant cardiac surgeon at Bristol Royal Infirmary and a researcher at Bristol University. "We need to look at whether with holding blood transfusion or giving low levels of blood transfusion is any better or worse for patients than giving high levels of blood transfusion. Most studies show an association between blood transfusion and adverse outcomes in patients, but we still don't understand the cause."

In a study of 8,500 cardiac patients over eight years, Murphy and his colleagues found a three-fold increase in the risk of dying in the year following surgery among patients who had received a transfusion. Patients also suffered an increased risk of complications after their operation, mainly associated with a lack of oxygen to key organs. The results,which are supported by other international studies, are at odds with the widely held beIief that transfusions of red blood cells can help aid patients' recovery by carrying oxygen to their tissues.

Since these concerns were first raised, Murphy and his colleagues have halved the number of their own cardiac surgery patients who receive blood transfusions, without any adverse reactions. They now hope to identify exactly wiry blood
transfusions may be having this harmful effect.

Their latest research, which is still to be published, provides some dues. They found that patients who have received blood transfusions during cardiac surgery also suffered increased levels of inflammation through out their bodies.

Murphy believes that problems develop when donated blood is stored for transfusion and there is build-up of toxic biological chemicals mleased as red blood cells age and disintegrate. Under normal circumstances in the body, the byproducts of red blood cell death are processed or excreted,But in stored blood, they accumulate and may trigger an inflammatory reaction in the patient's body when they are transfused.

Murphy said: "When red blood cells break down, they release phospholipids. These are really nasty molecules that are almost
identical to the inflammatory molecules that are released by the body during infection and trauma."

Haemoglobin, the large, iron containing molecule that binds oxygen in red blood ceils, also accumulates in the stored blood. Usually this is packaged safely inside the blood cells but, once free in the blood stream, it can be toxic to the kidney and affect circulation in small blood vessels.

These findings, combined with the risks posed by blood-borne infections and the shortage of blood donors, have given scien-
tists a new impetus in the quest to find an artificial alternative to donated blood.

Artificial blood
For decades, they have worked on blood substitutes but have been unsuccessful due to the toxicity of many of the resulting products. Only one country - South Africa, where high levels of HIV make blood transfusions high-risk - has so far licensed an artificial blood product for use in emergency situations. But now a new generation of artificial blood products is on the horizon that scientists hope will overcome the toxic effect.

Most previous blood substitutes have attempted to harness the ability of haemoglobin to carry oxygen around the body,
but, as described above, without the protective shell of a red blood cell, the haemoglobin molecules can roam freely through the body and damage tissue. Researchers at Essex University, however, have discovered one of the underlying reasons why free
haemoglobin is so harmful without the protection of a red prevent this process.

Prof Chris Cooper, who is leading the research, said: '~fhe challenge is to make artificial molecules as good as red blood ceils at carrying and releasing oxygen while avoiding the harmful effects. We think that by modifying the part of the haemoglobin that facilitates this rusting process, it will be possible to reduce the free radical production.

Having effective artificial blood substitutes could help overcome the difficulties we face with maintaining the supply of blood donations, ensuring blood is clean and also avoid the harm that is associated with biological transfusions."

Cooper and his team have now applied for two patents for their approach to manipulate haemoglobin.

Stem cells
Other scientists are attempting a more ambitious approach by using stem cells - a basic cell which has the potential to develop into any other cell type in an organism - to grow replacement blood for patients, Scientists at Edinburgh University have managed to harness blood stem cells from mice so that they multiply 150 times. They hope their findings will lead to transplantable blood stem cells that could multiply within the body and help renew patients' own blood supply.

Dr Lesley Forrester, a reader in stem cell biology at Edinburgh University who has been involved in the research, said: "Ultimately we want to be able to grow blood stem cells from embryonic stem cells so they can be used as a treatment for patients. Other groups in the United States have shown that it is possible to grow red blood cells in the laboratory
from embryonic stem cells, hut we still need to find out how these ceils will behave in the body."

A spokesman for NHS Blood and Transplant said that they were aware of concerns around the use of blood transfusions in
routine surgery, but added: "The current evidence is not sufficient to change policies and better clinical studies are required to answer this question,"

For surgeons, the artificial products are still too far in the future to help their current patients, Murphy believes that
simply using surgical techniques that reduce blood loss could help patients in many routine cases, This would also mean that more donated blood would be available for emergency cases where trans fusions can zenuinelv heln to