Leukocyte Reduced Blood Products

As more studies on leukocyte reduction are conducted, the Red Cross is moving toward universal leukocyte reduction as evidence mounts that leukocyte reduction is a prudent choice for quality patient care.

Why universal leukocyte reduction?

The benefits of leukocyte reduction include reduced incidence of adverse reactions to blood transfusions. Such reactions can be mild, such as fever ("febrile" reactions) or chills ("rigors"). However, leukocytes in reduced blood have been associated with more serious problems, such as the increased risk of transmission of certain viruses, including cytomegalovirus (CMV) and human T-cell lymphotropic virus (HTLV-I/II) and reactivation of latent CMV. Additionally, the formation of HLA antibodies may occur upon exposure to leukocytes, and these antibodies may make future transfusions less likely to be effective and more likely to cause a reaction. Therefore, removing leukocytes from donated blood may decrease the risk of both transfusion reactions and infections. During September 1998, the United States Food & Drug Administration (FDA) Blood Products Advisory Committee (BPAC) unanimously agreed that the "benefit-to-risk ratio associated with leukoreduction is sufficiently great to justify requiring universal leukoreduction of all non-leukocyte cellular transfusion blood components." The committee did not suggest a particular timeline or mechanism for implementing universal leukocyte reduction.

Why Prestorage Leukocyte Reduction?

There are several methods for removing leukocytes from blood, the most common of which is filtration. Additionally, there are different options for when leukocyte reduction can be performed. Blood can undergo leukocyte reduction at the bedside at the time of transfusion ("poststorage bedside filtration"), in the hospital blood bank during component preparation ("poststorage laboratory filtration"), or as part of the manufacturing process ("prestorage leukocyte reduction").

Studies show that blood products that have undergone prestorage leukocyte reduction are more effective at preventing leukocyte-related transfusion reactions than blood products that have undergone poststorage filtration either at the bedside or in the laboratory. For this reason, Red Cross is transitioning its cellular blood products toward eventual conversion to universal prestorage leukocyte reduction.

By decreasing the risk of some transfusion-transmitted viruses and health problems from future transfusions, universal leukocyte reduction may improve patient outcomes that result in shorter hospital stays and thus reduce overall health care costs.

Do adverse reactions occur frequently?

Febrile reactions, the most common adverse transfusion reactions, occur with approximately one percent of red blood cell transfusion and up to 30 percent of platelet transfusions.

How does leukocyte reduction reduce the risk of CMV and HTLV-I/II?

CMV and HTLV-I/II are viruses that remain within white blood cells for long periods of time. Removing leukocytes may remove the virus, which may reduce the risk of transmission.

CMV is common. More than 50 percent of the population in North America has evidence of past or present CMV infection—and it usually has no effect on transfusion recipients. However, in newborns or patients with weakened immune systems, CMV can cause pneumonia and other complications, which in rare cases can be fatal.

HTLV-I and HTLV-II may cause blood or neurological diseases. Both viruses are rare in the United States. Very few people have contracted HTLV from transfusions because of the relatively small transfusion risk and the implementation of tests to detect HTLV antibodies. HTLV-I is most prevalent in southwestern Japan and the Caribbean.

How does the leukocyte reduction process work?

The most common method of leukocyte reduction is filtration, when a filter separates leukocytes from other blood components, based on their size and stickiness.

This filtration may occur shortly after blood is collected at the blood center, known as prestorage leukocyte reduction; at the hospital after the blood has been delivered, known as in-lab post-storage leukocyte reduction; or at the patient’s bedside, known as bedside leukocyte reduction.

Prestorage leukocyte reduction is performed using standardized, quality controlled processing methods that help to ensure a consistent level of leukocyte reduction.

Other than removing leukocytes, does filtration have any effect on blood components?

The clinical effectiveness of blood components is not impaired by filtration. The removal of leukocytes early in the storage period may actually improve the quality of transfused cells.

How long has leukocyte reduction technology been around? Why is the Red Cross just implementing it now?

Blood centers and hospitals in the United States have been removing white blood cells from blood for more than a decade. Leukocyte-reduced blood is often used for newborns, patients with weakened immune systems, and patients who require long-term, intensive transfusion support. Much of the leukocyte removal was performed by filtration at the time of transfusion.

Red Cross blood centers have maintained an inventory of leukocyte-reduced blood components to meet the limited demand from hospitals who preferred to purchase, rather than prepare, leukocyte reduced components.

In part because of the increasing evidence of the benefits of transfusing leukocyte reduced blood components, the FDA BPAC unanimously agreed that the benefit-to-risk ratio associated with leukoreduction justifies requiring the universal leukoreduction of cellular transfusion blood components.

Safe blood products are the top priority of the Red Cross. Studies on prestorage leukocyte reduction demonstrate the benefits of prestorage leukocyte reduction to quality patient care.

How will universal leukocyte reduction improve the health of patients who receive transfusions?

Studies have shown that patients receiving leukocyte reduced blood have fewer acute transfusion reactions. Transfusing leukocyte reduced blood may decrease the risk of transfusion-transmitted CMV and may reduce the reactivation of latent CMV. Leukocyte reduction also lessens the formation of antibodies from transfusion, a natural process that often results in problems with future transfusions.

Another potential indirect benefit of transfusing patients with leukocyte-reduced blood is shorter hospital stays because patients may not experience adverse reactions or develop transfusion-related infections that require additional medical attention.

Are there any risks associated with leukocyte reduced blood?

There are two rare transfusion reactions that may be linked to the process of leukocyte reduction. In some patients, particularly those taking angiotensin converting enzyme (ACE) inhibitors, leukocyte removal by bedside filtration has been associated with hypotension in the recipient. In the late 1990s, cases of acute conjunctivitis ("red eye syndrome") occurred in patients receiving red cells that had been leukocyte reduced using one specific filter that is no longer on the market.

Some investigators are concerned that leukocyte removal which occurs very soon after the blood is donated may interfere with the clearance of any bacteria that may have entered the collection bag. While the results of laboratory studies show variable results, there is no evidence that leukocyte reduced transfusions may have any higher risk of septic transfusion reactions than with unmodified transfusions.

Are other countries implementing universal leukocyte reduction or is the United States the first to implement this process?

Several European countries, including Austria, France, Great Britain, Ireland, Norway and Portugal are already implementing universal leukocyte reduction of their blood supplies, and Canada has committed to leukocyte reduction as well.

Are all Red Cross blood centers moving ahead at the same pace? If not, does that mean that the blood in one area of the country is "safer" than in another?

All Red Cross blood centers will be converted to universal leukocyte reduction by the end of the year 2000. In the meantime, hospitals may order prestorage leukocyte reduced components from their Red Cross Blood Services Region, or perform leukocyte reduction at the bedside or in the hospital blood bank.

The United States blood supply is safer than it has ever been. The Red Cross continually looks for ways to improve the safety of the blood supply. The Red Cross is proactively moving forward with universal leukocyte reduction because it believes this process may add to the safety of the blood supply.

Does universal leukocyte reduction mean blood will cost more? How do hospitals benefit from this added cost?

Most improvements in the safety of the nation’s blood supply result in additional costs. Hospitals will no longer incur the costs of materials, filters, a quality control program and operator training for their own leukocyte reduction programs, as all cellular components will be leukocyte reduced before being placed into hospital inventory.

Significant indirect benefits such as shorter hospital stays and better patient outcomes may also contribute to cost savings for the hospital and the patient.

Plas+SD

American Red Cross Biomedical Services has introduced a new product, Plas+SD (Pooled Plasma, Solvent Detergent treated) which is an ABO bloodgroup specific, pooled human plasma preparation, that is an alternative to fresh frozen plasma (FFP). Plas+SD has been treated with a solvent/ detergent (SD) process to virtually eliminate the risk of transmitting lipid-enveloped viruses such as the ones that cause AIDS (HIV), hepatitis B (HBV) and hepatitis C (HCV). The SD process has been utilized in the manufacture of Factor VIII, IVIG and pooled plasma for more than a decade worldwide. Non-enveloped viruses are not affected by the SD process.

In many ways, PLAS+SD is similar to the FFP you are currently using. PLAS+SD looks the same, has the same coagulation factors (minus the largest von Willebrand Factor multimers) and has the same ABO blood-group specific labeling as FFP. Indications for use and adverse reactions are similar to FFP. PLAS+SD, however, has these added benefits:

• the product has been solvent/ detergent treated to destroy lipid-enveloped viruses
• the amount of coagulation factors in each unit is consistent
• all PLAS+SD units are standardized to 200mL unit volumes
• each unit is leukocyte reduced

SD-treated plasma has been used successfully in Europe. SD-treated plasma has been licensed in Germany since 1991, and a product manufactured by the same methodology is in routine use in Austria, Germany, France, and the Netherlands. SD-treated plasma has completely replaced FFP in Norway and Belgium.