BBI Contributing Writer

SAN DIEGO, California Blood donations are decreasing. Demand for blood transfusions is increasing. The public worries about contaminated blood. Processing of blood components, in turn, becomes more complex. Blood is currently tested for HIV and hepatitis viruses, but not for common pathogens. According to the National Blood Data Resource Center (Bethesda, Maryland), nearly 29 million units of blood components were transfused last year. Each of these is at risk for bacterial contamination. Now the American Association of Blood Banks (AABB; also Bethesda), the professional association of the blood banking and transfusion medicine community, is calling for testing for pathogens, with a new standard to be implemented by March 1. The issue was a dominant topic of discussion during the AABB's annual meeting here in November.

After reviewing various methods to reduce the risk of infectious disease transmission, Harvey Klein, MD, of the department of transfusion medicine at the National Institutes of Health (NIH; also Bethesda), compared the step-wise advances in pathogen reduction technologies matched by advances in donor testing. Despite these efforts, blood is not screened for many agents known to be transmitted by transfusion. Considering proposed efforts for pathogen reduction in transfused components, Klein cited the risks: "These techniques will not eliminate infection transmission. They will require more donations/transfusions. They may decrease component shelf life and may have unsuspected toxicity." On the benefit side: "Such efforts are proactive. They add a layer of safety. They will reduce future infections and will reduce future testing." Klein noted that a "tolerable" risk-benefit profile for any pathogen reduction technology should offer "a broad inactivation spectrum, minimal damage to cells, little potential for toxicity and a fail-safe manufacturing system."

Bacterial contamination of blood has long been a concern, but processes to actually test for pathogens are quite new. Development of new technologies has in part been driven by the U.S. Department of Health and Human Services (HHS). In February of last year, the Blood Safety and Availability Committee of HHS issued a recommendation for "expedited implementation of available measures to reduce the risk of bacterial contamination in platelets." Echoes were heard from both AABB and the College of American Pathologists (Northfield, Illinois).

Platelets are a blood component required for clotting. They are most often given to immunocompromised patients as a life-saving treatment for cancer, leukemia and other blood disorders. Some 2.1 million platelets are transfused each year in the U.S. Platelets are the blood component most vulnerable to bacterial contamination because they must be stored at room temperature facilitating bacterial growth. The bacterial contamination rate is estimated at anywhere from one in 2,000 to one in 3,000, and the prevalence of severe episodes of transfusion-associated sepsis is probably on the order of 1:50,000 platelet transfusions.

During the Transfusion Exposition at the AABB meeting a number of manufacturers addressed pathogen reduction. The BBI Newletter also visited some of the vendors offering blood bank managers options to cope with increasing blood demand and decreasing blood supply.

The risk of receiving a platelet concentrate contaminated with bacteria may be 1000-fold greater than that of pathogenic viral transmission, yet surveillance for this risk is not generally practiced. Recent reports to the Centers for Disease Control and Prevention (CDC; Atlanta, Georgia) suggest that platelet-related bacteremia occurs at a frequency approximately 50 times greater than that for red blood cells (RBCs). Mortality in those bacteremic patients approaches 25%. Pall (East Hills, New York) highlighted its Bacteria Detection System (BDS) as an answer to pathogen reduction.

"The Pall BDS gives us a unique and cost-effective way to address the long-standing problem of bacterial contamination of platelets. With this new system, we will be able to test apheresis platelet samples and detect bacterial contamination right in our blood center, thus ensuring a safer product for patients," said Dan Waxman, MD, executive vice president and chief medical director of the Indiana Blood Center (Indianapolis, Indiana), where the BDS has recently been adopted.

"Since our center operates in a decentralized manner with multiple processing and distribution sites, the Pall BDS enables us to test platelets for bacterial contamination in our operating environment," said Nora Hirschler, MD, president and chief executive officer of Blood Centers of the Pacific (San Francisco, California). "We'll have the results before the platelets are shipped, thus improving the safety of transfusions."

Studies have shown that Pall's Bacteria Detection System detects the strains of bacteria reported to cause more than 98% of the fatalities resulting from the transfusion of contaminated platelets. The system accurately detects both gram-positive and gram-negative bacteria. According to Pall, the system can be easily incorporated into the blood banking process with minimal cost, time and training of technicians.

Another option for pathogen detection, the Verax Platelet PBD Test from Verax Biomedical (Worcester, Massachusetts), is currently in development and not yet cleared for marketing by the FDA. The product is designed to be rapid (less than 20 minutes to result), simple (just add platelet sample), sensitive and specific and it requires a small sample volume of 300 mL.

The test consists of a small disposable plastic cartridge incorporating dry reagents that can be stored at room temperature until used. A platelet sample is applied to the sample well on the test cartridge. In less than 20 minutes a red colored bar will appear in one of the two reading windows on the cartridge if either gram-positive or gram-negative bacteria are detected in the sample. Negative samples show no color bar in the read windows. The test is designed to be completely self-contained.

Enhanced automation of blood handling is available from Chiron (Emeryville, California). Chiron's partner, Gen-Probe (San Diego, California), has developed the Procleix Tigris System a one-step testing solution based on nucleic acid testing (NAT). Nucleic acid amplification technology is the method of choice for identification of a large and still growing number of microorganisms. The promise of molecular diagnostics lies in the improvement of its specimen-processing, amplification and target-detection steps and in the integration of these steps into an automated process.

The Procleix Assay family combines the early detection capabilities of NAT with the high-throughput advantages of transcription-mediated amplification (TMS) technology. By performing every step in the same tube, Procelix assays are revolutionizing the entire blood screening process. Procelix assays deliver significant benefits. The single-tube technology minimizes sample handling and reduces the risk of contamination. A unique target capture process requires no sample preparation, extraction or ultra-centrifugation. Isothermal amplification technology eliminates thermal cycling, probes and primers targeting conserved regions of a viral genomic sequence to maximize detection of known variants and genotypes.

Proceleix assays currently available or in development include those for HIV-1/HCV (human immunodeficiency virus/hepatitis C virus), WNV (West Nile virus) and the Ultrio Assay for simultaneous, single-tube NAT for HIV-1, HCV and HBV (hepatitis B virus).

Automated blood collection is Gambro BCT's (Lake- wood, Colorado) suggestion to blood bank managers faced with shortages, shrinking donor pools and increasingly demanding quality assurance standards. The Trima automated blood collection system is a transportable, automated system that separates whole blood into its major components red blood cells, platelets and plasma. The Trima system's flexibility allows collection of one or all of these components leukoreduced in any combination, on a single platform, in a single procedure, from a single donor. And, regardless of the collection protocol, Trima returns unneeded components to the donor, enabling more frequent donation.

Through Gambro BCT's patented LRS technology, the unique design of Trima's separation channel and an integrated red blood cell leukoreduction filter, platelets, plasma and red blood cells are leukoreduced at the collection site, minimizing additional processing steps. The unit is compact and easy to transport, making it well suited for mobile drives and other off-site operations.

Optimizing blood collection is a major goal for all blood banks. The ALYX Component Collection System from Baxter Healthcare (Deerfield, Illinois) is an evolution in automation technology that could transform the landscape of component collection. The company states the ALYX System will help the blood center realize more value from each donation, discover a more efficient process, reach a higher level of consistency and create a comfortable environment for donors.

Using the ALYX, the value of each blood donation is multiplied. Without enlarging the donor pool, the blood bank manager can increase the red cell supply, allowing more effective management of both inventory and costs. The ALYX System collects two red cell units from a single donor. This maximizes donation from the existing donor pool and captures more value from the infrequent donor. The system can increase the total supply of red cells and may also assist the blood center in selectively increasing the availability of certain types of red cells.

From the donor's view, ALYX needs an average of only 22 minutes of collection time for 360 ml of absolute red cells. The system includes multiple safety features to monitor and protect donors at all times during collection. These include a donor safety clamp that isolates the donor in case of alarm, power loss or stop button activation. Clinical trials report high donor acceptance and comfort levels using the ALYX when compared to traditional manual processes.

Two other companies Cerus (Concord, California) in partnership with Baxter, and V.I. Technologies (Vitex; Watertown, Massachusetts) also have been pursuing pathogen inactivation efforts in recent years. But each has encountered rough sledding in both the clinical and financial areas of late and neither was among AABB exhibitors.