Vol. 13 •Issue 20 • Page 8
Transitioning Transfusion Medicine
By Daniella King
Blood banking has always been a special branch of the laboratory industry because of the complexity of its technology, the competency demanded of transfusion medicine specialists and the ever-changing way technology has influenced the field. Ironically, today’s blood banking industry finds itself in the middle of a complex world of advancing procedures and technologies that can be viewed as both helpful and harmful. As these trends continue to advance, experts offer mixed opinions on how the blood banking industry will change and how it will stay the same in the years ahead.
Changes in the Field
Though automation and computerization in the blood bank were lagging behind the rest of the laboratory field in the past, new infectious disease testing as well as state-of-the-art leukocyte reduction filtration technology have brought the industry up to speed, illustrated by several breakthroughs over the past few years. At a time when emerging infectious agents such as new variant Creutzfeldt-Jakob Disease (nvCJD) are threatening every day, these new advances have arrived just in time.
Perhaps the biggest advance to hit the blood banking field was the announcement of nucleic acid amplification testing (NAT) in the spring of 1999. The major benefit of this technology is that the interval when donors transmit human immunodeficiency virus (HIV) or hepatitis C virus (HCV) but lack anti-HIV or anti-HCV antibodies is shortened. Based on reports involving more than 5 million donations screened by NAT, one per 250,000 donors was found anti-HCV negative/HCV NAT positive. In November 1999, only one donor out of more than 5 million was HIV antibody negative/HIV NAT positive.1, 2
“NAT has proven to be more effective in improving the safety of transfusion therapy than any other known technology,” said Jay E. Menitove, MD, executive director and medical director of the Community Blood Center of Greater Kansas City, MO. “This test is a natural progression in closing the window of residual risk between when a donor would be positive with antibody testing, compared to when there is the first evidence of viral particles circulating in the blood. NAT is also a natural progression of advanced technologies in terms of identifying and characterizing viruses. The weakness of NAT is expense and the limited number of labs that do this testing. My sense, though, is overtime it will be cost effective.”
While NAT testing can detect known viruses such as HIV and HCV, it does not prevent transmission of emerging or newly discovered pathogens, nor does it eliminate transfusion-associated bacterial infections. According to Dr. Menitove, scientists are trying to combat this through intense efforts to develop techniques that destroy viral and bacterial pathogens.
“Right now, the safety of the blood supply depends on asking donors questions about their medical history and lifestyle and testng their blood,” noted Laurence Corash, MD, vice-president of Medical Affairs, Cerus Corp., Concord, CA. “Testing has undoubtedly improved the safety of our blood supply, but it is a reactive strategy and may take years to implement new tests as viruses are identified. Pathogen inactivation is a prospective strategy.”
Pathogen inactivation strategies seek to eliminate known and unknown pathogens such as viruses, bacteria and parasites, from blood products for transfusion. One strategy that has been in use is solvent-detergent (SD) treated plasma.
“SD plasma eliminates risk of transmission of all lipid-enveloped viruses,” explained Dr. Menitove. “Hepatitis A virus (HAV) and human parvovirus B19 are non-lipid enveloped and may still exist in SD plasma. The pooling nature of SD plasma leaves it more vulnerable than the single-unit nature of pathogen inactivation testing.”
One company making strides in the pathogen inactivation arena is Gambro BCT, based in Lakewood, CO. Gambro’s unique Pathogen Eradication Technology (PET) program uses Riboflavin, or vitamin B2, and visible light to inactivate pathogens in blood components.
“The trick with any bloodborne pathogen inactivation technology is to find a sensitizer that will inactivate the pathogen while minimizing damage to the blood component and toxicities to the patient,” said Jon Weston, senior business unit manager, Gambro BCT. “Riboflavin is highly water soluble, allowing it to easily penetrate pathogens. It has a flat structure that allows it to slip through cell walls and insert itself into the DNA chain of the pathogen. It then reacts with light energy in a chemical reaction that breaks the DNA chain. Riboflavin is also regarded as generally safe to the public.”
Riboflavin is generally considered non-toxic and is ingested in large quantities in normal diets.
Gambro’s PET process works by mixing Riboflavin into a blood product, which is then exposed to light for a short period. During this illumination, a chemical reaction occurs that destroys any viral DNA and RNA. Because these nucleic acids are the mechanism for reproducing the pathogen, viruses, bacteria and other cells with nuclei are inactivated because they are unable to replicate and spread.
Along the same lines, Dr. Corash’s Cerus Corp. uses a chemistry based on a class of compounds known as psoralens with their pathogen inactivation technology. Psoralens are small, three-ringed compounds that occur in nature and are present in everyday foods such as lemons or celery.
According to Dr. Corash, robust pathogen inactivation systems for treatment of each blood component have been developed and are in various stages of clinical trials in both the United States and Europe.
“The availability of pathogen inactivation systems in the near future may permit modification of current testing strategies to take advantage of an integrated approach using pathogen inactivation and testing to improve blood component safety,” he explained. “As new pathogens of clinical importance are identified in the donor population, both pathogen inactivation and testing strategies will require further modification.”
In addition, Dr. Corash noted that pathogen inactivation may offer additional opportunties for improving transfusion safety beyond infectious pathogen inactivation with more advanced technologies such as leukocyte inactivation.
Leukocyte reduction of blood has become an increasingly important part of transfusion medicine over the past several years. Leukocytes are unnecessary contaminants in unfiltered blood products and have been reported to be responsible for a variety of adverse reactions including alloimmunization, febrile non-hemolytic transfusion reactions, immunosuppression, transmission or reactivation of intracellular viruses and T-cell lymphotro- pic virus type 1.3
Leukocytes can be removed from blood components by methods that include filtration, centrifugation followed by buffy coat removal, freezing and deglycerolization and standard saline washing.
Most professionals will say filtration has become the method of choice because it is simple, rapid and reproducible. Filtration can be performed during the course of transfusion or in the blood center at the time of component processing.
Prestorage filtration, within 24 hours of blood collection, is rapidly becoming the international standard because it prevents accumulation of proinflammatory cytokines, resulting in fewer febrile transfusion reactions.
Prestorage filtration also allows for improved standardization and quality control as compared to bedside leukocyte reduction, primarily because it is performed by trained technical personnel and is subject to specified quality assurance measures.4
Leukocyte reduction has been used for several years to eliminate infectious viral contaminants (primarily cytomegalovirus) from platelet and red cell units.
“The use of leukocyte reduction is well accepted as a method to decrease the incidence of other adverse transfusion reactions.,” Dr. Menitove added. “There are clear benefits of using leukocyte reduction, including a lowered incidence of chill fever reactions, alloimmunization and risk of cytomegalovirus.”
In addition, recent studies have shown evidence supporting the use of leukocyte reduction to prevent immunosuppression of the recipient immune system following blood transfusion. However, there are no well-accepted guidelines for the application available as of yet.
In March 2001, the Advisory Committee on Blood Safety and Availability for the Department of Health and Human Services (HHS) recommended that pre-storage universal leukocyte reduction (ULR) be implemented “as soon as feasible.” The committee asked that the action of the HHS regarding ULR implementation strive to minimize the impact on supply, assure adequate funding for the effort and issue regulations to implement ULR that address the committee’s concerns. Before ULR becomes policy, the Food and Drug Administration (FDA) will discuss the best ways to implement it. Issues of cost and reimbursement will most likely require intra-agency cooperation between the FDA and HHS.
While experts on the committee agreed on the proven benefits of ULR, there was some disagreement over whether those benefits justified an estimated annual cost of approximately $500 million and whether ULR will hinder future randomized trials comparing leukocyte reduced blood to non-leukocyte reduced blood. Critics of ULR felt the decision to use leuko-reduced blood should be left to doctors, not become a mandated policy.
With the probability that 100 percent leuko-reduced blood products will soon be a reality, hospitals will most likely face tremendous increases in their blood product budgets. Advances in automated technology have provided the blood bank an opportunity to now run more efficiently, improving service, quality and the bottom line.
Ortho-Clinical Diagnostics, Raritan, NJ, now offers the ID-Micro Typing System (ID-MTS) Gel Test. The method requires reactants be added to the chamber and incubated if necessary. The gel test has a broad range of applications, including antibody screening and identification, ABO blood grouping and Rh phenotyping, compatibility testing, reverse serum grouping and antigen typing.
The Capture-R Solid Phase Red Cell Adherence Immunoassay from Immucor, Norcross, GA, is a microwell, antiglobulin-based technique with sensitivity and specificity to clinically significant antibodies. This solid-phase technology also has a broad range of applications including antibody screening, and identification and compatibility testing. The microwell hemagglutination technology that comes with the immunoassay offers patient and donor ABO grouping, reverse serum grouping and Rh typing. All microwell tests can be batched by manual, semi-automated or fully automated methods.
According to Dr. Menitove, these strides in technology coupled with the increasing interest in blood safety measures will make the blood banking field one to watch in the near future.
“The technological advances in the blood banking field are exciting, particularly in the realm of pathogen inactivation. The preliminary results are fantastic and very promising,” he said. “I think the future holds possibilities for stem cell isolation and gene therapy as well as increased public involvement in the blood bank arena.”
Daniella King is assistant editor of ADVANCE. She can be reached at email@example.com.
1. Stramer SL, Waldman KJ, Brodsky JP, et al. Investigational screening of whole blood donations for HIV-1 and HCV by nucleic acid testing (NAT). Transfusion 1999;39:84S (S381-030F).
2. Caglioti S, McAuley J, Spizman R, Busch MP. Value of sorting samples for NAT based on first time and repeat donation status. Transfusion 1999;39:93S (S422-030J).
3. Answers to Frequently Asked Questions About Using Leukocyte Reduction Filters. Pall Corporation. Accessed Aug. 24, 2001 at www.pall.com/blood/faq.asp.
4. Anonymous. The use and quality control of leukocyte-depleted cell concentrates. Vox Sang 1998;75:82-92.