By Lisa Fratt
Maintaining a safe blood supply has always been a tricky business. Red blood cells can be a powerful channel for the transmission of viruses, parasites, and bacteria. Over the last 40 years, contaminated blood has infected recipients with Hepatitis B and C, HIV, and West Nile Virus. Moreover, plasma proteins and cellular debris can cause allergic or immune reactions ranging from chills and fever to death in 1% of the population. In fact, Transfusion Related Acute Lung Injury (TRALI) has caused 40 deaths since the early 1990s.
Tests and screening questions make it possible to prevent most transmissions of infectious agents. But this process is far from perfect. For starters, it can be labor-intensive and inefficient. And there are other major concerns associated with the status quo. John Barr, president and CEO of Vitex of Boston, says, “The screening questions are increasingly screening out healthy donors, which creates scarcity. The diagnostic tests themselves are not completely sensitive. These tests are also highly inefficient; each new pathogen [eg, West Nile Virus] requires a whole new test or series of screening questions. Moreover, new tests are reactive. That is, a test is developed only after a new pathogen has been introduced into the blood supply.”
West Nile Virus exemplifies the pitfalls of the current system. In the fall of 2002 the Centers for Disease Control and Prevention (CDC) confirmed that the virus had entered the blood supply and identified the virus as a blood safety risk. Blood centers responded and voluntarily removed blood collected during the West Nile Virus season from their inventories. Nevertheless, 13 cases of West Nile Virus infection by blood transfusion were reported by January 2003. The West Nile virus story will likely follow a reactive pattern similar to that of other blood-borne pathogens such as Hepatitis B and C. That is, a diagnostic test will be used to screen donated blood for the virus. This year, community blood banks purchased and implemented a new experimental test to reduce the risk of infection via transfusion. Although this pattern is familiar, there are a few unknowns. The cost of the diagnostic test is unknown, and its sensitivity is uncertain. One fact, however, cannot be disputed: The experimental test does add another layer to an already complex process.
Other blood-borne agents further complicate the picture. Take Chagas’ disease, which has infected millions of people in Central and South America. The disease is responsible for 50,000 deaths each year, but blood banks in the United States do not screen donors for Chagas’ disease. Nor do they test or screen for Parvovirus 19, a highly prevalent virus that represents a significant health risk to immune-compromised and pregnant patients.
Blood centers have taken a different stance with Creutzfeld-Jakob disease, the human form of mad cow disease. Because of the theoretical risk of infection via blood transfusion, the Food and Drug Administration (FDA) restricts individuals from donating blood if they have spent more than 3 months in the United Kingdom or 5 years in Europe. Although such restrictions serve as an important safety measure, they also narrow the pool of eligible donors.
Despite the complexity, inefficiency, and costs, blood centers need to follow this multilayered screening and testing process to maintain a safe blood supply. Unlike other widely used therapeutic agents, red blood cells have not had a sterilization or pathogen-reduction step in the manufacturing process, but that could change.
Vitex has developed INACTINE, a new, comprehensive pathogen-reduction system for red blood cells. The system is currently in Phase III clinical trials and could receive FDA approval in 2005. “INACTINE represents a fundamental shift in the whole philosophy of blood supply safety,” Barr says. “The proactive technology can eliminate viruses, bacteria, pathogens, and proteins before they reach the patient. The introduction of the new technology could allow community blood banks to transition from multiple reactive, inefficient testing and screening processes to a comprehensive and cost-efficient system. Efficiency, however, is a mere corollary benefit. The primary benefit of INACTINE is a safer blood supply.”
INACTINE in Action
Tests and screening questions make it possible to prevent most transmissions of infectious agents in blood transfusions.
The current blood supply screening and testing system addresses one target at a time. It relies on a series of labor-intensive screening questions and individual diagnostic tests. As each new blood safety risk arises, another layer of questions or tests is added. INACTINE takes an entirely different approach. The pathogen-reduction technology can be easily integrated into existing systems at community blood banks. After blood is donated and separated into platelets, plasma, and red blood cells, an automated delivery systems adds the INACTINE molecule to a unit of red cells. INACTINE does its work during an 18- to 24-hour incubation period. Barr explains, “It’s a targeted and triggered chemistry. The molecule is triggered by DNA and RNA, and the only DNA and RNA in red blood cells is a bad guy.”
The INACTINE molecule inactivates the pathogens by bonding with their genetic material, which prevents them from multiplying. Red blood cells don’t contain DNA and RNA, so the INACTINE molecule leaves them unharmed. Following the incubation period, an automated cell-washing process removes INACTINE and other cellular debris. The cleansed red blood cells can be used for immediate transfusion or stored for 42 days.
The tremendous potential of INACTINE lies in its broad-spectrum approach. It can inactivate or “kill” a wide range of bacteria, viruses, and parasites. How does it effectively inactivate this broad range of pathogens? The answer lies in the molecule’s minute proportions, which help it handle both enveloped and nonenveloped viruses. Enveloped viruses are actually fairly easy to manage. The fatty lipid membrane that surrounds them is easily penetrated. Nonenveloped viruses, on the other hand, are a different story. They have a tough outer shell, which is difficult for larger molecules to penetrate. But because the INACTINE molecule is very small, it can readily penetrate the membranes of nonenveloped viruses.
The INACTINE technology could represent substantial gains in both safety and efficiency. Currently, blood centers conduct nine tests on donated blood to screen for five blood-borne pathogens: Hepatitis B and C, HIV, human T-lymphotropic viruses, and syphilis. But the tests are not always effective. In 2002, there were two confirmed cases of HIV transmission via transfusion of infected blood. Then there are other new threats to blood safety, including West Nile Virus. When blood centers removed from their inventories blood collected during the West Nile Virus season, the chronic blood shortage was exacerbated. Although the new test for West Nile virus might address the problem and identify infected blood, it will not solve the blood safety puzzle. It will not address problems associated with other pathogens that lack a diagnostic test. This forces blood centers to rely on screening guidelines to reduce risks of transferring these pathogens. Again these guidelines relieve the symptoms but do not attack the root of the problem. In fact, travel restrictions actually aggravate another problem—scarcity of blood. Travel restrictions to prevent transmission by blood transfusion of parasitic disease such as malaria and Chagas’ disease defer approximately 2% of the donor pool. In fact, new FDA restrictions have eliminated about 5% of the eligible pool of donors.
Currently, blood centers conduct nine tests on donated blood to screen for five blood-borne pathogens.
Furthermore, each pathogen, potential pathogen, and antigen adds a layer of testing, screening, and cost to the process. INACTINE, however, represents an entirely new way of doing business, Barr says, “INACTINE is inherently more efficient because of its breadth and scope. Labor-intensive and costly steps may be eliminated from the screening and testing process. For example, INACTINE kills white blood cells in addition to pathogens, so leukoreduction can be eliminated. It also eliminates the need to gamma-irradiate blood to prevent transfusion-associated graft-versus-host disease because the system removes immunologic threats. Patient reactions could be reduced or eliminated.”
A safer blood supply is not the only benefit associated with INACTINE. The system could reintroduce potential donors who have been eliminated through FDA screening restrictions back into the donor pool. This means that more blood could be available. And increasing the US blood supply is critical as demand for blood products is growing 4% to 5% annually.
Finally, there are the countless new and emerging pathogens that lack diagnostic tests. These tests may be developed, but they will, of course, carry a price tag. The price tag comes in the traditional costs of developing and purchasing a new test. But there is another side to the price tag—human health and safety. The lag between identifying a new pathogen and removing potentially contaminated blood means that at least a handful of recipients will receive contaminated blood. “INACTINE is an efficient approach with lasting benefits that could offset almost all of the costs of the system,” Barr says.
Lisa Fratt is a contributing writer for Clinical Lab Products.
