Celso Bianco, MD Addresses the 15th Annual Bill T. Teague lectureship: Blood Safety: How Safe is Safe?
In his lecture "Blood Safety: How Safe is Safe?", Dr. Bianco focused on two questions: 1) Why did FDA and the blood bank community moved to a zero-risk policy, and 2) with the changes in healthcare and the state of the economy, will there be a future shift in this approach, starting with policies from FDA?
Dr. Bianco first reviewed the cumulative U.S. AIDS cases and other events in past decades including the 5 to 10 percent donor loss from variant Creutzfeldt–Jakob disease (vCJD) deferrals; transmission of West Nile virus (WNV) by blood; FDA guidance on smallpox vaccination; white particulate matter in blood components; AABB Standard 126.96.36.199 on the detection of bacterial contamination in all platelet components; severe acute respiratory syndrome (SARS); screening of recovered plasma for B19; alert about Monkeypox virus infections; and Leishmania deferral for travel to Iraq.
For the period of 1999 to 2010, the number of deaths as a result of WNV is 1,200, but the number of infections is between 1.9 million and 4.4 million. Implementation of WVN NAT screening in 2003 has been a success and has resulted in the interdiction of approximately 2,600 WNV NAT-reactive units, preventing up to 7,800 potential cases of transfusion-transmitted WNV.
The years 2003 to 2007 saw FDA guidance including HIV NAT and HCV NAT; assessment of donor suitability and product safety in cases of WNV; appropriate screening for HBV (increased sensitivity requirements); screening for antibodies to T. cruzi (Chagas); as well as AABB bulletins on bacterial detection and transfusion-related acute lung injury (TRALI).
From 2008 to 2010, additional FDA guidance was issued for platelets collection by automated methods (statistical process control); management of donors positive on NAT HIV, HCV and HBV; prevention of vCJD transmission; "lookback" for HCV; pre-storage leukoreduction with statistical methods; as well as AABB bulletins on "triggering" ID-NAT for WNV and screening for antibodies to T. cruzi.
Blood is now safer than it has ever been, but fear of the unknown and the uncontrollable still exists. The major challenges are environmental/social, where the public and recipient advocacy organizations expect zero risk based on the Precautionary Principle, and the reaction of accreditation organizations and regulatory agencies to these expectations. An example of perception of transfusion risk is that HHV-8 is not dreaded and has unknown risk, while chagas and dengue are known and dreaded risks.
Next, Dr. Bianco reviewed the transmission and chronology of vCJD. The risk appears to be declining, but the number of exposed individuals is unknown, and a "second wave" is possible. In 2002 alone, the total loss from vCJD deferral was approximately 1.1 million donors and 1.7 million units. The deferral numbers are additive and still growing. Dr. Bianco referred to transfusion-associated vCJD as the smallest human epidemic ever recorded in medical history.
The emerging infection du jour is xenotropic murine leukemia virus–related virus (XMRV), which is associated with chronic fatigue syndrome (CFS). Given that infectious virus is present in blood cells and plasma, blood-borne transmission is a possibility. XMRV is unknown and unpredictable; it is a dreaded disease with a long incubation. XMRV transmission is documented, already widespread and with viral drift increasing pathogenicity. The literature is controversial with no causality established in prostate cancer or CFS, no gold standard test and no other predictive intervention available. Given the previous HIV experience, XMRV presents a high concern. AABB recommends that blood collecting organizations make educational information available regarding the reasons why an individual diagnosed with CFS should not donate blood.
Other unresolved and partially resolved blood safety issues include babesia, dengue, bacterial detection, TRALI, blood utilization and medical errors. Dr. Bianco pointed out our largest risks are not emerging infections, but other causes such as death in hospitals from medical errors.
A concern for the transfusion community is that diagnostics manufacturers shy away from donor screening and choose not to submit assays for U.S. clearance. Another concern is the business challenge of oversupply and competition. Changes are needed for transfusion medicine to become financially more attractive for product manufacturers in the current environment; to overcome the inhibitory effect of the recent U.S. history of regulatory failures for oxygen carriers and pathogen inactivation; to find alternative pathways for approval/licensure of assays with a limited market (e.g. confirmatory assays, HTLV-I/II, confirmation for HIV-2, malaria, babesia); to deal with public concerns about blood; and finally, to encourage and actively support the development of evidence-based policies, as opposed to rigid precautionism that does not tolerate potential risks and inhibits innovation.
There are consensuses for possible solutions, including a comprehensive approach to blood safety that requires the development of an integrated risk management framework that encompasses "vein to vein" and beyond; decision making based on transparent principles of risk management; a system that balances risks, costs and benefits in a sustainable manner; meaningful engagement with interested and affected parties throughout the process of risk decision making; and adherence to well-established ethical principles, including autonomy, beneficence, nonmaleficence and justice to ensure that the rights of both donors and patients are respected.
With changes in healthcare and the state of the economy, is there a future shift in this approach, starting with policies from FDA? Dr. Bianco concluded "Yes, there will be a shift. The evolving social and economic environment will drive changes. Public perception will be the last to change, based on evidence, education and on availability of care; and FDA will change after public perception changes. Unfortunately, it will take a while; only the very young among us will see the changes."