Like most efforts to improve health care, the drive to improve safety has sparked heated scientific and political debates. While no one questions the goal of a “risk-free” blood supply, the means by which this is achieved often tracks through difficult and tortuous routes that are not necessarily in our nation's best interest. The US blood safety vigilance system is composed of a network of interwoven programs, now organized under a formal structure, with the assistant secretary of health and various committees bearing overall responsibility. In essence, the Food and Drug Administration (FDA) and Department of Health and Human Services (HHS) oversee our nation's blood supply. But while safety and economics are intrinsically linked, the government regards them as distinct entities and places them under the supervision of 2 different federal committees. While the FDA's Blood Products Advisory Committee is confined to the medical and scientific aspects of safe blood procurement, the HHS's Advisory Committee on Blood Safety and Availability examines the economic, legal, and public health implications of blood safety issues. Complications arise when concerns over financial feasibility conflict with consensus over safety. This conflict often results in the formulation of unfunded mandates and an inadequate reimbursement system that does not recognize the true cost of blood (1). Furthermore, this state of affairs is impacted by the fact that the overseeing committees may not have representatives from physician or hospital groups or even from the blood banking industry.

Recently, 3 issues have impacted our nation's citizens and the blood supply: hepatitis C virus (HCV) look-back, universal leukoreduction (ULR), and the bovine spongiform encephalitis (BSE) epidemic in Western Europe, otherwise known as “mad cow disease.”

Despite vigorous medical objections, a targeted HCV look-back program was mandated that applied only to the recipients of potentially anti-HCV-positive blood. As predicted, not only were donors and recipients unnecessarily alarmed, but also the public health rewards were minimal, if nonexistent. The vast majority of recipients of “suspect” blood transfusions either had died of their initial disease process or tested negative. Since it is well known that <10% of all HCV infections could have been transfusion acquired, would it not have been wiser to test all individuals, if they so desired? However, even though numerous studies have concluded that the mandate was ineffective, both the FDA and the HHS have proposed extending the HCV look-back to include the findings of the now-obsolete first-generation HCV 1.0 test (with its 70% false-positive rate) and contacting the legal representatives of deceased patients. Surely this measure can only contribute further to the spiraling cost of blood and benefit the legal profession.

The issue of ULR can be approached medically on a more rational basis. A number of studies have shown that transfused leukocytes are immunosuppressive, can lead to severe febrile reactions, and can initiate cytomegalovirus infection in individuals with weakened immune systems. Also, transfused leukocytes can cause alloimmunization and, on rare occasions, mount a graft-vs-host disease response in bone marrow transplant patients. For these reasons and for some time now at Baylor University Medical Center, the Transfusion Service has issued leukoreduced packed red cells and platelets to newborn infants, transplant patients, and cancer patients on a rational “indication” basis developed by the Transfusion Committee.

In the USA, the FDA has championed the cause for ULR and will most likely mandate this measure in the very near future. ULR is already carried out in Canada, England, France, Norway, and Portugal. Hence, with regards to ULR, the issue is cost and not medical science. Its implementation will increase the cost of a unit of blood by 25% to 30%. It should be mentioned that approximately 3% to 5% of units cannot be leukoreduced. This mandate will serve to further exclude some valuable and rare donors.

Since the HIV epidemic, the possible but as yet unproven transmission of new variant Creutzfeld-Jakob disease (nvCJD) by transfusion in humans represents yet another major threat to the safety and availability of our blood supply. It has been known for some time that several fatal diseases are caused by modified prions, including scrapie of sheep, bovine and feline spongiform encephalitis, chronic wasting disease of deer and elk, and CJD of humans. The latter condition presents clinically with a rapidly dementing illness associated with myoclonic jerks. The average duration of the disease is 14 months but can range from 7 to 38 months. The accumulation of modified prion proteins in the central nervous system causes fine spongiform change, microvascularization, and consequent neuronal loss and reactive gliosis. Characteristic amyloid-rich plaques (so-called Kuru plaques) are present, and immunostaining and blotting can aid in the histologic diagnosis. In life, the electroencephalogram may show triphasic waves with frontodistal delay. Magnetic resonance imaging of the brain and tonsillar biopsy are considered reliable tests in the detection of nvCJD in living patients when taken together with other symptom-based criteria. As yet, no diagnostic blood test has been developed for this disease, although the observation of specific binding of the malignant prion protein to circulating plasminogen, recently reported by Zurich scientists, could serve as the basis for a diagnostic test for nvCJD (2). However, to date there is no evidence in humans that nvCJD can be transmitted by transfusion.

An outbreak of BSE occurred in British cattle in the late 1980s and early 1990. To contain the epidemic, thousands of cattle were slaughtered. Also, some younger individuals in Britain developed a new, more aggressive type of CJD. This led British scientists in 1996 to speculate that BSE had jumped a species barrier and was responsible for the nvCJD in humans. To date, almost 100 cases of the human disease have been reported in Britain, Ireland, and France. It was felt that the transmission of the malignant prion in humans occurred from eating infected beef, which itself had been infected by tainted protein feed made from the carcasses of sick animals. Hence, as a precautionary measure in the USA, the FDA recommended that blood donors who had visited the United Kingdom between 1980 and 1996 for a cumulative period of 6 months or more be permanently deferred. Other countries such as Australia implemented a similar ban. According to Dr. Merlyn Sayers, chief executive officer of Carter BloodCare, this stipulation alone has resulted in the loss of >500 donors from our community's blood program. Two recent published reports will have significant repercussions for blood banking as the FDA and HHS promulgate future safety measures. Researchers in Scotland have shown that it is possible to transmit BSE to a sheep by transfusion with whole blood taken from another sheep during the symptom-free phase of an experimental BSE infection (3). Other researchers in California were able to transmit BSE from diseased cows to transgenic mice, implying that the species barrier between these mammals could be crossed (4).

It is clear that blood and its components are not entirely safe and probably never will be. However, they provide a vital and indispensable therapeutic modality in the practice of modern medicine. As new infectious agents and diseases continue to be reported, the risk-benefit analysis of blood transfusion will require continual reevaluation. The availability and safety of blood remain the 2 principal issues. Hence, what can we, as physicians, do to assist with the forthcoming blood shortage as the FDA and HHS implement new safety regulations that can only further deplete our national blood supply? Three measures can be implemented immediately:

1. Assist the local blood center in all ways possible. Since only 5% of eligible adults donate blood, we should all become active recruiters. Also, we should be mindful that our community blood program can be strong only to the extent that its mission is endorsed by influential individuals, such as physicians and hospital administrators, who recognize the importance of blood transfusion in patient care.
2. Implement the strategy of “type and screen” instead of “type and cross” often and whenever feasible. This measure alone serves to increase the shelf life of packed red blood cells and reduces wastage by 10%. Wastage can be further diminished by not thawing fresh frozen plasma and cryoprecipitate before they are needed.
3. Transfuse blood and blood components only when these are deemed necessary. Follow nationally acceptable guidelines promulgated by professional medical organizations (5, 6).

In 1999 blood transfusion costs at Baylor University Medical Center rose a whopping 25% over the previous year. The American Hospital Association is asking Congress to annually evaluate the real costs of blood and blood component procurement. Previously, this had been neglected. There should be no disconnect between the FDA, the Advisory Committee on Blood Safety and Availability, and the Health Care Financing Administration, all of which are part of HHS. The American Hospital Association is asking that mechanisms be put in place so that if one agency mandates a new measure, the other agency pays for it.

Finally, I would like to take this opportunity to thank Baylor administrators and, in particular, Mr. Steve Trowbridge for taking a major interest in the problems unique to blood transfusion in the Dallas-Fort Worth metroplex.

1. Marengo-Rowe AJ. Testimony on behalf of the American Hospital Association to the US Department of Health and Human Service Advisory Committee on Blood Safety and Availability. Washington, DC, April 26, 2000.
2. Fischer MB, Roeckl C, Parizek P, Schwarz HP, Aguzzi A. Binding of disease-associated prion protein to plasminogen. Nature 2000;408:479-483.
3. Houston F, Foster JD, Chong A, Hunter N, Bostock CJ. Transmission of BSE by blood transfusion in sheep. Lancet 2000;356:999-1000.
4. Scott MR, Will R, Ironside J, Nguyen HO, Tremblay P, DeArmond SJ, Prusiner SB. Compelling transgenetic evidence for transmission of bovine spongiform encephalopathy prions to humans. Proc Natl Acad Sci U S A 1999;96:15137-15142.
5. American College of Physicians. Practice strategies for elective red blood cell transfusion. Ann Intern Med 1992;116:403-406.
6. American Society of Anesthesiologist Task Force. Practice guidelines for blood component therapy. Anesthesiology 1996;84:732-743.