Peter L Page and HF Pizer

It is estimated that each year more than 81 million units of blood are collected worldwide, but the availability of this blood for medical use is not evenly distributed across the globe. The average number of blood donations per 1000 population is 12 times greater in high-income countries and 3 times greater in medium-income countries than in low-income countries (WHO, 2005a). Only about 27 million of the 81 million units (approximately 33 percent) are collected in low- and medium-income countries, where 82 percent of the world's population resides. In developed nations about one patient in ten admitted to the hospital receives blood or some type of blood product, while in developing countries the number is much smaller because of financial constraints, limited access to advanced medical procedures, and a lack of a modern, effective blood-banking system. It is estimated that 70 percent of blood transfusions in Africa go to children with malaria and to treat women with post-partum hemorrhage, and that perhaps 100,000 people die annually because of unsafe transfusion practices (Heyns et al., 2005). Still, the demand grows for safe blood products in developing nations.

About 8 million people in the United States voluntarily donate about 12 million units of blood each year. These units are then processed into about 20 million units of blood components, such as red blood cells, platelet, and plasma units (The National Blood Data Resource Center of the United States, 2005; US General Services, Administration, 2006). Modern medical care would not be possible without a safe and dependable blood supply to treat leukemia and certain cancers; to perform complex surgical procedures like heart operations, liver transplants and joint replacement; and to treat blood diseases like sickle cell anemia and tha-lassemia. Blood replacement is essential in acute trauma care, including accidents, burns, and battlefield injuries. The demand for blood is also growing in response to the world's aging demographics - for example, in the United States people over the age of 69 make up about 10 percent of the population, but receive about 50 percent of components.

This chapter is primarily about components of volunteer blood donations that are each transfused as a single unit, usually "as is." A single donation of a pint of whole blood is virtually always separated by centrifugation into a unit of red blood cells and a unit of plasma; a unit of platelets or a unit of cryoprecipitated plasma can also be prepared, but this is done for less than half of whole blood donations, since patients' clinical needs for platelets and cryoprecipitated plasma are much less than patients' needs for red blood cell transfusion. Each of these units is labeled, and regulated as a drug, following FDA regulations. While today virtually all of these blood components from whole blood donation are from volunteer donors, the FDA would permit paying these donors, but requires that the component's label be marked conspicuously with the words "PAID DONOR" as opposed to "VOLUNTEER DONOR." Whole blood donation is permitted no more often than once every eight weeks (to prevent development of iron deficiency in the donor).

Most of the plasma separated from red blood cell units is not needed for direct transfusion to patients, and so it is provided as "Recovered Plasma" to large multi-national for-profit companies that pool and fractionate it into plasma derivatives. The major source of plasma for plasma derivative manufacture, however, is "Source Plasma" collected by plasmapheresis (not whole blood collection). In the US, as well as many other countries, this Source Plasma is collected from donors who are paid (i.e. not volunteer), and the units of Source Plasma are labeled "Paid Donor." Plasmapheresis today is an automated procedure in which blood is removed from a donor, and the red cells are returned but the plasma is retained outside the body. Donors may undergo this procedure as often as twice a week. Source Plasma from tens of thousands of donations is pooled by the plasma fractionators who then, utilizing a series of complex processes, chemically and physically separate the plasma into lots of several plasma derivatives, including albumin, gamma globulin, and sometimes Factor VIII and Factor IX concentrates (used in developing parts of the world to treat patients with hemophilia A and B respectively), as well as alpha 1 anti-trypsin. Currently, the process of plasma fractionation includes several purifying and sterilizing steps which render these derivatives essentially safe, even though the source material is from pools of plasma from thousands of paid donors (each donation is, though, still tested for hepatitis B and C, as well as HIV). Prior to the availability of HIV and hepatitis C testing, and prior to the addition of sterilizing steps in plasma fractionation in the 1980s, large numbers of patients with hemophilia were regularly exposed to hepatitis C and HIV, which resulted in a number of national scandals and law suits (see p. 208; Negligence, human error, and failed oversight). Today in the US most patients with hemophilia A and B are treated with synthetic preparations of Factor VIII and Factor IX (respectively), which are viewed as essentially virally safe but also much more expensive. The sterilizing steps used in plasma fractionation are not suited to the single blood components used for direct transfusion, since these processes would damage red blood cells, platelets, and whole plasma, such that these components would not be efficacious.

Testing of blood donations for infectivity is viewed as part of the manufacturing process for the pharmaceutical drug (red blood cells, platelets, or plasma), and the test is to "determine the suitability for human use" of the blood component. This is the "purpose" for this testing, rather than for making a clinical diagnosis in the person donating the blood (who is presumed to be healthy and not a "patient") or screening the blood donor population for syphilis or HIV. Accordingly, it is very important that the false-negative rate in testing be as low as it can be (to prevent disease transmission by transfusion) - this would be good "sensitivity." However in doing this, the false-positive rate increases - this would be bad "specificity." Since there is a false-positive rate, and since blood centers view it as their obligation to inform donors of unsuitable test results, even false-positive test results make donors ineligible for subsequent blood donation. More important, though, is for donors to know if they are truly positive, in which case counseling is required to prevent future transmission to others (e.g. to sex partners), and referral to a health-care facility to initiate treatment, if appropriate, is required. It is therefore important that there be a "confirmatory" test to complement each reactive screening test result. To use anti-HIV testing as an example, the screening assay is an automated enzyme-linked immunoassay (EIA); if the EIA is repeatedly reactive then the donor is deferred in any event, but a Western blot (the confirmatory assay) is performed; if the WB is positive, the donor is considered infected and needs to be counseled to avoid exposing others, and to seek treatment for HIV. The more difficult counseling, however, is of the donor whose screening assay is repeat-reactive and whose confirmatory assay is negative - a false positive. This person is healthy and not infected, but is not permitted to donate blood any more (by federal regulation; there are complicated "re-entry" algorithms available which some blood centers use).

As we shall discuss, the social ecology for maintaining a safe blood supply is complex, but one point cannot be overemphasized: voluntary donation is its cornerstone. Where blood is in short supply and nations are poor, it is common to pay donors. Time and again this practice has been shown to increase the risk of introducing potentially lethal infectious agents. To date, the Government of Malawi is one of only a few in developing nations to establish a national voluntary blood donation system. It took two years to set up the system and its benefits were rapidly seen: the death rate from malarial anemia dropped by 60 percent and pregnancy-related mortality fell by more than 50 percent (Heyns et al., 2005). Even with a purely voluntary donor system, blood must be screened for transmissible infectious agents. The strategies for optimal screening are based on the human social environment, which include factors related to demography, behavior, and geography. For example, in South Africa and Zimbabwe it is estimated that the overall rate of HIV infection is greater than 20 percent of the population. Based on the risk factors known to be associated with HIV transmission, both countries instituted appropriate donor-screening procedures and reduced the rate of HIV positivity in blood donations to below 0.5 percent (and these units are discarded, not used). This has not been accomplished throughout sub Saharan Africa. The World Health Organization (WHO) estimates that HIV-contaminated blood still accounts for 5 percent of HIV infections throughout the region (Heyns et al, 2005).

0 0

Post a comment