Impact of AIDS on blood donors

Plasma Ther Transjus Technol 1988; 9:241-256 Printed in Great Britain. All rights reserved

0278-6222188 $3.00+0.00 Copyright 0 1988 Pergamon Pm8 plc

Impact of AIDS on Blood Donors Peter L. Page, MD

The blood banking industry’s primary emphasis with respect to Human Immunodeficiency Virus (HIV) has appropriately been on the safety of blood components and plasma derivatives for transfusion. In addition to changes in processing of donated blood and educating health care providers [and concerned members of the public) about the indications for transfusion and alternatives to homologous transfusion, this has required major new approaches toward prospective blood donors. These meaures have contributed early and significantly toward increasing the safety of blood for transfusion, but have not been altogether well-received by blood donors and prospective blood donors. To a large degree these measures, and their success, are not appreciated by those worried about transfusion safety with respect to HIV. Focussing on prospective blood donors is very important for several reasons: first, the donor’s honesty and altruistic motivation for donating have been demonstrated to play a key role in reducing the incidence of post-transfusion hepatitis-both before and after implementation of sensitive and specific testing of donated units for HBsAg,i4 and

would be expected to play an important role in reducing transfusion associated HIV infection-both before and after implementation of testing for HIV. Second, maintaining suitable donors’ trust and respect is necessary to retain them as volunteer donors in the future, which is essential in order to maintain an adequate blood supply. Enlisting the cooperation of unsuitable donors in not donating is also important to optimize the safety of the blood supply. Appropriate followup and counselling of tmsuitable donors is important to prevent them from being blood donors in the future. Education of these apparently healthy individuals is important also, although it falls outside of the traditional area of interest and assumed responsibility of some blood bankers, to help prevent further spread of HIV infection to others (e.g. by sexual contact), including other potential blood donors.

From the American Red Cross Blood Services, Northeast Region, Dedham, Mass., Harvard Medical School, Boston, Mass., and Beth Israel Hospital, Boston, Mass., U.S.A.

Active measures to exclude prospective blood donors at risk for AIDS began in early 1983, just after it became apparent that AIDS could be transmitted by trans-

MEASURES TO EXCLUDE “HIGHRISK” BLOOD DONORS AND THE EFFECT OF THESE MEASURES ON THE SAFETY OF TRANSFUSION Measures to Exclude Donors and Donations at Risk

Reprint requests to Dr P. L. Page American Red Cross Blood Services, Northeast Region, bedham, Mass., U.S.A.

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fusion of blood components5 and by anti-hemophilic factor.6 These measures take a number of forms and have become increasingly more strict. Persons at risk for HIV are discouraged from presenting as potential donors in the first place; all presenting donors are given information, asked questions, and examined prior to being accepted as donors; and successful or “productive” donors are given opportunities to indicate that their blood should not be used for transfusion. These three areas of effort (prior to the donor presenting, while the donor is presenting, and after the donation itself] will be considered separately. Prior to the Donor Presenting Him or Herself at the Blood Collection Site Avoid High Risk Settings. Not having an individual at risk for HIV infection come to the blood collection site in the first place is optimal, thus avoiding potential embarassment to the prospective donor, avoiding costs to the blood collecting agency in processing a donor who is deferred, or collecting a unit which will be discarded. Most importantly, that eliminates the possibility of having a potentially infectious blood component or plasma derivative being transfused. For many years, blood collection agencies have avoided collecting blood in settings where there is an increased risk for hepatitis, most notably from prison inmates. Since the modes of transmission (and risk groups) for hepatitis B and AIDS are so similar, it was helpful that such policies were in place before the appearance of HIV in the United States. Most blood collectors have had experience in actively denying prisoners opportunities to donate blood, often against the strong and apparently well-meaning objections of individual prisoners or prisoner advocacy groups. It has become increasingly important with the onset of the AIDS epidemic in the United States to educate judges and correction officers that blood donation should not be proposed to reduce a

sentence in lieu of a fine or other penalty for violation of a law, since in at least one survey in an urban area suggested an anti-HIV incidence of increased positivity.7 Active deferral or refusal to draw such individuals at blood collection sites for that reason on occasion has resulted in their going to another blood collection site and not revealing the reason for the donation until after it has been completed, when they ask for proof of blood donation to present to their parole officer. Educate Persons in Risk Groups Not to Donate. While quantitation is not

available, several indirect and nonrandom surveys suggest that men who have had sex with another man donated blood prior to being asked not to do so.819Ads were run in, and articles written for, newspapers and periodicals read by gay men (as well as articles in the general press and media] stressing the importance of persons at any risk for HIV exposure not to donate blood for transfusion. Similar information was regularly placed in handouts and brochures to educate such persons about reducing risk of acquiring HIV infection by other means. Gay men’s groups that had previously sponsored bloodmobiles soon (but not necessarily immediately) understood why blood collection agencies no longer conducted blood mobiles for their volunteer whole blood donors. Source plasma operations closed down collection facilities for paid plasma donors in predominantly gay communities in several major cities .iONongay business people in communities perceived to be gay have not always been understanding of refusal to collect in their commumties, as they felt it reflected negatively upon the general community to have bloodmobiles cancelled for that reason.11 Discontinuation of and refusal to provide bloodmobiles in Haitian communities has occurred, and been difficult to justify to leaders in these communities in many instances.‘2 Provide Alternate Opportunites For Anti-HIV Testing. Since early 1985 when

anti-HIV testing of blood donors was first

Impact of AIDS on Blood Donor8 243

available, there has been a concern that persons curious about their test status would abuse the blood collection system by donating to obtain free and confidential testing. Accordingly “Alternative Testing Sites” (ATSs) were set up, particularly in areas where risk in the community was perceived to be high, often free and by the Department of Public Health; but also in some cases, usually for a modest fee by regional blood centers (e.g. those headquartered in St Louis, Detroit, and Boston] or by hospitals themselves. These sites have been advertised and promoted, not necessarily to promote testing in general or of individuals at risk, but to provide a secure confidential (and even anonymous) opportunity for reliable testing, in order to divert individuals curious about their test results, or not comfortable to have testing performed by their physician, from being blood donors in order to obtain this information.

At the Blood Collection Site If a prospective blood donor comes to a blood collection site, knowing or not knowing that he or she is at risk for HIV infection, several mechanisms are in place to prevent the donation or to divert the donation from release for transfusion. Some of these mechanisms may alert the otherwise unknowing prospective blood donor to his or her possible risk for HIV. Written Information For All Presenting Blood Donors. For many years

blood collecting agencies have provided written information to all prospective blood donors explaining that even people who feel well and have not been sick can transmit hepatitis or malaria by transfusion; that persons with a history compatible with possible recent exposure should not donate blood for transfusion to avoid potentially infecting transfusion recipients.13 This has been particularly important since there is no specific test for noti, nonB hepatitis infectivity, nor is a test performed for malaria. While history of, or exposure to, hepatitis was

included in the written information, sexual transmission of hepatitis was not specifically mentioned as a possible route of exposure. Nonetheless it is believed a substantial number of cases of transfusion-associated AIDS (TA-AIDS) have been prevented due to the long standing discouragment from donating due to risk for hepatitis. In early 1985, additional information was included in the brochure or pamphlet provided to all prospective blood donors that spectied the groups at risk for AIDS. Persons entering from Haiti since 1977 remained on this listing even during the period they were not considered a risk group by CDC for reporting purposes. As information became available from counseled anti-HIV confirmed positive blood donors, many of whom had not considered themselves at risk since their exposure had not been recent or solely with one other sexual partner, the specificity of the written information provided to all prospective blood donors increased. Modifications have been made to indicate that now the following persons should not donate blood: 0 You are a man who has had sex with another man since 1977, even once. 0 You have ever taken illegal drugs by needle. 0 Your are a native of Haiti, or Sub-Saharan Africa who entered the United States after 1977. 0 You have AIDS or one of its signs or symptoms 0 You have ever had a positive test for HIV antibody, showing past exposure to the AIDS virus. 0 You have hemophilia and have received clotting factor concentrates. 0 Your are or have been the sex partner of any person described ,above since 1977. 0 You have been the heterosexual sex partner of a male or female prostitute within the last 6 months. 0 If you have ever had hepatitis (a liver disease that may be caused

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by a virus), do not give blood or plasma. 0 If you have active syphilis, do not give blood or plasma. 0 If you have visited or lived in a country where malaria exists, do not give blood or plasma for 6 months after you leave that country. If you are a native of a country where malaria exists, do not give blood for 3 years after you enter the United States. You must wait to give blood for 3 years after you have had malaria or have taken anti-malarial drugs. Clearly modifications to this list of exclusions will be made as new information regarding spread of HIV and other diseases potentially transmitted by transfusion becomes available. What has just been described is part of the self-exclusion process, meaning that the prospective donor has excluded himself. In addition, the blood collection agency may actively defer an individual from donating (even against the prospective donor’s will, since blood donation is considered a privilege rather than a right). This “active” deferral is accomplished by evaluating the prospective donor’s answers to a number of questions and by a limited examination of each prospective donor. Direct Questioning of Prospective Donors. For many years presenting

donors have been asked about previous history of illegal intravenous drug use, and deferred if indicating such use. For many years they have also been asked about history of hepatitis, exposure to hepatitis, and previous positive test result for hepatitis; and if admitting to such exposure they would be deferred (or possibly evaluated further by a responsible physician, e.g. for exposure that may not have been significant or for an illness not certain to have been viral hepatitis, e.g. hepatitis due to halothane). Due to the transmission of AIDS by sharing needles by intravenous drug abusers, and the similarity of routes of transmission of hepatitis B and AIDS, these questions have certainly eliminated a number of

HIV carriers (not known to be carriers) from being successful blood donors. Beginning in 1983, a number of additional questions have been added to the battery of questions asked of all prospective donors, with respect to possible exposure to, symptoms of, or previous test positivity for HIV. Currently, the additional and AIDS-specific questions asked by American Red Cross Blood Services regions include “Have you . . . : 0 Ever had yellow jaundice, liver disease, hepatitis, or a positive blood test for hepatitis? 0 Ever taken self-injected drugs? 0 In the past 6 months received blood transfusions, blood injections or tattoos. 0 In the past 6 months been exposed to anyone with yellow jaundice, hepatitis, or on a kidney machine? 0 Ever had malaria? 0 In the past 3 years been outside the United States? 0 Ever had any serious illness? 0 In the past 6 months been hospitalized? 0 In the past month taken any medications? 0 Ever been deferred as a blood donor or had problems donating? 0 Ever had heart disease, chest pain, or shortness of breath? 0 Ever had convulsions, seizures, or fainting spells? 0 Ever had a blood disease or cancer? 0 In the past year had any vaccinations or immunizations? 0 Any acute respiratory disease or trouble breathing now? 0 In the past 3 days had any dental work? 0 Had night sweats, unexplained fever or weight loss, lumps in neck, arm pits or groin, discolored areas of skin or mouth, persistent cough, or persistent diarrhea? 0 Ever had a positive test for HTLV III (HIV)antibody or been exposed to anyone with AIDS? 0 Been to Haiti or Zaire?

Imppctof AIDS on Blood Donm l

Been pregnant in the past 6 months?” They are also asked: l “Are you feeling well today?” and asked to sign below the statement: l “The information I have given for this form is correct. I donate my blood or plasma for use as needed. I understand the information that has been given to me today about the spread of the AIDS virus through donated blood and plasma. If I am at risk for spreading the AIDS virus, I agree not to donate blood or plasma for transfusion to another person.” As more information becomes available, these questions are apt to change by becoming even more limiting on prospective donors’ eligibility. It should be pointed out that for some possible exposures via less efficient routes of transmission, or due to sources quite unlikely to be infectious, 6 months is the period of time listed since possible exposure, rather than since 1977 (when HIV is thought first to have appeared in the U.S.). This is based upon the reliability of the development and detection of anti-HIV within 6 months of exposure, particularly in low risk populations (e.g. volunteer blood donors] and the fact that all blood donations are being tested for anti-HIV. Specific direct questioning of prospective blood donors as to membership in a high risk group is not performed by all blood collectors. Instead, many blood collectors require that the prospective donor sign that he or she has read and understands the written information provided which stipulates that persons in risk groups should not donate their blood ‘for transfusion (see section on Confidential Unit Exclusion) in order to be accepted as a blood donor. The argument not to ask directly about membership in a high risk group is that it is felt that some high risk group members donating blood despite their status would be as (or perhaps more) untruthful in response to direct questioning, and that such a procedure might encourage people PLASklAT9:2-G

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in a risk group to donate and say they were not in a risk group if doing so might provide a perceived advantage over admitting such membership directly. Physical Examination of Prospective Donors. In the United States pre-

donation screening has included taking the donor’s pulse, assessing the hemoglobin or hematocrit, and examining the arms for needletracks or other evidence of parenteral drug abuse. An abnormality in any of these areas would be cause for active deferral of the individual from donating blood on that occasion. While it is true that many HIV carriers are afebrile and not yet anemic, abnormalities in these areas in blood donor screening often are the first indication to the apparently healthy prospective donor of a condition requiring medical attention. Shortly after it was clear that HIV could be transmitted by lyophilized clotting factor concentrates, physical examination of source plasma donors to rule out lymphadenopathy was instituted as part of the regular procedure of plasmapheresis donor evlauation. At least one collector of whole blood from volunteer donors implemented this procedure for a while (American Red Cross Blood Services, Northeast New York Region, Albany), but it is not generally performed on prospective volunteer whole blood donors. “Confidential

Unit Exclusion”. An

additional procedure developed to opimize transfusion safety regarding HIV infection was instituted by the New York Blood Center.14 This provided the opportunity for an individual at risk not wishing to self-exclude him or herself from the donation process, to indicate that his or her donation should not be utilized for transfusion. A confidential opportunity was provided for persons at risk to donate without demonstrating to friends, co-workers, or their employer that they were actually ineligible. There was concern that closeted gay men, for example, might feel unduly coerced to donate and would not be comfortable indicating that they should not donate. Early experience in New York indicated

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that these donors “checking off” that their blood should only be used for laboratory studies (i.e. not transfusion) demonstrated a higher incidence of markers for hepatitis B as well as antibodies to CMV, both of which laboratory findings are increased in groups at risk for HIV. White cell counts and helper/suppressor T lymphocyte ratios were not different in those indicating OK for transfusion than from those indicating for laboratory testing only. Early experience suggested that some donors were confused by this additional requirement, as a number of donors did not indicate either choice (and hence their blood could not be released for transfusion) and there appeared to be a substantial number of donors indicating for laboratory study only when blood was collected in educational institutions (assumed to be due to students’ interest in supporting research, not their risk for HIV). With greater experience of collection staff and education of donors these percentages decreased. Based in large part upon this study14 and similar findings of Nusbacher, the FDA recommended that the opportunity for confidential unit exclusion be included for all blood donors. Just prior to the FDA recommendation regarding “check-off” or “Confidential Unit Exclusion (CUE)“, two Red Cross regions not yet using this procedure presented data to the FDA concerning what HIV positive donors would have done had check-off been available at the time of their positive donationsr5li6 Of the flrst 57 Western blot confirmed positive donors counselled by the American Red Cross Blood Services, Southeastern Michigan Region, 44/53 males and O/4 females admitted to risk factor. If “check-off” had been offered, 55/57 would have indicated that their donation was OK to transfuse, and two (both admitting to risk) would have indicated that their donation should be “for lab use only”. One of these two was the only one of the 57 in whom it appeared that peer pressure may have been a factor in donating. ATS were

available in the Detroit area at this time.16 As part of the prospective study of anti-HIV confirmed positive blood donors by American Red Cross Blood Services, Northeast Region, these donors were asked to complete a questionnaire anonymously. Three of 10 would have indicated that their donation should be diverted to research, and five of these would have indicated that their blood was OK to transfuse, one didn’t know, and one didn’t respond.16 After implementing CUE in the Northeast Region in 1986, analysis of the first 5 17 donors indicating “do not transfuse” (0.25% of the 205,981 donations during that period) demonstrated a slight increase in the percentages of males and of first time donors, but no sign&ant increase in hepatitis B markers and there were no HIV positives. During that period all of the Western blot positive donors indicated that their blood would be “OK for transfusion”.i5 This suggests that addition of all these procedures, while well-intended and possibly helpful, may also be contributing to donor confusion. Increased education of prospective donors, as well as consideration of simplifying the written material provided to donors, may be in order. Generally, all volunteer blood donations now are collected with the CUE opportunity. Initially this was performed by placing a ballot on which do or do not transfuse, was checked off, and placed by the donor into a locked ballot box at the blood collection site. The box was later opened in the laboratory and ballots identified by whole blood number. Some centers have subsequently developed bar coded sticky labels with the choice of OK to transfuse or not, one of which the donor places on the donor registration form. In this way it is not readily apparent to those seeing the donor registration form and a bar code label what the bar code indicates. This is laser scanned by the laboratory staff and the inappropriate units prevented from being released. Theoretically since it should be assumed that donors indicating that their

Impact of AIDS on Blood Donor6

blood should not be used for transfusion have had an exposure to HIV, their blood donations in the subsequent 6 months should not be used for transfusion even if they then indicate that their blood could be used for transfusion. This is because it might take up to 6 months for seroconversion and a donor once concerned about a recent exposure may not understand that not hearing that he or she is positive after the fist donation does not necessarily mean they they have not been infected. Assuming that exposed persons should have developed detectable anti-HIV within 6 months, it should be reasonable to remove such donors from a deferral list 6 months after indicating “do not transfuse” if they indicate “OK to transfuse” subsequently. Since the process of indicating “do not transfuse” is confidential, it is difficult to justify contacting the donor in followup to asking if he or she really meant “do not transfuse”. The donor who has something to hide or keep confidential at the time of donation would not be expected to admit his or her risk to a blood center physician later, and then could lose trust in the blood center due to such a confrontation. It is advisable not to risk this sense of trust since cooperation of persons at risk remains very important. Due to public confusion about risk factors for AIDS, concern about confidentiality, and concern about abuse of the volunteer blood donation system by individuals curious about their anti-HIV status, it appears that having CUE in place may be better than not having it in place, particularly in areas without convenient access to ATS or other options for obtaining HIV testing. Subsequent to the Blood Donation “Call Back”. Blood donors are given written information to take with them after the blood donation, which states that if they feel on further consideration that their blood should not be used for transfusion, they should call the blood center, but they should do it quickly (e.g. by the next morning). Blood centers have

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set up mechanisms to handle such calls discreetly and promptly on a 24 hour-aday basis. For instance, a donor may not need to provide his or her name, but just the unique whole blood collection number, which can be provided to each donor. The donor also need not specify why the blood should not be used, as the blood center will destroy all components from the donation in any event no matter what the test results. Usually delayed call-backs are from donors who develop hepatitis or the flu shortly after the donation. If this information is received after components from the donation have been released to transfusion services, they are recalled. In the case of hepatitis, if transfusion has taken place, the recipients’ clinicians should be notified, along with any information as to whether the hepatitis is A, B, or nonA, nor& If the information is received in time the recipient, if susceptible, may benefit from ISG, HBIG, or surveillance. In other cases the medical director of the transfusion service is advised and decides whether notification of the clinician is warranted. If a donor develops chicken pox shortly after donation the blood collection center should be notified so that the recipients (if susceptible or immunosuppressed) can receive Varicella Zoster Immune Globulin (VZIG).” These and other nonAIDS examples are typical of reasons that donors called blood centers, even in the years prior to being specifically instructed to do so, suggesting the basic longstanding responsibilities volunteer blood donors have naturally assumed. Donor Deferral Registry. Each blood collecting facility is required to maintain a list of unsuitable donors, to prevent release for transfusion of components from a donor previously determined to be unsuitable from a recipient safety point of view.18 In areas where there are independent collection agencies, an unsuitable donor deferred by one facility could present at another unaffiliated facility and upon misrepresentation of pertinent information, not be found unsuitable and have patients

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receive components from his or her donation. Donors are placed in the donor deferral registry based upon information the donor has provided, or based upon information the collection facility has elicited from the donor or from testing a blood sample, or based upon information reported to the collecting facility that the recipient(s) of components from previous donations of a donor have developed an infection (e.g. hepatitis B, or nonA, nonB, or malaria). Unsuitable donors are informed that they are being listed in a donor deferral registry. Effectiveness of Methods For Donor/ Donation Exclusion on Transfusion Safety

Precise of direct measures of the effectiveness of any of the measures employed for donor exclusion are not possible. However there is substantial indirect information suggesting there are major beneficial effects. Changes in Donor Demographics and Test Results. Just after educational

efforts to discourage blood donations from groups at risk for HIV were implemented, particularly those targeted at men having had sex with another man, dramatic decreases in donations from men, particularly in urban areas were noted, in contrast to donations from women which remained stable or increased.19 Significant decreases in the rate of HBsAg positivity were noted, attributable to the decrease in male HBsAg positives, while the positive rate in females remained little changed.20 A similar, but not statistically significant, drop in the already quite low STS confirmed positive rates was also noted at this time. Pertinent Reasons for Donor Deferral. The percentage of presenting donors actively deferred for AIDS-related reasons, is generally small, but is important. In general, after a new question is added to the process for evaluating suitability of presenting donors, the number

of donors deferred for that question would be relatively higher and then abate somewhat over time. Presumably this is related to concern and appropriate conservatism of staff charged with responsibility for evaluating donor suitablility for transfusion safety, as well as general education of persons potentially exposed of the newer and more stringent criteria for blood donor acceptability. Changes in Rates of Post-Transfusion Hepatitis. Apart from carefully im-

plemented prospective studies of posttransfusion hepatitis, this complication of transfusion is greatly underreported. However, in the Philadelphia area, where there had been consistent reporting, and no change in procedures or reminders, there was a dramatic decrease in reports to the Penn Jersey Red Cross Regional Blood Services of post-transfusion hepatitis about 6 months after initiation of vigorous donor exclusion measures.19 This would be compatible with a significant decrease in donations from persons at risk for hepatitis, who would also have been candidates for exclusion for HIV reasons. ATS. While the justification for ATS seems obvious and logical, success of such a program was documented early in Massachusetts. In the first 7 weeks of operation in 1985,29% of clients coming to the ATSs, who completed a voluntary and anonymous questionnaire, indicated that they would have been a blood donor if an ATS had not been available. Most of these individuals were anti-HIV negative and in a risk group indicating that seronegative persons at risk had been diverted from the blood donor setting. While not all clients availing themselves of ATS are at risk (e.g. “worried well”), 42% of these ATS clients had donated blood in the past, but only 11% in the previous 2 years (i.e. since 1983); thus confirming the beneficial effect of having discouraged persons at risk from donating blood for transfusion.21 Analysis of interviews with the first blood donors confirmed positive for anti-HIV in 1985 indicated that they were not aware of the availability of ATSs and those perceiving

fmpact of AIDS on Blood Donors

themselves at risk for HIV would have used an ATS instead of donating blood.22 Accordingly, more ATS sites were added, and their availability, as well as other mechanisms for obtaining testing (e.g. through one’s physician or an STD clinic) were publicized. The anti-HIV confirmed positive rate in volunteer blood donors then decreased (see below). With increased interest in testing various groups (e.g. military entrants, some persons considering foreign travel, women considering pregnancy, potentially some life insurance applicants, etc.) and due to the “window” period (after infection but before development of anti-HIV test positivity), it appears to remain important that convenient access to confidential (and probably anonymous) testing continue to be available in the interest of making blood for transfusion as safe as possible. Surveys in the Gay Community. A nonrandom survey of almost 1000 gay men in the Boston area in October 1984 showed that while over half had been a blood donor, only 7% had donated blood in the previous year. Those with a recent donation history were generally younger and less open about their sexual preference. Many of those engaging in behavior exposing them to potential risk of AIDS did not realize their risk at that time.8 Since then public and specific education efforts have increased and information presented to blood donors is more specific and opportunities for CUE have been introduced. Decreases in Rates of Anti-HIV Confirmed Positive Blood Donors. An early summary of anti-HIV experience within the American Red Cross system indicated an overall rate of 4/ 10,000 productive donors to be confirmed positive.= This rate varied geographically in parallel with the variation in population rates of AIDS cases. For 12 months during the 1986-7 period, the rate was 1.7/10,000.24 The confirmed positive rate in the Red Cross has decreased from 0.035% in mid-1985 to 0.012% in mid-1987.25 This is presumably due to informing those few co-ed positives and instructing

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them not to donate blood again, due to the more specific information being provided to presenting blood donors, and due to continuing and increased cooperation in persons at risk in not donating blood for transfusion, particularly in view of the continuing increase in spread of HIV infection in the U.S. population. CUE Studies. A number of studies have been conducted to assss the effectiveness of CUE. The earliest CUE program, before the availability of anti-HIV testing, was instituted by the Greater New York Blood Program.14 A study of that program demonstrated efficacy of CUE, perhaps because the general population from which donors recruited there has a greater incidence of HIV infection. In this study, the donors who indicated that their blood should not be used for transfusion included a higher percentage of males and anti-HBc positivity. At least two surveys of donors (Boston and Detroit) who were confirmed positive for anti-HIV before CUE was instituted, indicated they would not have considered their blood unfit for transfusion had CUE been in place at the time of donation because they did not believe themselves to be at risk for HIV infection. l6 There is evidence of donor confusion around CUE from a more recent prospective analysis in the Boston area (since CUE has been in place there) of donors who indicated “do not transfuse”. About 0.22% of donors so indicated, but none tested anti-HIV or HBsAg positive, there was no increase in anti-I-& or STS positives, nor any increase in male or first time donors among the first 900 surveyed. In addition, although a number of donors in this group returned to donate subsequently, none has yet seroconverted, and a significant percentage of donors who indicated not for transfusion once, subsequently indicated OK for transfusion. Thus it would appear that some donors do not understand the instructions, or may be healthy individuals concerned about a recent exposure. Due to the confidential nature of the exclu-

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sion, it is difficult to determine the relative importance of each. The lack of increase in other markers or seroconversions suggest that donor confusion plays a substantial part.15 Patterns of Anti-HIV Test Utilization. Both utilization of ATSs and anti-

HIV tests ordered by physicians have increased with the increase in media attention to anti-HIV testing issues. Projections of heterosexual spread of HIV have been publicized as have Centers for Disease Control (CDC) recommendations for testing of persons transfused with untested blood components between 1977 and 1985. With the increased volume of testing, the rate of positives among those being tested has decreased, apart from testing of specific groups known to be at risk. These rates are still many times that of volunteer blood donors while the rate of positives among blood donors continues to go down. Some level of abuse of the blood donor process may occur, but it appears not to be increasing and not to be by those at particular risk. The temporal length of the window of infectivity between exposure and development of detectable antigen or antibody may become shorter with HIV antigen testing or earlier detection of anti-HIV (e.g. with an IgM antibody assayzb), but there always will be a window of some length. THE IMPACT OF THE AIDS EPIDEMIC ON BLOOD DONORS AND DONATIONS

While the previous section has described the substantial beneficial impact of blood collection agencies’ efforts excluding as potential donors those at some risk for HIV infection, there appear also to have been neutral as well as negative effects of the AIDS epidemic upon potentially suitable volunteer blood donors. Some intelligent persons, knowing themselves not to be at risk for HIV, refuse to donate blood solely because they do not want to risk being identified as a “false positive” for anti-HIV. While

they may understand the nature (and necessity of) of such false positives, they may not want to be faced with the information, and they may fear being listed on a donor surveillance registry, in spite of the lack of demonstration of abuse of such registries. It is surprising to some blood bankers that in spite of the massive amount of AIDS educational material that has barraged the public, a substantial proportion of the general public still feel incorrectly that it is possible to contract AIDS from donating blood. Perhaps the associations of AIDS with needles (reuse by intravenous drug abusers) and with blood (TA-AIDS prior to screening) have prompted the inappropriate association of AIDS with the sterile nonreusable needle utilized in the collection of blood for transfusion. Sixty percent of adolescents in Massachusetts surveyed in 1986 thought that one could get AIDS from donating blood. 27 Serial public opinion surveys commissioned by the MBB have indicated that the percentage of the general public thinking that one can get AIDS from a blood donation decreased from 34% to 27% from 1985 to 1986.z8 Unpublished observations have been made about decreases in donations from military personnel after announcement of HIV testing, as well as after announcement of deferral for prostitute contact within the previous 6 months. It appears that blood donations decreased after major media coverage of AIDS related stories, particularly those that had to do with blood transfusion, hemophilia, or testing. A loose association of fewer than expected presenting donors (or an increase in the donor “no show” rate) after such publicity in the Boston area was found in the early years of AIDS. With the subsequent daily coverage of AIDS related stories, and with the forceful public relations campaigns pointing out that you can’t get AIDS by donating blood, this association is no longer apparent. In addition to these generic effects upon the potentially eligible donor pool,

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there have been specific and variable effects upon individual blood donors. For example, in the investigation of each case of transfusion associated AIDS or HIV infection reported to it, the blood collection agency reviews the records of the donors involved to see if any of these donors has been found to be confhmed positive for anti-HIV on any donations made subsequent to the implementation of anti-HJV testing. Almost all of these cases involve donations prior to the availability of anti-HIV testing in the spring of 1985. If a donor is infected, and unknowingly infected, this person should be identified, notified, and counseled for his or her own sake, but also to prevent further spread through his or her subsequent sexual contacts. Since the average patient with TA-AIDS has received a dozen or more blood components, a number of uninfected donors may need to be contacted and asked to be tested before the infected donor is identified. This notification and request for testing due to possible implication in TA-AIDS is not always well received by the unsuspecting donor. Donors to whom the investigation is well explained and who know that they could not be the suspect donor usually cooperate quite willingly, In other cases, there may be substantial anxiety in the donor, and in some cases other family members, until negative test results are available. Unfortunately the more regular donor (who stopped donating by early 1985) is at greater risk of being involved in such an investigation since components of his or her donations will have been transfused to a larger number of patients. Concerned donors who do test negative at the time of the investigation (which is virtually always more than 6 months after the donation due to the dating period of the components, the incubation period of TA-AIDS or TA-HIV-positive, the delay in reporting, and the time required in fInding the donors) are still often relieved to learn that another donor to “their” case of TA-AIDS has been found to be confhmed positive for anti-HIV. This is particularly true if such a donor learns

that he or she has been a “false positive”, which is ordinarily difficult to explain but is exceptionally more so in this situation. Prior to FDA licensure of anti-HIV testing, several tens of thousands of blood donors were asked to participate, with informed consent, in a clinical trial of prelicensure versions of the test. IIIformed consent was necessary since the significance of the screening test, and of the conf%rmatory test at that time, in a low risk population (i.e. blood donors) was not yet known. Having the blood donation experience prolonged by being asked to participate in the clinical trial and having to understand the lengthy informed consent was an additional demonstration of the dedication of committed blood donors. Then, in particular, it was not easy for the donor or the inexperienced notifier (counsellor ) when notification had to be made of a positive test result, the significance of which was unclear. As concern continues about new infections and new tests for “old” infections, blood donors will continue to be asked to participate in such necessary clinical trials at times when we know less than we would wish about the significance of these new screening tests. Unfortunately it is apparent from interviews with anti-HIV confirmed positive donors that some of them donated primarily to learn their test results. This behavior is also suggested by the fact that now most anti-HIV confirmed positive donors are fist time donors, male, and with a higher likelihood of positivity for a hepatitis B marker. While this effect is very small compared to the large number of negative donors (currently national rate of confirmed positives is less than 1 in 10,000 donations in the Red Cross system), it is a qualitatively negative effect of the AIDS epidemic upon blood donations. With respect to transfusion safety, the concern is not so much the positives (whose donations are not released for transfusion), but the recently exposed but not yet seroconverted donors who do not indicate not for transfusion using the CUE mechanism. This under-

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scores the importance of providing not only clear and simple instructions to prospective and productive blood donors (concerning self-exclusion, deferral, and CUE), but also providing convenient and comfortable opportunities for anti-HIV testing outside the blood donor setting, e.g. ATSs.

THE NOTIFICATION PROCEDURE FOR DONORS SEROPOSITIVE FOR HIV

When donor anti-HIV testing was implemented just after licensure in the spring of 1985, donors found positive were generally not notified immediately for several reasons. One was to avoid perception among high risk groups that donating blood for transfusion would be a quick, free, and confidential way to learn one’s anti-HIV test status. Legislation in some areas prevented donor notification for a time, and in other areas notification of confirmed positive donors was purposefully delayed until ATS programs were in place and publicized. FDA licensure of an ELISA test for anti-HIV screening was based upon data regarding test performance in high risk populations as well as in blood donors from several centers. The licensure review and granting process was rapid, but there was concern about the implications of notifying blood donors based upon a test with which most blood collection center directors had as yet no experience-a test with incredible implications for the person being notified. With virtually nationwide implement of testing, data became available within months which demonstrated that the rate of anti-HIV ELISA reactivity or repeat reactivity in a given center bore no relationship to the prevalence of AIDS cases in that community. There was not an overrepresentation of males, or HBsAg or STS positivity in ELISA reactive, but unconfirmed donations; whereas the rate of Western blot confirmed positivity bore a remarkably clear relationship to the

prevalence of AIDS cases in the area, and anti-HIV Western blot confirmed positive donors included a greater percentage of males (in the age group at greatest risk for AIDS) than the donor population at large, and demonstrated a many-fold increase in the rate of HBsAg positivity. These data gave some comfort and greater justification to those responsible for donor notification of confirmed positive results. Notification of such confirmed positive donors with personal counseling revealed that almost all admitted to being at some risk for HIV infection. Some had donated to learn their test results thinking that if they were positive the blood would not be transfused (not realizing the danger of infectivity in the “window” period); others, not knowing the length of the incubation period, had donated not considering themselves at risk because of their last potential exposure being long ago; and others did not realize the possibility of HIV infection in asymptomatic individuals in risk groups and felt that exposure to only a single or a few sexual partners had not placed them at risk of infection. Such information from early notifications of confirmed positive donors justified the increasing strictness of the definition of risk groups in the information presented prior to donation (e.g. to exclude any man who has had sex with one other man since 1977, even oncei. Specific details of actual donor notification of confirmed positive anti-HIV results have varied among centers and evolved over time with experience and availability of other resources. The following procedure is not atypical. A registered letter, return receipt requested, which does not specifically mention anti-HIV positivity, is sent to the donor who is instructed to call for an appointment to discuss test results. A physician or experienced counsellor meets with the donor to discuss the meaning of the test result as known today, which includes: the test alone does not diagnose AIDS and one cannot predict illness; those positive should

Impact

consider themselves infectious and precautions must be taken to avoid infecting others; blood, organs, or semen must not be donated in the future; sexual contacts should be notified; referrals for medical or counseling followup are provided; they should notify their health care provider(s). In some areas, counseling of notified positives is performed by the department of public health or another agency with which the blood center may have an arrangement. It is important to maintain confidentiality for the donor in these situations in order to maintain the public’s trust for recruiting suitable donors in the future. In a few centers confirmed positive donors have been provided the opportunity to participate in a prospective study, designed to determine the significance of anti-HIV positivity (and other markers) in asymptomatic persons, by following them at 6 month intervals for up to 5 years.29 The blood center’s responsibility does not include direct medical care for participating individuals.

THE AMBIVALENT APPROACH TO ELISA POSITIVE/WESTERN BLOT NEGATIVE DONORS There has been great difficulty, and some disagreement, about how to deal with donors repeatably reactive by ELISA, but not confirmed by Western blot. Even though data supported no greater risk of HIV infectivity from ELISA repeat reactive Western blot negative than ELISA negative donations, 30without a licensed confirmatory test FDA did not condone use of such units for transfusion or even use of subsequent entirely negative donations from the same individual. Some ELISA repeat reactive but unconfirmed donors remained consistently repeat reactive on subsequent donations when using the same manufacturer’s test kit. These probably included those donors with ELISA reactivity against a tissue type (e.g. HLA) of the lymphocytes in which the test kit manufacturer main-

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tained virus used for production of the reagent. Some ELISA repeat reactive tmconfirmed donors were not still reactive on subsequent donations even with the same manufacturer (different lot). Since it was expected that all subsequent donations from such individuals would not be used for transfusion, blood collectors could either notify them, tell them not to donate, and put them on their donor deferral list-or just put them on the donor deferral list without notification and discard all subsequent donations from these individuals. For whole blood donors, many centers did not notify (although they may no longer have recruited these persons as donors again), and continued to discard subsequent donations until the “reinstatement” policy for “reentering” donors became acceptable in 1987 with FDA licensure of a Western blot test. Exceptions were usually made by such centers for plateletpheresis donors (and whole blood donors with rare red cell types), however, it was not appropriate to recruit a donor to donate by apheresis for a patient’s need and discard the platelets. Explaining to such apheresis donors, often long term regular donors, that they should not donate because they have a false positive test for AIDS is very difficult-much more difficult than explaining a false positive test for syphilis. In most cases, even after long, detailed, and caring explanations by several individuals, such donors often do not really understand why they have nothing to worry about but the blood can’t be used for transfusion; some have concluded that the blood center doesn’t know what it’s talking about (particularly when their doctor repeated the test on another sample and it was negative), and others that they really have AIDS and the blood center doesn’t want to tell themboth incorrect conclusions. Many expect that their name or identifying information would be placed on a list to ensure that subsequent donations will not be used for transfusion. Certainly this has been the case for I-IBsAgpositive donors (although in some

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areas I-IBsAg reactive but unconfirmed positives or biologically false positives for syphilis may not have been informed and allowed to continue to donate, with their subsequent donations discarded). Rationalizations for not informing ELISA reactive Western blot negative donors included: 0 Resources must first be devoted to informing and counseling confirmed positive donors, and discourage all at risk from coming to donate in the first place. 0 Pre- 1985 transfusion of units later found to be ELISA repeat reactive Western blot negative did not result in anti-HIV seroconversion in recipients as did transfusion of components from Western blot positive donors.30 ELISA repeat reactive 0 Those Western blot positive donors notified demonstrated no other evidence of HIV infection or AIDS risk by other laboratory tests (including HIV culture) or detailed history. 0 There was no demonstration that these ELISA only reactive donors were in the early stages of seroconversion. 0 There was no real “significance” of these test results to donors and the responsibility of blood collectors has been to notify donors only of findings of significance. 0 Donor deferral registry listing of ELISA repeat reactive Western blot negatives was really only on a temporary basis until the issue would become clarified. 0 Listing was really for surveillance and further analysis rather than deferral. l It was a greater disservice to the individual to become psychologically upset by a medically unimportant laboratory finding than to keep information from the donor until its real significance if any was determined. 0 It made no sense to notify a donor of a tiding that depended only

the manufacturer or the manufacturer’s lot of reagents used. On the other hand, an argument was made that donors had a right to know that their name was being kept on a list, and they therefore should be so informed. Due particularly to improvement in specificity of the ELISA screening test since its initial development, relatively fewer new donors were being entered into this deferral/surveillance category. Finally a Western blot test for anti-HIV was licensed by FDA, and a procedure for allowing use of subsequent negative donations from donors ELISA repeat reactive Western blot negative was found acceptable (see section below]. Early on, the commercial plasma industry in some cases took another approach to this problem with its paid plasmapheresis donors. Since plasma from donors found to be ELISA repeat reactive could not be used in any event, they did not perform confirmatory testing, but advised their repeat reactive paid donors not to return, and to see a physician for evaluation and confirmatory testing. Assuredly this approach was not well received by these donors. How well they followed up for testing, and counselling is probably not known. THE REINSTATEMENT POLICY FOR RE-ENTERING ELISA POSITIVE/ WESTERN BLOT NEGATIVE BLOOD DONORS

In spite of no evidence indicating risk of transmitting HIV from ELISA reactive Western blot negative units, and the accumulation of an estimated 50,000 donors in this state of limbo, it was not until an FDA licensed Western blot became available in 1987 that the FDA would condone release for transfusion of ELISA negative units from donors previous found to be ELISA only reactive. The procedure required to remove such donors from the surveillance list and permit transfusion of subsequent donations (“re-entry”) is quite involved. It requires freezing of an aliquot of the ELISA repeatedly reactive Western blot

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negative sample and testing it later along with another sample from the same donor drawn at least 6 months after the original ELISA reactive donation. Both samples must be tested by ELISA again each using ELISA tests developed from the original as well as from another cell line. The second sample must also be tested by Western blot. If these tests are then all negative, the donor may be “re-entered”. This 6 month period is based upon the fact that if the donor were to seroconvert it would be expected to have happened during this period.

REFERENCES 1. Goldfield M, Black HC, Bill J, et al.: The consequences of administering blood pretested for HBsAg by third-generation techniques: a progress report. Am 1 Med Sci 1975; 270:335-342. HJ, 2. Seeff LB, Wright EC, Zimmerman Hoofnagle JH, Dietz AA, Gelsher BF, Garcia-Pont PH, Gerety RJ, Greenlee HB, Kieman T, Leevy CM, Nath N, Schiff EJ, Schwartz C, Tabor E, Tamburro C, Vlahcevic Z, Zemel R, Zimmon DS: Posttransfusion hepatitis, 1973-1975: a verterans administration cooperative study, in Vyas GN, Cohen SN, Schmid R (eds): Viral Hepatitis Philadelphia, PA, The Franklin Institute Press, 1978. 3. Aach RD, Lander JJ, Sherman LA, Miller WV, Kahn RA, Gitnick GL, Hollinger FB, Werch J, Smuness W, Stevens CE, Keller A, Weiner JM, Mosley JW: Transfusiontransmitted viruses: interim analysis of hepatitis among transfused and nontransfused patients, in Vyas GN, Cohen SN, S&mid R (eds): Viral Hepa this Philadelphia PA, The Franklin Institute Press, 1978. 4. Goldfield M, Bill J, Colosimo F: The control of transfusion-associated hepatitis, in Vyas GN, Cohen SN, S&mid R (eds): Philadelphia PA, The Franklin Institute Press, 1978. associated AIDS5. Possible transfusion California. Morbid Mortal Weekly Rep 1982; 311652-654. carinii pneumonia among 6. Pneumocystic persons with hemophilia A. Morbid MOItal Weekly Rep 1982; 31:365367. De7. Lamb GA: Personal communication. puty Commissioner for Clinical Programs and Community Health, Boston Department of Health and Hospitals.

8. Seage GR, Barry MA, Landers S, Silvia AM, Lamb GA: Patterns of blood donations among individuals at risk for AIDS. Am I Public Health. In press. 9. Massachusetts Alternative Testing Site experience reviewed at FDA Blood Products Advisory Committee Meeting on 13-14 February 1986 by PL Page. 10. Plasma Quarterly 1984; 55-64. 11. Personal experience of author regarding

refusal to continue to run bloodmobiles in Provincetown, Mass. any more.

12. Hirsch A: Personal communication, New York Blood Center. 13. What you must know about donating blood. American Red Cross Blood Services, late 1987 version. 14. Pindyck J, Waldman A, Zang E, Oleszko W, Lowy M, Bianco C: Measures to decrease the risk of acquired immunodeficiency syndrome transmission by blood transfusion-evidence of vohmteer blood donor cooperation. Transfusion 1985; 2513-9. 1.5. Popovsky MA, McGuff J, Chambers LA, Volpp J, Page PL: Confidential Unit Exclusion (check-off )-is it valuable? Transfusion 1987; 27:520 (abstr. S55). to FDA Blood 16. Page PL: Presentation Products Advisory Committee on 11 September 1986 of AW Shafer and PL Page data. 17. Recommendations of the Immunization Practices Advisory Committee (ACIP). Morbid Mortal Weekly Rep 1984; 33:8418. ~~CFR606.I60Records(b)/l)(ii):Permanent and temporary deferrals for health reasons including reason(s) for deferral (p 37 in 1 April 1987 edition). 19. Dahlke M: Designated blood donations. N Engl 1 Med 1984; 310:1195. self20. Grindon A: Efficacy of voluntary deferral of donors at high risk of AIDS. Transfusion 1984; 24~434 (absts.]. 21, Grady G, Carr R, Kunches L: Personal communication. MA ATS success in deterring at-risk individuals from donating blood for transfusion. 22, Chambers LA: Personal communication. Several HIV+ donors not aware of ATS. 23. Schorr JB, Berkowitz A, Cumming PD, Katz AJ, Sandler SG: Prevalance of HTLV-III antibody in American blood donors. N Engl I Med 1985; 313:384385. PD, Schorr JB, Wallace EL: 24. Cumming Annual blood facts. Prepared by the American Red Cross, 16 September 1987. R: Personal communication. 25. Dodd American Red Cross. 26. JoHer-Jemelka H, Grob PJ: HIV-Serologie

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in der Fruhphase einer HIV-Infektion. Schweiz Med Wochenschr 1987; 117:1283-1288. Stnmin L, Hingson R: Acquired immunodeficiency syndrome and adolescents: knowledge, beliefs, attitudes, and behaviors. Pediatrics 1987; 79:825-888. AABB News Briefs 1987; lO(3). Williams AE, prince HE, Epley KM and the American Red Cross Collaborative

Study Group: Clinical progression of infection in former blood donors infected with HIV-I. Abstract presented at 4th ht. Conf. on ADS, Stockholm, Sweden, June 12-16, 1988. 30. Alter HJ, Esteban JI, Shih JW-K, Kay J, Tai CC: A prospective study of the infectivity of anti-HTLV-III positive blood $b;i;;. hansfusion 1985; 25:479(S137) ..