Should all blood from related donors be irradiated?
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Biomedical subjects
Publications and source records attributed to H A Perkins.
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BACKGROUND: Reports of transmission of the human immunodeficiency virus type 1 (HIV-1) from transfusions of screened blood and reports of silent, antibody-negative HIV-1 infections in persons at high risk continue to foster concern about the safety of the blood supply. Previous estimates of the risk of HIV-1 range from 1 in 38,000 to 1 in 300,000 per unit of blood but are based on either epidemiologic models or the demonstration of seroconversion in recipients. METHODS: We isolated peripheral-blood mononuclear cells from blood that was fully screened and found to be seronegative, combined them into pools of cells from 50 donors, and tested them for HIV-1 by viral culture and the polymerase chain reaction, using protocols specifically adapted for this analysis. RESULTS: The 1530 pools of mononuclear cells were prepared from 76,500 blood donations made in San Francisco between November 1987 and December 1989. Of these pools, 1436 (representing 71,800 donations) were cultured successfully; 873 (43,650 donations) were evaluated by the polymerase chain reaction. Only one pool was confirmed as HIV-1--infected by both methods. After adjustment for sample-based estimates of the sensitivity of the detection systems using culture and the polymerase chain reaction, the probability that a screened donor will be positive for HIV-1 was estimated as 1 in 61,171 (95 percent upper confidence bound, 1 in 10,695). CONCLUSIONS: Silent HIV-1 infections are exceedingly rare among screened blood donors, so the current risk of HIV-1 transmission from blood transfusions, even in high-prevalence metropolitan areas, is extremely low.
Little information is available regarding the risk of human immunodeficiency virus type 1 (HIV-1) infection for patients transfused before routine anti-HIV-1 screening of blood donors was instituted in March 1985. A model was developed for estimating both the proportion and the number of transfusion recipients in the San Francisco Bay area who were infected by HIV-1 during each of the 7 years preceding routine donor screening for anti-HIV-1. The model is based on analysis of 1) donation histories of HIV-1-infected donors identified at the regional blood center; 2) HIV-1 seroprevalence estimates for homosexual and bisexual men in San Francisco; and 3) HIV-1 infection and survival rates for recipients traced by the Transfusion Safety Study and Irwin Memorial Blood Centers' Look Back Program. The incidence of transfusion-associated HIV-1 infection is estimated to have risen rapidly from the first occurrence in 1978 to a peak in late 1982 of approximately 1.1 percent per transfused unit. The decrease after 1982 coincided with the implementation of high-risk donor deferral measures. It is estimated that, overall, approximately 2135 transfusion recipients were infected with HIV-1 in the San Francisco region alone. This number suggests a higher prevalence of transfusion-associated HIV-1 infection than has been generally recognized and indicates the need for continued tracing of potentially exposed recipients. The data also strongly support the effectiveness of early donor education and self-exclusion measures and emphasize the importance of continued research and development in this area.
A large number of well-characterized HLA typing sera were used in a standard cytotoxicity technique to evaluate the frequency with which homozygous cells reacted to antisera directed against a crossreacting specificity. Four of 15 anti-HLA-A1 sera reacted with cells homozygous for HLA-A11 bet not with A11 heterozygotes. Similar dosage effects were noted with anti-A3 sera and A11 cells, with anti-A28 sera and A2 cells, with anti-A23 sera and A24 cells, and with anti-A24 sera and A23 cells. No dosage effects were seen with anti-A1 sera and A3 cells, with anti-A3 sera and A1 cells, and with anti-A11 sera and either A1 or A3 cells. Dosage effects were also not seen with anti-B51 or -B35 sera and cells containing antigens of the B5 crossreacting group. Dosage is a property of the individual serum and does not occur with all samples sharing the same primary specificity. As noted by red cell serologists, sera demonstrating dosage effects are common with some specificities but absent with others. The reactions noted may be a quantitative effect of epitopes present on certain antigens. Caution should be observed when interpreting an HLA phenotype that appears to contain two crossreacting antigens at the same locus, unless the sera used have been shown not to manifest dosage effects.
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Patients infected by the human immunodeficiency virus (HIV) as a result of blood transfusions are unique in that their dates of infection are well defined and their medical conditions before infection are known. To characterize the natural history of transfusion-associated HIV infection, we studied 694 recipients of blood from 112 donors in whom AIDS later developed and from 31 donors later found to be positive for HIV antibody. Of the recipients tested, 85 were seronegative, 116 were seropositive, and 19 had AIDS. Of 101 HIV-seropositive recipients followed for a median of 55 months after infection, 54 had Centers for Disease Control Class IV disease, including 43 with AIDS. Life-table analysis suggested that AIDS will develop in 49 percent of infected recipients (95 percent confidence limits, 36 to 62 percent) within seven years after infection. As compared with recipients without AIDS, the 43 recipients with AIDS had received more transfusions at the time of infection (median, 21 vs. 7; P = 0.01). HIV-infected blood donors in whom AIDS developed were grouped according to whether AIDS developed within 29 months (the median) after donation (Group 1) or 29 or more months after donation (Group 2). As compared with the 31 recipients of blood from Group 2 blood donors, the 31 recipients of blood from Group 1 donors were more likely to have AIDS four years after infection (49 percent vs. 4 percent; P = 0.005) and illnesses resembling acute retroviral syndrome (14 of 24 vs. 5 of 22; P = 0.03). We conclude that most recipients of HIV-infected blood become seropositive, that AIDS develops in about half these recipients within seven years, and that the risk may be higher when AIDS develops in the blood donor soon after donation.
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Several filters for leukocyte removal were evaluated in terms of their ability to reduce the cell-associated human immunodeficiency virus (HIV) load in units of blood either inoculated in vitro with lymphocytes from a chronically infected cell line or collected directly from seropositive donors. Filtration of the experimentally inoculated units of blood resulted in a 5.9 log 10 mean reduction (95% confidence interval:7.4-4.5) of tissue culture infectious units (TCIU) as assayed by end-point titration using the coculture assay. Filtration of the units of blood from anti-HIV positive donors lowered the infectivity by over 2 logs, as detected by the coculture and polymerase chain reaction (PCR) techniques. However, residual cell-associated virus was detected in the majority of experiments. Clinical studies are warranted to determine if leukocyte filtration of blood will reduce the risk of transfusion transmitted viral infections.
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Acquired Immunodeficiency Disease (AIDS) may be transmitted by transfusion of blood components, although the risk remains extremely small. This report reviews the evidence for transmission by transfusion, the risk in several different situations, and the steps blood banks have taken to prevent transfusion of blood from donors at risk for AIDS. A test for the antibody to the virus responsible for AIDS (HTLV-III) will shortly be in routine use in blood banks, but the frequency with which the results will be falsely negative or falsely positive in a blood donor population remains to be established.
An enzyme immunoassay (EIA) system has been developed to measure factor VIII-related antigen (VIIIAGN). This assay gives similar results to the commonly used Laurell electroimmunodiffusion (EID) assay for VIIIAGN as shown by comparison of both techniques with samples from healthy controls, patients with hemophilia A, and patients with von Willebrand's disease. The assay also has a greater precision than the EID technique as demonstrated by multiple assays of aliquots of a single sample. The use of this EIA test for VIIIAGN is simple and employs inexpensive reagents and equipment. The use of expensive antisera is minimized. EIA for VIIIAGN has the advantage of increased sensitivity compared to Laurell EIA.
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The recent withdrawal of commercial fibrinogen from the market makes alternate sources most important. Although it has been previously reported that single-donor cryoprecipitate contains appreciable amounts of fibrinogen, most clinicians need to be reminded of the reliability of cryoprecipitate for replacement of both fibrinogen and factor VIII. We assayed fibrinogen from 88 bags of cryoprecipitate prepared by five different blood banks in California and Oregon; we found that the average bag of cryoprecipitate contains at least 250 mg of fibrinogen depending on the volume of plasma processed. Cryoprecipitate was found to be a poor source of factors II, V, IX, X, XI, and XII.
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Diagnosis of deficiencies of coagulation factor VIII can be difficult to establish in some cases. The use of the factor VIII-related antigen and the use of the ristocetin cofactor assays have increased the reliability of diagnosis of factor VIII deficiency in patients with hemophilia A or von Willebrand's disease, and in carriers of hemophilia A. The authors re-evaluated samples, from frozen storage, of blood from patients previously diagnosed as having von Willebrand's disease. This diagnosis was based on clinical history, family history, bleeding time, factor VIII procoagulant activity, and response to ristocetin in platelet-aggregation studies. Eleven cases were studied by the review of previously obtained data and the addition of the factor VIII-related antigen and ristocetin-cofactor assays. In two of eleven cases, the diagnosis was changed to possible hemophilia A carrier state.
Definition of one unit of factor VIII procoagulant activity may be imprecise, for a number of reasons. Levels in individual normal plasmas differ sufficiently that small pools do not have equivalent activities. Large pools cannot be prepared without loss of activity because of the lability of factor VIII. Human factor VIII may not be stable at --20 C. Lyophilized standards may vary in activity because of difficulties in dissolving the materials. The authors have prepared standards that are stable at --20 C for years using beef plasma diluted in outdated human blood bank plasma. The level of activity of this working standard is verified by repeated assays of lyophilized national standards and of small pools of normal donor plasma. The standard is equally applicable to one- or two-stage assays for factor VIII.