Herbert A. Perkins

EVALUATION OF SCREENED BLOOD DONATIONS FOR HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 INFECTION BY CULTURE AND DNA AMPLIFICATION OF POOLED CELLS

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.

Nonhemolytic Febrile Transfusion Reactions

The conditions under which nonhemolytic febrile transfusion reactions developed in eight afebrile patients were investigated. Recipients invariably developed a reaction on transfusion of incompatible white cells if a sufficient quantity of leukocytes was infused. The sensitivity of each patient differed with respect to the number of incompatible white cells which could be tolerated without a reaction. In general, the in vivo reaction to blood from an individual donor could be predicted by the routine leukocyte agglutination test. Mild febrile reactions were inconstantly observed in three patients transfused with presumably compatible leukocytes. Further investigation suggested that the cells inducing reaction were probably incompatible, and that in vivo reactions were a more sensitive index than the in vitro test. Granulocytes, lymphocytes or platelets, separately administered, all induced febrile reactions, provided that the routine leukocyte agglutinin test demonstrated an incompatibility. There was no direct evidence that febrile reactions had occurred in response to plasma infusion. It is concluded that white cell antibodies were the primary cause of nonhemolytic febrile transfusion reactions in this series, and that the detection of white cell antibodies and preparation of leukocyte‐poor blood continue to be procedures of practical importance in modern transfusion therapy.

Risk of human immunodeficiency virus (HIV) transmission by blood transfusions before the implementation of HIV-1 antibody screening

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.

Transfusion-associated infections: 50 years of relentless challenges and remarkable progress

T he possibility of transfusion-transmitted infections has been a worry from the beginning of the modern era of blood banks. Beginning with the evidence that syphilis could be transmitted by blood transfusion and followed by increasing concerns about hepatitis, alarm peaked in the 1980s with the recognition of transfusion-associated AIDS and appreciation of the magnitude of transfusion transmission of hepatitis C virus (HCV). In more recent years the story has been one of remarkable successes in reducing transmission of known viral agents and rapid responses to emerging infectious diseases that are documented to be transmitted by blood transfusion. This review will address the response of the blood banking community to the major transfusion-transmitted infectious diseases (TTIDs) over the past 50 years, during which time the evolving appreciation of risk and progress in addressing TTIDs has been documented by more than 1000 publications in TRANSFUSION. Figure 1, which presents the annual number of publications in the journal focused on TTIDs relative to total publications, serves to demonstrate the increasing importance of TTIDs to the transfusion medicine community. It is evident that papers on TTIDs grew from a handful of papers per year that represented a minor proportion of the journal’s publications to more than 50 papers per year representing 25% of articles appearing in TRANSFUSION in the 1980s and 1990s. The papers represented in the figure chronicle the remarkable contributions of several generations of scientists who not only aggressively addressed blood safety concerns but also advanced our understanding of methods of detection, natural history, and pathogenesis of TTIDs through studies of infected donors and recipients.

The natural history of alloimmunization to platelets.

Sixty‐three patients have provided evidence that platelets are highly immunogenic even in recipients of potentially immunosuppressive therapy for malignant diseases. Approximately 70 per cent of patients who receive repeated transfusions of platelets from random donors over a prolonged period can be expected to develop lymphocytotoxic antibodies. Antibodies became detectable in one patient ten days after his first exposure to HLA antigens in the form of platelet concentrates, and as early as four days in two patients with prior exposure to HLA antigens. In the most heavily immunized patients, the presence of antibody correlated with poor increments of platelets after transfusion. Patients with prior exposure to HLA antigens are more likely to have antibodies resulting in poor platelet survival. On the other hand, 30 per cent of recipients of repeated platelet transfusions show no tendency to form cytotoxic antibodies.

Prevalence of Human Immunodeficiency Virus Type 1 p24 Antigen in U.S. Blood Donors — An Assessment of the Efficacy of Testing in Donor Screening

Abstract Background. We performed a multicenter study in 1989 to determine whether screening whole-blood donors for human immunodeficiency virus type 1 (HIV-1) p24 antigen would improve transfusion safety by identifying carriers of the virus who are seronegative for HIV-1 antibody. Methods. More than 500,000 donations were tested at 13 U.S. blood centers with test kits from two manufacturers. Units found repeatedly reactive were retested in a central laboratory; if the results were positive, they were confirmed by a neutralization assay. A subgroup of units was also tested for HIV-1 by the polymerase chain reaction. Selected donors confirmed or not confirmed as having p24 antigen were contacted for follow-up interviews to identify risk factors and undergo retesting for HIV-1 markers. Results. Positive tests for p24 antigen were confirmed by neutralization in five donors (0.001 percent of all donations tested), all of whom were also positive for HIV-1 antibody and HIV-1 by polymerase chain reaction. Three ...

Enzyme-Linked Antiglobulin Test: An Accurate and Simple Method to Quantify Red Cell Antibodies

An enzyme‐linked antiglobulin test was used to quantify the amount of IgG antibodies on red blood cells. Erythrocytes were sensitized with various blood group antibodies, washed, incubated with antiglobulin conjugated with alkaline phosphatase, washed, substrate was added and the optical density of the product was measured. This optical density was linearly proportional to the concentration of red blood cell antibodies incubated with the cells. The assay was easy to perform, had a standard deviation of 7 per cent on replicated assays, and was more sensitive than the manual antiglobulin test.

The Transplanted Kidney As a Source of Hepatitis B Infection

Excerpt Hepatitis B infection is relatively common in renal transplant patients. Sources of infection include multiple blood product transfusions, hemodialysis machines, and close contact of the im...

Studies in Regional Heparinization

WHEN artificial-kidney hemodialysis is performed, the patient is ordinarily heparinized to prevent activation of the coagulation mechanism as the blood passes through the extracorporeal circuit. Th...

Immunologic factors determining survival of cadaver-kidney transplants. The effect of HLA serotyping, cytotoxic antibodies and blood transfusions on graft survival.

We assessed immunologic factors determining graft survival in 510 recipients of primary cadaver allografts at one center. The degree of HLA match grade did not directly affect graft survival (54 per cent in no-antigen match, and 42 per cent in three-antigen match, at two years). There was no correlation between the HLA match grade and the degree of stimulation of the mixed lymphocyte culture. Patients receiving more than five blood transfusions had a significantly better graft survival than nontransfused recipients (52 versus 23 per cent, respectively, at two years, P less than 0.001). The beneficial effect of transfusions was noted whether or not lymphocytotoxic antibodies were produced, provided adequate screening was performed before transplantation. Transfusions did not alter the degree of stimulation in the mixed lymphocyte culture. More liberal use of transfusions and frequent screening for cytotoxic antibodies would probably result in more effective cadaver-kidney transplantation.