Steven H. Kleinman

The Risk of Transfusion-Transmitted Viral Infections

Background Accurate estimates of the risk of transfusion-transmitted infectious disease are essential for monitoring the safety of the blood supply and evaluating the potential effect of new screening tests. We estimated the risk of transmitting the human immunodeficiency virus (HIV), the human T-cell lymphotropic virus (HTLV), the hepatitis C virus (HCV), and the hepatitis B virus (HBV) from screened blood units donated during the window period following a recent, undetected infection. Methods Using data on 586,507 persons who each donated blood more than once between 1991 and 1993 at five blood centers (for a total of 2,318,356 allogeneic blood donations), we calculated the incidence rates of seroconversion among those whose donations passed all the screening tests used. We adjusted these rates for the estimated duration of the infectious window period for each virus. We then estimated the further reductions in risk that would result from the use of new and more sensitive viral-antigen or nucleic acid s...

Red blood cell transfusion: A Clinical practice guideline from the AABB

DESCRIPTION Although approximately 85 million units of red blood cells (RBCs) are transfused annually worldwide, transfusion practices vary widely. The AABB (formerly, the American Association of Blood Banks) developed this guideline to provide clinical recommendations about hemoglobin concentration thresholds and other clinical variables that trigger RBC transfusions in hemodynamically stable adults and children. METHODS These guidelines are based on a systematic review of randomized clinical trials evaluating transfusion thresholds. We performed a literature search from 1950 to February 2011 with no language restrictions. We examined the proportion of patients who received any RBC transfusion and the number of RBC units transfused to describe the effect of restrictive transfusion strategies on RBC use. To determine the clinical consequences of restrictive transfusion strategies, we examined overall mortality, nonfatal myocardial infarction, cardiac events, pulmonary edema, stroke, thromboembolism, renal failure, infection, hemorrhage, mental confusion, functional recovery, and length of hospital stay. RECOMMENDATION 1: The AABB recommends adhering to a restrictive transfusion strategy (7 to 8 g/dL) in hospitalized, stable patients (Grade: strong recommendation; high-quality evidence). RECOMMENDATION 2: The AABB suggests adhering to a restrictive strategy in hospitalized patients with preexisting cardiovascular disease and considering transfusion for patients with symptoms or a hemoglobin level of 8 g/dL or less (Grade: weak recommendation; moderate-quality evidence). RECOMMENDATION 3: The AABB cannot recommend for or against a liberal or restrictive transfusion threshold for hospitalized, hemodynamically stable patients with the acute coronary syndrome (Grade: uncertain recommendation; very low-quality evidence). RECOMMENDATION 4: The AABB suggests that transfusion decisions be influenced by symptoms as well as hemoglobin concentration (Grade: weak recommendation; low-quality evidence).

A new strategy for estimating risks of transfusion-transmitted viral infections based on rates of detection of recently infected donors

BACKGROUND:  Estimates for human immunodeficiency virus (HIV)‐1 and hepatitis C virus (HCV) transfusion‐transmitted risks have relied on incidence derived from repeat donor histories and imprecise estimates for infectious, preseroconversion window periods (WPs).

Emerging infectious disease agents and their potential threat to transfusion safety

BACKGROUND: Emerging infections have been identified as a continuing threat to human health. Many such infections are known to be transmissible by blood transfusion, while others have properties indicating this potential. There has been no comprehensive review of such infectious agents and their threat to transfusion recipient safety to date.

The effect of previous pregnancy and transfusion on HLA alloimmunization in blood donors: implications for a transfusion-related acute lung injury risk reduction strategy

BACKGROUND: Antibodies to human leukocyte antigens (HLA) in donated blood have been implicated as a cause of transfusion‐related acute lung injury (TRALI). A potential measure to reduce the risk of TRALI includes screening plateletpheresis donors for HLA antibodies. The prevalence of HLA antibodies and their relationship to previous transfusion or pregnancy in blood donors was determined.

Motivations to donate blood: demographic comparisons

BACKGROUND: Understanding blood donor motivations is crucial to improving effectiveness of donor recruitment and retention programs.

Frequency of HBV DNA detection in US blood donors testing positive for the presence of anti-HBc: implications for transfusion transmission and donor screening

BACKGROUND: An estimate of the rate of HBV DNA‐positive, anti‐HBc‐positive units is important for evaluating the need for anti‐HBc donor screening, especially in the context of HBV NAT.

Infection with Human Immunodeficiency Virus Type 1 (HIV-1) among Recipients of Antibody-Positive Blood Donations

OBJECTIVE To assess the incidence of human immunodeficiency virus type 1(HIV-1) transmission by antibody (anti-HIV-1)-positive blood components, and to determine the immunologic and clinical course in HIV-1-infected recipients. DESIGN AND SUBJECTS We retrospectively tested approximately 200,000 donor blood component specimens stored in late 1984 and 1985 for anti-HIV-1, and we contacted recipients of positive specimens to determine their serologic status. They were compared with both recipients of HIV-1-negative transfusions and healthy (untransfused) controls. Subjects were seen at 3- to 6-month intervals for up to 4 years for clinical and immunologic evaluations. MEASUREMENTS AND MAIN RESULTS Of 133 recipients, 9 had other possible exposures. Excluding these cases, 111 of 124 (89.5%) were anti-HIV-1-positive (95% CI, 84.1% to 94.5%). The recipients sex, age, underlying condition, and type of component did not influence infection rates. The cumulative risk for developing the acquired immunodeficiency syndrome (AIDS) within 38 months after transfusion was 13% (CI, 7.5% to 21.6%). At 36 +/- 3 months after the index transfusion, seropositive recipients had lower counts of CD2+CDw26+, CD4+, CD4+CD29+, and CD4+CD45RA+subsets and more CD8+I2+ lymphocytes than did recipients of anti-HIV-1-negative transfusions. The CD4+ and CD2+CDw26+subsets changed the most rapidly. The absolute CD8+ count remained normal. CONCLUSIONS Transfusion of anti-HIV-1-positive blood infected 90% of recipients. The rate of progression to AIDS within the first 38 months after infection was similar to that reported for homosexual men and hemophiliacs. Although most lymphocyte subset counts changed over time, CD8+ counts were constant.

Infectivity of human immunodeficiency virus‐1, hepatitis C virus, and hepatitis B virus and risk of transmission by transfusion

A s the safety of blood transfusion has dramatically improved with respect to transmission of viral infection, one of the remaining challenges has been to accurately estimate the risk (termed the residual risk) of transfusion-transmitted viral infection for those viruses (human immunodeficiency virus [HIV], hepatitis C virus [HCV], hepatitis B virus [HBV]) for which donor screening is routinely performed. The basic tool applied to this task has been mathematical modeling, with the most commonly used model being the incidence rate–window period (I-WP) model. Originally developed in the mid-1990s, this model has been accepted as a valid and accurate approach by blood bankers and regulators around the world and it has widely been used by many international investigators to generate country specific residual risk estimates. An understanding of the relationship between viral load and infectivity is important for calculating the residual risk of infection using the I-WP model. An important variable in the model is the appropriate assignment of infectious risk to blood units (and their associated components) collected in the diagnostic window period (i.e., the time from the donor being exposed to the virus until the infection is detectable by a blood screening assay). From the transfusion safety as opposed to the diagnostic perspective, the window period used in the model ideally would correspond exactly to the time interval during which a donation is infectious. The most updated version of the I-WP model utilizes the observed consistent loglinear increase of viremia in early infection and the assumption that a unit collected during the window period will be infectious if at least one HIV, HCV, or HBV virion is present in the transfused component; the authors of this iteration of the model have assumed that additive solution (AS) red blood cells (RBCs) contain between 20 and 40 mL of plasma and that infectivity would occur at a 100% rate at a concentration of one viral genome/20 mL of plasma. This is clearly a worst-case scenario and leads to a more conservative (i.e., higher) estimate of residual risk than may exist. Others have proposed an alternative method for estimating the infectivity of a unit collected during the window period; this approach assigns a probability of infection to units with a specific nucleic acid (virion) concentration, rather than assuming that transmission at a given nucleic acid concentration occurs as an all-or-none phenomenon. Support for this probabilistic modeling is provided by experimental animal model systems in which the dose that causes infection in 50% of the animals has been routinely calculated based on a probability distribution. Not only is the understanding of the relationship of viral load to infectivity important in applying the I-WP model, it also is important for understanding the potential for transfusion transmission during early recovery and later chronic stages of viral infection. Because of differences in viral dynamics and antibody titer, specificity, and avidity during various phases of infection, it is plausible that infectivity at a given nucleic acid concentration may substantially differ across various stages of acute and chronic infection. For example, the correlation of infectivity with viral load may be expected to differ for window period, late acute phase, and chronic phases of infection due to the presence of neutralizing antibodies and/or development of more or less infectious (“fit”) viral quasispecies as they escape from humoral and cellular From the University of British Columbia, Vancouver, British Columbia, Canada; Novartis Vaccines and Diagnostics, Suresnes, France; and Blood Systems Research Institute, San Francisco, California. Address correspondence: Steven Kleinman, 1281 Rockcrest Avenue, Victoria, BC, Canada V9A 4W4; e-mail: skleinman@shaw.ca. Received for publication March 19, 2009; revision received May 8, 2009; and accepted May 8, 2009. doi: 10.1111/j.1537-2995.2009.02322.x TRANSFUSION 2009;49:2454-2489. ABBREVIATIONS: CID50 = 50% chimp infectious dose; geq = genome equivalents; ID = individual donation; I-WP model = incidence rate–window period model; MP(s) = minipool(s); OBI = occult hepatitis B infection; SIV = simian immunodeficiency virus; TC = target capture; TMA = transcription-mediated amplification; TTVS = Transfusion-Transmitted Viruses Study.

Dynamics of viremia in early hepatitis C virus infection.

BACKGROUND: It is important to characterize viral dynamics in early hepatitis C virus (HCV) infection to further our understanding of viral pathogenesis and the potential for secondary transmission in acute infection through blood transfusion or other routes.