Publications by authors named "Steven H Kleinman"

Red blood cell (RBC) metabolism regulates hemolysis during aging in vivo and in the blood bank. However, the genetic underpinnings of RBC metabolic heterogeneity and extravascular hemolysis at population scale are incompletely understood. Based on the breeding of 8 founder strains with extreme genetic diversity, the Jackson laboratory diversity outbred population can capture the impact of genetic heterogeneity in like fashion to population-based studies.

View Article and Find Full Text PDF

Background: Exposure to antiretrovirals at or early after HIV acquisition can suppress viral replication and blunt antibody (Ab) responses; a reduced HIV detectability could impact diagnosis and blood donation screening.

Methods: We used three antigen (Ag)/Ab assays and one nucleic acid test (NAT) to analyze samples collected in pre-exposure prophylaxis (PrEP) trials (iPrEx; Partners PrEP) before infection detection by Ab-only rapid diagnostic tests (RDTs), and in early antiretroviral treatment (ART) initiation studies (RV254; SIPP).

Results: Reactivity using NAT and Ag/Ab assays in samples collected up to 8 weeks prior to the first reactive RDT from 251 PrEP trials participants varied between 49-61% for active PrEP users and between 27-37% for placebo users.

View Article and Find Full Text PDF
Article Synopsis
  • A study tested plasma samples from 1596 donors who reported COVID-19 symptoms after donating blood for SARS-CoV-2 RNA and specific antibodies.* -
  • Results showed that having prior infection or vaccination provided protection against developing SARS-CoV-2 RNAemia and symptomatic infection.* -
  • The rates of RNAemia remained consistent regardless of whether the samples were taken during the Delta or Omicron variant phases.*
View Article and Find Full Text PDF

Background: Due to platelet availability limitations, platelet units ABO mismatched to recipients are often transfused. However, since platelets express ABO antigens and are collected in plasma which may contain ABO isohemagglutinins, it remains controversial as to whether ABO non-identical platelet transfusions could potentially pose harm and/or have reduced efficacy.

Study Design And Methods: The large 4-year publicly available Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) database was used to investigate patient outcomes associated with ABO non-identical platelet transfusions.

View Article and Find Full Text PDF
Article Synopsis
  • * A study tested 2,250 blood donors who had possible COVID-19 symptoms after donation, finding that the presence of SARS-CoV-2 RNA peaked at 9%-15% in late 2020, dropping to about 4% after vaccinations were released.
  • * Although RNA was detectable in some donors, no infectious virus was found in their plasma, indicating that blood transfusions are very unlikely to transmit SARS-CoV-2.
View Article and Find Full Text PDF

Restless legs syndrome (RLS) is a common sensorimotor disorder, which can disrupt sleep and is thought to be caused in part by low cellular iron stores. Proton pump inhibitors (PPI) and histamine H2-receptor antagonists (H2A) are among the most commonly used drugs worldwide and show evidence of causing iron deficiency. We conducted a case/non-case observational study of blood donors in the United States (N = 13,403; REDS-III) and Denmark (N = 50,323; Danish Blood Donor Study, DBDS), both of which had complete blood count measures and a completed RLS assessment via the Cambridge-Hopkins RLS questionnaire.

View Article and Find Full Text PDF
Article Synopsis
  • The study addresses how HIV incidence is estimated among blood donors in regions where many repeat donors only donate once in a given interval, which may skew standard estimates.
  • Two new methods for including these donors in estimates were tested: one treats partial cases based on time since the last donation, while the other counts a full case only if sufficient time has passed.
  • Results showed that the partial-case approach had less bias and performed better overall, suggesting it is a more reliable method for estimating HIV incidence in populations with high rates of single donations.
View Article and Find Full Text PDF

Background: Consensus definitions for transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) have recently been revised; however, pulmonary transfusion reactions remain difficult to diagnose. We hypothesized that N-terminal pro-brain natriuretic peptide (NT-proBNP) levels could have utility in the identification and classification of pulmonary transfusion reactions.

Study Design And Methods: We performed a secondary analysis of a case-control study of pulmonary transfusion reactions at four academic hospitals.

View Article and Find Full Text PDF

Significant research has focused individually on blood donors, product preparation and storage, and optimal transfusion practice. To better understand the interplay between these factors on measures of red blood cell (RBC) transfusion efficacy, we conducted a linked analysis of blood donor and component data with patients who received single-unit RBC transfusions between 2008 and 2016. Hemoglobin levels before and after RBC transfusions and at 24- and 48-hour intervals after transfusion were analyzed.

View Article and Find Full Text PDF

Objectives: Transfusion-associated circulatory overload is characterized by hydrostatic pulmonary edema following blood transfusion. Restrictive transfusion practice may affect the occurrence and severity of transfusion-associated circulatory overload in critically ill patients. We sought to examine contemporary risk factors and outcomes for transfusion-associated circulatory overload.

View Article and Find Full Text PDF

A decade ago, definitions of "transfusionߚrelated acute lung injury (TRALI)" and "possible TRALI" were standardized for research and clinical diagnosis. Since then, evidence has confirmed that TRALI is often due to transfusion of white blood cell antibodies to at-risk patients, and the term "TRALI, antibody mediated" is appropriate for such cases. Other TRALI cases are non-antibody mediated.

View Article and Find Full Text PDF

Background: The incidence of human immunodeficiency virus (HIV) in repeat blood donors has been estimated using seven methods. Although incidence is always calculated as cases per person-time, approaches to selecting cases and calculating person-time vary. Incidence estimates have not been compared among methods.

View Article and Find Full Text PDF

Importance: Although blood donation is allowed every 8 weeks in the United States, recovery of hemoglobin to the currently accepted standard (12.5 g/dL) is frequently delayed, and some donors become anemic.

Objective: To determine the effect of oral iron supplementation on hemoglobin recovery time (days to recovery of 80% of hemoglobin removed) and recovery of iron stores in iron-depleted ("low ferritin," ≤26 ng/mL) and iron-replete ("higher ferritin," >26 ng/mL) blood donors.

View Article and Find Full Text PDF

Background: Blood conservation strategies have been shown to be effective in decreasing red blood cell (RBC) utilization in specific patient groups. However, few data exist describing the extent of RBC transfusion reduction or their impact on transfusion practice and mortality in a diverse inpatient population.

Study Design And Methods: We conducted a retrospective cohort study using comprehensive electronic medical record data from 21 medical facilities in Kaiser Permanente Northern California.

View Article and Find Full Text PDF

Background: This study assessed the clinical sensitivity of three fully automated, human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV) triplex nucleic acid test (NAT) assays by individual donation (ID-NAT) and at operational minipool (MP-NAT) sizes used worldwide.

Study Design And Methods: MPX, Ultrio, and Ultrio Plus were used to test 2222 pedigreed, marker-positive samples with varying viral loads, each from a unique US blood donor. NAT-positive, seronegative yield samples (16 HBV, 156 HCV, and 23 HIV) were tested in replicates of three; undiluted; and in 1:6, 1:8, and 1:16 dilutions (MP6, MP8, and MP16), simulating various MP sizes.

View Article and Find Full Text PDF

Serial plasma aliquots (50 mL) obtained from 10 commercial donors who converted from hepatitis C virus (HCV) RNA negative to positive were transfused into 2 chimpanzees to assess infectivity during early HCV infection. Plasma, obtained 4 days before HCV RNA detectability by licensed assays, transmitted HCV infection to chimpanzee X355. The infectious PCR-negative plasma was subsequently shown to be positive in 2 of 23 replicates using a sensitive transcription-mediated amplification (TMA) assay, and estimated to contain 1.

View Article and Find Full Text PDF

Background: Genetic variations of human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV) can affect diagnostic assays and therapeutic interventions. Recent changes in prevalence of subtypes/genotypes and drug/immune-escape variants were characterized by comparing recently infected vs more remotely infected blood donors.

Methods: Infected donors were identified among approximately 34 million US blood donations, 2006-2009; incident infections were defined as having no or low antiviral antibody titers.

View Article and Find Full Text PDF

Background: Fingerstick blood samples are used to estimate donor venous hemoglobin (Hb).

Study Design And Methods: Fingerstick Hb or hematocrit (Hct) was determined routinely for 2425 selected donors at six blood centers, along with venous Hb. Using sex and measures of iron status including absent iron stores (AIS; ferritin < 12 ng/mL), linear regression models were developed to predict venous Hb from fingerstick.

View Article and Find Full Text PDF

Most industrialized countries maintain surveillance programs for monitoring transmissible infection in blood donations, revising approaches to methodology and risk assessment as new threats emerge. A comparison of programs in the United States, Canada, France, the UK, and Australia indicates that they have similar function, although the structure of blood programs vary as does the extent and nature of formal ties with public health. The emergence of HIV in the late 1970s and early 1980s was key in recognizing that surveillance systems specific to blood transfusion were essential.

View Article and Find Full Text PDF

Background: There have been no comparisons of the relative sensitivity of the two Food and Drug Administration-licensed multiplex (MPX) nucleic acid test (NAT) systems (Procleix Ultrio [Gen-Probe], TIGRIS platform [Novartis]; and cobas TaqScreen MPX [Roche Molecular Systems], cobas s 201 platform [Roche Instrument Center]) for detecting hepatitis B virus (HBV)-infected donors in minipool sizes (MP) used in the United States.

Study Design And Methods: Routine blood samples from Thailand were obtained from plasma units from 129 hepatitis B surface antigen (HBsAg)-negative, HBV NAT-yield donations. Blinded US testing included antibody to hepatitis B core antigen (anti-HBc), NAT using both manufacturers' systems (undiluted-individual donation [ID], in singlet and diluted 1:6 and 1:16 in triplicate), quantitative antibody to hepatitis B surface antigen, HBV DNA viral loads, and HBV genotyping.

View Article and Find Full Text PDF

Background: We used a multicenter retrospective cohort study design to evaluate whether human leukocyte antigen (HLA) antibody donor screening would reduce the risk of transfusion-related acute lung injury (TRALI) or possible TRALI.

Study Design And Methods: In the Leukocyte Antibody Prevalence Study-II (LAPS-II), we evaluated pulmonary outcomes in recipients of 2596 plasma-rich blood components (transfusable plasma and plateletpheresis) sent to participating hospitals; half of the components were collected from anti-HLA-positive donors (study arm) and half from anti-HLA-negative donors (control arm) matched by sex, parity, and blood center. A staged medical record review process was used.

View Article and Find Full Text PDF