Why do US source plasma donors stop donating?

BACKGROUND: In the United States, source plasma (SP) donors can donate up to 104 times per year. Considering the global need for SP and plasma-derived medicinal products, it is critical to maintain the health of frequent donors. This study explores SP donors' self-reported reasons for a lapse in donating. STUDY DESIGN AND METHODS: There were 5608 SP donors from 14 SP centers who enrolled in a longitudinal cohort study to assess self-reported functional health and well-being. Donors were assigned to one of four groups, according to the frequency of SP donation in the 12 months before enrollment. One thousand four hundred forty-eight SP donors who lapsed in donating during 6 months or greater during the study follow-up were asked to complete a survey. RESULTS: There were 545 lapsed SP donors who returned surveys (37.6%); 63% were female. Most responses given for stopping SP donation were categorized as convenience reasons (69.1%). Self-reported health concerns, including being deferred multiple times, which were categorized as possibly related or unable to determine a relationship to plasmapheresis, represented 45.5% of the responses. DISCUSSION: Primary reasons US SP donors report for a lapse in donation were categorized as convenience (e.g., schedule conflicts/lack of time). Donor responses categorized as health concerns which have a possible or uncertain relationship to plasmapheresis were less frequent but present in all frequency groups. This study adds to the body of evidence that SP donors cease donating for a variety of self-reported reasons with the majority not directly related to a perceived negative impact on their health.

Effects of donation frequency on U.S. source plasma donor health.

BACKGROUND: Plasma-derived medicinal products (PDMPs) are essential, life-saving medicines manufactured from plasma donated by healthy human volunteers. PDMPs are used to treat a range of rare, serious, and chronic conditions, often genetic in origin. Approximately 70% of the Source Plasma (SP) used for PDMP manufacturing comes from United States (US). The hypothesis of the study is that US donation frequency does not impair donor self-reported functional health and well-being. STUDY DESIGN AND METHODS: A total of 5608 SP donors from 14 US SP centers were enrolled in a cross-sectional study to assess self-reported health related quality of life (HRQoL) and well-being. By sex, donors were assigned to one of four groups, according to their frequency of SP donation in the 12 months before enrollment. The SF-36v2® Health Survey (SF-36v2) and a survey assessing the frequency of various health conditions that may be associated with impaired immune function over different time periods were used. RESULTS: There were no statistically significant differences in SF-36v2 scores between any of the donor frequency groups, compared with new donors after controlling for potential confounding and accounting for multiple comparisons among males and females. Cough, cold, occasional fatigue, and sore throat were the most reported health conditions or symptoms, but there was no clear difference among sex or frequency groups. DISCUSSION: The self-reported data in this study support the hypothesis that compensated donations at US FDA permitted frequencies and volumes are consistent with maintaining donor health. Compared with the general population, SP donors have comparable or better health than the general population.

Prospective, open-label, multicenter clinical study to assess the performance of a new donation system for the collection of source plasma.

BACKGROUND: Safe, efficient, and reliable innovations among donation systems are needed to meet the growing global demand for source plasma. This study assessed the ability of a new donation system to collect appropriate product weights based on the US Food and Drug Administration nomogram for source plasma collections. Procedure duration and safety endpoints were also collected. STUDY DESIGN AND METHODS: The Rika Plasma Donation System (Terumo BCT, Inc., Lakewood, CO) was evaluated in a prospective, open-label, multicenter study. Healthy adults meeting FDA and Plasma Protein Therapeutics Association requirements for source plasma donor eligibility were consented and enrolled in the study resulting in 124 evaluable products. RESULTS: The target product collection weights (ie, including plasma and anticoagulant) by participant weight category were: 705 g (110-149 lbs), 845 g (150-174 lbs), and 900 g (≥175 lbs). The mean reported product collection weights by participant weight category were 705.0 ± 0.00, 845.0 ± 0.20, and 899.9 ± 0.31 g, respectively. The mean overall procedure time was 31.5 ± 5.41 minutes. The mean procedure times by participant weight category were 25.6 ± 3.13, 30.5 ± 4.45, and 33.7 ± 4.80 minutes, respectively. Procedure-emergent adverse events (PEAEs) occurred in five participants. All PEAEs were consistent with known risks for apheresis donation, and none were related to the donation system. CONCLUSIONS: The new donation system collected the target product collection weight in 100% of evaluable products. The mean procedure collection time was 31.5 minutes. The system is a new efficient platform that consistently collects the appropriate weight of the source plasma.

Source plasma deferral trends: A 3-year analysis of 255 centers in the United States.

BACKGROUND: Plasma contains many important proteins of therapeutic interest including albumin, clotting factors, and antibodies. Source plasma (SP) is in great demand particularly due to a shortage of immunoglobulin. To better understand how to increase supply, we examined SP donor deferrals for the previous 3 years. STUDY DESIGN: This is a description of donor deferrals at 255 plasma donation centers in the United States for April 1, 2017 to March 31, 2020. RESULTS: A total of 4 587 923 events were evaluated for the 3-year period 2017-2020. There were 873 227 deferrals analyzed for 2017-2018, 1 765 582 in 2018-2019, and 1 949 114 for 2019-2020. The most common deferral each year was for unacceptable blood pressure (BP) or pulse which comprised 27.9%, 28.2%, and 28.3% of deferrals in 2017-2018, 2018-2019, and 2019-2020, respectively. The second most common cause of deferral was for unacceptable hematocrit which comprised 14.1% of deferrals in 2017-2018, and 16.0% in 2018-2019 and 2019-2020. The majority of these deferred donors had low hematocrits and were predominately (~80%) female. Deferral for unacceptable total protein comprised a smaller percentage (~4%) of deferrals. DISCUSSION: Most donor deferrals were due to unacceptable screening results, particularly high BP, elevated pulse, low protein, and low hematocrit. Although rates of deferrals in other categories have been slightly increasing over time, they comprise a small percentage. Donor education regarding healthy lifestyle choices may improve overall donor health, decrease deferrals, and increase SP supply.

Analysis of 52 240 source plasma donors of convalescent COVID-19 plasma: Sex, ethnicity, and age association with initial antibody levels and rate of dissipation.

BACKGROUND: COVID-19 convalescent plasma (CCP) was approved under emergency authorization to treat critically ill patients with COVID-19 in the United States in 2020. We explored the demographics of donors contributing plasma for a hyperimmune, plasma-derived therapy to evaluate factors that may be associated with anti-SARS-CoV-2 antibody response variability and, subsequently, antibody titers. STUDY DESIGN: An electronic search of CCP donors was performed across 282 US plasma donation centers. Donations were screened for nucleocapsid protein-binding-IgG using the Abbott SARS-CoV-2 IgG assay. RESULTS: Overall, 52 240 donors donated 418 046 units of CCP. Donors were of various ethnicities: 43% Caucasian, 34% Hispanic, 17% African American, 2% Native American, 1% Asian, and 3% other. Females had higher initial mean anti-SARS-CoV-2 antibody titers but an overall faster rate of decline (P < .0001). Initial antibody titers increased with age: individuals aged 55 to 66 years had elevated anti-SARS-CoV-2 titers for longer periods compared with other ages (P = .0004). African American donors had the lowest initial antibody titers but a slower rate of decline (P < .0001), while Caucasian (P = .0088) and Hispanic (P = .0193) groups had the fastest rates of decline. Most donor antibody levels decreased below the inclusion criteria (≥1.50) within 30 to 100 days of first donation, but donation frequency did not appear to be associated with rate of decline. CONCLUSION: Several factors may be associated with anti-SARS-CoV-2 antibody response including donor age and sex. Evaluating these factors during development of future hyperimmune globulin products may help generation of therapies with optimal efficacy.

Hepatitis A Virus Incidence Rates and Biomarker Dynamics for Plasma Donors, United States.

The United States is currently affected by widespread hepatitis A virus (HAV) outbreaks. We investigated HAV incidence rates among source plasma donors in the United States since 2016. Serial donations from HAV-positive frequent donors were analyzed for common biologic markers to obtain a detailed picture of the course of infection. We found a considerable increase in incidence rates with shifting outbreak hotspots over time. Although individual biomarker profiles were highly variable, HAV RNA typically had a high peak and a biphasic decrease and often remained detectable for several months. One donor had a biomarker pattern indicative of previous exposure. Our findings show that current HAV outbreaks have been spilling over into the plasma donor population. The detailed results presented improve our comprehension of HAV infection and related public health aspects. In addition, the capture of full RNA curves enables estimation of HAV doubling time.

Determination of neutralising anti-SARS-CoV-2 antibody half-life in COVID-19 convalescent donors.

Despite the burgeoning field of coronavirus disease-19 (COVID-19) research, the persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralising antibodies remains unclear. This study validated two high-throughput immunological methods for use as surrogate live virus neutralisation assays and employed them to examine the half-life of SARS-CoV-2 neutralising antibodies in convalescent plasma donations made by 42 repeat donors between April and September 2020. SARS-CoV-2 neutralising antibody titres decreased over time but typically remained above the methods' diagnostic cut-offs. Using this longitudinal data, the average half-life of SARS-CoV-2 neutralising antibodies was determined to be 20.4 days. SARS-CoV-2 neutralising antibody titres appear to persist in the majority of donors for several months. Whether these titres confer protection against re-infection requires further study and is of particular relevance as COVID-19 vaccines become widely available.

Plasmavigilance-Adverse events among US Source plasma donors.

BACKGROUND: Source plasma (SP) is the primary starting material for 87% of plasma-derived medicinal products globally. Plasmavigilance is a program designed to collect, analyze, and monitor donor adverse events (AEs) across the SP collection industry. Donor retention depends on donors having a safe and satisfactory experience. This study analyzes AE rates and SP donor characteristics that may be predictors of an AE. STUDY DESIGN AND METHODS: Donation data for 1.1 million donors making 12,183,182 SP donations over a 4-month period were analyzed. This represented approximately 72% of the donations collected by the U.S. plasma industry. The Standard for Recording Donor Adverse Events was used for AE definitions and classifications. RESULTS: The overall AE rate was 15.85/104 donations. The two AEs with the highest rates were Hypotensive and Phlebotomy events (8.32 and 5.91/104 donations, respectively). Females had higher overall AE rates than males (25.76 vs. 9.85/104 donations), and first-time donors had higher overall AE rates than repeat donors (136.66 vs. 12.37/104 donations). Weight, body mass index, age, and pre-donation estimated blood volume also were predictors of AE. DISCUSSION: SP donors have low AE rates with 90% being events classified as Hypotensive or Phlebotomy. Special attention and mitigation strategies should be directed to donors who are young, lightweight (between 100 and 124 pounds), female, or first-time donors to further reduce the incidence of AE, continue to ensure the donor has a safe experience, and facilitate donor retention.

Anti-A/B isoagglutinin reduction in an intravenous immunoglobulin product and risk of hemolytic anemia: a hospital-based cohort study.

BACKGROUND: Intravenous immunoglobulins (IVIG) are derived from large human plasma pools. IVIG-associated hemolytic anemia (HA) is a known class effect, likely attributed to dose-dependent passive transfer of anti-A/B isoagglutinins. Two isoagglutinin reduction steps were implemented in the manufacturing process of Privigen (human 10% liquid IVIG): exclusion of high-anti-A-titer donors in 2013, replaced by specific immunoaffinity chromatography in 2015. We aim to estimate the clinical effectiveness of both measures. STUDY DESIGN AND METHODS: Using the US hospital-based Premier Healthcare Database, three Privigen cohorts were generated based on calendar periods indicative of manufacturing changes: Period 1 (baseline) January 2008 to December 2012, Period 2 (high-anti-A-titer donor exclusion) October 2013 to December 2015, and Period 3 (immunoaffinity chromatography) October 2016 to April 2019. HA within a 10-day at-risk period after Privigen administrations was identified from review of patient record summaries. Incidence rate ratios (IRRs) were estimated from Poisson regression (Period 1 reference) adjusting for hospital setting, sex, age, Privigen indication, dose, and first use. RESULTS: Crude incidence rates of HA were 1.49 per 10,000 person-days in Period 1 (38 HA, 9439 patients), 1.01 in Period 2 (20 HA, 7710 patients), and 0.14 in Period 3 (3 HA, 7759 patients). Adjusted IRR for HA in Period 2 was 0.71 (95% confidence interval [CI], 0.41-1.23), and in Period 3 was 0.10 (0.03-0.33) compared with Period 1. The IRR for HA in Period 3 compared with Period 2 was 0.14 (95% CI, 0.04-0.47). CONCLUSION: Implementation of immunoaffinity chromatography in Privigen manufacturing resulted in a significant 90% reduction of HA risk. HA has become a rare event in association with Privigen use.

Manufacturing of plasma-derived C1-inhibitor concentrate for treatment of patients with hereditary angioedema.

Background: Replacement therapy with plasma-derived C1-inhibitor (C1-INH) has been used for decades to treat patients with hereditary angioedema (HAE) with C1-INH deficiency. Objective: This article reviewed the rationale for using C1-INH replacement therapy in patients with HAE and the process of manufacturing plasma-derived C1-INH. Methods: The manufacture of C1-INH is an involved and carefully monitored process that includes screening and selection of prospective donors, the collection of source plasma, and purification with dedicated pathogen reduction steps. Donor eligibility is determined by restrictive criteria established and monitored by regulatory agencies as well as voluntary standards implemented by plasma collection centers that exceed government regulations. Individual and pooled donations are tested for transfusion-transmissible infections, including hepatitis B virus, hepatitis C virus, human immunodeficiency virus, parvovirus B19, and hepatitis A virus, by using enzyme-linked immunosorbent assays or nucleic acid amplification technologies. Frozen plasma that is cleared for manufacturing undergoes controlled thawing and centrifugation, and the resulting supernatant (i.e., cryoprecipitate-depleted plasma) is used to manufacture several plasma-derived therapies, including C1-INH. In addition to chromatography steps, the manufacturing process consists of dedicated and effective pathogen reduction steps, including pasteurization, hydrophobic interaction chromatography or polyethylene glycol precipitation, and virus filtration. Manufacturers continuously monitor the safety profile of C1-INH products by robust pharmacovigilance processes that enable systematic collection and evaluation of all suspected adverse drug reaction reports as well as evaluation of safety information from all other sources. Results and Conclusion: These procedures used in donor screening, donation and manufacturing pool testing, manufacturing, and pharmacovigilance ensure that plasma-derived C1-INH products have the safety, quality, identity, potency, and purity that is necessary to provide the intended therapeutic effect.

Longitudinal changes in measles antibody titers in plasma donors and minimum antibody levels of immunoglobulin products for treatment of primary immunodeficiency.

BACKGROUND: To ensure that immunoglobulin (Ig) products have adequate functional antibody, the US Food and Drug Administration (FDA) requires that Ig lots contain minimum levels of measles neutralizing antibody; the current minimum is 0.48 x US Reference Ig 176. STUDY DESIGN AND METHODS: In the first part of the study, measles antibody titers were measured in donor plasma samples collected in 2007, 2011, and 2017. In the second part, trough or steady-state serum levels of measles neutralizing antibody were measured in two studies of patients with primary immunodeficiency (PID) who were treated with intravenous (Study 1; N = 46) or subcutaneous (Study 2; N = 18) Ig replacement therapy, meeting previous requirements for lot potency (≥0.6 x US Reference Ig 176). Serum measles neutralizing antibody titers were then estimated for conditions in which the potency of the Ig replacement product was 0.48 or 0.30 x US Reference Ig 176. RESULTS: Measles antibody titers in donated plasma samples declined in donors born after 1963. In the two studies of patients with PID who were treated with intravenous or subcutaneous Ig replacement therapy, all patients exhibited trough (intravenous Ig) or steady-state (subcutaneous Ig) measles neutralizing antibody titers above 0.12 IU/mL, which has been shown to protect against clinical measles in the general population. Estimates suggest that all patients except one would have continued to meet this standard if the Ig lot potency had been 0.48 or 0.30 x US Reference Ig 176. CONCLUSION: These studies provide supporting evidence that the lot release specification can be safely lowered from 0.48 to 0.30 x US Reference Ig 176, which will accommodate declining measles neutralizing antibody levels in donor plasma.

Frequent source plasma donors are not at risk of iron depletion: the Ferritin Levels in Plasma Donor (FLIPD) study.

BACKGROUND: Whole blood and red blood cell (RBC) donors are at risk of iron deficiency. Since Source plasma (SP) donors have RBCs returned during apheresis, risk of iron depletion appears low. However, SP donors can donate frequently and assessment of frequent donor iron status is needed. STUDY DESIGN AND METHODS: A total of 1254 SP donors were enrolled in four frequency groups determined by donations in the prior 12 months: no donations and 1 to 24, 25 to 69, and 70 or more donations. Ferritin was determined for each donor. Donors with ferritin levels of less than 12 ng/mL were classified as having absent iron stores (AIS). RESULTS: Compared to new donors, ferritin for females was higher in each successive frequency group. For 70 or more donations, ferritin was 13 ng/mL higher than in new donors (p = 0.02). For males, 1 to 24 donations had the highest ferritin levels. Compared to new donors, highest-frequency donors had lower ferritin levels, 114 ng/mL versus 100 ng/mL (p = 0.14). Age for females and males increased with each successive frequency group. Age adjustment resulted in smaller ferritin differences for females and larger differences for males in the high-frequency groups; AIS for females was highest in new donors (7%) and lowest in the highest-frequency group (1%). In aggregate, AIS occurred in less than 1% of all male donors. Male new and highest-frequency donors had 1% AIS with none in the other groups. CONCLUSION: Few SP donors have iron depletion and it is not higher in frequent donors. Frequent SP donation does not adversely impact iron stores. Thus, monitoring donor iron status or iron supplementation is not necessary.

Sensitivity and specificity of a new automated system for the detection of hepatitis B virus, hepatitis C virus, and human immunodeficiency virus nucleic acid in blood and plasma donations.

BACKGROUND: Use of nucleic acid testing (NAT) in donor infectious disease screening improves transfusion safety. Advances in NAT technology include improvements in assay sensitivity and system automation, and real-time viral target discrimination in multiplex assays. This article describes the sensitivity and specificity of cobas MPX, a multiplex assay for detection of human immunodeficiency virus (HIV)-1 Group M, HIV-2 and HIV-1 Group O RNA, HCV RNA, and HBV DNA, for use on the cobas 6800/8800 Systems. STUDY DESIGN AND METHODS: The specificity of cobas MPX was evaluated in samples from donors of blood and source plasma in the United States. Analytic sensitivity was determined with reference standards. Infectious window periods (WPs) before NAT detectability were calculated for current donor screening assays. RESULTS: The specificity of cobas MPX was 99.946% (99.883%-99.980%) in 11,203 blood donor samples tested individually (IDT), 100% (99.994%-100%) in 63,012 donor samples tested in pools of 6, and 99.994% (99.988%-99.998%) in 108,306 source plasma donations tested in pools of 96. Seven HCV NAT-yield donations and one seronegative occult HBV infection were detected. Ninety-five percent and 50% detection limits in plasma (IU/mL) were 25.7 and 3.8 for HIV-1M, 7.0 and 1.3 for HCV, and 1.4 and 0.3 for HBV. The HBV WP was 1 to 4 days shorter than other donor screening assays by IDT. CONCLUSION: cobas MPX demonstrated high specificity in blood and source plasma donations tested individually and in pools. High sensitivity, in particular for HBV, shortens the WP and may enhance detection of occult HBV.

Measles Virus Neutralizing Antibodies in Intravenous Immunoglobulins: Is an Increase by Revaccination of Plasma Donors Possible?

We report a screen of plasma donors confirming that widespread use of childhood measles vaccination since 1963 resulted in a decrease in average measles virus antibody titers among plasma donors, which is reflected in intravenous immunoglobulins (IVIGs). The measles virus antibody titer, however, is a potency requirement for IVIGs, as defined in a Food and Drug Administration regulation. To mitigate the decline in measles virus antibody titers in IVIGs and to ensure consistent product release, revaccination of plasma donors was investigated as a means to boost titers. However, revaccination-induced titer increases were only about 2-fold and short-lived.

Safety of a pasteurized plasma-derived Factor VIII and von Willebrand factor concentrate: analysis of 33 years of pharmacovigilance data.

BACKGROUND: Haemate-P/Humate-P (Humate-P) is a pasteurized human plasma-derived concentrate containing both Factor VIII and von Willebrand factor for treatment of hemophilia A and von Willebrand disease (VWD). STUDY DESIGN AND METHODS: We analyzed the safety of Humate-P based on more than 33 years of postmarketing pharmacovigilance data, representing an estimated exposure of approximately 25,000 patient-years. The analysis comprises reports of potential adverse drug reactions (ADRs) from all sources, reported as part of routine pharmacovigilance at CSL Behring. ADRs considered clinically relevant or potential risks of Humate-P were identified based on defined and standardized Medical Dictionary for Regulatory Activities queries. Recognizing the limitations of spontaneous reporting, we also reviewed the literature, including clinical trials with mandatory reporting. RESULTS: From 1982 to 2015, a total of 670 postmarketing cases had been reported via pharmacovigilance, for an overall reporting rate of approximately one ADR per 3900 administered standard doses. Of these cases, 343 involved ADRs considered clinically relevant risks (33 thromboembolic complications, 97 inhibitor formation, 110 hypersensitivity or allergic reactions) or potential risks (103 suspected virus transmissions) for Humate-P. Most thromboembolic complications occurred in patients undergoing surgery or with other known risk factors. Inhibitor formation occurred mostly in patients with hemophilia A (24 cases were high titer). Most patients with hypersensitivity or allergic reactions had VWD. None of the reported suspected virus transmission cases were confirmed to be associated with Humate-P. Reported results of company-sponsored studies showed a low incidence of adverse events possibly or probably related to Humate-P. CONCLUSIONS: More than 33 years of pharmacovigilance data continue to support the safety of Humate-P.

Low hepatitis E virus RNA prevalence in a large-scale survey of United States source plasma donors.

BACKGROUND: Hepatitis E virus (HEV) is a small, nonenveloped, single-stranded, RNA virus of emerging concern in industrialized countries. HEV transmission through transfusion of blood components has been reported, but not via plasma-derived medicinal products (PDMPs) manufactured with virus inactivation and/or removal steps. This study aimed to determine the prevalence of HEV among US source plasma donors. STUDY DESIGN AND METHODS: Samples were collected from US source plasma donors at centers across the United States and were initially screened for HEV RNA in 96-sample minipools using the Roche cobas HEV test on the cobas 8800 system. Assuming a sensitivity of 18.6 IU/mL, the minipool screening strategy allowed for reliable detection of individual donations with HEV RNA titers of more than 2 × 103 IU/mL. Reactive minipools were resolved to individual donations, which were further analyzed to quantify viral RNA concentration, determine HEV genotype, and immunoglobulin (Ig)G and IgM HEV antibody status. RESULTS: A total of 128,020 samples were collected from 96 CSL Plasma centers in the United States, representing 27 states. The prevalence of HEV RNA-positive samples was 0.002% with three unique HEV-positive donors identified, all HEV Subgenotype 3a. Virus titers of HEV-positive samples were relatively low (103 -104 IU HEV RNA/mL). One positive donation was HEV IgG seropositive. CONCLUSION: Routine screening of US source plasma donations for HEV would not substantially improve the safety of most PDMPs. The low prevalence and potential viral load of HEV, together with effective virus reduction steps in manufacturing processes, results in a low residual risk and acceptable safety margins for PDMPs derived from US plasma donors.

Pathogen inactivation and removal methods for plasma-derived clotting factor concentrates.

Pathogen safety is crucial for plasma-derived clotting factor concentrates used in the treatment of bleeding disorders. Plasma, the starting material for these products, is collected by plasmapheresis (source plasma) or derived from whole blood donations (recovered plasma). The primary measures regarding pathogen safety are selection of healthy donors donating in centers with appropriate epidemiologic data for the main blood-transmissible viruses, screening donations for the absence of relevant infectious blood-borne viruses, and release of plasma pools for further processing only if they are nonreactive for serologic markers and nucleic acids for these viruses. Despite this testing, pathogen inactivation and/or removal during the manufacturing process of plasma-derived clotting factor concentrates is required to ensure prevention of transmission of infectious agents. Historically, hepatitis viruses and human immunodeficiency virus have posed the greatest threat to patients receiving plasma-derived therapy for treatment of hemophilia or von Willebrand disease. Over the past 30 years, dedicated virus inactivation and removal steps have been integrated into factor concentrate production processes, essentially eliminating transmission of these viruses. Manufacturing steps used in the purification of factor concentrates have also proved to be successful in reducing potential prion infectivity. In this review, current techniques for inactivation and removal of pathogens from factor concentrates are discussed. Ideally, production processes should involve a combination of complementary steps for pathogen inactivation and/or removal to ensure product safety. Finally, potential batch-to-batch contamination is avoided by stringent cleaning and sanitization methods as part of the manufacturing process.

Laboratory variables for assessing iron deficiency in REDS-II Iron Status Evaluation (RISE) blood donors.

BACKGROUND: Iron deficiency is common in regular blood donors. We evaluated the diagnostic sensitivity and specificity of red blood cell (RBC) hematology analyzer indices to assess iron status as a part of donor management. STUDY DESIGN AND METHODS: A total of 1659 male and female donors from the Retrovirus Epidemiology Donor Study-II (REDS-II) Donor Iron Status Evaluation (RISE) study who were either first-time/reactivated (FT/RA; no donations for 2 years) or frequent donors were recruited into a longitudinal study of regular donation of RBCs. Of these, 1002 donors returned 15 to 24 months later for a final assessment. Absent iron stores (AIS) was defined as plasma ferritin level of less than 12 µg/L. Logarithm of the ratio of soluble transferrin receptor to ferritin of at least 2.07 (≥97.5% in FT/RA males) was used to define iron-deficient erythropoiesis (IDE). Receiver operating characteristics analysis was performed to assess selected RBC indices (e.g., percentage of hypochromic mature RBCs, proportion of hypochromic mature RBCs [HYPOm], and hemoglobin [Hb] content of reticulocytes [CHr]) in identifying AIS and IDE. RESULTS: HYPOm and CHr detected IDE with comparable sensitivity, 72% versus 69%, but differed in specificity: HYPOm 68% and CHr 53%. For detecting AIS, sensitivity was improved to 85% for HYPOm and 81% for CHr but specificity was reduced for both. Venous Hb had high specificity but poor sensitivity for IDE and AIS. A plasma ferritin level of less than 26.7 µg/L was a good surrogate for assessing IDE. CONCLUSION: RBC indices correlate with AIS and IDE and are more informative than Hb measurement, but lack sufficient sensitivity and specificity to be used as diagnostic tools in blood donors at risk for iron deficiency.