Incorporating the entity of under-transfusion into hemovigilance monitoring: Documenting cases due to lack of inventory.

BACKGROUND: Under-transfusion is an underreported entity within most hospitals and hemovigilance systems. While critical blood shortages are being reported more frequently, without incident codes to document instances of under-transfusion due to lack of inventory, estimating its impact on patient care as it relates to hemotherapy (HT) has hampered our ability to assess and inform strategic initiatives to combat inventory issues as well as prepare for future blood supply threats. STUDY DESIGN AND METHOD: An 11-member working group of the AABB (Association for the Advancement of Blood and Biotherapies) Hemovigilance Committee was formed in October 2020 to study the topic of under-transfusion including its potential causes and clinical expressions. The group was also charged with proposing simple definition/incident codes to be used by hemovigilance systems to document such instances. RESULTS: The working group proposed four simple incident codes under the new process code-No Blood (NB)-that can be used by hemovigilance systems to appropriately document instances of under-transfusion due to lack of inventory. The codes were described as: (1) NB 01-Inventory less than usual level due to supplier shortage; (2) NB 02-Demand for blood product exceeding usual inventory levels; (3) NB 03-Substitution with incompatible/inappropriate units; and (4) NB 04-Suboptimal dose/no transfusion given. CONCLUSION: The adoption of these codes within hemovigilance systems globally would assist in recognition and reporting instances of under-transfusion due to inventory, thus supporting development of better collection strategies, inventory management techniques as well as effective policies to improve blood safety and availability.

The safety of COVID-19 convalescent plasma donation: A multi-institutional donor hemovigilance study.

BACKGROUND: Although the safety and therapeutic efficacy of COVID-19 convalescent plasma (CCP) has been extensively evaluated, the safety of CCP donation has not been explored in a multi-institutional context. STUDY DESIGN AND METHODS: Nine blood collection organizations (BCOs) participated in a multi-institutional donor hemovigilance effort to assess the safety of CCP donation. Donor adverse events (DAEs) were defined according to the Standard for Surveillance of Complications Related to Blood Donation, and severity was assessed using the severity grading tool. Multivariate analysis was performed to determine attributes associated with DAE severity. RESULTS: The overall DAE rate was 37.7 per 1000 donations. Repeat apheresis and apheresis-naïve donors experienced adverse event rates of 19.9 and 49.8 per 1000 donations, respectively. Female donors contributed 51.9% of CCP donations with a DAE rate of 49.4 per 1000 donations. The DAE rate for male donors was 27.4 per 1000 donations. Vasovagal reactions accounted for over half of all reported DAEs (51.1%). After adjustment, volume of CCP donated was associated with vasovagal reaction severity (odds ratio [OR] 6.5, 95% confidence interval [CI] 2.5-17.1). Donor age and donation history were also associated with DAE severity. Considerable differences in DAE types and rates were observed across the participating BCOs despite the use of standardized hemovigilance definitions. CONCLUSION: The safety of CCP donation appears comparable to that of conventional apheresis plasma donation with similar associated risk factors for DAE types and severity.

Probable transfusion transmission of West Nile virus from an apheresis platelet that screened non-reactive by individual donor-nucleic acid testing.

BACKGROUND: Despite West Nile virus (WNV) blood donation screening using nucleic acid testing (NAT), donors with low viral loads not detected by mini-pool-NAT have led to transfusion transmitted (TT)-WNV infection. We describe a probable case of fatal TT-WNV infection from an individual donor (ID)-NAT non-reactive apheresis platelet donation. STUDY DESIGN AND METHODS: An apheresis platelet donation was WNV ID-NAT reactive and prior donations from the same donor were investigated. A WNV ID-NAT non-reactive apheresis platelet unit collected 26 days earlier was transfused during heart transplantation to a patient who subsequently developed WNV neuroinvasive disease and expired. The source of the recipient's WNV infection was investigated. RESULTS: Twenty-six days after collection of the suspect platelet unit, a donation from the same donor was WNV ID-NAT reactive and WNV IgM and IgG positive. In addition to the suspect platelet unit, the heart transplant recipient who developed WNV infection received 17 blood components from 24 donors. Serologic testing performed on 11 of the remaining 24 donors (46%) was WNV IgM negative. Pre-transplant recipient and heart donor samples tested WNV RNA and IgM negative. CONCLUSION: A probable case of fatal neuroinvasive TT-WNV was linked to an infectious apheresis platelet unit undetected by WNV ID-NAT. It is hypothesized that the suspect unit was collected early in the viremic period when viral RNA was below the limit-of-detection of the ID-NAT assay. Implementation of ID-NAT screening of blood donors has not entirely eliminated the risk of TT-WNV infections, which may best be addressed by pathogen inactivation technologies.

Sepsis from an apheresis platelet contaminated with Acinetobacter calcoaceticus/baumannii complex bacteria and Staphylococcus saprophyticus after pathogen reduction.

BACKGROUND: Strategies to reduce platelet (PLT) bacterial contamination include donor screening, skin disinfection, sample diversion, bacterial culture, pathogen reduction (PR), and day-of-transfusion tests. We report bacterial sepsis following a pathogen-reduced PLT transfusion. CASE REPORT: An adult male with relapsed acute lymphoblastic leukemia was successfully treated for central catheter-associated Staphylococcus aureus bacteremia. A peripherally inserted central catheter (PICC) was placed. Chills, rigors, and flushing developed immediately after PICC-infused pathogen-reduced PLTs, progressing to septic shock requiring intensive care management. METHODS: PICC and peripheral blood (PB), transfused bag saline flushes (TBFs), environmental samples, and the pathogen-reduced untransfused co-component (CC) were cultured. Plasma metagenomic and bacterial isolate whole-genome sequencing; PLT mitochondrial DNA (mtDNA) testing of untransfused CC and TBF; CC testing for amotosalen (S-59)/S-59 photoproducts; isolate PR studies (INTERCEPT); and TBF polymerase chain reaction for recipient Y-chromosome DNA were performed. RESULTS: PB and PICC cultures grew Acinetobacter calcoaceticus/baumannii complex (ACBC). TBF was gram-positive; mass spectrometry identified ACBC and Staphylococcus saprophyticus (SS). CC Gram stain and cultures were negative. Environmental cultures, some done after decontamination, were ACBC/SS negative. Posttransfusion patient plasma and TBF ACBC sequences were genetically identical. No Y-chromosome signal was detected in TBF. S-59 photoproducts and evidence of mtDNA amplification inhibition were found in the CC. Spiking PR studies showed >5.9-log inactivation for both isolates. Donor skin cultures for Acinetobacter were negative. CONCLUSION: CC sterility, PR studies, residual S-59 photoproducts, and mtDNA amplification inhibition suggest successful PR. Unidentified environmental sources and inherent or acquired bag defects may have contributed to postmanufacturing pathogen-reduced PLT contamination.

Sepsis Attributed to Bacterial Contamination of Platelets Associated with a Potential Common Source - Multiple States, 2018.

During May-October 2018, four patients from three states experienced sepsis after transfusion of apheresis platelets contaminated with Acinetobacter calcoaceticus-baumannii complex (ACBC) and Staphylococcus saprophyticus; one patient died. ACBC isolates from patients' blood, transfused platelet residuals, and two environmental samples were closely related by whole genome sequencing. S. saprophyticus isolates from two patients' blood, three transfused platelet residuals, and one hospital environmental sample formed two whole genome sequencing clusters. This whole genome sequencing analysis indicated a potential common source of bacterial contamination; investigation into the contamination source continues. All platelet donations were collected using apheresis cell separator machines and collection sets from the same manufacturer; two of three collection sets were from the same lot. One implicated platelet unit had been treated with pathogen-inactivation technology, and two had tested negative with a rapid bacterial detection device after negative primary culture. Because platelets are usually stored at room temperature, bacteria in contaminated platelet units can proliferate to clinically relevant levels by the time of transfusion. Clinicians should monitor for sepsis after platelet transfusions even after implementation of bacterial contamination mitigation strategies. Recognizing adverse transfusion reactions and reporting to the platelet supplier and hemovigilance systems is crucial for public health practitioners to detect and prevent sepsis associated with contaminated platelets.

Fatal Sepsis Associated with Bacterial Contamination of Platelets - Utah and California, August 2017.

During August 2017, two separate clusters of platelet transfusion-associated bacterial sepsis were reported in Utah and California. In Utah, two patients died after platelet transfusions from the same donation. Clostridium perfringens isolates from one patient's blood, the other patient's platelet bag, and donor skin swabs were highly related by whole genome sequencing (WGS). In California, one patient died after platelet transfusion; Klebsiella pneumoniae isolates from the patient's blood and platelet bag residuals and a nontransfused platelet unit were matched using WGS. Investigation revealed no deviations in blood supplier or hospital procedures. Findings in this report highlight that even when following current procedures, the risk for transfusion-related infection and fatality persists, making additional interventions necessary. Clinicians need to be vigilant in monitoring for platelet-transmitted bacterial infections and report adverse reactions to blood suppliers and hemovigilance systems. Blood suppliers and hospitals could consider additional evidence-based bacterial contamination risk mitigation strategies, including pathogen inactivation, rapid detection devices, and modified screening of bacterial culture protocols.

Association of projected transfusional iron burden with treatment intensity in childhood cancer survivors.

BACKGROUND: Packed red blood cell (PRBC) transfusion is a mainstay in childhood cancer treatment, but has potential for inducing iron overload. The purpose of this study was to determine whether treatment intensity is predictive of projected iron burden resulting from PRBC transfusions among survivors of several forms of childhood cancer. PROCEDURE: This retrospective cohort study involved patients treated at Children's Hospital Los Angeles (CHLA) between June 1, 2004 and December 31, 2009. Clinical/demographic data were abstracted from medical records. Treatment Intensity Level was determined for each patient using a published scale. Adjusted cumulative PRBC transfusion volume for each patient (ml/kg) was used to compute the adjusted total iron burden (mg/kg) based upon the average hematocrit of the product. RESULTS: Median age of the cohort (n = 214) was 7.9 years (range 0.2-20.2). One hundred and fourteen (53.3%) were male and 129 (60.3%) were Hispanic/Latino. Diagnoses included acute leukemia and six solid tumors, management of which represents a range of cancer treatment intensities. The number of transfusions, transfusion volumes, and projected iron burden were significantly increased and exceeded upper limits of normal among patients with higher treatment intensity. Multivariate analysis found younger age and lower hemoglobin at diagnosis to be associated with greater iron burden after adjusting for treatment intensity. CONCLUSION: Greater treatment intensity is associated with need for more PRBC transfusions, and thus increased risk of iron overload among childhood cancer survivors. Iron overload may represent another clinically significant late effect following childhood cancer treatment.

Long-term increases in lymphocytes and platelets in human T-lymphotropic virus type II infection.

Human T-lymphotropic viruses types I and II (HTLV-I and HTLV-II) cause chronic infections of T lymphocytes that may lead to leukemia and myelopathy. However, their long-term effects on blood counts and hematopoiesis are poorly understood. We followed 151 HTLV-I-seropositive, 387 HTLV-II-seropositive, and 799 HTLV-seronegative former blood donors from 5 U.S. blood centers for a median of 14.0 years. Complete blood counts were performed every 2 years. Multivariable repeated measures analyses were conducted to evaluate the independent effect of HTLV infection and potential confounders on 9 hematologic measurements. Participants with HTLV-II had significant (P < .05) increases in their adjusted lymphocyte counts (+126 cells/mm(3); approximately +7%), hemoglobin (+2 g/L [+0.2 g/dL]) and mean corpuscular volume (MCV; 1.0 fL) compared with seronegative participants. Participants with HTLV-I and HTLV-II had higher adjusted platelet counts (+16 544 and +21 657 cells/mm(3); P < .05) than seronegatives. Among all participants, time led to decreases in platelet count and lymphocyte counts, and to increases in MCV and monocytes. Sex, race, smoking, and alcohol consumption all had significant effects on blood counts. The HTLV-II effect on lymphocytes is novel and may be related to viral transactivation or immune response. HTLV-I and HTLV-II associations with higher platelet counts suggest viral effects on hematopoietic growth factors or cytokines.

A question of clarity: redesigning the American Association Of Blood Banks blood donor history questionnaire--a chronology and model for donor screening.

A new donor history questionnaire, introduced by the American Association of Blood Banks in 2004 and approved by Food and Drug Administration in 2006, is now in widespread use in the United States. The development of this questionnaire involved an in-depth look at the entire system of donor screening questions, and is notable for its use of survey design experts as well as blood banking experts, government agencies, and an ethicist who represented the public interest in developing the actual questions. The end result is a questionnaire that uses capture questions in a time bounded format, donor educational materials, and a medication deferral list. Detailed instructions for donor screeners include follow-up questions in easy-to-follow flow-charts. Most importantly, for the first time in the history of developing donor history questions, all materials were tested for donor comprehension using cognitive interview evaluation. This article discusses the development of the questionnaire, explains the methodology, and describes the thinking and rationale for decisions made during redesign of the questionnaire.

Increased all-cause and cancer mortality in HTLV-II infection.

BACKGROUND: Human T-lymphotropic virus (HTLV)-I and HTLV-II cause chronic human retroviral infections, but few studies have examined the impact of either virus on survival among otherwise healthy individuals. The authors analyzed all-cause and cancer mortality in a prospective cohort of 155 HTLV-I, 387 HTLV-II, and 799 seronegative subjects. METHODS: Vital status was ascertained using death certificates, the US Social Security Death Index or family report, and causes of death were grouped into 9 categories. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. RESULTS: After a median follow-up of 15.9 years, there were 105 deaths: 22 HTLV-I, 41 HTLV-II, and 42 HTLV-seronegative. Cancer was the predominant cause of death, resulting in 8 HTLV-I, 17 HTLV-II, and 15 HTLV-seronegative deaths. After adjustment for confounding, HTLV-I status was not significantly associated with increased all-cause mortality, though there was a positive trend (HR: 1.6, 95% CI: 0.8 to 3.1). HTLV-II status was strongly associated with increased all-cause (HR: 2.4, 95% CI: 1.4 to 4.4) and cancer mortality (HR: 3.8, 95% CI: 1.6 to 9.2). CONCLUSIONS: The observed associations of HTLV-II with all-cause and cancer mortality could reflect biological effects of HTLV-II infection, residual confounding by socioeconomic status or other factors, or differential access to health care and cancer screening.

Peripheral blood hematopoietic stem cell mobilization and collection efficacy is not an independent prognostic factor for autologous stem cell transplantation.

BACKGROUND: The successful mobilization and collection of hematopoietic stem cells are dependent on a number of clinical factors such as previous chemotherapy and disease stage. The aim of this retrospective study was to determine whether the effectiveness of mobilization and collection is an independent prognostic factor for autologous stem cell transplantation outcome. STUDY DESIGN AND METHODS: A total of 358 patients who received transplants from January 2003 to December 2004 (201 male and 157 female patients, ages from 2.7 to 77.3 years with median of 53 years of age) underwent autologous hematopoietic stem cell collection after mobilization with granulocyte-colony-stimulating factor (G-CSF) or G-CSF plus chemotherapy priming. This retrospective study included patients with diagnoses of acute myelogenous leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, multiple myeloma, and solid tumors. All patients underwent stem cell collection until a target or a minimum CD34+ cell dose was reached. Correlations were performed between stem cell mobilization and/or collection efficacy and transplantation outcomes. RESULTS: In general, both larger reinfused CD34+ cell dose and shorter number of days for the stem cell count to reach the minimum of 2 x 10(6) per kg CD34+ cells do not foster quicker engraftment. Reinfused CD34+ cell dose of less than 12 x 10(6) and number of days stem cell collection to reach this minimum CD34+ cell dose did not independently affect the overall survival (OS) or disease-free survival (DFS). CONCLUSION: The effectiveness of hematopoietic stem cell mobilization and collection as defined as number of days to reach a CD34+ cell dose of 2 x 10(6) per kg should not be used independently to forecast posttransplantation prognosis, engraftment, DFS, and OS.

The impact of male-to-male sexual experience on risk profiles of blood donors.

BACKGROUND: Men who have had sex with men (MSM) since 1977 are permanently deferred from donating blood. Excluding only men who engaged in male-to-male sex within either the prior 12 months or 5 years has been proposed. Little is known about infectious disease risks of MSM who donate blood. STUDY DESIGN AND METHODS: Weighted analyses of data from an anonymous mail survey of blood donors were conducted to examine the characteristics of men reporting male-to-male sex during specified time periods. RESULTS: Of the 25,168 male respondents, 569 (2.4%) reported male-to-male sex, 280 (1.2%) since 1977. Compared to donors who did not report male-to-male sex, the prevalence of reactive screening test results was higher among donors who reported the practice within the past 5 years (< or =12 months odds ratio [OR] 5.3, 95% confidence interval [CI] 2.6-10.4; >12 months to 5 years, OR 7.1, 95% CI 1.2-41.7); however, no significant difference was found for donors who last practiced male-to-male sex more than 5 years ago (>5 years-after 1977, OR 1.4, 95% CI 0.7-2.6; 1977 or earlier, OR 1.6, 95% CI 0.7-3.7). The prevalence of unreported deferrable risks (UDRs) other than male-to-male sex was significantly higher for all donors who reported male-to-male sex with ORs ranging from 3.1 to 18.9 (p < or = 0.01). CONCLUSIONS: No evidence was found to support changing current policy to permit donations from men who practiced male-to-male sex within the past 5 years. For donors with a more remote history of male-to-male sex, the findings were equivocal. A better understanding of the association between male-to-male sex and other UDRs appears needed.

Attitudes toward blood donation incentives in the United States: implications for donor recruitment.

BACKGROUND: The potential effectiveness of various donation incentive programs may vary by demographics, first-time or repeat status, and collection site. STUDY DESIGN AND METHODS: Attitudes toward future incentives were obtained from a 1998 anonymous survey sent to 92,581 US blood donors. Responses (encouraged, discouraged, no difference) to incentives were compared within demographic groups, donations sites, and between first-time and repeat community whole-blood (WB) donors using chi-square tests and logistic regressions adjusted for sample design. RESULTS: Incentives most likely to encourage donation return among all 45,588 WB respondents were blood credits (61%), cholesterol screening (61%), and prostate-specific antigen (PSA) screening (73% of men). Younger donors (< or = 25 years old) were 4 to 5 times more likely to be encouraged to donate if offered compensatory incentives (tickets to events, discounts or lottery and/or raffle tickets), gifts, or a token of appreciation than were those donors older than 55. This age effect influenced positive attitudes toward incentives in first-time donors and in donors giving at schools, universities, or military sites. Among all donors, up to 7 to 9 percent reported they would be discouraged to return if offered compensatory incentives. CONCLUSIONS: Blood credits and cholesterol and PSA screening would be well received at all donation sites. Gifts, compensatory incentives, and tokens of appreciation appeal more to younger donors. These data may allow blood centers to optimize recruitment by tailoring limited incentive resources more effectively.

Behavioral and infectious disease risks in young blood donors: implications for recruitment.

BACKGROUND: Recruitment of young donors is critical to expand the donor base and sustain the blood supply. Nevertheless, there is concern that younger blood donors may have a higher risk profile than their older counterparts. STUDY DESIGN AND METHODS: The prevalence of behavioral risks associated with transfusion-transmissible viral infections and the incidence of viral markers were compared between younger and older donors. Behavioral risks included unreported deferrable risks (UDRs) and HIV test seeking estimated from anonymous donor surveys administered in 1993 and 1998. The incidence of HIV, HCV, or HBV was estimated from donors giving at five US blood centers between 1996 and 2000. RESULTS: Donors younger than 25 years of age were significantly more likely to report a UDR or HIV test seeking than those 25 years or older. ORs comparing donors 18 to 19 and 20 to 24 years of age to those 25 years or older were 2.0 (95% CI, 1.5-2.6) and 1.5 (95% CI, 1.2-1.9) for UDR and 4.5 (95% CI, 3.0-6.9) and 5.5 (95% CI, 4.2-7.1) for test seeking, respectively. Although incidence estimates did not significantly differ between age groups, HIV incidence appeared to be highest in 18- to 19-year-old donors, whereas HBV incidence was highest in 20- to 24-year-old donors. CONCLUSIONS: Donors younger than 25 years of age appeared to have a higher behavioral risk profile than older donors. The message not to donate when a behavioral risk is present or for obtaining HIV tests needs to be reinforced in younger donors.

Respiratory and urinary tract infections, arthritis, and asthma associated with HTLV-I and HTLV-II infection.

Human T-lymphotropic virus types I and II (HTLV-I and -II) cause myelopathy; HTLV-I, but not HTLV-II, causes adult T-cell leukemia. Whether HTLV-II is associated with other diseases is unknown. Using survival analysis, we studied medical history data from a prospective cohort of HTLV-I- and HTLV-II-infected and -uninfected blood donors, all HIV seronegative. A total of 152 HTLV-I, 387 HTLV-II, and 799 uninfected donors were enrolled and followed for a median of 4.4, 4.3, and 4.4 years, respectively. HTLV-II participants had significantly increased incidences of acute bronchitis (incidence ratio [IR] = 1.68), bladder or kidney infection (IR = 1.55), arthritis (IR = 2.66), and asthma (IR = 3.28), and a borderline increase in pneumonia (IR = 1.82, 95% confidence interval [CI] 0.98 to 3.38). HTLV-I participants had significantly increased incidences of bladder or kidney infection (IR = 1.82), and arthritis (IR = 2.84). We conclude that HTLV-II infection may inhibit immunologic responses to respiratory infections and that both HTLV-I and -II may induce inflammatory or autoimmune reactions.

Therapeutic efficacy and safety of platelets treated with a photochemical process for pathogen inactivation: the SPRINT Trial.

We report a transfusion trial of platelets photochemically treated for pathogen inactivation using the synthetic psoralen amotosalen HCl. Patients with thrombocytopenia were randomly assigned to receive either photochemically treated (PCT) or conventional (control) platelets for up to 28 days. The primary end point was the proportion of patients with World Health Organization (WHO) grade 2 bleeding during the period of platelet support. A total of 645 patients (318 PCT and 327 control) were evaluated. The primary end point, the incidence of grade 2 bleeding (58.5% PCT versus 57.5% control), and the secondary end point, the incidence of grade 3 or 4 bleeding (4.1% PCT versus 6.1% control), were equivalent between the 2 groups (P =.001 by noninferiority). The mean 1-hour posttransfusion platelet corrected count increment (CCI) (11.1 x 10(3) PCT versus 16.0 x 10(3) control), average number of days to next platelet transfusion (1.9 PCT versus 2.4 control), and number of platelet transfusions (8.4 PCT versus 6.2 control) were different (P <.001). Transfusion reactions were fewer following PCT platelets (3.0% PCT versus 4.4% control; P =.02). The incidence of grade 2 bleeding was equivalent for PCT and conventional platelets, although posttransfusion platelet count increments and days to next transfusion were decreased for PCT compared with conventional platelets.