Blood transfusion safety in sub-Saharan Africa: A literature review of changes and challenges in the 21st century.

BACKGROUND: Access to a safe, adequate blood supply has proven challenging in sub-Saharan Africa, where systemic deficiencies spanning policy, collections, testing, and posttransfusion surveillance have long been recognized. Progress in transfusion safety in the early 2000s was in large part due to intervention by the World Health Organization and other foreign governmental bodies, coupled with an influx of external funding. STUDY DESIGN AND METHODS: A review of the literature was conducted to identify articles pertaining to blood safety in sub-Saharan Africa from January 2009 to March 2018. The search was directed toward addressing the major elements of the blood safety chain, in the countries comprising the World Health Organization African region. Of 1380 articles, 531 met inclusion criteria and 136 articles were reviewed. RESULTS: External support has been associated with increased recruitment of voluntary donors and expanded testing for the major transfusion-transmitted infections (TTIs). However, the rates of TTIs among donors remain high. Regional education and training initiatives have been implemented, and a tiered accreditation process has been adopted. However, a general decline in funding for transfusion safety (2009 onwards) has strained the ability to maintain or improve transfusion-related services. Critical areas of need include data collection and dissemination, epidemiological surveillance for TTIs, donor recruitment, quality assurance and oversight (notably laboratory testing), and hemovigilance. CONCLUSION: Diminishing external support has been challenging for regional transfusion services. Critical areas of deficiency in regional blood transfusion safety remain. Nonetheless, substantive gains in education, training, and accreditation suggest durable gains in regional capacity.

A multicentre study investigating vital sign changes occurring in complicated and uncomplicated transfusions.

BACKGROUND AND OBJECTIVES: Many hospitals require transfusions to be discontinued when vital signs stray from predetermined ranges, regardless of clinical symptoms. Variations in vital signs may be unrelated to transfusion, however, and needlessly stopping a transfusion may delay medical care while increasing donor exposures and healthcare costs. We hypothesized that a detailed study of vital sign changes associated with transfusion of blood product by component, including those associated with potential reactions (complicated) and those deemed to be uncomplicated, would establish a useful framework of reference for treating clinicians and transfusion services alike. MATERIALS AND METHODS: A retrospective electronic record review of transfusion service and transfusion recipient data was completed on 3852 inpatient transfusion episodes over a 6-month period at four academic tertiary care hospitals across the United States. Vital signs pre- and post-transfusion were recorded by trained clinical research nurses. Serious reactions were adjudicated by a panel of transfusion medicine experts. RESULTS: In both uncomplicated transfusions (n = 3765) and those including an adverse reaction (n = 87), vital sign fluctuations were generally modest. Compared to uncomplicated transfusions, transfusions complicated by febrile reactions were associated with higher pretransfusion temperature and higher pretransfusion pulse rates. Episodes of transfusion circulatory overload were associated with higher pretransfusion respiration rates compared to uncomplicated transfusions. CONCLUSION: Most transfusions are associated with only modest changes in vital signs. Pretransfusion vital signs may be an important yet previously understudied predictor of vital sign changes during transfusion. The optimal role of vital sign assessment during blood transfusion deserves further study.

Pathogen reduction and blood transfusion safety in Africa: strengths, limitations and challenges of implementation in low-resource settings.

Transfusion-transmitted infection risk remains an enduring challenge to blood safety in Africa. A high background incidence and prevalence of the major transfusion-transmitted infections (TTIs), dependence on high-risk donors to meet demand, suboptimal testing and quality assurance collectively contribute to the increased risk. With few exceptions, donor testing is confined to serological evaluation of human immunodeficiency virus (HIV), hepatitis B and C (HBV and HCV) and syphilis. Barriers to implementation of broader molecular methods include cost, limited infrastructure and lack of technical expertise. Pathogen reduction (PR), a term used to describe a variety of methods (e.g. solvent detergent treatment or photochemical activation) that may be applied to blood following collection, offers the means to diminish the infectious potential of multiple pathogens simultaneously. This is effective against different classes of pathogen, including the major TTIs where laboratory screening is already implemented (e.g. HIV, HBV and HCV) as well pathogens that are widely endemic yet remain unaddressed (e.g. malaria, bacterial contamination). We sought to review the available and emerging PR techniques and their potential application to resource-constrained parts of Africa, focusing on the advantages and disadvantages of such technologies. PR has been slow to be adopted even in high-income countries, primarily given the high costs of use. Logistical considerations, particularly in low-resourced parts of Africa, also raise concerns about practicality. Nonetheless, PR offers a rational, innovative strategy to contend with TTIs; technologies in development may well present a viable complement or even alternative to targeted screening in the future.

An Empirical Method of Detecting Time-Dependent Confounding: An Observational Study of Next Day Delirium in a Medical ICU.

Longitudinal research on older persons in the medical intensive care unit (MICU) is often complicated by the time-dependent confounding of concurrently administered interventions such as medications and intubation. Such temporal confounding can bias the respective longitudinal associations between concurrently administered treatments and a longitudinal outcome such as delirium. Although marginal structural models address time-dependent confounding, their application is non-trivial and preferably justified by empirical evidence. Using data from a longitudinal study of older persons in the MICU, we constructed a plausibility score from 0 - 10 where higher values indicate higher plausibility of time-dependent confounding of the association between a time-varying explanatory variable and an outcome. Based on longitudinal plots, measures of correlation, and longitudinal regression, the plausibility scores were compared to the differences in estimates obtained with non-weighted and marginal structural models of next day delirium. The plausibility scores of the three possible pairings of daily doses of fentanyl, haloperidol, and intubation indicated the following: low plausibility for haloperidol and intubation, moderate plausibility for fentanyl and haloperidol, and high plausibility for fentanyl and intubation. Comparing multivariable models of next day delirium with and without adjustment for time-dependent confounding, only intubation's association changed substantively. In our observational study of older persons in the MICU, the plausibility scores were generally reflective of the observed differences between coefficients estimated from non-weighted and marginal structural models.

Parallel enzyme-linked immunosorbent assay screening for human immunodeficiency virus among blood donors in five Chinese blood centres: a retrospective analysis.

AIMS: To evaluate the strategy of parallel screening with different enzyme-linked immunosorbent assays (ELISA) among Chinese blood donors. BACKGROUND: Parallel screening with ELISA has been the main strategy to detect human immunodeficiency virus (HIV) in blood donations in China for more than a decade. The performance of the strategy should be analysed. METHODS: A total of 821,927 donations collected from five Chinese blood centres in 2008-2010 were tested using two third-generation ELISAs by different manufacturers licenced and confirmed by the Western blot (WB) in this study. The confirmatory positive predictive values (PPV), false positive rates (FPR), false negative rates (FNR) and potential risks for transfusion resulting from single or sequential ELISA screening were evaluated. RESULTS: A total of 5318 (0·647%) of donations screened HIV reactive and were discarded. WB confirmatory results on 1668 available samples suggested that PPVs for dual ELISA, one round ELISA reactive and grey zone samples were 75·1, 0·7 and 0·5%, respectively. Eight out of 1124 one round ELISA reactive and 1 out of 195 grey zone samples were WB confirmed positive. All but one ELISA assay displayed comparable PPVs but variable FPRs and FNRs that differed by blood centre. CONCLUSIONS: In the absence of nucleic acid testing (NAT), parallel ELISA screening prevented a substantial number of HIV infected donations from entering the Chinese blood supply. However, the loss of false positive donors should be re-evaluated especially given the frequently reported blood supply shortage in China.

The impact of platelet transfusion characteristics on posttransfusion platelet increments and clinical bleeding in patients with hypoproliferative thrombocytopenia.

Platelet characteristics, such as platelet dose, platelet source (apheresis vs pooled), platelet donor-recipient ABO compatibility, and duration of platelet storage, can affect posttransfusion platelet increments, but it is unclear whether these factors impact platelet transfusion efficacy on clinical bleeding. We performed secondary analyses of platelet transfusions given in the prospective randomized Platelet Dose Study, which included 1272 platelet-transfused hematology-oncology patients who received 6031 prophylactic platelet transfusions. The primary outcome of these analyses was time from first transfusion to first World Health Organization ≥ grade 2 bleeding. Platelet transfusion increments were assessed at 0.25 to 4 hours and 16 to 32 hours after platelet transfusion. There were 778 patients evaluable for analysis of time to bleeding. Adjusted models showed that randomized dose strategy, platelet source, ABO compatibility, and duration of storage did not predict this outcome. Platelet increments were generally higher for transfusions of apheresis platelets, ABO-identical platelets, and platelets stored 3 days versus 4 to 5 days. Thus, although platelet source, ABO compatibility, and duration of storage exert a modest impact on both absolute and corrected posttransfusion platelet increments, they have no measurable impact on prevention of clinical bleeding. This trial was registered at www.clinicaltrials.gov as #NCT00128713.

First-time donors responding to a national disaster may be an untapped resource for the blood centre.

BACKGROUND: On 12 May 2008, a severe earthquake struck Sichuan in China. Many people donated blood for the first time, leading us to question whether these donors might become repeat donors in the future. The return pattern of post-earthquake first-time donors (PEFTD) was compared with that of first-time donors (FTD) in a comparable period. METHODS: Demographic characteristics, transfusion-transmissible infection rates and 1-year return rates were compared between 5147 PEFTD (5/13-5/19, 2008) and 3176 FTD (5/13-5/19, 2009) from five Chinese blood centres using chi-squared tests. Adjusted logistic regression was used to detect earthquake effect on donor return. RESULTS: Post-earthquake first-time donors were more frequently between 26 and 45 years, men, and better educated compared with the control group. Slightly higher but not statistically significant increased rates of hepatitis B virus surface antigen (HBsAg) (0·87% vs. 0·50%, P=0·054), hepatitis C virus (HCV) (0·70% vs. 0·63%, P=0·414), syphilis (0·9% vs. 0·7%, P=0·489) and lower rates of human immunodeficiency virus (HIV) (0·31% vs. 0·60%, P=0·078) reactivity were detected for PEFTD. The 1-year return rate for PEFTD was significantly lower than that of the controls (8·0% vs. 13·0%, P<0·001). After adjusting for demographic factors, donation volume and sites, the PEFTD were less likely to return in 1 year than the controls (OR: 0·520; 95% CI: 0·442, 0·611). CONCLUSION: Post-earthquake first-time donors may be less likely to donate again without continuing motivation strategies. Further studies on PEFTD's lack of motivation to return for donation are needed to design recruitment strategies to convert PEFTD to become repeat donors to continuously replenish the blood supply.

Quality improvement in neurology: AAN epilepsy quality measures: Report of the Quality Measurement and Reporting Subcommittee of the American Academy of Neurology.

OBJECTIVE: Epilepsy is a common neurologic condition with significant personal, societal, medical, and economic burdens. There are considerable gaps in the quality of care delivered. Measuring the quality of care delivered is the first step to its improvement. Performance measures are easily identified and quantitated ways to assess whether specific activities were carried out during a patient encounter. Therefore, epilepsy performance measures were derived through a standardized systematic process and may be the basis for pay-for-performance initiatives and maintenance of certification requirements. METHODS: Epilepsy measures were developed through the American Medical Association-convened Physician Consortium for Performance Improvement (PCPI) independent measure development process, which marked the first time a medical specialty society followed this process. Guidelines, measures, and consensus papers reviewed for the period 1998 to 2008 using the National Guidelines Clearinghouse, the National Quality Measures Clearinghouse, PubMed, MEDLINE, and the Cochrane Library were evaluated using a framework to determine the acceptability of each guideline or other evidence review document for measures development. Recommendation statements based on level of evidence, importance, validity, and gap in care were developed into candidate measures. A panel of experts from representative organizations vetted the measures. A period of public comment was followed by approval from the American Academy of Neurology and the PCPI. RESULTS: Literature search identified 160 relevant recommendation statements from 19 guidelines and 2 consensus papers. Systematic assessment resulted in 20 recommendation statements that were refined to 8 candidate measures by the expert panel. The measures are relevant to seizure type and frequency, etiology or epilepsy syndrome, EEG, neuroimaging, antiepileptic drug side effects, safety issues, referral for refractory epilepsy, and issues for women of childbearing potential. CONCLUSION: There is a reasonable evidence base, and consensus for, deriving performance measures for quality of epilepsy care. It is anticipated that implementation of these performance measures will improve care for patients with epilepsy if adopted by providers.

ABO antibody titer and risk of antibody-mediated rejection in ABO-incompatible renal transplantation.

Therapeutic plasma exchange (TPE) preconditioning with immunosuppressive therapy reduces ABO antibody titers, permitting engraftment of ABO-incompatible (ABO-I) kidney transplants. The posttransplant predictive role of ABO antibody titers for antibody-mediated rejection (AMR) is unknown. This retrospective study evaluated 46 individuals who received TPE to permit ABO-I kidney transplantation. ABO antibody titers were performed using donor-type indicator red cells. Seven individuals (15.2%) experienced clinical or subclinical AMR. There was no significant difference between recipient blood group, number of pretransplant TPE and baseline titer between those with and without AMR. At 1-2 weeks posttransplant the median titer was 64 (range 4 - 512) among individuals with AMR and 16 (range 2 - 256) among individuals without AMR. Total agglutination reactivity score was significantly higher among individuals with AMR (p = 0.046). The risk of AMR was significantly higher among individuals with an elevated posttransplant titer of >or=64 (p = 0.006). The sensitivity of an elevated posttransplant titer was 57.1% with a specificity of 79.5%. The positive predictive value was 33.3% and the negative predictive value was 91.2%. Most individuals with AMR have an elevated titer, however, the positive predictive value of a high titer for AMR is poor.

Psychological and behavioural impacts of the 2008 China earthquake on blood donors.

BACKGROUND AND OBJECTIVES: On May 12, 2008, a severe earthquake hit Sichuan province in China. A post-earthquake survey was conducted to study the earthquake's effect on blood donor behaviour and stress at three blood centres at varying distances from the epicentre. MATERIALS AND METHODS: A questionnaire was developed to assess donor post-traumatic stress disorders (PTSD) and attitudes toward giving blood. Responses were compared by centre and donor characteristics using multivariate logistic regression techniques. RESULTS: Of all 17 456 donors, the overall prevalence of PTSD was 13.2%. Donors who knew someone killed or injured by the earthquake were 2.1 times more likely to have PTSD than others (95% CI: 1.8-2.4). 85.2% of donors cited the earthquake as their reason for donating. 16.1% of donors felt it acceptable to be less honest about one's health history in an emergency. After adjusting for PTSD, geographic and demographic characteristics, the donors knowing someone killed or injured by the earthquake were 1.4 times (95% CI: 1.2-1.7) more likely to cite the earthquake as reason for donating, and 1.8 times (95% CI: 1.5-2.1) more likely to accept being less honest about one's health history in case of national emergency. CONCLUSIONS: The psychological and behavioural impacts of the earthquake on blood donors extended far from the epicentre. After a disaster, it is important to emphasize that donors must be truthful on the donor questionnaire as some donors appear willing to be less than honest when they perceive an increased need for blood products.

Detecting differential memory performance among Spanish-speaking patients with temporal lobe epilepsy.

There is relatively little research pertaining to neuropsychological assessment of Spanish-speaking individuals with intractable temporal lobe epilepsy (TLE). The current study examined verbal and visual memory performances in 38 primarily Spanish-speaking patients with TLE (Right = 15, Left = 23) of similar epilepsy duration to determine if lateralizing differences can be found using verbal and nonverbal memory tests. On a test specifically designed to assess auditory learning and memory among Spanish-speaking individuals, the Spanish Verbal Learning Test (SVLT), patients with left TLE performed significantly worse than patients with right TLE. In contrast, no significant differences in story or visual memory were seen using common memory tests translated into Spanish. Similar to what has been found in English speakers, these results show that verbal memory differences can be seen between left and right sided TLE patients who are Spanish-speaking to aid in providing lateralizing information; however, these differences may be best detected using tests developed for and standardized on Spanish-speaking patients.

Knowledge, attitude and practice survey regarding blood donation in a Northwestern Chinese city.

Recruitment of low-risk blood donors in developing countries is challenging. We studied the attitudes towards blood donation in several populations in a city in Western China. A survey of knowledge, attitude and practice was performed including 1280 individuals from eight distinct populations in Urumqi, Xinjiang Uyghur Autonomous Region, China. Included were Han Chinese and Uyghur populations of blood donors, non-donors, injection drug users, students and factory workers. Knowledge about blood donation varied between the groups. Factors motivating blood donation included social pressure, desire to know screening results and altruism. Inhibiting factors included fear of contracting an infection and other adverse health effects, including loss of vitality. Misconceptions about the effects of blood donation are widespread, even among educated persons in Urumqi. Fear of acquiring a serious infection may have been increased by the reports of HIV acquisition during plasma donations in China.

Qualitative analysis of WMS-III Logical Memory and Visual Reproduction in temporal lobe epilepsy.

Clinical observation of performance on the Logical Memory (LM) and Visual Reproduction (VR) subtests from the WMS-III has revealed some variability in retention rates across stories and figures. This paper examined the degree to which this variability occurs in lateralized temporal lobe epilepsy (TLE) in comparison to a matched group from the WMS-III standardization sample, and explored whether analysis of qualitative aspects of LM and VR performance yield additional lateralizing information in TLE. Analysis of LM and VR scaled scores revealed differences between the TLE groups for LM, but not VR scores. All subjects benefited from repetition of LM Story B, with greater improvement in story retention in the Left versus Right TLE group. Variability in VR recall across figures was seen in all groups, with a bimodal distribution of retention rates for each figure and a sizable percentage of each group completely forgetting two or more figures. These results suggest that more careful analysis of individual LM story performance may be useful in some patients with TLE, whereas variability in VR retention across figures is common and should not be over interpreted.

Prophylactic antigen-matched donor blood for patients with warm autoantibodies: an algorithm for transfusion management.

BACKGROUND: Patients with warm autoantibodies are at high risk for delayed hemolytic transfusion reactions due to the presence of alloantibodies. To provide blood safe for transfusion and to avoid adsorption studies in some cases, the provision of prophylactic antigen-matched donor blood where feasible for patients with warm autoantibodies is advocated. STUDY DESIGN AND METHODS: Twenty consecutive adult patients with warm autoantibodies (January 1999 to February 2000) received chronic RBC transfusions by use of this protocol: the serology consistent with warm autoantibodies was confirmed; the alloantibodies were identified; the complete phenotype was determined (i.e., C, E, c, e, K, Jk(a), Jk(b), Fy(a), Fy(b), S, and s); and prophylactic antigen-matched (i.e., donor RBCs matched with the patient's phenotype), WBC-reduced donor RBCs were provided for transfusion. On subsequent admissions, samples were evaluated by panel studies and DATs. If the serology remained consistent with previous findings, prophylactic antigen-matched, WBC-reduced RBCs were transfused without further testing. RESULTS: Eight of 20 (40%) patients had existing, clinically significant alloantibodies. In 12 of 20 (60%) patients, a phenotype was determined and the patients received transfusion of a total of 149 prophylactic antigen-matched RBC units (mean, 15 units per patient) precluding adsorption studies on 51 pretransfusion samples. In 8 of 20 (40%) cases (2 with alloantibodies), phenotypes were indeterminant, necessitating differential allogeneic adsorption studies on 39 samples before transfusion of 144 RBC units (mean, 18 units per patient). CONCLUSIONS: Determining complete phenotypes should be a routine component of the serologic evaluation of patients with warm autoantibodies. Our algorithm for providing prophylactic antigen-matched RBCs to these patients when a complete phenotype can be determined provides flexibility in their transfusion management while maintaining safety and circumvents or simplifies pretransfusion adsorption studies.

The contribution of sociodemographic, medical, and attitudinal factors to blood donation among the general public.

BACKGROUND: Few studies have simultaneously assessed the relative importance of sociodemographic, medical, and attitudinal factors in explaining which individuals are more likely to donate blood. STUDY DESIGN AND METHODS: A cross-sectional telephone survey of households in Maryland was conducted to identify the relation of sociodemographic, medical, and attitudinal factors to blood donation history among the general public. Random digit dialing was used to identify households; individuals aged 18 to 75 years were randomly selected within households. In multivariate analyses, the independent relationship of these factors with prior history of blood donation was assessed, and the amount of variation in prior history of blood donation among the study population that could be explained by these factors was determined. RESULTS: Of 385 participants (84% of randomized homes), 228 (59%) had donated blood at least once in the past. After adjusting for potential confounders, women, black participants, and those agreeing with the statement "I am afraid of hospitals" had 60 to 80 percent lower odds of prior donation when compared with men, white participants, and those who did not agree with the statement (OR [95% CI]: 0.2 [0.1-0.4], 0.4 [0.2-0.8], and 0.3 [0.2-0.6], respectively). The effect of fear of hospitals was consistent across sex and race. Trust, fear, and suspicion of hospitals were among factors contributing most to variation in prior donation history. CONCLUSION: Female sex, black race, and fear of hospitals are three major factors negatively associated with prior history of blood donation. Fear of hospitals affects blood donation patterns across race and sex groups. Future study is needed to determine whether recruitment of blood donors may be more efficient if focused toward women, minorities, and donors' fears of healthcare facilities or hospitals.

The concept of risk in biomedical research involving human subjects.

An established ethical principle of biomedical research involving human subjects stipulates that risk to subjects should be proportionate to an experiment's potential benefits. Sometimes this principle is imprecisely stated as a requirement that 'risks and benefits' be balanced. First, it is noted why this language is imprecise. Second, the persistence of such language is attributed to how it functions as a rhetorical trope. Finally, an argument is made that such a trope is infelicitous because it may not achieve its intended persuasive purposes. More importantly, it should be avoided because it masks the important role that chance plays in clinical research. Risk is the possibility of harm. As a precondition of harm it is unintended and undesirable in projects of biomedical research. It requires ethical vigilance. As a vehicle of chance, however, it is both intended and desirable. It requires methodological appreciation.

An animal model for delayed hemolytic transfusion reactions.

Delayed hemolytic transfusion reactions (DHTRs) are a well-known complication of transfusion that may be defined as immune-mediated hemolysis of allogeneic donor red cells that occurs approximately 3 to 5 days after transfusion. In general, DHTRs occur in patients who have been alloimmunized previously, but the antibody titers have fallen below serologically detectable levels. Transfusion of seemingly compatible blood and exposure to the putative alloantigen results in an anamnestic immune response that may lead to in vivo accelerated destruction of donor red cells. Symptoms may include a drop in hemoglobin and hematocrit, fever, jaundice, and renal insufficiency. More recent studies have shown that there is a subset of cases called delayed serologic transfusion reactions (DSTRs) when there are serologic findings consistent with DHTRs but no clinical evidence of hemolysis. In both DHTRs and DSTRs, direct antiglobulin tests are often persistently positive long after the transfused donor red cells should have been removed from the circulation. Because the studies required to investigate the immunologic and clinical aspects of these reactions are precluded in humans, we developed an animal model for the study of DHTRs and DSTRs. Our article provides a comprehensive review of DHTRs and DSTRs, the role of complement and cytokines in these reactions, and the phenomenon of bystander hemolysis. We describe our studies using the rabbit as a model for the study of DHTRs and bystander hemolysis.

Single donor versus pooled random donor platelet concentrates.

Both platelet concentrates (PC) derived from whole blood or single donor platelets (SDP) obtained from a single donor by apheresis are indicated to treat acute hemorrhage secondary to thrombocytopenia or to provide prophylaxis from hemorrhage in patients with bone marrow aplasia. Currently platelet transfusion therapy is limited by several concerns, including the consequences of alloimmunization in chronically transfused patients and septic reactions caused by bacterial contamination. There is debate about which platelet product should be used; many transfusion services favor the primary use of PC, whereas others favor SDP. This review will discuss five areas that should be considered when considering the use of SDP or PC: (1) the impact on infectious complications, (2) transfusion reaction rate, (3) leukodepletion, (4) reduction of transfusion frequency in patients with bone marrow suppression and, (5) the treatment and prevention of alloimmunization. The authors believe that SDP offers major advantages over PC for most of these issues, particularly when improved patient care is given primary emphasis.