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.

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.

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.

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.

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.

Validating billing data for RBC transfusions: a brief report.

BACKGROUND: Administrative data are used often for research, but without validation of their accuracy. The validity of the billing for blood transfusion was assessed in one tertiary-care hospital. MATERIALS AND METHODS: Patient discharge data were retrieved from a database containing demographics, diagnoses, and charges. There was random selection of 358 patients who were billed for RBC transfusion and 358 who were not, within a 2-month period. The blood bank's transfusion records were reviewed. Sensitivity was defined as the proportion of transfused patients who were billed, and specificity as the proportion of nontransfused patients who were not billed. Patient characteristics were compared by using Wilcoxon's rank sum test and the chi-square test. RESULTS: Sixty-one transfused patients were not billed for the transfusion. No patient was billed without transfusion. Thus, the sensitivity and specificity were 83 percent (95% CI, 79-87%) and 100 percent, respectively. Nine patients who were not issued RBCs were appropriately not billed for RBCs, although the billing record suggests they had a procedure involving transfusion. These patients were called true-negative. The patients not billed were older (58 years vs. 55 years; p = 0.046) and less likely to have commercial insurance (5% vs. 15%; p = 0.035) than billed patients. CONCLUSIONS: The billing for RBC transfusion in one large institution is reassuringly valid. The specificity is excellent, and the sensitivity is higher than that seen in other studies of coding validity.

Evidence of Trypanosoma cruzi infection (Chagas' disease) among patients undergoing cardiac surgery.

BACKGROUND: Trypanosoma cruzi, the agent of Chagas' heart disease, is transmitted by triatomine insects and by blood transfusion. The emigration of several million people from T cruzi-endemic countries to the United States has raised concerns regarding a possible increase in cases of Chagas' heart disease here, as well as an increased risk of transfusion-transmitted T cruzi. To investigate these 2 possible outcomes, we tested a repository of blood specimens from multiply transfused cardiac surgery patients for antibodies to T cruzi. METHODS AND RESULTS: Postoperative blood specimens from 11 430 cardiac surgery patients were tested by enzyme immunoassay, and if repeat-reactive, were confirmed by radioimmunoprecipitation. Six postoperative specimens (0.05%) were confirmed positive. Corresponding preoperative specimens, available for 4 of these patients, were also positive. The other 2 patients had undergone heart transplantations. Tissue samples from their excised hearts were tested for T cruzi by polymerase chain reaction and were positive. Despite the fact that several of these 6 patients had histories and clinical findings suggestive of Chagas' disease, none of them were diagnosed with or tested for it. Patient demographics showed that 5 of 6 positive patients were Hispanic, and overall, 2. 7% of Hispanic patients in the repository were positive. CONCLUSIONS: No evidence for transfusion-transmitted T cruzi was found. All 6 seropositive patients apparently were infected with T cruzi before surgery; however, a diagnosis of Chagas' disease was not known or even considered in any of these patients. Indeed, Chagas' disease may be an underdiagnosed cause of cardiac disease in the United States, particularly among patients born in countries in which T cruzi is endemic.

Transfusion medicine: an overview and update.

The discovery of AIDS in the 1980s and its rapid evolution as a major concern for physicians and their patients have led to many questions about the safety of the blood supply. The attention placed on AIDS has led to new discoveries and technologies to reduce the risk of other transfusion complications such as hepatitis, bacterial contamination, and transfusion-associated graft-vs-host disease. Concerns about blood safety have focused much attention on alternative blood transfusion strategies such as autologous blood, viral inactivation, and artificial blood substitutes. This review describes the transfusion medicine delivery system in the United States, with special emphasis on evolving developments and their implications for the discipline of chemical pathology.

An acute hemolytic transfusion reaction due to anti-IH in a patient with sickle cell disease.

BACKGROUND: A hemolytic transfusion reaction (HTR) due to anti-IH is reported in a patient with sickle cell disease (SCD). CASE REPORT: An 18-year-old woman with SCD and a complete phenotype on file had been identified as group B-positive with negative antibody-screening tests and had received 1 unit of packed RBCs. Ten days later, she was readmitted in painful crisis with a Hb of 4.2 g per dL. Antibody-screening tests and panel cells were positive at all test phases with a negative autocontrol, which suggested alloantibodies. Phenotypically matched group O RBCs were issued emergently. After the transfusion of 100 mL, the patient had an HTR with chills, fever, and tachycardia and laboratory findings of hemoglobinemia, hemoglobinuria, and negative DATs. A high-titer, IgM anti-IH with a high thermal amplitude (reactive with group O, but not group B RBCs at 37 degrees C) was identified. Autologous RBCs appeared to have normal I antigen expression, but less H antigen than pooled group B RBCs. She was given group B RBCs, uneventfully, by use of a blood warmer. CONCLUSIONS: This is a rare case of anti-IH as the cause of a HTR, as a serologic problem that may be seen in SCD, and as an autoantibody that may mimic an alloantibody. Ironically, this HTR resulted from the effort to provide phenotypically matched RBCs, which necessitated the selection of group O RBCs.

Automated RBC exchange transfusion:treatment for cerebral malaria.

BACKGROUND: Cerebral malaria is a life-threatening complication of Plasmodium falciparum infection. RBC exchange transfusion can reduce the level of parasitemia in this setting. Experience with automated RBC exchange for cerebral malaria may be limited, as most cases occur when the necessary equipment and blood components are not readily available. CASE REPORTS: Three patients were admitted with cerebral malaria. Parasites were found in more than 30 percent of RBCs in two cases and in more than 60 percent of RBCs in the third case. Many RBCs contained multiple organisms. In each case, antimalarial therapy was begun, and an automated RBC exchange was performed emergently with a cell separator. Exchange transfusion was repeated within 24 hours for two patients. Parasitemia levels were less than 1 percent in all patients 24 hours after the last exchange. The neurologic status of these patients returned to baseline, and they were discharged 7 to 18 days after admission. CONCLUSION: Automated RBC exchange transfusion can rapidly reduce the level of parasitemia and restore neurologic functioning in patients with cerebral malaria.

Retention of coagulation factors in plasma frozen after extended holding at 1-6 degrees C.

BACKGROUND AND OBJECTIVES: The ability to use plasma, isolated from units of whole blood and frozen within 24 h of phlebotomy, as a substitute for plasma frozen within 8 h of phlebotomy would have several advantages for blood centers. It should provide increased flexibility pertaining to the freezing of plasma for clinical use. We have conducted studies to assess the influence of an extended holding time for separated plasma, prior to freezing, on the retention of coagulation factor activity. STUDY DESIGN AND METHODS: Freshly harvested plasma from each of 10 units of CPD-whole blood was divided into four equal aliquots. These aliquots were held in plastic packs at 1-6 degrees C for a total of 0, 8, 15 and 24 h. Subsequently, the plasma aliquots were frozen rapidly and stored at -20 degrees C for 4 months. The thawed plasma was tested for coagulant factors V and IX, factor VIII coagulant activity (factor VIII:C), von Willebrand factor antigen (vWF:Ag) and ristocetin cofactor of von Willebrand factor. RESULTS: The levels of factor V, factor vWF:Ag, factor IX and ristocetin cofactor were not influenced by holding the plasma for up to 24 h prior to freezing. Factor VIII:C activity was reduced with extended holding at 1-6 degrees C; the percentage at time zero activity was 75.9+/-2.4% for samples frozen immediately after a 24-hour period. CONCLUSIONS: The data indicate that coagulation factor properties of harvested plasma are retained except for factor VIII for at least 24 h prior to freezing.

Analysis of hepatitis G virus (HGV) RNA, antibody to HGV envelope protein, and risk factors for blood donors coinfected with HGV and hepatitis C virus.

Serologic, biochemical, and molecular analyses were used to study hepatitis G virus (HGV), antibody to the HGV envelope protein (anti-E2), risk factors, clinical significance, and the impact of HGV on coexistent hepatitis C virus (HCV). Among 329 donors with confirmed HCV infection, 12% were HGV RNA-positive and 44% were anti-E2-positive (total exposure, 56%). HGV RNA and anti-E2 were mutually exclusive except in 9 donors (1.5%); 8 of 9 subsequently lost HGV RNA but anti-E2 persisted. HGV had little impact on alanine aminotransferase, aspartate aminotransferase, or gamma-glutamyl transpeptidase in donors with HGV infection alone or those coinfected with HCV. A multivariate analysis showed that intravenous drug abuse was the leading risk factor for HGV transmission, followed by blood transfusion, snorting cocaine, imprisonment, and a history of sexually transmitted diseases. In summary, HGV and HCV infections were frequently associated and shared common parenteral risk factors; HGV did not appear to cause hepatitis or to worsen the course of coexistent hepatitis C.