Search

BACKGROUND: The 1000 Genomes Project provides a database of genomic variants from whole genome sequencing of 2,504 individuals across 5 continental superpopulations. This database can enrich our background knowledge of worldwide blood group variant geographic distribution, and identify novel variants of potential clinical significance. STUDY DESIGN AND METHODS: The 1000 Genomes database was analyzed to 1) expand knowledge about continental distributions of known blood group variants; 2) identify novel variants with antigenic potential and their geographic association; and 3) establish a baseline scaffold of chromosomal coordinates to translate Next Generation Sequencing (NGS) output files into a predicted RBC phenotype. RESULTS: Forty-two genes were investigated. A total of 604 known variants were mapped to the GRCh37 assembly; 120 of these were reported by 1000 Genomes in at least one superpopulation. All queried variants, including the ACKR1 promoter silencing mutation, are located within exon pull-down boundaries. The analysis yielded 41 novel population distributions for 34 known variants, as well as 12 novel blood group variants that warrant further validation and study. Four prediction algorithms collectively flagged 79 of 109 (72%) known antigenic or enzymatically-detrimental blood group variants, while 4 of 12 variants that do not result in an altered RBC phenotype were flagged as deleterious. CONCLUSION: NGS has known potential for high-throughput and extended RBC phenotype prediction; a database of GRCh37 and GRCh38 chromosomal coordinates for 120 worldwide blood group variants is provided as a basis for this clinical application.

AIM: To evaluate risks of restrictive red-blood cell transfusion strategies (hemoglobin 7–8 g/dL) in patients with and without known cardiovascular disease (CVD). BACKGROUND: Recent guidelines recommend restrictive strategies for CVD-patients hospitalized for non-CVD indications, patients without known CVD and patients hospitalized for CVD corrective procedures. METHODS/MATERIALS: Database searches were conducted through December 2017 for randomized-clinical trials that enrolled patients with and without known CVD, hospitalized either for CVD corrective procedures or non-cardiac indications, comparing effects of liberal to restrictive strategies on major adverse coronary events (MACE) and death. RESULTS: In CVD patients not undergoing cardiac interventions, a liberal strategy decreased (p=0.01) the relative risk (95%CI) (RR) of MACE [0.50 (0.29–0.86)] (I(2)=0%). Among patients without known CVD, the incidence of MACE was lower (1.7 vs 3.9%), and the effect of a liberal strategy on MACE [0.79, (0.39–1.58)] was smaller and nonsignificant, but not different from CVD patients (p=0.30). Combining all CVD and non-CVD patients, a liberal strategy decreased MACE [0.59, (0.39–0.91); p=0.02]. Conversely, among studies reporting mortality, a liberal strategy decreased mortality in CVD patients (11.7% vs.13.3%), but increased mortality (19.2% vs. 18.0%) in patients without known-CVD [interaction p=0.05; ratio of RR 0.73, (0.53–1.00)]. A liberal strategy also did not benefit patients undergoing cardiac surgery; data was insufficient for percutaneous cardiac procedures. CONCLUSIONS: In patients hospitalized for non-cardiac indications, liberal transfusion strategies are associated with a decrease risk of MACE in both those with and without known CVD. However, this only provides a survival benefit to CVD-patients not admitted for CVD corrective procedures.

The advent of preservative solutions permitted refrigerated storage of red blood cells. However, the convenience of having red blood cell inventories was accompanied by a disadvantage. Red cells undergo numerous physical and metabolic changes during cold storage, the "storage lesion(s)". Whereas controlled clinical trials have not confirmed the clinical importance of such changes, ethical and operational issues have prevented careful study of the oldest stored red blood cells. Suggestions of toxicity from meta-analyses motivated us to develop pre-clinical canine models to compare the freshest vs the oldest red blood cells. Our model of canine pneumonia with red blood cell transfusion indicated that the oldest red blood cells increased mortality, that the severity of pneumonia is important, but that the dose of transfused red blood cells is not. Washing the oldest red blood cells reduces mortality by removing senescent cells and remnants, whereas washing fresher cells increases mortality by damaging the red blood cell membrane. An opposite effect was found in a model of haemorrhagic shock with reperfusion injury. Physiological studies indicate that release of iron from old cells is a primary mechanism of toxicity during infection, whereas scavenging of cell-free haemoglobin may be beneficial during reperfusion injury. Intravenous iron appears to have toxicity equivalent to old red blood cells in the pneumonia model, suggesting that intravenous iron and old red blood cells should be administered with caution to infected patients.

Spray-drying techniques are commonly utilized in the pharmaceutical, dairy, and animal feed industries for processing liquids into powders but have not been applied to human blood products. Spray-dried protein products are known to maintain stability during storage at room temperature.Plasma units collected at the donor facility were shipped overnight at room temperature to a processing facility where single-use spray drying occurred. After 48 hours' storage at room temperature, the spray-dried plasma product was split in two and rehydrated with 1.5% glycine or deionized water and assayed for chemistry analytes and coagulation factors. Matched fresh-frozen plasma was analyzed in parallel as controls.Reconstitution was achieved for both rehydration groups within 5 minutes (n = 6). There was no significant intergroup difference in recovery for total protein, albumin, immunoglobulin (Ig)G, IgA, and IgM (96% or higher). With the exception of Factor VIII (58%), the recovery of clotting factors in the glycine reconstituted products ranged from 72% to 93%. Glycine reconstitution was superior to deionized water.We documented proteins and coagulation activities were recovered in physiologic quantities in reconstituted spray-dried plasma products. Further optimization of the spray-drying method and reconstitution fluid may result in even better recoveries. Spray drying is a promising technique for preparing human plasma that can be easily stored at room temperature, shipped, and reconstituted. Rapid reconstitution of the microparticles results in a novel plasma product from single donors.

Human leucocyte antigen (HLA) antibodies have been implicated in transfusion-related acute lung injury, but the probability that the transfusion of a blood component containing HLA antibodies will cause a reaction is not known. This study compared the prevalence of reactions associated with the transfusion of platelet components with and without HLA antibodies.This retrospective study tested 96 consecutive apheresis platelet donors for HLA class I and II antibodies. Matched control donors without HLA antibodies were selected and records were reviewed to determine the proportion of components from each group that caused reactions. In addition, all apheresis platelet donors involved with two or more reactions were identified and tested for HLA class I antibodies.Five of the 96 donors had antibodies to class I or class II antigens and, of these, four had components transfused. The prevalence of reactions to components from these four donors with HLA antibodies and the 12 matched control donors without antibodies was similar (three reactions to 167 transfusions or 1.8% vs. three to 295 or 1.0%, respectively, P = 0.32). A retrospective review of the transfusion records from all platelet donors found that components from 22 caused two or more reactions and three (13.6%) had antibodies to HLA class I compared to 4.2% of the consecutively selected donors (P = 0.12). None of the patients experienced transfusion-related acute lung injury.Reactions associated with transfusion of apheresis platelets containing HLA antibodies are unusual.