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BACKGROUND: Post-transfusion survival of donor red blood cells (RBCs) is important for effective chronic transfusion therapy in conditions including sickle cell disease (SCD). Biotin labeling RBCs allows direct in vivo measurement of multiple donor RBC units simultaneously post-transfusion. STUDY DESIGN AND METHODS: In an observational trial of patients with SCD receiving monthly chronic transfusion therapy, aliquots of RBCs from one transfusion episode were biotin-labeled and infused along with the unlabeled RBC units. Serial blood samples were obtained to measure RBC survival. Donor units were tested for RBC indices, hemoglobin fractionation, and glucose-6-phosphate dehydrogenase (G6PD) enzyme activity. For microcytic donor RBCs (MCV < 70 fL), HBA1 and HBA2 genetic testing was performed on whole blood. RESULTS: We present one recipient, a pediatric patient with SCD and splenectomy who received two RBC units with aliquots from each unit labeled at distinct biotin densities (2 and 18 µg/mL biotin). One donor unit was identified to have microcytosis (MCV 68.5 fL after biotinylation); whole blood sample obtained at a subsequent donation showed 2-gene deletion alpha-thalassemia trait (É-3.7kb/É-3.7kb) and normal serum ferritin. G6PD activity was >60% of normal mean for both. The RBCs with alpha-thalassemia RBC had accelerated clearance and increased surface phosphatidylserine post-transfusion, as compared with the normocytic RBC (half life 65 vs. 86 days, respectively). DISCUSSION: Post-transfusion RBC survival may be lower for units from donors with alpha-thalassemia trait, although the impact of thalassemia trait donors on transfusion efficacy requires further study.
Asunto(s)
Anemia de Células Falciformes , Donantes de Sangre , Transfusión de Eritrocitos , Eritrocitos , Talasemia alfa , Humanos , Anemia de Células Falciformes/terapia , Anemia de Células Falciformes/sangre , Talasemia alfa/terapia , Talasemia alfa/sangre , Eritrocitos/metabolismo , Masculino , Supervivencia Celular , Biotinilación , Femenino , NiñoRESUMEN
BACKGROUND: Viscoelastic hemostatic assays (VHAs) provide more comprehensive assessments of coagulation compared with conventional coagulation assays. Although VHAs have enabled guided hemorrhage control therapies, improving clinical outcomes in life-threatening hemorrhage, the role of VHAs in intracerebral hemorrhage (ICH) is unclear. If VHAs can identify coagulation abnormalities relevant for ICH outcomes, this would support the need to investigate the role of VHAs in ICH treatment paradigms. Thus, we investigated whether VHA assessments of coagulation relate to long-term ICH outcomes. METHODS: Patients with spontaneous ICH enrolled into a single-center cohort study receiving admission Rotational Thromboelastometry (ROTEM) VHA testing between 2013 and 2020 were assessed. Patients with previous anticoagulant use or coagulopathy on conventional coagulation assays were excluded. Primary ROTEM exposure variables were coagulation kinetics and clot strength assessments. Poor long-term outcome was defined as modified Rankin Scale ≥ 4 at 6 months. Logistic regression analyses assessed associations of ROTEM parameters with clinical outcomes after adjusting for ICH severity and hemoglobin concentration. RESULTS: Of 44 patients analyzed, the mean age was 64 years, 57% were female, and the median ICH volume was 23 mL. Poor 6-month outcome was seen in 64% of patients. In our multivariable regression models, slower, prolonged coagulation kinetics (adjusted odds ratio for every second increase in clot formation time 1.04, 95% confidence interval 1.00-1.09, p = 0.04) and weaker clot strength (adjusted odds ratio for every millimeter increase of maximum clot firmness 0.84, 95% confidence interval 0.71-0.99, p = 0.03) were separately associated with poor long-term outcomes. CONCLUSIONS: Slower, prolonged coagulation kinetics and weaker clot strength on admission VHA ROTEM testing, not attributable to anticoagulant use, were associated with poor long-term outcomes after ICH. Further work is needed to clarify the generalizability and the underlying mechanisms of these VHA findings to assess whether VHA-guided treatments should be incorporated into ICH care.
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Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy in humans. G6PD is an essential enzyme in the pentose phosphate pathway (PPP), generating NADPH needed for cellular biosynthesis and reactive oxygen species (ROS) homeostasis, the latter especially key in red blood cells (RBCs). Beyond the RBC, there is emerging evidence that G6PD exerts an immunologic role by virtue of its functions in leukocyte oxidative metabolism and anabolic synthesis necessary for immune effector function. We review these here, and consider the global immunometabolic role of G6PD activity and G6PD deficiency in modulating inflammation and immunopathology.
Asunto(s)
Deficiencia de Glucosafosfato Deshidrogenasa , Glucosafosfato Deshidrogenasa , Humanos , Glucosafosfato Deshidrogenasa/metabolismo , Deficiencia de Glucosafosfato Deshidrogenasa/inmunología , Deficiencia de Glucosafosfato Deshidrogenasa/metabolismo , Animales , Especies Reactivas de Oxígeno/metabolismo , Vía de Pentosa Fosfato , Inmunidad , Infecciones/inmunología , Inflamación/inmunología , Inflamación/metabolismoRESUMEN
Oxidative stress can damage tissues and cells, and their resilience or susceptibility depends on the robustness of their antioxidant mechanisms. The latter include small molecules, proteins, and enzymes, which are linked together in metabolic pathways. Red blood cells are particularly susceptible to oxidative stress due to their large number of hemoglobin molecules, which can undergo auto-oxidation. This yields reactive oxygen species that participate in Fenton chemistry, ultimately damaging their membranes and cytosolic constituents. Fortunately, red blood cells contain robust antioxidant systems to enable them to circulate and perform their physiological functions, particularly delivering oxygen and removing carbon dioxide. Nonetheless, if red blood cells have insufficient antioxidant reserves (e.g., due to genetics, diet, disease, or toxin exposure), this can induce hemolysis in vivo or enhance susceptibility to a "storage lesion" in vitro, when blood donations are refrigerator-stored for transfusion purposes. Ergothioneine, a small molecule not synthesized by mammals, is obtained only through the diet. It is absorbed from the gut and enters cells using a highly specific transporter (i.e., SLC22A4). Certain cells and tissues, particularly red blood cells, contain high ergothioneine levels. Although no deficiency-related disease has been identified, evidence suggests ergothioneine may be a beneficial "nutraceutical." Given the requirements of red blood cells to resist oxidative stress and their high ergothioneine content, this review discusses ergothioneine's potential importance in protecting these cells and identifies knowledge gaps regarding its relevance in enhancing red blood cell circulatory, storage, and transfusion quality.
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This systematic review evaluates the evidence for accuracy of automated analyzers that estimate cerebrospinal fluid (CSF) white blood cell counts (WBC) compared to manual microscopy. Inclusion criteria of original research articles included human subjects, English language, and manual microscopy comparator. PUBMED, EMBASE and Cochrane Review databases were searched through 2019 and QUADAS-2 Tool was used for assessment of bias. Data were pooled and analyzed by comparison method, using random effects estimation. Among 652 titles, 554 abstracts screened, 104 full-text review, 111 comparisons from 41 studies were included. Pooled estimates of sensitivity and specificity (n = 7) were 95% (95%-CI 93%-97%) and 84% (95%-CI: 64%-96%), respectively. Pooled R2 estimates (n = 29) were 0.95 (95%-CI: 0.95-0.96); Pooled spearman rho correlation (n = 27) estimates were 0.95 (95% CI 0.95-0.96). Among those comparisons using Bland-Altman analysis (n = 11) pooled mean difference was estimated at 0.98 (95% CI-0.54-2.5). Among comparisons using Passing-Bablok regressions (n = 14) the pooled slope was estimated to be 1.05 (95% CI 1.03-1.07). Q tests of homogeneity were all significant with the exception of the Bland-Altman comparisons (I2 10%, p value 0.35). There is good overall accuracy for CSF WBC by automated hematologic analyzers. These findings are limited by the small sample sizes and inconsistent validation methodology in the reviewed studies.
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Background: Viscoelastic hemostatic assays (VHA) provide more comprehensive assessments of coagulation compared to conventional coagulation assays. While VHAs have enabled guided hemorrhage control therapies, improving clinical outcomes in life-threatening hemorrhage, the role of VHAs in intracerebral hemorrhage (ICH) is unclear. If VHAs can identify coagulation abnormalities relevant for ICH outcomes, this would support the need to investigate the role of VHAs in ICH treatment paradigms. Thus, we investigated whether VHA assessments of coagulation relate to long-term ICH outcomes. Methods: Spontaneous ICH patients enrolled into a single-center cohort study receiving admission Rotational Thromboelastometry (ROTEM) VHA testing between 2013 and 2020 were assessed. Patients with prior anticoagulant use or coagulopathy on conventional coagulation assays were excluded. Primary ROTEM exposure variables were coagulation kinetics and clot strength assessments. Poor long-term outcome was defined as modified Rankin Scale ≥ 4 at 6 months. Logistic regression analyses assessed associations of ROTEM parameters with clinical outcomes after adjusting for ICH severity and hemoglobin concentration. Results: Of 44 patients analyzed, mean age was 64, 57% were female, and the median ICH volume was 23 mL. Poor 6-month outcome was seen in 64%. In our multivariable regression models, slower, prolonged coagulation kinetics (adjusted OR for every second increase in clot formation time: 1.04, 95% CI: 1.00-1.09, p = 0.04) and weaker clot strength (adjusted OR for every millimeter increase of maximum clot firmness: 0.84, 95% CI: 0.71-0.99, p = 0.03) were separately associated with poor long-term outcomes. Conclusions: Slower, prolonged coagulation kinetics and weaker clot strength on admission VHA ROTEM testing, not attributable to anticoagulant use, were associated with poor long-term outcomes after ICH. Further work is needed to clarify the generalizability and the underlying mechanisms of these VHA findings to assess whether VHA guided treatments should be incorporated into ICH care.