Passive order auditing associated with reductions in red blood cell utilization: National blood shortage experience.

BACKGROUND: Decreased blood collection during the Coronavirus Disease 2019 (COVID-19) pandemic resulted in long-term red blood cell (RBC) shortages in the United States. In an effort to conserve RBCs, the existing passive alert system for auditing inpatient transfusions was modified to activate at a lower hemoglobin threshold (6.5 g/dL instead of 7.0 g/dL for stable, nonbleeding inpatients) during a 9-month shortage at an academic medical center. Hemoglobin levels prior to RBC transfusions were compared for inpatients receiving RBC transfusions to determine whether RBC utilization changed during the intervention. STUDY DESIGN AND METHODS: This retrospective study compared the number of single-unit RBC transfusions and hemoglobin levels prior to RBC transfusion among inpatients during the 9 months of the intervention (Period 2, 06/01/2021-2/28/2022) to the same period of the previous year (Period 1, 06/01/2020-2/28/2021). RESULTS: Overall full unit RBC transfusions to inpatients decreased by 15% from 5182 to 4421. Of all transfusions, 50.3% and 49.8% were single-unit RBC transfusions in Period 1 and Period 2, respectively. The incidence rate difference and incidence rate ratio of single RBC units transfused per 1000 patient days were significantly decreased (p = 0.0007). The average pre-transfusion hemoglobin level significantly decreased from 7.18 g/dL to 7.05 g/dL (p = 0.0002), largely due to significant decreases in hemoglobin transfusion triggers for adult inpatient ward transfusions. DISCUSSION: Modification of the passive alert system was associated with significantly decreased RBC utilization during a long-term RBC shortage. Modification of transfusion criteria recommended by passive alerts may be a feasible option to decrease RBC utilization at centers during long-term RBC shortages.

Red blood cell distribution width as a marker of hyperinflammation and mortality in COVID-19.

BACKGROUND: Red blood cell distribution width (RDW) could reflect interleukin-6 (IL-6) systemic activity since anisocytosis represents the inhibition of erythropoiesis, leaded by the hyperinflammatory background. Our objective was to analyze RDW performance to predict outcome in coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS). METHODS: Retrospective observational study including 173 patients with COVID-19-associated ARDS. Data was analyzed at hospital admission, inclusion in the TOCICOV Study (day 0), days 1, 3, 7 and 15 post-inclusion. RESULTS: Overall, 57% patients received tocilizumab. Overall mortality was 20.8%. RDW was higher in non-survivors compared to survivors at admission (13.53% vs. 14.35, P=0.0016), day 0 (13.60% vs. 14.42, P=0.026), day 3 (13.43% vs. 14.36, P<0.001) and day 7 (13.41% vs. 14.31, P=0.046), presenting better discrimination ability for mortality than other prognostic markers [area under the curve-receiver operating characteristic (AUC-ROC) =0.668 for admission RDW, 0.680 for day 0 RDW, 0.695 for day 3 RDW and 0.666 for day 7 RDW]. RDW values did not vary significantly according to tocilizumab treatment. When adjusted by hemoglobin and tocilizumab treatment, only RDW at admission, day 0, day 3 and C reactive protein (CRP) at day 0 and day 1 were associated with mortality (P<0.05). Only in non-tocilizumab treated patients, IL-6 levels at day 0 were correlated with day 3 RDW (r=0.733, P=0.004) and with day 3 CRP (r=0.727, P=0.022). Both parameters showed significant statistical correlation (r=0.255 for day 1 RDW and CRP in the overall cohort and r=0.358 for day 3 RDW and CRP in patients not treated with tocilizumab, P<0.015). CONCLUSIONS: RDW predicts COVID-19-associated ARDS mortality and reflects the hyperinflammatory background and the effects of cytokines such as IL-6, irrespective of tocilizumab treatment.

Morphofunctional Characteristics of Erythrocytes and Blood Erythropoietin Level in Patients as Predictors of Severe Course of COVID-19.

Morphological and functional characteristics of erythrocytes, hemoglobin, and erythropoietin level in the venous blood were evaluated by laser interference microscopy, Raman spectroscopy with a short-focus extreme aperture lens monochromator, and by ELISA, respectively, in 30 patients with verified moderate COVID-19 at the time of hospitalization and 30 healthy volunteers. The patients whose course of COVID-19 has worsened to critical by day 5 had already had lower (p<0.001) indicators at the time of hospitalization such as the area and thickness of erythrocytes, the hemoglobin distribution and packing density, hemoglobin conformation index (I1355/I1550)/(I1375/I1580) reflecting its oxygen affinity, and blood erythropoietin content. Our findings suggest that these characteristics of erythrocytes, hemoglobin, and erythropoietin can serve as potential predictors of COVID-19 aggravation in hospitalized patients.

Conus venom fractions inhibit the adhesion of Plasmodium falciparum erythrocyte membrane protein 1 domains to the host vascular receptors.

Using high-throughput BioPlex assays, we determined that six fractions from the venom of Conus nux inhibit the adhesion of various recombinant PfEMP-1 protein domains (PF08_0106 CIDR1α3.1, PF11_0521 DBL2ß3, and PFL0030c DBL3X and DBL5e) to their corresponding receptors (CD36, ICAM-1, and CSA, respectively). The protein domain-receptor interactions permit P. falciparum-infected erythrocytes (IE) to evade elimination in the spleen by adhering to the microvasculature in various organs including the placenta. The sequences for the main components of the fractions, determined by tandem mass spectrometry, yielded four T-superfamily conotoxins, one (CC-Loop-CC) with I-IV, II-III connectivity and three (CC-Loop-CXaaC) with a I-III, II-IV connectivity. The 3D structure for one of the latter, NuxVA = GCCPAPLTCHCVIY, revealed a novel scaffold defined by double turns forming a hairpin-like structure stabilized by the two disulfide bonds. Two other main fraction components were a miniM conotoxin, and a O2-superfamily conotoxin with cysteine framework VI/VII. This study is the first one of its kind suggesting the use of conotoxins for developing pharmacological tools for anti-adhesion adjunct therapy against malaria. Similarly, mitigation of emerging diseases like AIDS and COVID-19, can also benefit from conotoxins as inhibitors of protein-protein interactions as treatment. BIOLOGICAL SIGNIFICANCE: Among the 850+ species of cone snail species there are hundreds of thousands of diverse venom exopeptides that have been selected throughout several million years of evolution to capture prey and deter predators. They do so by targeting several surface proteins present in target excitable cells. This immense biomolecular library of conopeptides can be explored for potential use as therapeutic leads against persistent and emerging diseases affecting non-excitable systems. We aim to expand the pharmacological reach of conotoxins/conopeptides by revealing their in vitro capacity to disrupt protein-protein and protein-polysaccharide interactions that directly contribute to pathology of Plasmodium falciparum malaria. This is significant for severe forms of malaria, which might be deadly even after treated with current parasite-killing drugs because of persistent cytoadhesion of P. falciparum infected erythrocytes even when parasites within red blood cells are dead. Anti-adhesion adjunct drugs would de-sequester or prevent additional sequestration of infected erythrocytes and may significantly improve survival of malaria patients. These results provide a lead for further investigations into conotoxins and other venom peptides as potential candidates for anti-adhesion or blockade-therapies. This study is the first of its kind and it suggests that conotoxins can be developed as pharmacological tools for anti-adhesion adjunct therapy against malaria. Similarly, mitigation of emerging diseases like AIDS and COVID-19, can also benefit from conotoxins as potential inhibitors of protein-protein interactions as treatment.

Evidence of Structural Protein Damage and Membrane Lipid Remodeling in Red Blood Cells from COVID-19 Patients.

The SARS-CoV-2 beta coronavirus is the etiological driver of COVID-19 disease, which is primarily characterized by shortness of breath, persistent dry cough, and fever. Because they transport oxygen, red blood cells (RBCs) may play a role in the severity of hypoxemia in COVID-19 patients. The present study combines state-of-the-art metabolomics, proteomics, and lipidomics approaches to investigate the impact of COVID-19 on RBCs from 23 healthy subjects and 29 molecularly diagnosed COVID-19 patients. RBCs from COVID-19 patients had increased levels of glycolytic intermediates, accompanied by oxidation and fragmentation of ankyrin, spectrin beta, and the N-terminal cytosolic domain of band 3 (AE1). Significantly altered lipid metabolism was also observed, in particular, short- and medium-chain saturated fatty acids, acyl-carnitines, and sphingolipids. Nonetheless, there were no alterations of clinical hematological parameters, such as RBC count, hematocrit, or mean corpuscular hemoglobin concentration, with only minor increases in mean corpuscular volume. Taken together, these results suggest a significant impact of SARS-CoV-2 infection on RBC structural membrane homeostasis at the protein and lipid levels. Increases in RBC glycolytic metabolites are consistent with a theoretically improved capacity of hemoglobin to off-load oxygen as a function of allosteric modulation by high-energy phosphate compounds, perhaps to counteract COVID-19-induced hypoxia. Conversely, because the N-terminus of AE1 stabilizes deoxyhemoglobin and finely tunes oxygen off-loading and metabolic rewiring toward the hexose monophosphate shunt, RBCs from COVID-19 patients may be less capable of responding to environmental variations in hemoglobin oxygen saturation/oxidant stress when traveling from the lungs to peripheral capillaries and vice versa.