Background Exchange transfusion is a mainstay in the treatment of sickle cell anemia. Sickle cell recipients can be transfused over 10 units per therapy, an intervention that replaces circulating sickle red blood cells (RBCs) with donor RBCs. Storage of RBCs makes the intervention logistically feasible. The average storage duration for units transfused at the Duke University Medical Center is ~two weeks, a time window that should anticipate the accumulation of irreversible storage lesion to the erythrocyte. However, no metabolomics study has been performed to date to investigate the impact of exchange transfusion on recipients’ plasma and red blood cell phenotypes. Study design and Methods Plasma and red blood cells were collected from sickle cell patients before transfusion and within 5h from exchange transfusion with up to 11 units, prior to metabolomics analyses. Results Exchange transfusion significantly decreased plasma levels of markers of systemic hypoxemia like lactate, succinate, sphingosine 1-phosphate and 2-hydroxyglutarate. These metabolites accumulated in transfused RBCs, suggesting that RBCs may act as scavenger/reservoirs. Transfused RBCs displayed higher glycolysis, total adenylate pools and DPG, consistent with increased capacity to deliver oxygen. Plasma levels of acyl-carnitines and amino acids decreased, while fatty acids and potentially harmful phthalates increased upon exchange transfusion. Conclusion Metabolic phenotypes confirm the benefits of the transfusion therapy in sickle cell recipients and the reversibility of some of the metabolic storage lesion upon transfusion in vivo in two-week-old RBCs. However, results also suggest that potentially harmful plasticizers are transfused.

BACKGROUND: Red blood cell exchange (RCE) transfusions are a mainstay in the treatment of sickle cell anemia (SCA), and allow a temporary restoration of physiological parameters with respect to erythrocyte oxygen carrying capacity and systems metabolism. Recently, we noted that 1) RCE significantly impacts recipients' metabolism in SCA; 2) fresh and end-ofstorage red blood cell (RBC) units differently impact systems of metabolism in healthy autologous recipients; and 3) phosphate/inosine/pyruvate/adenine (PIPA) solution reverses the metabolic age of stored RBCs. Therefore, we hypothesized that RCE with PIPA-treated RBC units could further increase the metabolic benefits of RCE in SCA patients. STUDY DESIGN AND METHODS: Circulating plasmaand erythrocytes were collected from patients with SCA before and after RCE, with either conventional or PIPAtreated RBC units, prior to metabolomics analyses. RESULTS:Consistent with prior work, RCE significantly decreased circulating levels of markers of systemic hypoxemia (lactate, succinate) and decreased plasma levels of acyl-carnitines and amino acids. However, PIPA-treated exchanges were superior to untreated RCEs, with a higher energy state and an increased capacity to activate the pentose phosphate pathway and glutamine metabolism. In addition, RBCs and plasma from recipients of PIPA-treated RBC units resulted in significantly decreased levels of post-transfusion plasticizers, though at the expense of higher circulating levels of oxidized purines (hypoxanthine, xanthine, and the antioxidant urate). CONCLUSION: Transfusion of PIPA-treated RBCsfurther increases the metabolic benefits of RCE to patients with SCA, significantly reducing the levels of post-transfusion plasticizers.From the

Objectives To examine the effect of implementing postcatheterization ultrasound (US) on femoral arterial thrombosis detection rates and factors associated with thrombosis in infants. Background Although femoral arterial thrombosis is an uncommon complication of cardiac catheterization, it can cause limb threatening complications. Previous studies assessing the utility of postprocedure US to detect thrombosis in infants have utilized US as an adjunct to standard clinical detection methods, are small scale, or include small cohorts of infants within older populations. Methods We reviewed institutional records of patients 0–12 months undergoing catheterization from 2007 to 2016. Demographics and procedural data were compared between the thrombosis and non‐thrombosis group. Pre‐ and post‐US groups were compared for detected thrombosis rate. Using univariate and multivariable analyses, we identified factors associated with thrombosis. Results In total, 270 patients underwent 509 catheterizations, with 40 (7.9%) documented thromboses. The rate of thrombus detection in patients younger than 6 months increased from 8.3% to 23.4% (P = 0.006) after implementing routine US. On multivariable analysis, lower weight (P < 0.001), larger arterial sheath size (P < 0.001), and longer procedure duration (P = 0.003) were independently associated with higher odds of thrombosis. Conclusions Higher rates of femoral arterial thrombosis detection were observed since implementing an US screening program. Further studies are needed to evaluate age‐related changes in hemostasis in this population and how advanced screening methods and anticoagulation protocols may help improve short‐term and long‐term sequelae of femoral arterial thrombosis.