scholarly journals Selenium Status and Hemolysis in Sickle Cell Disease Patients

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2211 ◽  
Author(s):  
Emília Delesderrier ◽  
Cláudia S. Cople-Rodrigues ◽  
Juliana Omena ◽  
Marcos Kneip Fleury ◽  
Flávia Barbosa Brito ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Linear Regression ◽  
Sickle Cell ◽  
Complete Blood Count ◽  
Hematological Parameters ◽  
Linear Regression Analysis ◽  
Selenium Deficiency ◽  
Alpha Tocopherol ◽  
Cell Disease ◽  
Chronic Hemolysis

Sickle cell disease (SCD) is a genetic hemoglobinopathy characterized by chronic hemolysis. Chronic hemolysis is promoted by increased oxidative stress. Our hypothesis was that some antioxidant micronutrients (retinol, tocopherol, selenium, and zinc) would be determinant factors of the degree of hemolysis in SCD patients. We aimed to investigate the nutritional adequacy of these antioxidants and their relationships to hemolysis. The study included 51 adult SCD patients regularly assisted in two reference centers for hematology in the State of Rio de Janeiro, Brazil. Serum concentrations of retinol, alpha-tocopherol, selenium, and zinc were determined by high-performance liquid chromatography or atomic absorption spectrometry. Hematological parameters (complete blood count, reticulocyte count, hemoglobin, direct and indirect bilirubin, total bilirubin, lactate dehydrogenase) and inflammation markers (leukocytes and ultra-sensitive C-reactive protein) were analyzed. A linear regression model was used to test the associations between the variables. Most patients presented selenium deficiency and low selenium consumption. Linear regression analysis showed that selenium is the main determinant of hemolysis among the antioxidant nutrients analyzed. Thus, data from this study suggest that the nutritional care protocols for patients with SCD should include dietary sources of selenium in order to reduce the risk of hemolysis.

scholarly journals To Give or Not to Give: RhD Immunoglobulin for an RHD*39 Pregnant Woman with Sickle Cell Disease

2021 ◽  
pp. 1-5
Author(s):  
Justin E. Juskewitch ◽  
Craig D. Tauscher ◽  
Sheila K. Moldenhauer ◽  
Jennifer E. Schieber ◽  
Eapen K. Jacob ◽  
...  
Keyword(s):  
Pregnant Woman ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Pregnancy Termination ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Childbearing Age ◽  
Procedural Complications ◽  
History Of ◽  
Chronic Hemolysis

Introduction: Patients with sickle cell disease (SCD) have repeated episodes of red blood cell (RBC) sickling and microvascular occlusion that manifest as pain crises, acute chest syndrome, and chronic hemolysis. These clinical sequelae usually increase during pregnancy. Given the racial distribution of SCD, patients with SCD are also more likely to have rarer RBC antigen genotypes than RBC donor populations. We present the management and clinical outcome of a 21-year-old pregnant woman with SCD and an RHD*39 (RhD[S103P], G-negative) variant. Case Presentation: Ms. S is B positive with a reported history of anti-D, anti-C, and anti-E alloantibodies (anti-G testing unknown). Genetic testing revealed both an RHD*39 and homozygous partial RHCE*ceVS.02 genotype. Absorption/elution testing confirmed the presence of anti-G, anti-C, and anti-E alloantibodies but could not definitively determine the presence/absence of an anti-D alloantibody. Ms. S desired to undergo elective pregnancy termination and the need for postprocedural RhD immunoglobulin (RhIG) was posed. Given that only the G antigen site is changed in an RHD*39 genotype and the potential risk of RhIG triggering a hyperhemolytic episode in an SCD patient, RhIG was not administered. There were no procedural complications. Follow-up testing at 10 weeks showed no increase in RBC alloantibody strength. Discussion/Conclusion: Ms. S represents a rare RHD*39 and partial RHCE*ceVS.02 genotype which did not further alloimmunize in the absence of RhIG administration. Her case also highlights the importance of routine anti-G alloantibody testing in women of childbearing age with apparent anti-D and anti-C alloantibodies.

scholarly journals Utility of Procalcitonin in Differentiating Acute Chest Syndrome from Vaso-Occlusive Crisis in Sickle Cell Disease

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 10-11
Author(s):  
Satish Maharaj ◽  
Simone Chang ◽  
Karan Seegobin ◽  
Marwan Shaikh ◽  
Kamila I. Cisak
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Complete Blood Count ◽  
Conflicts Of Interest ◽  
Statistical Significance ◽  
Acute Chest Syndrome ◽  
Adult Males ◽  
Cell Disease ◽  
Unequal Variances ◽  
Recorded Data

Background: Acute chest syndrome (ACS) frequently complicates sickle cell disease (SCD) and is a leading cause of hospitalization and mortality. Many factors have been implicated in ACS, including infections, thrombosis, fat and pulmonary emboli. However, a clear etiology is not defined in 50% of the cases and ACS is considered a clinical endpoint for different pathogenic processes (Vichinsky et al 2000). The non-specific nature of ACS makes diagnostic tests challenging, and there are no serum tests clinical used to aid diagnosis. Procalcitonin (PCT) is a prohormone of calcitonin and serum PCT rises within hours of an inflammatory stimulus. PCT has clinical utility as a marker of severe systemic inflammation, infection, and sepsis (Becker et al. 2008). Few studies have evaluated PCT as a biomarker for ACS in patients presenting with vaso-occlusive crises (VOC). Two studies have reported no difference in PCT (Biemond et al. 2018 and Stankovic et al 2011), while one study reported higher PCT between ACS and VOC (Patel et al 2014). Methods: We retrospectively reviewed 106 patients with SCD who presented to the emergency department with fever and painful crises during 2015-2019. The patients were divided into two categories based on discharge diagnoses - patients with VOC only (n=88) and patients with ACS (n=18). Inclusion criteria for both groups were patients with SCD, 17 years and older and PCT measurement on presentation. Exclusion criteria were defined as patients who had received empiric antibiotics prior to PCT testing. Data collected on presentation included genotype, age, gender, complete blood count, PCT, creatinine, total bilirubin and hydroxyurea use. Length of stay was recorded. Data was analyzed between the two groups using descriptive statistics and accounting for unequal variances, withp-value set at 0.05 for significance. Results: Demographics and clinical characteristics are summarized in Table 1 (Figure). The sample included primarily adult males (77%), with about two-thirds on hydroxyurea. Genotype HbSS (73.6%) was most prevalent followed by HbSC (22.6%) and HbSβ (3.8%). The ACS group had a higher percentage of HbSS, lower use of hydroxyurea and higher mean bilirubin. Mean PCT for the ACS group was 0.52 ng/mL (range, 0.05-2.04), compared to 0.31 ng/mL (range, 0.02-6.82) in the VOC group; withp=0.084. ROC analysis showed a PCT>0.5ng/mL had 39% sensitivity and 85% specificity for ACS in this sample. Conclusion: In this sample, PCT on presentation was higher in those with ACS compared to VOC, but this difference did not achieve statistical significance. Further study in a larger population would be useful to evaluate this finding. Disclosures No relevant conflicts of interest to declare.

Genetics of HbF and HbF Response to Hydroxyurea In Pediatric Sickle Cell Disease: A Multi-Site Pilot Analysis of Candidate SNP Variants

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2641-2641
Author(s):  
Nancy S. Green ◽  
Katherine Ender ◽  
Farzana Pashankar ◽  
Catherine Driscoll ◽  
Patricia Giardina ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Multiple Testing ◽  
Linear Regression Analysis ◽  
Minor Allele ◽  
Candidate Snps ◽  
Genetic Associations ◽  
Cell Disease ◽  
Bonferroni Adjustment ◽  
Snp Association

Abstract Abstract 2641 Abstract: Only few genes appear to strongly regulate HbF levels in adults with sickle cell disease (SCD). We aim to: (1) Extend these observations to children with SCD, who likely have better preserved marrow capacity; (2) Assess whether these same genes and other previously identified candidates (Ma et al., 2007) associate with HbF response to HU. Methods: We performed a retrospective analysis from 6 sites (see author affiliations) of children age 5–21 with HbSS or HbS-B thalassemia, untreated with HU or treated for > 6 months at comparable indications and dosing, using %HbF at steady state (baseline) and on HU at or near maximal tolerated dose (MTD), defined as >20mg/kg/day. Subject adherence to HU was assessed by report to their hematology clinician. Siblings were excluded to ensure genetic independence. Candidate 36 SNPs from 2 groups of genes were genotyped: 1) those from reported GWAS: 15 SNPs in BCL11A, 3 in HBS1L-MYB intron, 5' site in B globin, plus sar1; and 2) 15 candidate SNPs exhibiting the largest effect size on HbF with HU treatment (Ma, 2007). SNP genotyping (minor allele frequency (MAF) ranging from 0.10 to 0.50) was performed on the Sequenom MassArray iPLEX platform. (SNP sequences are available.) Duplicate samples assured genotype concordance. Genotype frequency distribution at each SNP was tested for deviations from Hardy-Weinberg equilibrium. MAFs were comparable across our 6 sites, to allele frequencies in HapMap for CEU populations, and CSSCD (Lettre et al., 2008), confirming validity of pooling SNP genotype data from the sites. Using HbF as a continuous trait, genetic associations were assessed from a total of 80 children, 29 of whom are on HU, between each of the 36 SNPs and: a) baseline %HbF; b) %HbF on HU treatment; c) delta %HbF (HU treatment - baseline). For each model, linear regression analysis was used to test quantitative trait and disease trait SNP associations assuming an additive effect for each copy of the minor allele on the phenotype. Resultant p-values were assessed for significance using Bonferroni adjustment for multiple testing. Results: Of the 80 children, comparing the 51 not on HU to those 29 on HU, no significance differences were seen in the distribution and average of baseline %HbF (9.2 vs. 8.9, p=0.820). SNP analyses are summarized in Table 1. 8 SNPs were nominally significantly associated with baseline %HbF. Direction of SNP association differed among these SNPs; some MAF may be reversed in this population compared to those previously reported. For %HbF on HU, the B globin SNP was significantly associated. The delta %HbF on HU is significantly associated with the B globin SNP and nominally so with BCLA11 and SAR1A gene. Our preliminary data begin to extend findings of specific genetic variants regulating HbF to children with SCD. Early data suggest that HbF in response to HU may share some of the mechanisms governing baseline HbF in SCD, not surprising given the commonality of enhanced erythropoiesis. Subject recruitment and analyses are on-going. Disclosure: Off Label Use: Hydroxyurea has not been FDA approved for use in children with sickle cell disease, a topic of the submitted abstract.

scholarly journals Ordering of Home Hydroxyurea By Residents for Hospitalized Patients with Sickle Cell Disease

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3521-3521
Author(s):  
Rebekah Shaw ◽  
Sarah Kappa ◽  
Robert Sheppard Nickel
Keyword(s):  
Sickle Cell Disease ◽  
Policy Change ◽  
Sickle Cell ◽  
Complete Blood Count ◽  
Conflicts Of Interest ◽  
Hospitalized Patients ◽  
Fisher Exact Test ◽  
Not Given ◽  
Cell Disease ◽  
Hospital System

Abstract Background: Hydroxyurea is daily oral medication proven to decrease complications of sickle cell disease (SCD). While concerns have been raised about the safety of hydroxyurea, it is now generally viewed as a well-tolerated medication for SCD. The primary toxicity of hydroxyurea that requires holding of treatment is reversible cytopenia. Due to its classification as a chemotherapeutic agent and safety concerns regarding inappropriate chemotherapy ordering, hydroxyurea can only be ordered by "chemotherapy-certified" providers at some hospitals. At our hospital system, pediatric resident physicians were restricted from ordering hydroxyurea. Instead of being a part of a resident's hospital admission orders, hydroxyurea for inpatients had to be ordered separately by a hematology fellow or attending physician. In June 2016 our hospital changed its policy to allow residents to order hydroxyurea for patients with SCD admitted to the hospital who were already on hydroxyurea at home. We hypothesized that this change in policy to allow residents to order hydroxyurea would increase the proportion of patients with SCD appropriately receiving their home hydroxyurea by hospital day 1. We also hypothesized that this policy change would not result in an increase in the proportion of patients inappropriately receiving hydroxyurea when it should have been held based on the admission complete blood count (CBC). Methods: We conducted a retrospective review of the medical records of a random sample of patients admitted to the hematology service the year before (2015) and the year after (2017) the policy change in 2016. Patients were eligible for study if they were admitted to the hematology service and were taking hydroxyurea as documented by a clinic note within the last three months. Patients were excluded if they were admitted to the intensive care unit or for surgery. Patients were also excluded if discharged on hospital day 0 or 1. Institutional guidelines advise holding hydroxyurea if any of the following: absolute neutrophil count <1250/µL; platelet count <80K/µL; reticulocyte count <100K/µL, unless hemoglobin >8.0 gm/dL. Hydroxyurea was classified as "inappropriately given" if a patient received hydroxyurea despite having an admission CBC value below a hold parameter. Hydroxyurea was classified as "appropriately not given" if a patient did not receive hydroxyurea when having a CBC value below a hold parameter. Patients who were on hydroxyurea who never received hydroxyurea inpatient with CBC values above the hold parameters were classified as "inappropriately not given." Patients admitted in 2015 (before resident ordering) were compared with patients admitted in 2017 (after resident ordering) using a chi-square test or Fisher exact test. Results: In total, 217 hospitalizations of eligible patients were reviewed: 91 before the policy change and 126 after the policy change. Based on the admission CBC, hydroxyurea should have been held for 8 patients. Excluding these patients who should not have received hydroxyurea, patients after the policy change were significantly more likely to have received their home hydroxyurea by hospital day 1: before 62/90 (69%) vs. after 105/119 (88%), p=0.0005. The proportion of patients who inappropriately received hydroxyurea was very low in both groups: before 1/91 (1%) vs. after 3/126 (2%), p=0.64. No serious adverse clinical events occurred from this "inappropriate" administration of hydroxyurea. The figure graphically displays the proportion of patients in the two groups who: appropriately received on hospital day 0/1/2+, inappropriately did not receive, appropriately did not receive, and inappropriately received hydroxyurea. Conclusion: Resident ordering of home hydroxyurea for hospitalized patients with SCD appears to be safe. Policies that permit residents to order hydroxyurea as part of a patient's admission orders can help increase the proportion of patients who receive this important medication while inpatient. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

Abstract 2303: Prospective Correlation of Echocardiography Findings with Hematologic and Pulmonary Function Parameters in Children with Sickle Cell Disease

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Niti Dham ◽  
Craig Sable ◽  
Caterina P Minnitti ◽  
Andrew Campbell ◽  
Manuel Arteta ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Sickle Cell Disease ◽  
Pulmonary Function ◽  
Diastolic Function ◽  
Sickle Cell ◽  
Linear Regression Analysis ◽  
Cell Disease ◽  
Pulmonary Pressure ◽  
Prospective Comparison ◽  
Lv Mass

Background Adults with sickle cell disease (SCD) have an increased prevalence of pulmonary hypertension (PAH), associated with significant morbidity and mortality. This finding has not been validated in children. We carried out a prospective comparison of echocardiography (echo) data between SCD and control patients and a correlation between echo findings and hematologic and pulmonary function testing (PFT) in SCD patients. Methods Children with SCD and age and gender matched controls were prospectively enrolled during well visits. Each subject underwent a history and examination, echo, hematologic testing, and PFT. Echo data was compared between SCD patients and controls, and regression analysis was performed to assess for correlation between echo parameters and anemia, markers of hemolysis, and PFT in SCD patients. Results Of the 194 SCD patients and 29 controls enrolled, 180 SCD patients and 26 controls had measurable tricuspid valve regurgitation (TR) to estimate systolic pulmonary pressure. TR, left ventricle (LV) size and LV mass were significantly higher in children with SCD (Table 1 ). Linear regression analysis in SCD patients showed that TR, LV size, LV mass, and diastolic function (E/E TDI ) correlated significantly with hemoglobin, markers of hemolysis, and obstructive pulmonary disease (Table 2 ). There was no correlation between echo parameters and age, blood pressure, or measures of restrictive lung disease Conclusion Children with SCD have higher estimated pulmonary pressure, LV size and mass and a trend toward worse diastolic function when compared to controls. TR and LV size and mass correlate with anemia, hemolysis, and obstructive patterns on PFT. Table 1 - Comparative Data Table 2 - Regression Analysis

Adding Hydroxyurea to Chronic Transfusion Therapy for Stroke in Sickle Cell Disease.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4620-4620
Author(s):  
Susan Claster ◽  
Keith C. Quirolo
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Reticulocyte Count ◽  
Conflicts Of Interest ◽  
Hematological Parameters ◽  
Fetal Hemoglobin ◽  
Venous Access ◽  
Time Frame ◽  
Cell Disease ◽  
Transfusion Therapy

Abstract Abstract 4620 Introduction Transfusions have clearly been shown to prevent stroke in patients with Sickle Cell Disease(SCD). The usual goal of transfusion therapy is to keep the percent sickle Hgb (%S) less than 30. %S greater than 30 has been associated with stroke reoccurance. Inability to transfuse adequately may result from poor vascular access or high hemolytic rate. Hydroxyurea, a drug which requires active erythropoeisis, is usually not given to patients who are chronically transfused. However, the presence of an elevated reticulocyte count in a transfused patient indicates ongoing sickle hematopoiesis. We added Hydroxyurea therapy to two patients who were unable to achieve %S levels less than 30 and who had elevated reticulocyte counts to assess whether this drug could improve their hematological parameters. Results We treated two post stroke patients, one receiving pheresis therapy, and the other on straight transfusion therapy who were unable to achieve 30% Hgb S despite regular transfusions. Patient 1, a 33 y/o female with Hgb SS had been on transfusions since childhood for multiple CVA's and resulting moya-moya. Her last stroke had occurred while she was being chronically transfused and had a % S of 40. Due to venous access issues the patient was receiving straight transfusion only and was unable to adequately suppress her marrow. In 8/07 her %S was greater than 40 and her reticulocyte count was 11.3 %. Hydroxyurea was started at 1500 mg daily(22 mg/kg). Over the next 24 months her Bilirubin dropped from 8.7mg/dl to 1.9 mg/dl, her reticulocyte count dropped to 4%(figure below) and her MCV increased to 104.6 from 90. Her Hgb F rose to 30%.Her %S has not changed. She has remained clinically stable with no new neurological findings. The second patient, a 17 y/o male had been on chronic transfusions since childhood for a stroke which resulted in a dense left hemiparesis. He has been on a pheresis program for 13 years. Despite this his % S remained greater than 40% and had been as high as 60% prepheresis. Hydroxyurea was added in 5/08 at a dose of 25mg/kg. Within 6 months his pretransfusion %S had dropped to 22-27%. No increase in fetal Hgb was detected, possibly due to the exchange transfusion process. His bilirubin, which had been running between 12-16 mg/dl dropped to 7.6-8.9 mg/dl and his reticulocyte count went from an average of 19.6% to 11.2% in the same time frame. He has also remained stable. Discussion These two patients demonstrate that the addition of Hydroxyurea to patients on chronic transfusion can be useful in decreasing hemolytic rate and improving the efficacy of transfusions by decreasing sickle erythropoiesis and increasing fetal hemoglobin synthesis. Further studies of the combination of these two modalities may be warranted in those patients who cannot achieve adequate suppression of sickle erythropoeisis. Disclosures: No relevant conflicts of interest to declare.

Gender Difference in Periodic Limb Movements in Adults with Sickle Cell Disease

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4843-4843 ◽  
Author(s):  
Suely Roizenblatt ◽  
Marina Roizenblatt ◽  
Frederico Pollack Filho ◽  
Sandra S Matsuda ◽  
Grazielle Mecabo ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Pain Perception ◽  
Conflicts Of Interest ◽  
Hematological Parameters ◽  
Periodic Limb Movements ◽  
Cell Disease ◽  
Limb Movements ◽  
Arousal Index ◽  
Hydroxyurea Treatment

Abstract Abstract 4843 Periodic limb movements during sleep (PLMS) are commonly described in children with Sickle Cell Disease (SCD), however the relevance of such events in sleep disturbance or complaint of daytime fatigue remain questionable. It has been known that the dopaminergic neurotransmission has a modulator role in pain perception. Since PLMS have been suggested to be a potential biological marker of dopaminergic mechanisms, this study aimed to assess PLMS in adults with SCD and its correlations with clinical and sleep parameters. Methods: Seventy adults with SCD (50% females, matched for age and body mass index), underwent Brief Pain Inventory, overnight polysomnogram and laboratorial tests for hemoglobin, reticulocytes, ferritin, transferin saturation, haptoglobin, fetal hemoglobin, lactate dehydrogenase (LDH), and bilirrubins. Results: The mean PLMS index was higher in females (16.5±10.7/h vs. 8.7±8.2/h, p< 0.05), with 88.6% of the females having increased PLMS index (≥ 15/h) in comparison to males (22.6), p<0.01. Total arousal index and PLMS arousal index were increased in females with PLMS ≥ 15/h compared to those with PLMS < 5/h (p<0.05, both), but not in males. Females also exhibited correlation of increased PLMS index and clinical parameters such as pain score (rS =0.71), indirect bilirrubin (rS =0.42) and LDH (rS =0.38), p<0.01 in all. An interaction effect of the non-use of hydroxyurea treatment in PLMS abnormality was also observed (p<0.05). Conclusions: Elevated PLMS were more common in females with SCD than in males and correlated with pain symptoms and hematological parameters of hemolysis. Hydroxyurea treatment showed a protective effect against the PLMS index increase. Supported by AFIP, CEPID-FAPESP 98/14303-3, and CAPES/SUS. Disclosures: No relevant conflicts of interest to declare.

Haptoglobin and Hemopexin Infusion Efficiently Activates the Nrf2/HO-1 Axis and Inhibits Inflammation and Vaso-Occlusion in Murine Sickle Cell Disease

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2477-2477 ◽  
Author(s):  
John D Belcher ◽  
Chunsheng Chen ◽  
Julia Nguyen ◽  
Fuad Abdulla ◽  
Phong Nguyen ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Research Funding ◽  
Cell Disease ◽  
Free Hemoglobin ◽  
Treatment Groups ◽  
Plasma Hemoglobin ◽  
Skin Fold ◽  
Chronic Hemolysis ◽  
Plasma Haptoglobin

Abstract Free hemoglobin and hemin, released by red blood cells during intravascular hemolysis, promote vasculopathy, inflammation, thrombosis, and renal injury. Plasma haptoglobin and hemopexin tightly bind free hemoglobin and hemin, respectively, thwarting these clinical sequelae. In sickle cell disease (SCD), chronic hemolysis can deplete plasma haptoglobin and hemopexin in humans and mice. To explore mechanisms mediating this protection and provide a basis for supplementation in SCD patients, dorsal skin fold chambers were implanted onto Townes-SS mice and microvascular stasis (% non-flowing venules) was measured in response to a hemoglobin challenge. Human haptoglobin, hemopexin, or albumin was co-infused with hemoglobin or 1 hour after hemoglobin at equimolar concentrations. Sickle mice co-infused with hemoglobin/haptoglobin, hemoglobin/hemopexin or hemoglobin/haptoglobin/hemopexin had less stasis 1 to 4 hours after infusion, compared to albumin- and saline-treated mice (*p<0.01, Figure A). Haptoglobin, hemopexin, or haptoglobin/hemopexin given to Townes-SS mice 1 hour after hemoglobin, decreased stasis 2 and 3 hours after supplementation, while the venules of mice treated with albumin remained static (*p<.01, Figure B). Plasma hemoglobin and heme levels in Townes-SS mice were not different between treatment groups 3 and 4 hours after supplementation. Haptoglobin or hemopexin infusion increased hepatic Nrf2 and HO-1 and decreased pro-inflammatory NF-ĸB phospho-p65 expression relative to albumin 3 and 4 hours after supplementation (p<.05). The combination of haptoglobin/hemopexin was similar to either scavenger alone. Inhibition of the enhanced HO-1 activity afforded by haptoglobin or hemopexin with tin protoporphyrin blocked the stasis protection, confirming the critical cytoprotective role of HO-1. Haptoglobin and hemopexin, but not albumin, are cytoprotective in part by efficiently delivering heme to CD163 and CD91 and activating the Nrf2/HO-1 axis. Figure Figure. Disclosures Belcher: CSL-Behring: Research Funding; Imara: Research Funding. Chen:Imara: Research Funding. Brinkman:CSL-Behring: Employment. Vercellotti:CSL-Behring: Research Funding; Imara: Research Funding.

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