Higher Hemoglobin Concentration Research Articles

Blood pressure profile, sympathetic nervous system activity, and subclinical target organ damage in patients with polycythemia vera.

Polycythemia vera (PV) is a rare myeloproliferative disease associated with an increased prevalence of hypertension and increased risk of cardiovascular complications. However, the precise mechanisms leading to the elevation of blood pressure (BP) and secondary target organ damage remain poorly understood. The study aimed to evaluate BP profile, assess the activity of the sympathetic nervous system and the renin‑angiotensin system, and provide a comprehensive assessment of subclinical target organ damage in patients with PV. Twenty consecutive patients with newly diagnosed PV and 20 control subjects were included. The following were assessed: BP, levels of catecholamines, urinary and plasma O‑methylated catecholamine metabolites, concentrations of aldosterone and renin. We also assessed microneurography sympathetic nervous system activity (MSNA) and baroreflex control of heart rate as well as subclinical target organ damage. At similar levels of BP, BP variability was decreased in the PV group (mean [SD] 24‑hour systolic BP, 9 [3] vs 12 [3] mm Hg; P = 0.003). Patients with PV had lower norepinephrine excretion (mean [SD], 16.54 [6.32] vs 25.46 [12.88] μg/d; P = 0.03) as well as decreased MSNA as assessed by microneurography compared with controls (mean [SD] MSNA, 30.7 [8.7] bursts/min vs 38.7 [5.4] bursts/min; P = 0.007 and MSNA 51.8 [11] bursts/100 beats vs 61.1 [11.3] bursts/100 heart beats; P = 0.04). Baroreflex control of HR was unaltered in the PV group. Increased hemoglobin levels and red blood cell count correlated with decreased retinal capillary flow in patients with PV. Patients with PV, characterized by high hemoglobin concentrations and hematocrit levels had lower sympathetic nervous activity and decreased BP variability as compared with controls. There was no relationship between hemoglobin plasma concentration, hematocrit level, and target organ damage.

Preoperative blood transfusions for sickle cell disease.

Preoperative blood transfusions for sickle cell disease.

Association Of Hemoglobin Concentration With Coronary Artery Calcification For Risk Of All-cause Mortality

Introduction: Both low and high hemoglobin (Hb) concentration related with adverse cardiovascular outcomes. To date, however, the relationship between Hb level and coronary artery calcium score (CACS) on risk of adverse outcomes has not been well studied. We assessed the association between baseline Hb level and the burden of subclinical atherosclerosis as measured by CACS in a large cohort of asymptomatic Korean adults.

Analysis of Dengue Infection Severity among Ethnics in Surabaya, Indonesia

Background: Dengue infection prevalence remains high in tropical countries, including Indonesia, whereas the government had struggled to overcome the disease. Indonesia has very diverse ethnicities living across the archipelago, there might be a wide variety of susceptibility and severity. Objective: This research was aimed to analyse ethnicity as a risk factor for dengue infection severity in Surabaya, Indonesia. Design and Methods: This research observed Dengue Hemorrhage Fever (DHF) or Dengue Fever (DF) patients aged over 12 years, who were hospitalized in three private hospitals in Surabaya. Data collection was conducted from March 20, 2013 to May 20, 2013 with a sample size of 95 patients. Ethnicity, dengue infection severity, clinical findings, and relevant laboratory information data were obtained. This was a cross-sectional study design with consecutive sampling. All data were analysed using SPSS 17.00 software. The statistical analysis was performed at a significance level of p-value <0.005 using the chi-square test. Results: The majority of patients who suffered from severe dengue infection based on WHO classification and bleeding symptoms were Chinese patients (82.1%). The laboratory results pointed out Chinese patients had the highest hemoglobin concentration (15.62 ± 1.70 %), highest PCV (44.90 ± 4.23 g/dl), and the lowest platelets (31.42 ± 22.05 x 103µl). There were significant dengue infection severity difference (p=0.015), hemoglobin increase (p=0.004), PCV (0.024), and platelets (p=0.006) between Chinese, Javanese, and other ethnicities. Conclusion: Chinese ethnic had the highest risk of suffering severe dengue infection in Surabaya.

Acute aerobic exercise impairs aspects of cognitive function at high altitude

Hypoxia-mediated cognitive dysfunction can be transiently mitigated by exercise in a laboratory-based setting. Whether this effect holds true in the context of high altitude hypoxia has not been determined. We investigated the effect of acute aerobic exercise on cognitive function (CF) at low (1400m) and high altitude (4240m). Fifteen volunteers (24.1±3.5yrs; 9 females) exercised for 20-min at 40-60% of their heart rate reserve at low and high altitude. CF was assessed before and 10-min after exercise using a tablet-based battery of executive function tests. A sea-level control group (n=13; 24.2±2.4 years; 9 females) performed time-matched CF tests to assess the contribution of a learning effects due to repeated testing. Measures of resting CF were unaffected by ascent to high altitude. Following high altitude exercise, performance significantly worsened on the digit symbol substitution task – a test of processing speed, working memory, and visuospatial attention (z=0.01 vs. -0.59, p=0.02, η2=0.35). No effect was found on other measures of CF following exercise. There was no association between changes in peripheral oxygen saturation and changes in CF following high altitude exercise (r=0.22, p=0.44), but higher hemoglobin concentration at high altitude was associated with a decline in CF following exercise at high altitude (r=-0.65, p=0.02). Acute aerobic exercise performed at high altitude impairs some aspects of CF, whereas other CF tests remain unchanged. The strong ecological validity of this study warrants attention and follow-up investigations are needed to better characterize selective impairment of CF with high altitude exercise.

The interaction between current smoking and hemoglobin on the risk of advanced fibrosis in patients with biopsy-proven nonalcoholic fatty liver disease.

Higher hemoglobin levels have been associated with an increased risk for nonalcoholic fatty liver disease. Although the mechanism underlying this association is elusive, smoking has been previously related to both higher hemoglobin concentrations and an increased risk of fibrosis in nonalcoholic fatty liver disease. The present study was conducted to investigate formally the interaction among current smoking, hemoglobin levels, and risk for advanced fibrosis in patients with biopsy-proven nonalcoholic fatty liver disease. We examined 433 Turkish patients with biopsy-proven nonalcoholic fatty liver disease. Advanced fibrosis (F ≥ 3) was identified on liver biopsy in 80 cases, whereas 84 patients were current smokers. Logistic regression models were used to evaluate the effect of current smoking on risk for advanced fibrosis, after adjusting for the effects of age, sex, BMI, diabetes, and metabolic syndrome. Preliminary analyses revealed the presence of substantial statistical interaction between current smoking and hemoglobin levels (P < 0.001). In separate multivariable analyses conducted in the entire cohort and in the subgroups of patients with high and low hemoglobin levels (according to median value in the study cohort: 14.4 g/l), current smoking was associated with increased risk for advanced fibrosis in patients with high hemoglobin (odds ratio: 3.32, 95% confidence interval: 1.23-7.21, P < 0.01) but neither in those with low hemoglobin (odds ratio: 0.71, 95% confidence interval: 0.28-1.81, P = 0.52) nor in the entire study cohort (odds ratio: 1.18, 95% confidence interval: 0.73-2.14, P = 0.79). Hemoglobin acts as a modifier in the association between current smoking and advanced fibrosis in nonalcoholic fatty liver disease.

Hematological Changes in Blood of Smokers of Cigarettes and Nargyle

The current study aimed at determining the effect of smoking cigarette and Narghile at some of bloody variables and Vitamin D in a sample of young smokers aged 20-35 in Ramadi.The study included complete blood count (C.B.C) tests including:Total White Blood Cell and Red Blood Cell Count, determination of the concentration of total hemoglobin and calculation of Platelet Count.Calculation of RBC Indicators: “mean corpuscular hemoglobin” (MCH), “Mean Corpuscular Hemoglobin Concentration” (“MCHC”) and Mean red blood Cell Volume (MCV). The study also evaluated the concentration of vitamin D. Results showed that: A rise in the number of white blood cells and red blood cells, as well as a high concentration of hemoglobin and platelet count in smokers.An increase in the volume of red blood cells, mean hemoglobin concentration, and Mean Corpuscular Hemoglobin Concentration in smokers’ blood. Decreased concentration of vitamin D .

Transient polycythemia during diabetic ketoacidosis triggered by dengue fever in a middle-aged woman

Either dengue fever or diabetic ketoacidosis can cause the high hemoglobin concentration due to intravascular volume loss. When both entities were found together as in our case, the hemoglobin concentration could access the strikingly high level until either of them could not contribute it. She was a Thai woman with 46 years of age presenting with fever, fatigue and severe sore throat for a few days. The physical examination showed she had mild dyspnea and oral thrush, the temperature was 36.4 degree Celsius, and her pulse rate was 102/min. Her blood tests showed: Hb 18.3 g%, WBC 9,850/mm3, atypical lymphocyte 10%, platelet 16,000/mm3, MCV 89.2 fl, Dengue NS1 antigen-positive, dengue IgG-positive, IgM-weakly positive, KOH preparation of curd from buccal mucosa-positive for budding yeasts and pseudo-hyphae, blood sugar 442 mg%, triglyceride 578 mg%, Na 122.8 mEq/L, K 6.28 mEq/L, Cl 90.6 mEq/L, CO2 9.2 mEq/L, blood ketone 53.6 mmol/L, lactate 4.5 mmol/L, pH 7.257, pCO2 27.4 mmHg, HCO3 11.9 mmo/L, BUN 22.9 mg%, creatinine 0.64 mg%, AST 375 U/L, ALT 224 U/L, alkaline phosphatase 151 U/L. She was diagnosed as having diabetes with diabetic ketoacidosis, dengue fever and polycythemia. She was immediately treated with intravenous fluid therapy to correct the metabolic acidosis, electrolyte imbalance and dehydration, insulin for hyperglycemia, clotrimazole for oral thrush and platelet transfusion. Her high hemoglobin level was dramatically lowered until became normal within one day of therapy whereas she also recovered from DKA although the platelet was progressively lowered every day. It suggested that transient polycythemia was solely contributed by DKA that was triggered by dengue fever hence DKA from dengue fever should be added in the list of unusual causes of transient polycythemia.

INFLUENCE OF RBC COUNT AND HAEMOGLOBIN CONCENTRATION ON PLATELET RICH FIBRIN NETWORK AMOMG DIFFERENT AGE GROUPS AND GENDER- A CROSS SECTIONAL STUDY.

AIM: To determine the influence of RBC count and hemoglobin concentration on the density of PRF network among individuals of different age groups and gender. MATERIALS AND METHODS: 82 individuals were divided into three groups based on their age, Group 1: 20-30 years, Group 2: 30-45 years, &amp; Group 3: 45-60 years. 3-4 ml of venous blood samples were collected, PRF were prepared and it was subjected to histological analysis to determine the age and gender related changes in the density of PRF network. Hematological parameters such as Hb concentration and RBC count were also evaluated and correlated with the density of PRF network. RESULTS: Group 1 showed predominantly dense fibrin network, Group 2 showed mixed pattern including both dense and loose fibrin network and Group 3 showed predominantly loose fibrin network. However the difference in fibrin network among different age groups was not statistically significant (p value-0.14). Among the gender, males showed dense fibrin network compared to females which was statistically significant with p value-0.03. There was no statistically significant correlation between RBC count and density of fibrin network with p value-0.11. There was a statistically significant correlation between Hb level and density of fibrin network with p value-0.05. CONCLUSION: The PRF which is widely used in periodontal regenerative therapy differ in densities between male (dense network) and female (loose network). It is found to be denser in individuals with high hemoglobin concentration.

Anemia in Critically Ill Patients With Acute Respiratory Distress Syndrome and Posthospitalization Physical Outcomes.

Anemia is common during critical illness and often persists after hospital discharge; however, its potential association with physical outcomes after critical illness is unclear. Our objective was to assess the associations between hemoglobin at intensive care unit (ICU) and hospital discharge with physical status at 3-month follow-up in acute respiratory distress syndrome (ARDS) survivors. This is a secondary analysis of a multisite prospective cohort study of 195 mechanically ventilated ARDS survivors from 13 ICUs at 4 teaching hospitals in Baltimore, Maryland. Multivariable regression was utilized to assess the relationships between ICU and hospital discharge hemoglobin concentrations with measures of physical status at 3 months, including muscle strength (Medical Research Council sumscore), exercise capacity (6-minute walk distance [6MWD]), and self-reported physical functioning (36-Item Short-Form Health Survey [SF-36v2] Physical Function score and Activities of Daily Living [ADL] dependencies). Median (interquartile range) hemoglobin concentrations at ICU and hospital discharge were 9.5 (8.5-10.7) and 10.0 (9.0-11.2) g/dL, respectively. In multivariable regression analyses, higher ICU discharge hemoglobin concentrations (per 1 g/dL) were associated with greater 3-month 6MWD mean percent of predicted (3.7% [95% confidence interval 0.8%-6.5%]; P = .01) and fewer ADL dependencies (-0.2 [-0.4 to -0.1]; P = .02), but not with percentage of maximal muscle strength (0.7% [-0.9 to 2.3]; P = .37) or SF-36v2 normalized Physical Function scores (0.8 [-0.3 to 1.9]; P = .15). The associations of physical outcomes and hospital discharge hemoglobin concentrations were qualitatively similar, but none were statistically significant. In ARDS survivors, higher hemoglobin concentrations at ICU discharge, but not hospital discharge, were significantly associated with improved exercise capacity and fewer ADL dependencies. Future studies are warranted to further assess these relationships.

Home fortification of foods with multiple micronutrient powders for health and nutrition in children under two years of age.

Home fortification of foods with multiple micronutrient powders for health and nutrition in children under two years of age.

Benefits of an anti-parasite treatment are influenced by within-brood size variation in Tree Swallows (Tachycineta bicolor)

AbstractIn all animals, susceptibility to parasites can differ among individuals. Young, nest-bound birds are exposed to a diversity of nest-dwelling ectoparasites that typically feed on their blood. Within broods, hatching asynchrony creates size hierarchies that result in morphological and physiological variation among nest mates, and susceptibility to parasites also may vary predictably with this size hierarchy. Our objective was to use a broad-spectrum, anti-parasite drug, ivermectin (IVM), to treat individual nestling Tree Swallows (Tachycineta bicolor) and assess how nestling susceptibility to parasites varied both within and among broods. Broods were either assigned to an IVM group, where half of the nestlings in a brood received IVM injections and half received control injections of pure sesame oil, or to a control group, where all nestlings received oil injections. We found that the IVM treatment reduced parasite loads for broods as a whole, thereby benefiting all nestlings in IVM broods and suggesting our treatment resulted in herd immunity. Specifically, nestlings from IVM broods had higher hemoglobin concentrations, regardless of whether they received injections with IVM or oil, and greater fledging success, than nestlings from control broods. On the contrary, IVM treatment did not strongly affect nestling morphology, with only marginal effects on the growth rate of ninth primary feathers, and the effects of the treatment on 2 other morphological traits depending on temporal factors. Variation in size within broods, however, influenced the chance of an individual fledging, which increased with relative size within a brood, but only under lower parasite loads (i.e. IVM broods). By experimentally manipulating nestling susceptibility to parasites, we have demonstrated variation in nestling response to an anti-parasite treatment both within and among broods, and future studies should investigate the underlying mechanism for why certain nestlings along the brood size hierarchy are more susceptible to parasites.

The potential of neurofilaments analysis using dry-blood and plasma spots

The lack of biomarkers for an early diagnosis of neurodegenerative disorders (NDs) has hampered the development of therapeutics whose effect would be enhanced by a timely intervention. Neurofilaments light chain (Nf-L), an integral part of the axonal structure, has emerged as a robust fluid biomarker for fatal neurodegenerative disorders like amyotrophic lateral sclerosis (ALS). To facilitate large-scale studies into early-stage neurodegeneration, reduce costs of samples collection/processing and cold-chain storage, we describe the measurement of Nf-L in blood fractions obtained from dry blood spots (DBS) and dry plasma spots (DPS), two filter paper-based remote blood collection tools. To test the feasibility of using this approach, Nf-L analysis in DBS/DPS is compared to that in plasma obtained from the same blood sample, looking at Nf-L discriminatory power in the clinical stratification of ALS compared to healthy controls. With the best pre-analytical treatment for total protein recovery and using highly sensitive immunoassays, we report the detection of different Nf-L levels in DBS elute compared to reference plasma and DPS from the same blood samples. However, Nf-L measurement in DBS elutes provides a very good discrimination of ALS from healthy controls which is comparable to that obtained using plasma Nf-L assays. With the available immunodetection methods, we show that Nf-L measurement based on DPS microsampling is similar to that in plasma. The filter-paper biophysical characteristics and the interference of high haemoglobin concentration released by erythrocyte lysis is likely to perturb Nf-L detection in DBS elute. Further studies into DBS-based Nf-L detection and its analytical optimization are needed to make this method suitable for routine Nf-L blood analyses in neurodegeneration.

Blood loss control during endoscopic vein harvesting for myocardial revascularization in patients with acute coronary syndrome

From 5 to 10% of patients presenting with acute coronary syndrome and receiving dual antiplatelet therapy require surgical myocardial revascularization. Dual antiplatelet therapy considerably increases the risk of surgical bleeding. Endoscopic harvesting of the great saphenous vein is a technique that can make it possible to decrease the injury and to minimize blood loss. The study included a total of 32 patients presenting with acute coronary syndrome and undergoing coronary artery bypass grafting. They were subdivided into two groups: Group One (study group) was composed of 17 patients subjected to endoscopic harvesting of the great saphenous vein in the flap. Group Two (comparison group) consisted of 15 patients undergoing an open technique of harvesting of the vein in the flap. During the entire perioperative period, the amount of discharge through drainages from the mediastinum did not differ significantly (958±173 ml for Group One patients and 1005±165 ml for Group Two patients, p=0.47). The amount of discharge from the bed of the great saphenous vein on the lower extremities in Group One patients turned out to be less than in Group Two patients (443±37 ml vs. 570±77 ml, p=0.04). A higher haemoglobin content in the total blood count was observed in the postoperative period in the Study Group patients (90±30 g/l vs. 74±21 g/l, respectively, p=0.03). The necessity to use donor blood preparations in Group One patients turned out to be less (transfusion of erythrocytic mass 0 and 2 (0; 2) doses, p=0.001; fresh frozen plasma 2 (0; 3) and 5 (3; 8) doses, respectively, p=0.0001). The duration of hospital stay amounted to 8±1.1 days in the study group and to 15±4.5 days in the comparison group (p<0.0001). Hence, this approach makes it possible to control blood loss in high-risk patients undergoing coronary artery bypass grafting on the background of dual antiplatelet therapy, to decrease the amount of donor blood, and to reduce the length of hospital stay.

Intravenous Versus Oral Iron Therapy for Postpartum Anemia

Postpartum iron deficiency anemia (IDA) is a common problem throughout the world. Various treatment modalities like oral iron therapy, parenteral iron therapy and blood transfusion are used to treat anemia in the postpartum period. This study aimed to compare efficacy, safety, tolerability and side effects of treatment with either intravenous iron sucrose or oral ferrous gluconate for postpartum iron deficiency anemia to ascertain whether administering intravenous iron sucrose to women with postpartum anemia results in higher hemoglobin concentration and improved iron stores than using standard treatment with oral iron. This comparative, randomized and prospective study conducted in Obstetrics and Gynecology Department of Benha University Hospital and Benha Teaching Hospital in the period from 1/11/2018 to 30/9/2019. This study was carried on 60 women with postpartum iron deficiency anemia. The inclusion criteria was hemoglobin concentration

Hemoglobin concentration and risk of arterial and venous thrombosis in 1.5 million Swedish and Danish blood donors

IntroductionThere are conflicting results whether elevated hematocrit is associated with an increased risk of thromboembolic events in individuals without polycythemia vera. To assess the risk of vascular events in relation to hemoglobin concentration, we conducted a large population-based cohort study based on Scandinavian health registers. Materials and methodsWe included 1,538,019 Swedish and Danish blood donors between 1987 and 2012. Hazard ratios (HRs) of arterial and venous thrombosis were estimated using Cox regression. Additionally, we fitted person-stratified models where each donor was compared only to him-/herself. ResultsThe risk of myocardial infarction and ischemic stroke increased with higher hemoglobin concentration in both men and women. The HRs for myocardial infarction and ischemic stroke in men with hemoglobin concentration ≥ 17.5 g/dL were 3.52 (95% confidence interval [CI], 2.85–4.36) and 2.36 (95% CI, 1.63–3.43), respectively, compared to the reference group. The corresponding HRs for women with hemoglobin concentration ≥ 16.0 g/dL were 3.22 (2.12–4.89) and 2.35 (1.37–4.02) for myocardial infarction and ischemic stroke, respectively. The risk of venous thrombosis was highest in men with subnormal hemoglobin concentration (<13.0 g/dL), HR 1.69 (95% CI, 1.40–2.04). In the person-stratified model, the association between elevated hemoglobin concentration and risk of myocardial infarction was attenuated but remained significant. ConclusionsIn this large cohort of Scandinavian blood donors, elevated hemoglobin concentration was associated with an increased risk of vascular events, primarily arterial events. Even though associations were weakened when each person served as their own control, a high hemoglobin concentration may serve as a cardiovascular risk marker.

Interference of hemolysis, hyperlipidemia, and icterus on plasma infrared spectral profile.

Recently, pre-analytical, analytical, and post-analytical issues have been addressed to implement biofluid FTIR spectroscopy as a novel diagnostic tool in the clinical setting. Although hemolysis, icterus, and hyperlipidemia are known to interfere with colorimetric and turbidimetric biochemical methods, there are no data on their impact on serum/plasma FTIR spectra. This study aimed at investigating the impact of hemoglobin, bilirubin, and triglycerides concentrations on plasma spectral analysis. Plasma samples with high concentrations of hemoglobin, conjugated bilirubin, or triglycerides were studied. To mimic the various concentrations observed in clinical setting, samples were diluted using normal plasma and analyzed using high-throughput FTIR spectroscopy. Hemolytic, icteric, and hyperlipidemic plasma spectra were compared with control plasma spectra. Unsupervised analysis of all spectra was performed using principal component analysis. The comparison between control and hemolytic plasmas did not show spectral differences in the range of hemoglobin concentrations observed in spurious or pathological hemolysis. By contrast, spectra from lipidemic plasmas had different spectral profiles compared with control plasma, exhibiting increased absorbance in lipid bands. Differences in the same spectral regions were observed in spectra from icteric plasma, which may be explained by the hyperlipidemia associated with cholestasis. PCA did not discriminate between control and hemolytic plasmas up to 1g/L hemoglobin but confirmed the interference of bilirubin and triglycerides concentrations on spectral classification. Our results show that hemolysis does not have an impact on the plasma spectral profile except for high concentrations of hemoglobin rarely observed in clinical practice, whereas icterus and hyperlipidemia constitute significant confounding factors. Graphical abstract.

Incidence of Adverse Drug Reactions in High-Risk Pregnancy: A Prospective Cohort Study in Obstetric Intensive Care.

To estimate the cumulative incidence of adverse drug reactions (ADRs) in women with high-risk pregnancy hospitalized in an obstetric intensive care unit, then to describe the medicines involved and to identify major risk factors. From June 2016 to December 2017, patients admitted to the ICU with high-risk pregnancy were considered eligible in this observational, longitudinal, prospective study. Patients were investigated daily for the occurrence of ADRs through pharmaceutical anamnesis, active search in medical records and questioning of the health team. Suspected ADRs were classified according to Naranjo's algorithm. Written informed consent was obtained from all patients. Univariate and multivariate logistic regression were used to identify risk factors of ADR. The study population consisted of 607 high-risk pregnancies from 851 women admitted to the ICU, of whom 244 admitted for non-obstetric conditions, with an ICU stay less than 24h or readmitted to the ICU were excluded. The mean age was 27.0 ± 7.5years-old, mean gestational age was 33.8 ± 6.3weeks. ADR were observed in 165 women (27.2%). No severe ADR was observed and 29.7% were of moderate severity. The most often implicated medicine was magnesium sulphate (25.2%) with 44.5% of patients administered that substance experiencing ADRs consisting of somnolence (68.6%), absent patellar reflex (21.6%) and hypotension (9.8%). Risk factors of ADR were blood pressure (adjusted odds-ratio (aOR) 1.02), haemoglobin level (aOR 1.21) and body temperature (aOR 0.71). ADRs affect about one third of high-risk pregnancies, mainly due to magnesium sulphate administrations. High blood pressure, lower body temperature, and high haemoglobin concentration on admission were associated with an increased risk of ADR.

Pharmacokinetics-Guided Dosing of Hydroxyurea Can Achieve Near-Pancellular Fetal Hemoglobin Expression in Sickle Cell Anemia: F-Cell Analysis As a Benchmark for Disease-Modifying Therapy

Background: Hydroxyurea is the standard of care for children with sickle cell anemia (SCA). We have developed and prospectively validated a population pharmacokinetics (PK)-based dosing model to initiate hydroxyurea at a personalized dose that achieves maximum tolerated dose (MTD) quickly and produces a more robust HbF response than traditional weight-based dosing. HbF is distributed unequally across RBCs, and most mature RBCs have no detectable HbF. Genetic traits and hydroxyurea increase the number of HbF-containing RBCs. Measurement of HbF alone reflects an average of the HbF content across all RBCs in a lysate, so the varying, cell-specific compartmentalization of HbF across RBCs is not evaluated. In contrast, flow cytometry can be used to detect HbF-containing RBCs (F-cells) and non-F-cells, and the amount of HbF per F-cell (F/F-cell) can also be quantified. Prior studies indicate that an F/F-cell of 10 pg should completely prevent sickling. Methods:We studied participants in the Therapeutic Response Evaluation and Adherence Trial (TREAT, ClinicalTrials.gov NCT02286154), which is a prospective study with the primary objective of developing and evaluating a population PK model to predict the MTD of hydroxyurea for individualized dosing. Individuals with genotype-confirmed HbSS or sickle-β0-thalassemia (both classified here as SCA) were enrolled; none had gene-deletion HPFH. We recently developed a multiparametric flow cytometric assay (F-cell analysis) to measure the amount and distribution of HbF in all RBCs and in immature (CD71+) reticulocytes. The total number of HbF-containing RBCs (F-cells) and HbF-containing immature reticulocytes (F-retics) were enumerated. Mean concentration of HbF per F-cell (F/F-cell) was calculated from F-cell number, Hb F quantitation by capillary zone electrophoresis, and automated blood counts (RBC count and hemoglobin concentration). Results:To date, 36 TREAT patients have had F-cell analysis with a mean age of 5.6 years (median 4.1; range 1.2-21.1). Mean age at start of hydroxyurea was 3.2 years (median 1.0; range 0.5-19.5) with a mean duration of hydroxyurea therapy of 2.4 years (median 2.1; range 0.5-4.1). Mean dose of hydroxyurea at the time of F-cell analysis was 27.0 mg/kg (median 27.6; range 17.8-38.6). HbF induction was robust with a mean HbF level of 30.8% (median 32; range 7.7-52.6). HbF level had a curvilinear association with F-cell fraction (Figure A). Mean total F-cell fraction (percent of all RBCs that are F-cells) was 82.2% (median 89.8; range 33.6-99.0); 24/36 (67%) had &amp;gt;80% F-cells, and 17/36 (47%) had &amp;gt;90% F-cells, indicating the ability to achieve a near pancellular distribution of HbF with PK-guided hydroxyurea therapy in a significant fraction of patients, especially those with high adherence (Figure B). The mean F/F-cell was 11.9 pg (median 11.5; range 5.1-19.4; Figure C), and 26/36 (72%) had an mean F/F-cell ≥10 pg, an amount of HbF in an individual RBC that completely prevents sickling (mean F/F-cell does not reflect the variance of F/F-cell across the RBC population). All patients who had a HbF level ≥30% (22/36, 61%) had mean F/F-cell ≥10 pg (Figure D). Of those with total F-cells ≥80%, 22/24 (91%) had mean F/F-cell ≥10 pg. As expected, higher total F-cells and mean F/F-cell were associated with higher hemoglobin concentration and lower reticulocyte counts. Mean F/F-cell &amp;gt;16 pg was associated with a mean hemoglobin &amp;gt;10 g/dL and mean absolute reticulocyte count &amp;lt;100x106/mm3. Bland-Altman analysis of total F-cells and F-retics showed a mean bias of 33.5 percentage points (total F-cells &amp;gt; F-retics), indicating the difference between F-cell production (F-retics) and peripheral survival advantage of F-cells. For F-cells &amp;gt;80%, however, the difference between F-cell and F-retic fraction decreased rapidly, consistent with little non-F-cell production by the bone marrow. Discussion: PK-guided dosing of hydroxyurea at MTD can achieve near-pancellular HbF expression in a large fraction of patients with sickle cell anemia. Our data suggest that an F-cell fraction of 80% and a mean F/F-cell of 10 pg should be the minimum goals for hydroxyurea therapy to minimize or prevent sickling, hemolysis, and anemia. These same minimum goals should apply to any HbF-inducing therapy, including genetic therapies, and F-cell analysis should be included in the standard laboratory analysis for these treatments. Figure Disclosures Quinn: Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen: Other: Research Support. Ware:Bristol Myers Squibb: Other: Research Drug Donation; Addmedica: Other: Research Drug Donation; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees; Nova Laboratories: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Membership on an entity's Board of Directors or advisory committees; Novartis: Other: DSMB.

Cardiopulmonary Bypass Strategy to Facilitate Transfusion-Free Congenital Heart Surgery in Neonates and Infants.

Priming the cardiopulmonary bypass (CPB) circuit without the addition of homologous blood constitutes the basis of blood-saving strategies in open-heart surgery. For low-weight patients, in particular neonates and infants, this implies avoidance of excessive hemodilution during extracorporeal circulation. The circuit has to be miniaturized and tubing must be cut as short as possible to reduce the priming volume to prevent unacceptable hemodilution with initiating CPB. During perfusion, measures should be taken to prevent blood loss from the primary circuit to avoid replacement by additional volume. Favorable factors such as mild hypothermia/normothermia and high heparin concentrations during extracorporeal circulation promote earlier hemostasis after coming off bypass.Lower mortality score, first chest entry, higher hemoglobin concentration before going on bypass, and shorter CPB duration support transfusion-free CPB procedure. Reduced postoperative morbidity and mortality were observed when CPB was performed without blood transfusion. In our experience, this can be achieved in at least 70% of CPBs, even in low-weight patients.Bloodless CPB circuit priming should become a widespread reality, even in neonates and young infants, in any open-heart procedure.