Study of the f-cell ratio using plasma dilution and albumin mass kinetics.

BACKGROUND: The f-cell ratio of 0.91 is a conversion factor between the hematocrit measured in peripheral blood and the hematocrit obtained by separate measurements of the red blood cell mass and plasma volume. The physiological background of the f-cell ratio is unclear. METHODS: Data were retrieved from 155 intravenous infusion experiments where 15-25 mL/kg of crystalloid fluid diluted the blood hemoglobin and plasma albumin concentrations. The hemodilution was converted to plasma dilution using the peripheral hematocrit, and the volume of distribution of exogenous albumin was calculated in 41 volunteers who received 20 % or 5 % albumin by intravenous infusion. Finally, the kinetics of plasma albumin was studied during 98 infusion experiments with 20 % albumin. RESULTS: Plasma dilution based on hemoglobin and albumin showed a median difference of -0.001 and a mean difference of 0.000 (N = 2184), which demonstrates that these biomarkers indicate the same expandable vascular space. In contrast, exogenous albumin occupied a volume that was 10 % larger than the plasma volume indicated by the anthropometric equations of Nadler et al. and Retzlaff et al. The kinetic analysis identified a secondary compartment that was 450 mL in size and rapidly exchanged albumin with the circulating plasma. CONCLUSIONS: The results suggest that the f-cell ratio is due to rapid exchange of albumin between the plasma and a non-expandable compartment located outside the circulating blood (possibly the liver sinusoids). This means that the hematocrit measured in peripheral blood correctly represents the ratio between the red cell volume and the circulating plasma volume.

Therapeutics of managing reduced red cell mass associated with chronic kidney disease - Is there a case for earlier intervention?

Reduced red cell mass is a poor prognostic indicator in chronic kidney disease (CKD) patients. Whilst overt anaemia impacts on the quality of life of patients with CKD, lowered red cell mass may also compromise oxygen delivery to proximal tubular cells and contribute to progressive kidney injury. Epidemiological data from cats with CKD support this hypothesis although controlled interventional studies involving drugs that raise red cell mass in trials designed to test this hypothesis are lacking in both human and veterinary medicine. Recombinant analogues of erythropoietin (EPO) are currently standard of care for human CKD patients where low red cell mass impacts on their quality of life. Resistance to EPO is encountered in 20% to 40% of patients treated, probably due to functional iron deficiency, reflecting the difficulties of managing iron deficiency associated with the chronic inflammation of CKD. Similar issues are likely faced in managing anaemia in feline CKD although published data on the use of human EPO analogues are limited as such treatment in cats risks antibody formation resulting in red cell aplasia and transfusion dependency and so is reserved for late stage cases only. This article reviews the recent alternative therapeutic approach to increase red cell mass using HIF-prolyl hydroxylase inhibitors and explains their mode of action and theoretical advantages over EPO analogues in the context of iron metabolism. The results of human clinical trials and the potential benefit of adopting this approach in feline CKD patients are discussed.

Impact of Preoperative Hematocrit, Body Mass Index, and Red Cell Mass on Allogeneic Blood Product Usage in Adult Cardiac Surgical Patients: Report From a Statewide Quality Initiative.

OBJECTIVE: The study aims were to evaluate current blood transfusion practice in cardiac surgical patients and to explore associations between preoperative anemia, body mass index (BMI), red blood cell (RBC) mass, and allogeneic transfusion. DESIGN: Multicenter retrospective study. SETTING: Academic and non-academic centers. PARTICIPANTS AND INTERVENTIONS: After Institutional Review Board approval, 26,499 patients who underwent coronary artery bypass grafting ± valve replacement/repair between 2011 and 2019 were included from the Maryland Cardiac Surgery Quality Initiative database. Patients were stratified into BMI categories (<25, 25 to <30, and ≥30 kg/m2), and a multivariable logistic regression model was fit to determine if preoperative hematocrit, BMI, and RBC mass were associated independently with allogeneic transfusion. RESULTS: Preoperative anemia was found in 55.4%, and any transfusion was administered to 49.3% of the entire cohort. Females and older patients had lower BMI and RBC mass. Increased RBC and cryoprecipitate transfusions occurred more frequently after surgery in the lower BMI group. After adjustments, increased transfusion was associated with a BMI <25 relative to a BMI ≥30 at an odds ratio (OR) of 1.26 (95% confidence interval [CI]: 1.08-1.39). For each 1% increase in preoperative hematocrit, transfusion was decreased by 9% (OR: 0.91; 95% CI: 0.90-0.92). For every 500 mL increase in RBC mass, there was a 43% reduction of transfusion (OR: 0.57; 95% CI: 0.55-0.58). CONCLUSIONS: Transfusion probability modeling based on calculated RBC mass eliminated sex differences in transfusion risk based on preoperative hematocrit, and may better delineate which patients may benefit from more rigorous perioperative blood conservation strategy.

Dose-Response Relationship between Red Blood Cell Distribution Width and In-Hospital Mortality in Oldest Old Patients with Acute Ischemic Stroke.

INTRODUCTION: It is crucial to identify predictors of mortality in the early stage of acute ischemic stroke for the oldest old (aged ≥80 years) because of their poor overall survival outcomes. However, limited data are available as the oldest old have often been excluded from previous clinical studies. Hence, we aimed to assess the predictive effect of red blood cell distribution width on in-hospital mortality and the dose-response relationship between the red blood cell distribution width and in-hospital mortality in oldest old with acute ischemic stroke. METHODS: A retrospective cohort study was performed in two tertiary hospitals. Patients aged ≥80 years admitted due to acute ischemic stroke from January 1, 2014, to January 31, 2020, were included in the study. We divided the eligible patients into 3 groups with tertiles of red blood cell distribution width. Restrictive cubic spline and robust locally weighted regression analysis were performed to test the dose-response relationship between red blood cell distribution width and the in-hospital mortality risk. All-cause in-hospital mortality was the main study outcome. RESULTS: Overall, 606 patients were included in the final analysis. Red blood cell distribution width was categorized into 3 groups (T1: <13.7%, T2: 13.8-15.7%, and T3: >15.7%). The rationality of this categorization was then validated with restricted cubic spline and robust locally regression smoothing scatterplot, respectively. After adjusting for demographic and clinical features, a higher red blood cell distribution width was independently associated with in-hospital mortality and the hazard ratio (HR) was 3.31 (95% CI 2.47-4.45, p < 0.001). There was a positive dose-response relationship between red blood cell distribution width and mortality risk. Sensitivity analysis identified no conspicuous change in the HR. CONCLUSIONS: Red blood cell distribution width may be a valuable and simple measure for predicting in-hospital mortality in oldest old patients with acute ischemic stroke.

Significance of two transmembrane ion gradients for human erythrocyte volume stabilization.

Functional effectiveness of erythrocytes depends on their high deformability that allows them to pass through narrow tissue capillaries. The erythrocytes can deform easily due to discoid shape provided by the stabilization of an optimal cell volume at a given cell surface area. We used mathematical simulation to study the role of transport Na/K-ATPase and transmembrane Na+ and K+ gradients in human erythrocyte volume stabilization at non-selective increase in cell membrane permeability to cations. The model included Na/K-ATPase activated by intracellular Na+, Na+ and K+ transmembrane gradients, and took into account contribution of glycolytic metabolites and adenine nucleotides to cytoplasm osmotic pressure. We found that this model provides the best stabilization of the erythrocyte volume at non-selective increase in the permeability of the cell membrane, which can be caused by an oxidation of the membrane components or mechanical stress during circulation. The volume of the erythrocyte deviates from the optimal value by no more than 10% with a change in the non-selective permeability of the cell membrane to cations from 50 to 200% of the normal value. If only one transmembrane ion gradient is present (Na+), the cell loses the ability to stabilize volume and even small changes in membrane permeability cause dramatic changes in the cell volume. Our results reveal that the presence of two oppositely directed transmembrane ion gradients is fundamentally important for robust stabilization of cellular volume in human erythrocytes.

Red blood cell volume, but not platelet or plasma volume is associated with mortality in neonatal ECMO.

BACKGROUND: Blood product transfusions are necessary for critically ill neonates on extracorporeal membrane oxygenation (ECMO). Transfusions are administered in response to unstudied arbitrary thresholds and may be associated with adverse outcomes. The objective of this study was to identify relationships between blood product components and mortality in neonates receiving ECMO support for respiratory indications. STUDY DESIGN AND METHODS: A retrospective review of neonates receiving ECMO for respiratory indications from 2002 to 2019 from a single quaternary-referral neonatal intensive care unit (NICU). Demographic and outcome data and transfusion volume (ml/kg/day) were harvested from the medical record, and baseline mortality risk was assessed using NEO-RESCUERS scores. The association between volume of red blood cells (RBC), platelet, plasma transfusion rates (ml/kg/day), and mortality on ECMO were assessed after adjustment for NEO-RESCUERS score. Cox proportional hazards (CPH) competing risk model was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for each variable and mortality outcome. MEASUREMENTS AND MAIN RESULTS: Among 248 neonates undergoing ECMO for respiratory failure, overall survival was 93%. RBC, platelet, and plasma volume were highly associated with mortality during ECMO in an unadjusted model. After adjusting for NEO-RESCUERS score, RBC volume was associated with increased mortality risk (HR 1.013, 95% CI 1.004-1.022, p = .0043), but platelet and plasma volume were not associated with mortality. CONCLUSIONS: RBC, but not platelet or plasma volume, is associated with mortality in neonates on ECMO. Our findings refute previous studies demonstrating an association between platelet volume and mortality for neonates on ECMO.

Heat suit training increases hemoglobin mass in elite cross-country skiers.

PURPOSE: The primary purpose was to test the effect of heat suit training on hemoglobin mass (Hbmass ) in elite cross-country (XC) skiers. METHODS: Twenty-five male XC-skiers were divided into a group that added 5 × 50 min weekly heat suit training sessions to their regular training (HEAT; n = 13, 23 ± 5 years, 73.9 ± 5.2 kg, 180 ± 6 cm, 76.8 ± 4.6 ml·min-1 ·kg-1 ) or to a control group matched for training volume and intensity distribution (CON; n = 12, 23 ± 4 years, 78.4 ± 5.8 kg, 184 ± 4 cm, 75.2 ± 3.4 ml·min-1 ·kg-1 ) during the five-week intervention period. Hbmass , endurance performance and factors determining endurance performance were assessed before and after the intervention. RESULTS: HEAT led to 30 g greater Hbmass (95% CI: [8.5, 51.7], p = 0.009) and 157 ml greater red blood cell volume ([29, 285], p = 0.018) post-intervention, compared to CON when adjusted for baseline values. In contrast, no group differences were observed for changes in work economy, running velocity, and fractional utilization of maximal oxygen uptake (V̇O2max ) at 4 mmol·L-1 blood lactate, V̇O2max or 15-min running distance performance trial during the intervention. CONCLUSION: HEAT induced a larger increase in Hbmass and red blood cell volume after five weeks with five weekly heat suit training sessions than CON, but with no detectable group differences on physiological determinants of endurance performance or actual endurance performance in elite CX skiers.

Revisiting Diagnostic performances of serum erythropoïetin level and JAK2 mutation for polycythemias: analysis of a cohort of 1090 patients with red cell mass measurement.

We assessed the diagnostic performances of erythropoietin and JAK2 mutations in 1,090 patients with suspected polycythemia who were referred for red cell mass (RCM) measurement. In patients with a high haematocrit and/or haemoglobin level, a low erythropoietin level (<=3·3 mUI/ml) and JAK2 mutation showed comparable positive predictive value (PPV) for true polycythemia (RCM>=125%), 92·1% and 90% respectively. A very-low erythropoietin level (<=1·99 mUI/ml) had a PPV of 100% for polycythemia vera (PV) diagnosis. We confirmed the correlations between RCM, erythropoietin and JAK2 variant allelic frequency in PV patients. This study prompts the need to revisit the role of EPO in PV diagnostic criteria.

Plasma Hemoglobin and Red Blood Cell Mass Levels as Dynamic Prognostic Markers for Progression and Survival in Pancreatic Neuroendocrine Tumors.

There are scarce data on readily available markers enabling immediate risk stratification and personalized management in patients with advanced pancreatic neuroendocrine tumors. This study explores the association of red blood cells-related parameters as prognostic markers in patients harboring pancreatic neuroendocrine tumors. Retrospective analysis of a tertiary medical center database, acquiring data of patients with pancreatic neuroendocrine tumors including demographics, tumor-related parameters and consecutive imaging results, vital status at last follow-up, and red blood cells parameters at baseline, last follow-up, and dynamics (last/baseline ratio). Univariate and multivariable analyses were performed. Sixty-seven patients were identified (mean age at diagnosis of 63±11 years, 56.7% males). Patients with disease progression had lower hemoglobin, red blood cells mass values and hematocrit at the last evaluation (p<0.001 for all comparisons), with red blood cells mass level<3.9 m/µl and a 6% and 9% relative reduction in hemoglobin and hematocrit levels, respectively, associated with an increased risk for disease progression. Similarly, patients deceased during the study period had lower hemoglobin, red blood cells mass values and hematocrit (p<0.03 for all) than those alive, at last follow-up. Eleven percent reduction in hemoglobin level was noted indicating a higher mortality risk (p=0.04). Negative hemoglobin and hematocrit dynamics were independently associated with increased risk for disease progression (p=0.03 and 0.049, respectively). In conclusion, decrease in red blood cells mass, hemoglobin and/or hematocrit levels are all associated with poor prognosis in patients with pancreatic neuroendocrine tumors. We suggest utilizing these parameters as complementary follow-up prognostic markers to radiologic imaging in this patients population.

Relation of Intravascular Volume Profiles to Heart Failure Progression and Clinical Outcomes.

Heart failure (HF) commonly progresses over time and identifying differences in volume profiles may help stratify risk and guide therapy. The aim of this study was to assess the pathophysiologic and prognostic roles of volume profiles for HF progression in stable ambulatory and hospitalized patients. HF patients who had undergone quantitative intravascular volume analysis (185 outpatients and 139 inpatients) were retrospectively assessed for the combined end point of HF-related hospital admissions (outpatients), HF-readmissions (inpatients), and overall all-cause mortality. After multivariate Cox regression analysis, greater total blood volume expansion was associated with higher risk of HF-admission in previously stable outpatients (HR: 1.023, CI 1.005 to 1.043; p = 0.013) while in more advanced HF (inpatients) total blood volume expansion was associated with lower risk for HF-readmission and mortality (HR: 0.982, CI 0.967 to 0.997; p = 0.017). Secondary analysis suggests that subclinical plasma volume expansion was a driving factor for the detrimental association in outpatients (HR: 1.018, CI 0.997 to 1.036; p = 0.054), while an increase in red blood cell mass was central to the beneficial association in advanced HF (HR: 0.979, CI 0.968 to 0.991; p <0.001). In conclusion, understanding differences in plasma volume and red blood cell mass profiles can provide insight into the pathophysiology and progression of HF.

Blood volume and hemoglobin mass in long-term heart transplant recipients with and without Anemia.

BACKGROUND: In systolic chronic heart failure, a heterogeneous blood volume (BV) regulation can be found with plasma volume expansion in many cases, possibly leading to pseudoanemia. Little is known about the volume status after heart transplantation (HTX). So far, anemia of HTX recipients was solely investigated using hemoglobin-concentration that may be misleading in a clinical context. The objective of the study was whether a difference in plasma volume and red cell volume can be observed in clinically stable heart transplant recipients compared to matched control subjects. Secondary, the aim was to describe anemia in the long-term after HTX based on quantitative data. METHODS: Blood volume and its constituents red cell volume and plasma volume were quantified using an abbreviated carbon monoxide rebreathing method (aCORM) with focus on its primary measure total hemoglobin mass (Hbmass) and coincidental anemia in 36 (7 women) heart transplant recipients. For comparison, a matched control group of 46 (5 women) healthy subjects was selected. RESULTS: Neither Hbmass nor blood volumes were significantly different in HTX patients compared to matched healthy control group subjects. The prevalence of anemia 6.3 ± 4.3 years after transplantation was 19%. Hbmass and red cell volume were significantly lower in anemic HTX patients compared to non-anemic patients while plasma volume was not expanded. Various immunosuppressant regimens did not have an effect on Hbmass, plasma volume or red cell volume. CONCLUSIONS: There was no difference in blood volumes and Hbmass between HTX patients and control subjects. The pathophysiologic blood volume regulation in chronic heart failure does not seem to be longer active in long-term HTX recipients. However, in the long-term after HTX, anemia occurs in a considerable number of patients as true anemia without a clear association with immunosuppression. TRIAL REGISTRATION: German registry for clinical studies, DRKS00006078. Registered 09 May 2014, https://www.drks.de/drks_web/navigate.do?navigationId=trial . HTML&TRIAL_ID=DRKS00006078.

Effects of Including Sprints in LIT Sessions during a 14-d Camp on Muscle Biology and Performance Measures in Elite Cyclists.

PURPOSE: This study investigated the effects of including sprints within low-intensity training (LIT) sessions during a 14-d training camp focusing on LIT, followed by 10-d recovery (Rec), on performance and performance-related measures in elite cyclists. METHODS: During the camp, a sprint training group (SPR; n = 9) included 12 × 30-s maximal sprints during five LIT sessions, whereas a control group (CON; n = 9) performed distance-matched LIT only. Training load was equally increased in both groups by 48% ± 27% during the training camp and subsequently decreased by -56% ± 23% during the recovery period compared with habitual training. Performance tests were conducted before the training camp (Pre) and after Rec. Muscle biopsies, hematological measures, and stress/recovery questionnaires were collected Pre and after the camp (Post). RESULTS: Thirty-second sprint (SPR vs CON: 4% ± 4%, P < 0.01) and 5-min mean power (SPR vs CON: 4% ± 8%, P = 0.04) changed differently between groups. In muscle, Na+-K+ ß1 protein content changed differently between groups, decreasing in CON compared with SPR (-8% ± 14%, P = 0.04), whereas other proteins showed similar changes. SPR and CON displayed similar increases in red blood cell volume (SPR: 2.6% ± 4.7%, P = 0.07; CON: 3.9% ± 4.5%, P = 0.02) and V˙O2 at 4 mmol·L-1 [BLa-] (SPR: 2.5% ± 3.3%, P = 0.03; CON: 2.2% ± 3.0%, P = 0.04). No changes were seen for V˙O2max, Wmax, hematological measures, muscle enzyme activity, and stress/recovery measures. CONCLUSIONS: Inclusion of 30-s sprints within LIT sessions during a high-volume training camp affected competition-relevant performance measures and Na+-K+ ß1 protein content differently from LIT only, without affecting sport-specific stress/recovery or any other physiological measure in elite cyclists.

The associations between red cell distribution width and lung function measures in a general population.

BACKGROUND: Red cell distribution width (RDW) reflects heterogeneity of the erythrocyte volumes. High RDW is a novel risk marker, which has been associated with mortality and morbidity both from cardiovascular and respiratory diseases, but the association between RDW and measures of lung function in the general population remains unclear. METHODS: The associations of RDW with spirometry, diffusing capacity (DLCO) and impulse oscillometry (IOS) were investigated among 5767, 5496 and 5598 subjects (aged 50-64 years), respectively, from the Swedish CArdioPulmonary bioImage Study (SCAPIS). Multiple linear regression and general linear models were performed to examine the relationships of lung function measures and RDW, with adjustment for potential confounding factors. RESULTS: Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC were significantly and inversely associated with RDW after multivariate adjustments. For 1- standard deviation (SD) increase in RDW, FEV1 decreased with 0.034 L (95%CI: -0.046 to -0.022 L), p < 0.001; FVC with 0.031 L (95%CI: -0.045 to -0.017 L), p < 0.001; and FEV1/FVC with 0.003 (95%CI: -0.004 to -0.001), p = 0.002. Significant associations of RDW and DLCO were only found among smokers. For IOS, pulmonary reactance rather than resistance was significantly associated with RDW: X5 decreased 0.002 kPa/(L/s) (95%CI: -0.003 to -0.0002 kPa/(L/s)), p = 0.025, per 1-SD higher RDW. CONCLUSIONS: We found significant negative associations between RDW and measures of lung function. However, the effect sizes are small and RDW is not likely to be a sensitive marker of impaired lung function in middle-aged individuals from the general population.

Effect of Massive Transfusion Protocol on Coagulation Function in Elderly Patients with Multiple Injuries.

OBJECTIVE: To evaluate the effect of massive transfusion protocol on coagulation function in elderly patients with multiple injuries. METHODS: In this retrospective cohort study, clinical data were collected from a total of 94 elderly patients with multiple injuries, including 44 cases who received routine transfusion protocol (control group) and 50 cases who concurrently received massive transfusion protocol in our hospital (research group). The changes in platelet parameters, coagulation function, and organ dysfunction scores at admission and 24 h after transfusion were compared between the two groups. The 24-hour plasma and red blood cell transfusion volume, length of stay, complications, and mortality of the two groups were analyzed statistically. RESULTS: Twenty-four hours after blood transfusion, the hematocrit, platelets, and hemoglobin in the research group were higher than those in the control group, while the activated partial thromboplastin time, prothrombin time, thrombin time, fibrinogen, and scores of Marshall scoring system and Sequential Organ Failure Assessment were lower than those in the control group (P < 0.01). The 24-hour plasma transfusion volume was higher, and the length of intensive care unit (ICU) stay and total length of stay were lower in the research group compared with the control group (P < 0.01). No significant difference was found in the mortality rate between the research group and the control group (10.00% vs. 13.64%, P > 0.05). The incidence of complications in the research group was lower than that in the control group (12.00% vs. 31.82%, P < 0.05). CONCLUSION: Massive transfusion protocol for elderly patients with multiple injuries can improve their coagulation function and platelet parameters, alleviate organ dysfunction, shorten length of ICU stay, and decrease the incidence of complications, which is conducive to improving the prognosis of patients.

Association between red blood cell distribution width and mortality of COVID-19 patients.

PURPOSE: We have previously reported an association between high red blood cell distribution width (RDW) and mortality in septic and brain infarction patients. However, no association between RDW and mortality in coronavirus disease 2019 (COVID-19) patients has been reported so far; thus, the objective of this study was to determine if that association exists. METHODS: Prospective and observational study carried out in 8 Intensive Care Units from 6 hospitals of Canary Islands (Spain) including COVID-19 patients. We recorded RDW at ICU admission and 30-day survival. RESULTS: We found that patients who did not survive (n=25) compared to surviving patients (n=118) were older (p=0.004), showed higher RDW (p=0.001), urea (p<0.001), APACHE-II (p<0.001) and SOFA (p<0.001), and lower platelet count (p=0.007) and pH (p=0.008). Multiple binomial logistic regression analysis showed that RDW was associated with 30-day mortality after controlling for: SOFA and age (OR=1.659; 95% CI=1.130-2.434; p=0.01); APACHE-II and platelet count (OR=2.062; 95% CI=1.359-3.129; p=0.001); and pH and urea (OR=1.797; 95% CI=1.250-2.582; p=0.002). The area under the curve (AUC) of RDW for mortality prediction was of 71% (95% CI=63-78%; p<0.001). We did not find significant differences in the predictive capacity between RDW and SOFA (p=0.66) or between RDW and APACHE-II (p=0.12). CONCLUSIONS: Our study provides new information regarding the ability to predict mortality in patients with COVID-19. There is an association between high RDW and mortality. RDW has a good performance to predict 30-day mortality, similar to other severity scores (such as APACHE II and SOFA) but easier and faster to obtain.

[Effect of 99mTc elution in vivo from red cells on red cell volumes measured using autologous 99mTc-labeled red cells: comparison with 51Cr method]. / Effet de l'élution in vivo du technétium sur les volumes globulaires mesurés à l'aide d'hématies autologues marquées au 99mTc : comparaison avec la technique au 51Cr.

The purpose of this work was to compare the measured red-cell volume (RCV) using sodium pertechnétate [RCV-99mTc] compared to the reference technique using sodium radiochromate [RCV-51Cr] and to assess the influence of technetium-99 elution on the RCV-99mTc value. Ten patients had simultaneous measurements of RCV-99mTc and RCV-51Cr. Elution of Tc-99m from red blood cells was 2.9% and led to an average overestimation of RCV-99mTc of 3.7%. The introduction of individual tracer elution rates in the RCV-99mTc calculation corrects this overestimation.