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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.

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+ β1 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+ β1 protein content differently from LIT only, without affecting sport-specific stress/recovery or any other physiological measure in elite cyclists.

NEW FINDINGS: What is the central question of this study? Does chronic mountain sickness (CMS) alter sympathetic neural control and arterial baroreflex regulation of blood pressure in Andean (Quechua) highlanders? What is the main finding and its importance? Compared to healthy Andean highlanders, basal sympathetic vasomotor outflow is lower, baroreflex control of muscle sympathetic nerve activity is similar, supine heart rate is lower and cardiovagal baroreflex gain is greater in mild CMS. Taken together, these findings reflect flexibility in integrative regulation of blood pressure that may be important when blood viscosity and blood volume are elevated in CMS. ABSTRACT: The high-altitude maladaptation syndrome chronic mountain sickness (CMS) is characterized by excessive erythrocytosis and frequently accompanied by accentuated arterial hypoxaemia. Whether altered autonomic cardiovascular regulation is apparent in CMS is unclear. Therefore, during the 2018 Global REACH expedition to Cerro de Pasco, Peru (4383 m), we assessed integrative control of blood pressure (BP) and determined basal sympathetic vasomotor outflow and arterial baroreflex function in eight Andean natives with CMS ([Hb] 22.6 ± 0.9 g·dL(-1) ) and seven healthy highlanders ([Hb] 19.3 ± 0.8 g·dL(-1) ). R-R interval (RRI, electrocardiogram), beat-by-beat BP (photoplethysmography) and muscle sympathetic nerve activity (MSNA; microneurography) were recorded at rest and during pharmacologically induced changes in BP (modified Oxford test). Although [Hb] and blood viscosity (7.8 ± 0.7 vs. 6.6 ± 0.7 cP; d = 1.7, P = 0.01) were elevated in CMS compared to healthy highlanders, cardiac output, total peripheral resistance and mean BP were similar between groups. The vascular sympathetic baroreflex MSNA set-point (i.e. MSNA burst incidence) and reflex gain (i.e. responsiveness) were also similar between groups (MSNA set-point, d = 0.75, P = 0.16; gain, d = 0.2, P = 0.69). In contrast, in CMS the cardiovagal baroreflex operated around a longer RRI (960 ± 159 vs. 817 ± 50 ms; d = 1.4, P = 0.04) with a greater reflex gain (17.2 ± 6.8 vs. 8.8 ± 2.6 ms·mmHg(-1) ; d = 1.8, P = 0.01) versus healthy highlanders. Basal sympathetic vasomotor activity was also lower compared to healthy highlanders (33 ± 11 vs. 45 ± 13 bursts·min(-1) ; d = 1.0, P = 0.08). In conclusion, our findings indicate adaptive differences in basal sympathetic vasomotor activity and heart rate compensate for the haemodynamic consequences of excessive erythrocyte volume and contribute to integrative blood pressure regulation in Andean highlanders with mild CMS.

The primary purpose was to test the effect of heat suit training on hemoglobin mass (HbTwenty-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·minHEAT led to 30 g greater HbHEAT induced a larger increase in Hb

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

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.

By blocking the oxygen binding sites on the hemoglobin molecule, chronic low-dose carbon monoxide (CO) administration may produce similar effects to those of exposure to altitude. PURPOSE This study aimed to determine the effect of chronic low-dose CO application on hemoglobin mass (Hbmass) and V˙O2max. METHODS For 3 wk, 11 healthy and moderately trained male subjects inhaled a CO bolus five times per day to increase their HbCO concentration by ~5%. Another 11 subjects received a placebo. Hbmass, serum erythropoietin concentration, ferritin, and basic hematological parameters were determined before and weekly during and until 3 wk after the CO inhalation period. V˙O2max tests on a cycle ergometer were performed before and after the CO administration period. RESULTS In the CO group, Hbmass increased from 919 ± 69 to 962 ± 78 g in week 3 (P < 0.001) and was maintained for the following 3 wk. Reticulocytes (%) and immature reticulocyte fraction significantly increased after 1 wk. Serum erythropoietin concentration tended to increase after 1 wk (P = 0.07) and was suppressed in the postperiod (P < 0.01). Ferritin decreased during the inhalation period (from 106 ± 37 to 72 ± 37 ng·mL, P < 0.001). V˙O2max tended to increase from 4230 ± 280 to 4350 ± 350 mL·min (P < 0.1) immediately after the inhalation period and showed a significant relationship to the change in Hbmass (y = 4.1x - 73.4, r = 0.70, P < 0.001). CONCLUSIONS Chronic continuous exposure to low-dose CO enhances erythropoietic processes resulting in a 4.8% increase in Hbmass. The individual changes in Hbmass were correlated to the corresponding changes in V˙O2max. Examination of ethical and safety concerns is warranted before the implementation of low-dose CO inhalation in the clinical/athletic setting as a tool for modifying Hbmass.

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; p0.001). In conclusion, understanding differences in plasma volume and red blood cell mass profiles can provide insight into the pathophysiology and progression of HF.

The purpose of this work was to compare the measured red-cell volume (RCV) using sodium pertechnétate [RCV

Background: Red blood cell distribution width (RDW) is a measure of the degree of heterogeneity of erythrocyte volume. Higher RDW levels are associated with increased mortality among patients with ...

Background: Although it is known that glucose concentration exhibits a time-dependent decay in uncentrifuged serum and lithium-heparin blood tubes, no evidence exists on how this variation may depend on blood cell counts (CBC) and volumes. Methods: Venous blood was drawn from 30 non fasting healthy volunteers into three serum and three lithium-heparin tubes. One serum and lithium-heparin tubes were centrifuged within 15 min after collection and glucose was measured with a hexokinase assay. The second and third serum and lithium-heparin tubes were maintained at room temperature for 1 and 2 h after the first tubes were centrifuged. These other tubes were then centrifuged and glucose was measured. CBC was performed in the first lithium-heparin tube, before centrifugation. Results: The mean decrease of glucose was higher in lithium-heparin plasma than in serum (0.33 vs. 0.24 mmol/L/h; p Conclusions: Glucose concentration decrease in uncentrifuged lithium-heparin and serum tubes depends on the baseline number of RBC, WBC, neutrophils and monocytes within the tubes.

Patient-specific instrumentation (PSI) may contribute to reduced blood loss related to total knee arthroplasty (TKA). The purpose of this study was to compare the estimated hemoglobin (Hb) and red blood cell volume (RBC) losses in two groups of patients undergoing TKA with PSI and conventional instrumentation. Pre- and postoperative blood samples were collected from 22 patients randomly assigned to receive a PSI-assisted or conventional TKA. Post- to preoperative Hb difference was calculated and RBC loss was estimated according to Sehat et al. A significant difference in Hb reduction in favor of the PSI group was registered on the last day of stay (p = 0.0084) and significant treatment effect (p = 0.027) on Hb reduction after intervention was found with a regression model for longitudinal measurements. This study demonstrated that PSI leads to a significant trend in earlier Hb regain. These promising results suggest a beneficial effect of PSI in blood loss reduction.

Regarding diagnosis of polycythemia vera (PV), discussion persists about hemoglobin (Hb) and/or hematocrit (Hct) threshold values as surrogate markers for red cell mass (RCM) and the diagnostic impact of bone marrow (BM) morphology. We performed a retrospective study on 290 patients with PV (151 males, 139 females; median age 65 years) presenting with characteristic BM features (initial biopsies, centralized evaluation) and endogenous erythroid colony (EEC) formations. This cohort included (1) a group of 229 patients when following the 2008 versus 256 patients diagnosed according to the 2016 World Health Organization (WHO) guidelines, all presented with increased RCM; (2) masked PV patients with low Hb (n = 143)/Hct (n = 45) recruited from the 2008 WHO cohort; (3) a cohort of 17 PV patients with elevated diagnostic Hb/Hct levels but low RCM; and (4) nine PV patients with increased RCM, opposing low Hb/Hct values. All patients were treated according to current PV guidelines (phlebotomies 87%, hydroxyurea 79%, and acetylsalicylic acid 87%). Applying the 2016 WHO criteria significantly increased concordance between RCM and Hb values compared with the 2008 WHO criteria (90 vs. 43% in males and 83 vs. 64% in females). Further analysis of the WHO 2016 PV cohort revealed that increased RCM is associated with increased Hb/Hct (93.8/94.6%). Our study supports and extends the diagnostic impact of the 2016 revised WHO classification for PV by highlighting the importance of characteristic BM findings and implies that Hb/Hct threshold values may be used as surrogate markers for RCM measurements.

Red blood cells of vertebrates can restore their cellular volume after hyposmotic swelling. The process strictly depends on oxygen availability in the environment. However, the role of hemoglobin in regulation of cell volume recovery is not clear yet. Little is known about the osmotic reactions and regulatory volume decrease of amphibian red blood cells. We investigated volume recovery process in oxygenated (oxyhemoglobin concentration 97 ± 3% of total hemoglobin) deoxygenated (96 ± 2% of deoxyhemolobin) and oxidized (47 ± 2% of methemoglobin, 41 ± 3% of deoxyhemoglobin) red blood cells of common frog (Rana temporaria) after hyposmotic swelling. Using the low-angle light scattering method we demonstrated the regulatory volume decrease in oxygenated cells and showed that the process was eliminated in hypoxic conditions. Reoxygenation of hypoxic cells restored the regulatory volume decrease. Oxidation of cellular hemoglobin to methemoglobin inhibited the volume recovery response in hyposmotically swollen oxygenated and reoxygenated hypoxic cells.

Urine specific gravity (UThe purpose of this study was to examine 24-hour changes in UNineteen healthy males were provided food and water over 24 hours with a total water volume of 35 ml·kgDespite presenting with an elevated spot UDespite a high preintervention U

To investigate the association between red cell distribution width (RDW) and elevation of glucose/glycated hemoglobin (HbA1c).An analysis was conducted using data from a prospective cohort study of adults. People without prediabetes or diabetes (n=7,795) were followed for a mean of 2.90years (range: 1-7years, 95% confidence interval: 2.86-2.94years). Glucose elevation is defined as fasting glucose levels exceeding 5.6mmol/l, or 2-hour glucose values in the oral glucose tolerance test exceeding 7.8mmol/l. HbA1c elevation is defined as a HbA1c value exceeding a normal limit of 39mmol/mol (5.7%). Adjusted Cox proportional hazards regression models were used to assess the association between RDW quartiles and elevation of HbA1c/glucose.The multiple-adjusted hazard ratios (95% confidence interval) of HbA1c elevation for increased quartiles of RDW were 1.00 (reference), 1.08 (0.89, 1.30), 1.28 (1.07, 1.54), and 1.54 (1.29, 1.85) (P for trend0.0001). However, no significant association was observed between RDW and blood glucose (fasting and postprandial).Elevated RDW is independently related to future HbA1c elevation, but not to glucose elevation. This suggests that RDW may associate with HbA1c through a non-glycemic way, which should be taken into consideration when using HbA1c as a diagnostic criterion of prediabetes or diabetes.

Northern fur seals (Callorhinus ursinus) are endemic to the North Pacific Ocean. They were hunted for their fur and became endangered in the late 1800s, but their populations recovered following the introduction of protection laws. Recently, populations have been decreasing again, although the reasons are unclear. For individuals that are bred and reared in captivity as part of ex situ conservation projects, details of blood characteristics are essential to ensure good health. However, the normal ranges of hematology and serum chemistry of captive northern fur seals have not been defined. This study determined the normal ranges of hematology and serum chemistry of captive fur seals. Blood samples were collected every month for 2 years from four captive northern fur seals in Japan (three born in an aquarium and one kept in the same aquarium following rescue). Fifteen blood characteristics and 29 serum chemistry properties were compared with those previously reported for wild northern fur seals in the USA. Several parameters were not within the normal ranges reported previously in wild northern fur seals. In particular, levels of alkaline phosphatase was outside of the normal ranges previously reported. The hematological and serum chemistry ranges in this study can help provide a guideline for understanding the health of northern fur seals in captivity.

Contains fulltext : 225283.pdf (Publisher’s version ) (Open Access) Extracorporeal circulation is accompanied by changes in red blood cell morphology and structural integrity that affect cell function and survival, and thereby may contribute to the various side effects of heart-lung machine-assisted surgery. Our main objectives were to determine the effect of circulation of red blood cells in a stand-alone extracorporeal circuit on several parameters that are known to be affected by, as well as contribute to red blood cell aging. As a source of RBCs, we employed blood bank storage units of different ages. In order to assess the relevance of our in vitro observations for the characterization of extracorporal circulation technology, we compared these changes in those of patients undergoing extracorporeal circulation-assisted cardiac surgery. Our results show that circulation in a heart-lung machine is accompanied by changes in red blood cell volume, an increase in osmotic fragility, changes in deformability and aggregation behavior, and alterations in the exposure of phosphatidylserine and in microvesicle generation. RBCs from 1-week-old concentrates showed the highest similarities with the in vivo situation. These changes in key characteristics of the red blood cell aging process likely increase the susceptibility of red blood cells to the various mechanical, osmotic, and immunological stress conditions encountered during and after surgery in the patient's circulation, and thereby contribute to the side effects of surgery. Thus, aging-related parameters in red blood cell structure and function provide a foundation for the validation and improvement of extracorporeal circulation technology.

Purpose of the study In ABO-incompatible bone marrow transplantation, an efficient depletion of red blood cells (RBC) within the graft is mandatory to avoid adverse events in transplanted patients. Using non therapeutic products, we evaluated the substitution of the standard density gradient-based separation (DGBS) over Ficoll-Paque with the use of an automated procedure intended for buffy coat only (SmartRedux software) introducing modifications within the settings to achieve a drastic reduction of the initial volume of the product. Both methods were conducted on the Sepax-2 device. Samples and methods RBC depletion rates and CD34+ cells recoveries from eight procedures with SmartRedux software using “in-house” settings (method A) were compared to those obtained from four procedures using NeatCell software, an automated DGBS over Ficoll-Paque (method B). Results Median erythrocyte depletion of 95,4% (92,7%–99,0%) and 99,8% (99,0%–99,9%) were observed using methods A and B, respectively. Median residual RBC volumes in the final product were 19 mL (4,4 mL–31,2 mL) and 0,7 mL (0,4 mL–4,7 mL), respectively (p = 0,014). CD34+ cells recoveries of 90,9% (62,7%–102,1%) and 78,4% (64,1%–86,2%) were achieved for methods A and B. Median platelet depletion was 16,6% (10%–42,7%) and 89,8% (88,5%-92,4%) using methods A and B, respectively (p = 0,004). Processing duration was shorter using method A (168 ± 29 min) than method B (295 ± 21 min) (p = 0,004). Conclusion Both methods achieved satisfactory erythrocyte depletion and CD34+ recovery. The use of Sepax-2 device in association with SmartRedux software could be extended to efficiently deplete RBC from large-volume BM in a raw instead of DGBS.

Background Patients with end-stage renal disease (ESRD) under hemodialysis (HD) are at greater risks of infectious spondylitis (IS), but there is no reliable predictor that facilitate early detection of this relatively rare and insidious disease. Methods A retrospective review of the medical records from patients with ESRD under HD over a 12-year period was performed at a tertiary teaching hospital, and those with a first-time diagnosis of IS were identified. A 1:4 propensity score-matched case-control study was carried out, and baseline characteristics, underlying diseases, and laboratory data were compared between the study group and the control group, one month before the date of diagnosis or the index date respectively. Results A total of 16 patients with IS were compared with 64 controls. After adjustment, recent access operation (odds ratio [OR], 13.27; 95% confidence interval [CI], 3.53 to 49.91; p

Piezo1, encoded by the gene

INTRODUCTION: Volume management is an essential component of anti-hypertensive therapy. Different volume phenotypes have been proposed. We sought to study the total blood volume (TBV), plasma volume (PV) and red blood cell volume (RBV) in hypertensive patients. METHODS: We included patients followed in an outpatient cardiology clinic from 1998–2003. Blood volume (BV) parameters were measured using radioisotope iodine-131-labeled albumin dilution technique. Values were expressed as percentage (%) deviation from ideal volumes. RESULTS: A total of 95 patients were included. The intravascular volume distribution as percent deviation from normal volume ranged from −23% to +28% for TBV, −22% to +36% for PV and −29% to +37% for RBV. There was no significant correlation between systolic BP and any of the BV parameters (TBV and SBP, r=−0.03; PV and SBP, r=−0.12; RBV and SBP, r=−0.08). DISCUSSION: Patients with hypertension have a wide variation in BV parameters. BV does not correlate with SBP.

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. (Less)

The time course of plasma volume (PV) reduction following an increased training load period is unknown and was investigated. The accompanying fluctuations in [Hb] and OFF-hr score were analyzed in the Athlete Biological Passport. Further, whether fluctuations in plasma albumin, soluble transferrin receptors (sTfR), and pro-atrial natriuretic peptide (proANP) concentrations correlate with PV fluctuations was investigated. Eleven high-level competitive cyclists were investigated for 3 weeks. After initial measurements in week 1, training load was increased ~250% in week 2 followed by a reversion to baseline training load in week 3. PV and hematological variables were determined frequently during all weeks. The higher training load in week 2 increased (P

Previous research investigating the potential influence of geomagnetic factors on human cardiovascular state has tended to converge upon similar inferences although the results remain relatively controversial. Furthermore, previous findings have remained essentially correlational without accompanying experimental verification. An exception to this was noted for human brain activity in a previous study employing experimental simulation of sudden geomagnetic impulses in order to assess correlational results that had demonstrated a relationship between geomagnetic perturbations and neuroelectrical parameters. The present study employed the same equipment in a similar procedure in order to validate previous findings of a geomagnetic-cardiovascular dynamic with electrocardiography and heart rate variability measures. Results indicated that potential magnetic field effects on frequency components of heart rate variability tended to overlap with previous correlational studies where low frequency power and the ratio between low and high frequency components of heart rate variability appeared affected. In the present study, a significant increase in these particular parameters was noted during geomagnetic simulation compared to baseline recordings.

In the last decade the identification of germline mutations in several genes such as EPOR, VHL, EGLN1, and EPAS1, helped the definition of several different subtypes of familial (congenital) erythrocytosis. Being rare disorders these entities often remain unrecognized or misdiagnosed, which necessitates the extensive reporting of newly identified cases.We applied a genetic approach including whole exome sequencing and Sanger sequencing for the identification of the causative germline mutation in a Bulgarian family with congential erythrocytosis.We identified EPAS1 (HIF2A) p. M535T heterozygous mutation carried by four members of the family over three generations. We provide also an extensive description of the clinical features of the affected family members.EPAS1 p.M535T appears to be found in different populations as a causative variation in familial erythrocytosis. Our findings support the notion that the affected patients present with variable clinical features and disease course. Furthermore, close clinical follow-up with phlebotomies on demand and regular intake of low doses of anticoagulants seem to prevent from serious complications such as thrombembolic events and pulmonary hypertension.This is the first description of an entire family with EPAS1 p. M535T mutation expanding our knowledge about the clinical features of the disease.

Highlights • Non-surviving showed higher RDW than surviving patients. • There is an association between RDW and mortality. • RDW could be used as mortality biomarker., 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

Few studies have paid attention to the performances of non-invasive models in diagnosing stages of liver fibrosis and inflammation, which are critical for early and accurate assessment of prognostication and decisions on antiviral treatment in chronic hepatitis B infection patients with high hepatitis B virus DNA and normal or mildly elevated alanine transaminase levels (≤2 times upper limit of normal (ULN)). This study aimed to investigate the value of routine serum markers in evaluation of liver inflammation and fibrosis in these patients. A total of 370 consecutive chronic hepatitis B virus-infected patients who underwent liver biopsy were retrospectively analyzed. The Scheuer scoring system was adopted as the pathological standard for diagnosing liver inflammation and fibrosis. The receiver-operating characteristic curves (ROC) and the area under the ROC curves (AUROCs) were used to analyze the performances of the models, including aspartate transaminase to platelet ratio index (APRI), fibrosis index based on the 4 factors (FIB-4), red cell volume distribution width-to-platelet ratio (RPR), globulin-platelet model (GP), and gamma-glutamyl transpeptidase to platelet ratio index (GPR). To predict significant inflammation (G ≥2), the AUROC of APRI was higher than that of FIB-4 (0.705 vs 0.629, P = .001), RPR (0.705 vs 0.593, P

BACKGROUND. The red cell distribution width (RDW) is associated with health outcomes. Whether non-RDW risk information is contained in RBC sizes is unknown. This study evaluated the association of the percentage of extreme macrocytic RBCs (%Macro, RBC volume > 120 fl) and microcytic RBCs (%Micro, RBC volume < 60 fl) and the RDW–size distribution (RDW-sd) with mortality and morbidity. METHODS. Patients (females, n = 165,770; males, n = 100,210) at Intermountain Healthcare were studied if they had a hematology panel between May 2014 and September 2016. Adjusted sex-specific associations of %Macro/%Micro and RDW-sd with mortality and 33 morbidities were evaluated. RESULTS. Among females with fourth-quartile values of %Macro quartile and %Micro (referred to throughout as 4/4), there was an average of 7.2 morbidities versus 2.9 in the lowest risk (LR1) categories, 1/1, 1/2, 2/1, and 2/2 (P < 0.001). Among males, those in the 4/4 category had 8.0 morbidities, while those in the LR1 had 3.4 (P < 0.001). Cox regressions found %Macro/%Micro (4/4 vs. LR1, females: hazard ratio [HR] = 1.97 [95% CI = 1.53, 2.54]; males: HR = 2.17 [CI = 1.72, 2.73]), RDW-sd (quartile 4 vs. 1, females: HR = 1.33 [CI = 1.04, 1.69]; males: HR = 1.41 [CI = 1.10, 1.80]), and RDW (quartile 4 vs. 1, females: HR = 1.59 [CI = 1.26, 2.00]; males: HR = 1.23 [CI = 0.99, 1.52]) independently predicted mortality. Limitations include that the observational design did not reveal causality and unknown confounders may be unmeasured. CONCLUSIONS. Concomitantly elevated %Macro and %Micro predicted the highest mortality risk and the greatest number of morbidities, revealing predictive ability of RBC volume beyond what is measured clinically. Mechanistic investigations are needed to explain the biological basis of these observations. FUNDING. This study was supported by internal Intermountain Heart Institute funds and in-kind support from Sysmex America Inc.

This study performed a retrospective outcome analyses of a large cohort of mixed ejection fraction patients admitted for acute heart failure (HF), whose inpatient care was guided by individual quantitative blood volume analysis (BVA) results.Decongestion strategies in patients hospitalized for HF are based on clinical assessment of volume and have not integrated a quantitative intravascular volume metric.Propensity score control matching analysis was performed in 245 consecutive HF admissions to a community hospital (September 2007 to April 2014; 78 ± 10 years of age; 50% with HF with reduced ejection fraction [HFrEF]; and 30% with Stage 4 chronic kidney disease). Total blood volume (TBV), red blood cell volume (RBCV), and plasma volume (PV) were measured at admission by using iodine-131-labeled albumin indicator-dilution technique. Decongestion strategy targeted a TBV threshold of 6% to 8% above patient-specific normative values. Anemia was treated based on cause. Hematocrit (Hct) measurements were monitored to assess effectiveness of interventions. Control subjects derived from Centers for Medicare and Medicaid Services data were matched 10:1 for demographics, comorbidity, and year of treatment.Although 66% of subjects had PV expansion, only 37% were hypervolemic (TBV10% excess). True anemia (RBCV ≥10% deficit) was present in 62% of subjects. Treatment of true anemia without hypervolemia resulted in a rise in peripheral Hct of 2.7 ± 2.9% (p 0.001), and diuretic treatment of hypervolemia in cases without anemia caused a 4.5 ± 3.9% (p 0.001) increase in peripheral Hct at 11.3 ± 7.5 days after admission. Subjects had lower 30-day rates of readmission (12.2% vs. 27.7%, respectively; p 0.001), of 30-day mortality (2.0% vs. 11.1%, respectively; p 0.001), and of 365-day mortality (4.9% vs. 35.5%, respectively; p 0.001) but longer lengths of stay (7.3 vs. 5.6 days, respectively; p 0.001) than control subjects.Retrospective outcomes using volume-guided HF therapy versus propensity-matched controls support the benefit of BVA in guiding volume management and reducing death and rehospitalization due to HF.

Erythropoietin (EPO) controls red cell volume (RCV) and plasma volume (PV). Therefore, injecting recombinant human EPO (rhEPO) increases RCV and most likely reduces PV. RhEPO-induced endurance improvements are explained by an increase in blood oxygen (O2) transport capacity, which increases maximum O2 uptake ( $$\dot{V}$$ O2max). However, it is debatable whether increased RCV or $$\dot{V}$$ O2max are the main reasons for the prolongation of the time to exhaustion (t lim) at submaximal intensity. We hypothesized that high rhEPO doses in particular contracts PV such that the improvement in t lim is not as strong as at lower doses while $$\dot{V}$$ O2max increases in a dose-dependent manner. We investigated the effects of different doses of rhEPO given during 4 weeks [placebo (P), low (L), medium (M), and high (H) dosage] on RCV, PV, $$\dot{V}$$ O2max and t lim in 40 subjects. While RCV increased in a dose-dependent manner, PV decreased independent of the rhEPO dose. The improvements in t lim (P +21.4 ± 23.8 %; L +16.7 ± 29.8 %; M +44.8 ± 62.7 %; H +69.7 ± 73.4 %) depended on the applied doses (R 2 = 0.89) and clearly exceeded the dose-independent $$\dot{V}$$ O2max increases (P −1.7 ± 3.2 %; L +2.6 ± 6.8 %; M +5.7 ± 5.1 %; H +5.6 ± 4.3 %) after 4 weeks of rhEPO administration. Furthermore, the absolute t lim was not related (R 2 ≈ 0) to RCV or to $$\dot{V}$$ O2max. We conclude that a contraction in PV does not negatively affect t lim and that rhEPO improves t lim by additional, non-hematopoietic factors.

Background The red cell distribution width (RDW) predicts mortality among many populations. RDW is calculated as the standard deviation (SD) of the red blood cell (RBC) volume divided by mean corpuscular volume (MCV). Because higher MCV also predicts mortality, we hypothesized that the RDW numerator (one SD of RBC volume or 1SD-RDW) predicts mortality more strongly than the RDW. Material and methods Adult subjects hospitalized during a contemporary clinical era (10/2005-1/2014, N = 135 963) and a historical era (1/1999-9/2005, N = 119 530) were studied. The RDW was obtained from the complete blood count (CBC), while 1SD-RDW was calculated (RDW multiplied by MCV and divided by 100). Results In univariable Cox regression (2005–2014 cohort), 1SD-RDW (quintile 5 vs. 1: hazard ratio [HR] = 8·38, 95% confidence interval [CI] = 7·94, 8·85; P

Background: We aimed to determine whether there are any alterations in red blood cell width in patients diagnosed with acute pancreatitis. Material/Methods: This was a retrospective study of records of patients treated in emergency units and diagnosed with acute pancreatitis between January 2011 and April 2013. Records were investigated regarding patient age, sex, and causes of acute pancreatitis. Red blood cell width and amylase values obtained from the patients during diagnosis and after a full recovery from acute pancreatitis were added to the records. Results: Recorded red blood cell width and amylase values of 104 patients diagnosed with acute pancreatitis were statistically compared according to the time of sample collection. Samples were collected in the post-diagnostic period and after full recovery. Values of red blood cell width and amylase were found to be significantly higher in samples collected during hospital admission in comparison to those obtained from patients after fully recovering from acute pancreatitis (p

Hyporesponders to erythropoietin-stimulating agents (ESAs) have been associated with an increased subsequent risk of death or cardiovascular events. We hypothesized that subjects who are hyporesponsive to erythropoietin alfa would have higher plasma volumes and lower red cell deficits than subjects who are responsive to therapy.As part of a prospective, single blind, randomized, placebo-controlled study comparing erythropoietin alfa with placebo in older adults (n = 56) with heart failure and a preserved ejection fraction (HFPEF), we performed blood volume analysis with the use of an indicator dilution technique with (131)iodine-labeled albumin. We evaluated differences in plasma volumes and red cell volumes in hyporesponders (eg,1 g/dL increase in hemoglobin within the first 4 weeks of treatment with erythropoetin alfa) compared with subjects who were responders and controls.Nine of 28 subjects (32%) assigned to ESA were hyporesponders. Hyporesponders did not differ from responders nor control subjects by any baseline demographic, clinical, or laboratory parameter, including hemoglobin. Hyporesponders had a greater total blood volume expansion (1,264.7 ± 387 vs 229 ± 206 mL; P = .02) but less of a red cell deficit (-96.2 ± 126 vs -402.5 ± 80.6 mL; P = .04) and a greater plasma volume expansion (+1,360.8 ± 264.5 vs +601.1 ± 165.5 mL; P = .01). Among responders, the increase in hemoglobin with erythropoietin alfa was associated primarily with increases in red cell volume (r = 0.91; P.0001) as well as a decline in plasma volume (r = -0.55; P = .06).Among older adults with HFPEF and anemia, hyporesponders to erythropoietin alfa had a hemodilutional basis of their anemia, suggesting that blood volume analysis can identify a cohort likely to respond to therapy.

SummaryBackground Respiratory adverse events are commonly observed after adenotonsillectomy in children with sleep-disordered breathing. Preoperative prediction of these events enhances quality of care and resource management in facilities while encouraging precautions against them. Red cell distribution width, a measure of erythrocyte size variability, has recently been linked to adverse outcomes in a variety of disorders. Red cell distribution width has also been found to be associated with severity of obstructive sleep apnea in adults due to hypoxia-mediated inflammation. Aim The objective of this study was to evaluate whether elevated red cell distribution width is associated with postoperative respiratory adverse events in children with symptoms of sleep-disordered breathing. Methods A prospective, observational, assessor-blinded study was conducted with consecutive children undergoing elective adenotonsillectomy for treatment of sleep-disordered breathing. Under general anesthesia, adenoidectomy was performed by curettage, and tonsillectomy was carried out by dissection. The primary outcome was the occurrence of an adverse event during emergence or in the postanesthesia care unit (PACU). Results Among 287 patients, with mean ± sd age 7.49 ± 3.21, the frequency of respiratory complications during emergence was 62 (22.30%) and in PACU was 56 (20.14%). Mean ± sd red cell distribution width was 14.36 ± 1.06 in patients with complications and higher than that in those without complications 13.53 ± 0.59. Red cell distribution width had an adjusted odds ratio 7.28 (95% CI: 4.30–13.28) and area under the curve value 0.74 (95% CI: 0.67–0.81) to predict postoperative complications. A cutoff value for red cell distribution width was found to be 14.7. Conclusion Our study showed that preoperative elevated red cell distribution width is associated with an increased risk of respiratory adverse events in children undergoing adenotonsillectomy for sleep-disordered breathing.

BackgroundRed blood cell distribution width (RDW) and neutrophil to lymphocyte ratio (NLR) have been reported to be associated with outcomes of acute cerebral infarction. However, their prognostic value in patients with subarachnoid haemorrhage (SAH) remains largely unknown. The aim of this study was to investigate the prognostic value of RDW and NLR in SAH patients.MethodsMedical records of adult SAH patients admitted to intensive care unit (ICU) were extracted from Multiparameter Intelligent Monitoring in Intensive Care II (MIMIC II, version 2.6), a publicly accessible ICU database. Prognostic value of RDW and NLR was analysed using logistic regression model, Kaplan-Meier curve analysis and Cox regression model.ResultsA total of 274 SAH patients were included. Patients died in hospital had significantly higher RDW and NLR. RDW and NLR were significantly associated with hospital death, with adjusted odds ratios of 1.39 (95% CI, 1.06–1.82) and 1.04 (95% CI, 1.00–1.08), respectively. Furthermore, increased RDW and NLR were associated with higher one-year mortality, with an adjusted hazard ratio of 1.20 (95% CI, 1.02–1.41) for per 1% increased RDW and 1.03 (95% CI, 1.00–1.05) for per 1 increased NLR.ConclusionRDW and NLR are useful indices to evaluate the outcomes of ICU admitted patients with SAH.

Red blood cell volume (RBCV) is a main determinant of cardiorespiratory fitness in healthy individuals. However, it remains controversial to what extent exercise training (ExT) enhances RBCV. Therefore, we sought to systematically review and determine the effect of ExT on RBCV in healthy individuals across all ages. We conducted a systematic search of MEDLINE, Scopus, and Web of Science, since their inceptions until February 2016 for articles assessing the effect of ExT interventions (not including hypoxic training) on blood volumes in healthy individuals. A meta-analysis was performed to determine the mean difference (MD) in RBCV between post- and pre-ExT measurements. Thirty studies were included after systematic review, comprising a total of 299 healthy individuals (mean age = 19–71 years, 271 males). Exercise training programs primarily consisted in lower limb endurance training interventions (mean duration = 15.2 weeks). After data pooling, RBCV was not increased following ExT (MD = 49 mL, 95% CI = −11, 108; P = 0.11). In subgroup analyses, RBCV was increased after ExT in young and middle-aged individuals (mean age

Plasma volume and red cell mass are key health markers used to monitor numerous disease states, such as heart failure, kidney disease, or sepsis. Nevertheless, there is currently no practically applicable method to easily measure absolute plasma or red cell volumes in a clinical setting. Here, a novel marker for plasma volume and red cell mass was developed through analysis of the observed variability caused by plasma volume shifts in common biochemical measures, selected based on their propensity to present with low variations over time. Once a month for 6 months, serum and whole blood samples were collected from 33 active males. Concurrently, the CO-rebreathing method was applied to determine target levels of hemoglobin mass (HbM) and blood volumes. The variability of 18 common chemistry markers and 27 Full Blood Count variables was investigated and matched to the observed plasma volume variation. After the removal of between-subject variations using a Bayesian model, multivariate analysis identified two sets of 8 and 15 biomarkers explaining 68% and 69% of plasma volume variance, respectively. The final multiparametric model contains a weighting function to allow for isolated abnormalities in single biomarkers. This proof-of-concept investigation describes a novel approach to estimate absolute vascular volumes, with a simple blood test. Despite the physiological instability of critically ill patients, it is hypothesized the model, with its multiparametric approach and weighting function, maintains the capacity to describe vascular volumes. This model has potential to transform volume management in clinical settings. Am. J. Hematol. 92:62-67, 2017. © 2016 Wiley Periodicals, Inc.

The intactness degree of glycocalyx and the thickness of endothelium layer in sublingual microvessels was determined by means of darkfield microscopy and GlycoCheck RI software in 35 patients (19 men and 16 women, aged 35 to 65 years) with chronic generalized severe periodontitis before and after anti-inflammatory and surgical treatment. The patients were divided into two groups. The first group recieved only local anti-inflammatory therapy while patients of group 2 underwent surgical intervention on the periodontium in addition to local anti-inflammatory therapy. In both groups the changes of parameters of endothelial glycocalyx (EGC) in the early stages of treatment were not significant. In long terms the changes were not revealed in group 1, but in group 2 6 months after surgical treatment in all patients the decrease in the thickness of the permeable glycocalyx decreased and increase of the volume of red blood cells filling was observed.С помощью темнопольной микроскопии и программного обеспечения - GlycoCheck RI - метрически определяли степень интактности и толщину гликокаликсового слоя эндотелия микрососудов подъязычной области у 35 пациентов (19 мужчин и 16 женщин в возрасте от 35 до 65 лет) с хроническим генерализованным пародонтитом (ХГП) тяжелой степени до противовоспалительного и хирургического лечения и в разные сроки после него. Пациенты были разделены на две группы. В 1-й группе проводилась только местная противовоспалительная терапия (МПВТ), во 2-й - в дополнение к МПВТ применялись хирургические вмешательства на пародонте. В обеих группах изменения параметров эндотелиального гликокаликса в ранние сроки лечения отсутствовали. В отдаленные сроки в 1-й группе изменения также не выявлены. Во 2-й группе через 6 мес после хирургического лечения у всех пациентов уменьшилась толщина проницаемого гликокаликса и увеличился объем тока эритроцитов.

Background and Objectives Cardiac surgery is currently considered one of the heaviest users of red blood cells. An explanation may be found, in part, in considering the effect of the heavy clear fluid load associated with cardiopulmonary bypass. This may result in the artificial depression of haemoglobin concentration, overestimating the requirement for red cell transfusion if this is the sole parameter considered. To address this issue, we examined the impact of a red cell volume-based transfusion guideline on transfusion requirement. Materials and Methods This was a single-centre, randomized controlled trial. The cohort of 86 patients was allocated to receive red cells as per the red cell volume guideline (group RCV) or standard haemoglobin concentration-based departmental policy (group C). Outcome measures were red cell transfusion and clinical outcome. Results All preoperative data were comparable between the two groups. A significantly fewer percentage of patients in group RCV were transfused red cells (RCV = 32·6% vs. C = 53·5%, P = 0·05). No significant difference was found between any of the outcome measures with the exception of median hospital stay (RCV = 5·9 days vs. C = 6·8 days, P = 0·02). Conclusion In elective cardiac surgery patients, considering haemoglobin concentration alone may overestimate the requirement for red cell transfusion. More research is required to determine the impact of restrictive transfusion policies on clinical outcome following cardiac surgery.

The cut off for hemoglobin or hematocrit that indicates the need for an isotopic red cell mass study was investigated in 179 patients with a presumptive diagnosis of polycythemia vera or essential thrombocythemia. Hematocrit showed better diagnostic accuracy than hemoglobin. Hemoglobin over 18.5 g/dL in males or over 16.5 g/dL in females showed a high specificity indicating that red cell mass study could be avoided in such cases, but it showed low sensitivity leading to 46% false negatives. The best value of hematocrit to indicate a red cell mass study was 0.50 L/L in males (specificity 75%, sensitivity 87.5%) and 0.48 L/L in females (specificity 73%, sensitivity 94%). Lowering the hematocrit threshold to 0.48 L/L in males increased sensitivity up to 95%. A red cell mass study should be performed in patients with suspected diagnosis of essential thrombocythemia or polycythemia vera and with hematocrit between 0.48 L/L and 0.52 L/L.

SummaryIncreased red blood cell distribution width (RDW), which is a marker of anisocytosis, is associated with mortality and cardiovascular events in the general population and in patients with heart failure or coronary heart disease. We investigated whether RDW in acute cerebral infarction is predictive of functional outcome and mortality. A total of 847 consecutive patients with first-ever acute cerebral infarction who presented to the emergency department within seven days of symptom onset were enrolled in this study. We investigated the association of RDW with poor functional outcome (modified Rankin Scale >2) and all-cause mortality at three months, as well as survival time for one year after stroke onset. Multivariate logistic regression revealed that higher RDW was independently associated with poor functional outcome (adjusted odds ratio [OR], 1.222 per 1% increment in RDW, 95% confidence interval [CI] 1.059–1.409, p=0.006) and all-cause death (adjusted OR, 1.395 per 1% increment in RDW, 95% CI 1.168–1.665, p

Plasma or serum hyperviscosity in plasma cell dyscrasias (PCD) has been described as a risk factor for circulatory disturbances. Whole blood viscosity (WBV) would theoretically be a better biomarker but has not been studied in PCD.Plasma viscosity (PV) and WBV were measured in 89 subjects with PCD and in 60 healthy blood donors by free oscillation rheometry. A complete blood count was obtained using an automated hematology analyzer. Plasma proteins were quantitated by immunoturbidimetry.The reference intervals for menwomen were 1.16-1.361.16-1.38 mPa for PV, and 4.9-6.34.4-6.2 mPa for WBV, respectively. Of the PCD patients, 71% had PV above the reference limit and 40% were above the WBV limit. Multivariate analysis showed that WBV was independently related to hematocrit, PV, concentration of the monoclonal protein (M-protein), plasma fibrinogen concentration and albumin concentration. This model accounted for 76% of the variance in WBV. When the same model was applied to PV, only the concentration of the M-protein was significantly related and the model accounted only for 20% of the variance in PV.PV cannot be used as a surrogate marker for WBV in PCD patients. Whole blood viscosity should replace plasma viscosity in patients with PCD.

Background The therapeutic use of bone marrow-derived mononuclear cells (MNCs) and mesenchymal stem cells for the treatment of soft tissue and orthopedic injuries in equine patients is expanding. After collection, bone marrow must be reduced in volume and depleted of RBCs for immediate therapeutic use or to prepare cells for culture or cryopreservation and storage. The MarrowXpress (MXP) System is an automated, closed, sterile system designed to process human bone marrow samples. Objectives The purpose of this study was to evaluate the capacity of the MXP System to process equine bone marrow to reduce volume, deplete RBCs, and enhance recovery of MNCs. Methods Bone marrow was collected from 47 horses into 2 60-mL syringes containing heparin and processed using the MXP System. HCT, total nucleated cell (TNC) count, and MNC count were obtained for each sample before and after processing using an Advia 120 hematology analyzer. Volume reduction, RBC depletion, and recovery of TNCs and MNCs were calculated. Results For equine bone marrow samples, mean values were 73.2% for RBC depletion and 78.0% for volume reduction. TNC count before processing was 2.5 ± 1.2 × 107 and after processing was significantly higher at 7.8 ± 3.3 × 107 (P

Increased red blood cell distribution width (RDW), a marker of anisocytosis, has been associated with adverse outcomes in multiple settings. Whether RDW is predictive of mortality in patients with peripheral artery disease (PAD) is unknown. We studied 13,039 consecutive outpatients (69.5 ± 12.0 years of age, 60.9% men, 97.6% white) with PAD identified by noninvasive lower-extremity arterial testing at the Mayo Clinic from January 1997 through December 2007, with follow-up through September 2009. We defined PAD as a low (≤ 0.9) or high (≥ 1.4) ankle-brachial index (ABI). Cardiovascular risk factors and co-morbidities were ascertained using electronic medical record-based algorithms. RDW was obtained from the complete blood cell count drawn around the time of arterial evaluation. Mortality was ascertained using the Mayo electronic medical record and Accurint databases. Association of RDW with all-cause mortality was analyzed by multivariable Cox proportional hazards regression. During a median follow-up of 5.5 years, 4,039 (31.0%) deaths occurred (28.7% in low and 38.9% in high ABI subsets). After adjustment for age, gender, cardiovascular risk factors, and co-morbidities, patients in the highest quartile of RDW (14.5%) had a 66% greater risk of mortality compared to the lowest quartile (12.8%, p0.0001); a 1% increment in RDW was associated with a 10% greater risk of all-cause mortality (hazard ratio 1.10, 95% confidence interval 1.08 to 1.12, p0.0001). The adjusted hazard ratio was similar in the low (1.10, 1.08 to 1.12) and high (1.09, 1.06 to 1.12) ABI subsets. In conclusion, RDW, a routinely available measurement, is an independent prognostic marker in patients with PAD.

Anemia is defined according to decreased blood hemoglobin concentration ([Hb]), which is considered a marker of low total red blood cell volume (RBCV). Alterations of plasma volume (PV) may also modify [Hb] without concomitant changes in RBCV. Since anemia and fluid retention are frequent complications of chronic kidney disease (CKD), we hypothesized that anemia during CKD may in part be related to expanded PV without a simultaneous decrease in RBCV. We quantified hemoglobin mass, RBCV, PV, and total blood volume (BV) using an automated carbon monoxide device in 40 consecutive stage 3–5 CKD patients not on dialysis and in seven healthy male controls of the same age range. These were compared within and to predicted volumes according to Nadler's formula. Arterial stiffness and NT‐proBNP were measured. RBCV was similar to predicted values range in anemic CKD patients 2073 (1818–2704) versus, 2061 (1725–2473) mL, P > 0.05. In contrast, PV was largely increased in anemic CKD patients (3881 (3212–4352) vs. 2916 (2851–3201)), P = 0.01. Of 26 anemic patients, only six had a >20% decrease in RBCV as the cause for their anemia, whereas 14 had a >20% increase of PV as a cause for their anemia. NT‐pro BNP correlated with eGFR but neither with PV nor BV, whereas arterial stiffness was not correlated to blood volumes. Anemia in CKD as diagnosed by low [Hb] is not necessarily associated to low RBCV but may reflect increased PV. This finding has implications for the treatment of CKD patients and may refrain from normalizing [Hb] levels in all CKD patients.

The monitoring of 6-thioguanine nucleotides (6-TGN) levels is warranted during thiopurine therapy for patients with inflammatory bowel diseases.The aim of this study was to elucidate the parameters that can predict the 6-TGN levels among Japanese patients with inflammatory bowel diseases undergoing thiopurine therapy.The 6-TGN levels were measured in 54 patients with inflammatory bowel diseases (32 with ulcerative colitis and 22 with Crohn's disease), who had been administered azathioprine or 6-mercaptopurine for more than 90 days. Possible correlations between the hematologic parameters and 6-TGN levels were investigated. The clinical and hematologic variables were evaluated to determine the 6-TGN levels of less than or over 235 pmol/8 x 10(8) RBCs.The 6-TGN levels correlated significantly with changes in the mean corpuscular volume (R = 0.423, p = 0.001) and the lymphocyte counts (R = -0.280, p = 0.04). A multivariate analysis revealed changes in the mean corpuscular volume (OR: 1.22, 95% CI: 1.07-1.40) and hemoglobin levels (OR: 0.59, 95% CI: 0.35-0.99) to be factors predictive of the 6-TGN levels. An increase in the mean corpuscular volume of 3.5 fl was determined to be the most preferable cut-off value to distinguish patients with 6-TGNor= 235 pmol/8 x 10(8) RBCs from those with a lower concentration.Changes in the mean corpuscular volume are considered to be predictive of the 6-TGN levels in patients with inflammatory bowel diseases receiving thiopurine therapy.

Understanding blood volume changes in children with malaria is important for managing fluid status. Traditionally, blood/red cell volume measurements have used radioactive chromium isotopes. We applied an alternative approach, using non-radioactive chromium-53 labelling and mass spectrometry to investigate red cell volume (RCV) in Gabonese children with malaria. Nineteen children with malaria participated (10 severe, 9 moderately severe; ages 15 months to 7 years). Blood labelled with 53Cr-chromate exvivo was re-injected, then sampled 30 min later. Pre- and post-injection 53Cr content were measured by gas chromatography/electron ionisation mass spectrometry of the chromium-trifluoroacetylacetone (TFA) chelate, calibrated against 50Cr standards. Blood and red cell volumes were calculated from isotopic dilution in 15 of 19 children (in four, insufficient signal mitigated analysis). In this small pilot study, there were no significant differences between moderate and severe cases. Including all subjects, the mean RCV was reduced compared with predicted values (184 vs. 269 mL; p = 0.016) but blood volume, 71 ± 33 mL/kg (normalised for weight), was close to predicted, ∼77 mL/kg, commensurate with reduced haematocrit. Blood lactate concentration correlated negatively with RCV/weight (r = −0.56, p = 0.028), consistent with anaemia. In one case, sequential samples over 42 days gave an estimated rate of 53Cr disappearance of 1.4%/day (equivalent half-life: 70 days). 53Cr-labelling of red cells may be used to estimate blood and red cell volumes and can be used as an investigative tool in situations such as childhood diseases and resource-constrained settings. Although the red cell mass is depleted in malaria, the blood volume appears relatively well preserved. Copyright © 2009 John Wiley & Sons, Ltd.

The high iron demand associated with enhanced erythropoiesis during high-altitude hypoxia leads to skeletal muscle iron mobilization and decrease in myoglobin protein levels. To investigate the effect of enhanced erythropoiesis on systemic and muscle iron metabolism under nonhypoxic conditions, 8 healthy volunteers were treated with recombinant erythropoietin (rhEpo) for 1 month. As expected, the treatment efficiently increased erythropoiesis and stimulated bone marrow iron use. It was also associated with a prompt and considerable decrease in urinary hepcidin and a slight transient increase in GDF-15. The increased iron use and reduced hepcidin levels suggested increased iron mobilization, but the treatment was associated with increased muscle iron and L ferritin levels. The muscle expression of transferrin receptor and ferroportin was up-regulated by rhEpo administration, whereas no appreciable change in myoglobin levels was observed, which suggests unaltered muscle oxygen homeostasis. In conclusion, under rhEpo stimulation, the changes in the expression of muscle iron proteins indicate the occurrence of skeletal muscle iron accumulation despite the remarkable hepcidin suppression that may be mediated by several factors, such as rhEpo or decreased transferrin saturation or both.