Are coagulation profiles in Andean highlanders with excessive erythrocytosis favouring hypercoagulability?

Chronic mountain sickness is a maladaptive syndrome that affects individuals living permanently at high altitude and is characterized primarily by excessive erythrocytosis (EE). Recent results concerning the impact of EE in Andean highlanders on clotting and the possible promotion of hypercoagulability, which can lead to thrombosis, were contradictory. We assessed the coagulation profiles of Andeans highlanders with and without excessive erythrocytosis (EE+ and EE-). Blood samples were collected from 30 EE+ and 15 EE- in La Rinconada (Peru, 5100-5300 m a.s.l.), with special attention given to the sampling pre-analytical variables. Rotational thromboelastometry tests were performed at both native and normalized (40%) haematocrit using autologous platelet-poor plasma. Thrombin generation, dosages of clotting factors and inhibitors were measured in plasma samples. Data were compared between groups and with measurements performed at native haematocrit in 10 lowlanders (LL) at sea level. At native haematocrit, in all rotational thromboelastometry assays, EE+ exhibited hypocoagulable profiles (prolonged clotting time and weaker clot strength) compared with EE- and LL (all P < 0.01). At normalized haematocrit, clotting times were normalized in most individuals. Conversely, maximal clot firmness was normalized only in FIBTEM and not in EXTEM/INTEM assays, suggesting abnormal platelet activity. Thrombin generation, levels of plasma clotting factors and inhibitors, and standard coagulation assays were mostly normal in all groups. No highlanders reported a history of venous thromboembolism based on the dedicated survey. Collectively, these results indicate that EE+ do not present a hypercoagulable profile potentially favouring thrombosis.

The Response of the Amputee Athlete Heart to Chronic Core Exercise: A Study on Hematological and Biochemical Parameters, and N-Terminal Pro Brain Natriuretic Peptide.

Background and Objectives: mortality and morbidity due to cardiovascular causes are frequently experienced in amputees. Research on the effects of chronic exercise on biomarkers and cardiac damage indicators in these individuals is limited. The aim of this study was to investigate the effects of a core training program on brain natriuretic-related peptide, as well as hematological and biochemical parameters in amputee soccer players. Materials and Methods: The participants were randomly allocated to the following two groups: a core exercise group (CEG) and a control group (CG). While the CG continued routine soccer training, the CEG group was included in a core exercise program different from this group. During the study, routine hemogram parameters of the participants, various biochemical markers, and the concentration of brain natriuretic-related peptide (NT-pro-BNP) were analyzed. Results: after the training period, notable improvements in various hematological parameters were observed in both groups. In the CEG, there were significant enhancements in red blood cell count (RBC), hematocrit (HCT), mean corpuscular hemoglobin concentration (MCHC), and mean corpuscular hemoglobin (MCH) values. Similarly, the CG also showed substantial improvements in RBC, HCT, mean corpuscular volume (MCV), MCHC, MCH, red cell distribution width-standard deviation (RDW-SD), platelet-to-lymphocyte ratio (PLCR), mean platelet volume (MPV), and platelet distribution width (PDW). Moreover, in the CEG, serum triglycerides (TG) and maximal oxygen uptake (MaxVO2) exhibited significant increases. Conversely, TG levels decreased in the CG, while high-density lipoprotein (HDL), low-density lipoprotein (LDL), and MaxVO2 levels demonstrated substantial elevations. Notably, the N-terminal pro-brain natriuretic peptide (BNP) levels did not undergo significant changes in either the CEG or the CG following the core exercise program (p > 0.05). However, in the CEG, a meaningful positive correlation was observed between NT-pro-BNP and creatine kinase (CK) levels before and after the core exercise program. Conclusions: the findings emphasized the potential benefits of core training in enhancing specific physiological aspects, such as erythrocyte-related parameters and lipid metabolism, as well as aerobic capacity. Furthermore, the observed correlation between NT-pro-BNP and CK levels in the CEG provides intriguing insights into the unique physiological adaptations of amputee athletes.

Characterization of a Novel Approach for Neonatal Hematocrit Screening Based on Penetration Velocity in Lateral Flow Test Strip.

Hematocrit (HCT) is a crucial parameter for both adult and pediatric patients, indicating potentially severe pathological conditions. Most common methods for HCT assessment are microhematocrit and automated analyzers; however, developing countries present specific needs often not addressed by these technologies. Paper-based devices can be suitable for those environments being inexpensive, rapid, easy to use, and portable. The aim of this study is to describe and validate against a reference method, a novel HCT estimation method based on penetration velocity in lateral flow test strips complying with the requirements in low- or middle-income country (LMIC) scenarios. To calibrate and test the proposed method, 145 blood samples of 105 healthy neonates with gestational age greater than 37 weeks were collected (29 calibration set, 116 test set) in the range of HCT values (31.6-72.5%). The time difference (Δt) from the whole blood sample loading into the test strip instant till the nitrocellulose membrane saturation instant was measured by a reflectance meter. A nonlinear relation was observed between HCT and Δt and was estimated by a third-degree polynomial equation (R2 = 0.91) valid in 30% to 70% HCT interval. The proposed model was subsequently used to estimate HCT values on the test set showing a good agreement between the estimated HCT and the HCT measured by the reference method (r = 0.87, p < 0.001), with a low mean difference of 0.53 ± 5.04% and a slight trend of overestimation for higher hematocrit values. The mean absolute error was 4.29%, while the maximum absolute error was 10.69%. Although the proposed method did not present a sufficient accuracy to be used for diagnostic purposes, it could be suitable as a fast, low-cost, easy-to-use screening tool especially in LMIC scenarios.

A General Model to Calculate the Spin-Lattice Relaxation Rate (R1) of Blood, Accounting for Hematocrit, Oxygen Saturation, Oxygen Partial Pressure, and Magnetic Field Strength Under Hyperoxic Conditions.

BACKGROUND: Under normal physiological conditions, the spin-lattice relaxation rate (R1) in blood is influenced by many factors, including hematocrit, field strength, and the paramagnetic effects of deoxyhemoglobin and dissolved oxygen. In addition, techniques such as oxygen-enhanced magnetic resonance imaging (MRI) require high fractions of inspired oxygen to induce hyperoxia, which complicates the R1 signal further. A quantitative model relating total blood oxygen content to R1 could help explain these effects. PURPOSE: To propose and assess a general model to estimate the R1 of blood, accounting for hematocrit, SO2 , PO2 , and B0 under both normal physiological and hyperoxic conditions. STUDY TYPE: Mathematical modeling. POPULATION: One hundred and twenty-six published values of R1 from phantoms and animal models. FIELD STRENGTH/SEQUENCE: 5-8.45 T. ASSESSMENT: We propose a two-compartment nonlinear model to calculate R1 as a function of hematocrit, PO2 , and B0. The Akaike Information Criterion (AIC) was used to select the best-performing model with the fewest parameters. A previous model of R1 as a function of hematocrit, SO2 , and B0 has been proposed by Hales et al, and our work builds upon this work to make the model applicable under hyperoxic conditions (SO2  > 0.99). Models were assessed using the AIC, mean squared error (MSE), coefficient of determination (R2 ), and Bland-Altman analysis. The effect of volume fraction constants WRBC and Wplasma was assessed by the SD of resulting R1. The range of the model was determined by the maximum and minimum B0, hematocrit, SO2 , and PO2 of the literature data points. STATISTICAL TESTS: Bland-Altman, AIC, MSE, coefficient of determination (R2 ), SD. RESULTS: The model estimates agreed well with the literature values of R1 of blood (R2  = 0.93, MSE = 0.0013 s-2 ), and its performance was consistent across the range of parameters: B0 = 1.5-8.45 T, SO2  = 0.40-1, PO2  = 30-700 mmHg. DATA CONCLUSION: Using the results from this model, we have quantified and explained the contradictory decrease in R1 reported in oxygen-enhanced MRI and oxygen-delivery experiments. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 1.

A Corrective Method for Different Hematocrit Values of Whole Blood Samples on the Detection of Procalcitonin.

BACKGROUND: We have explored that quantitative PCT detection can be conducted in different sample types (whole blood and/or plasma samples) with good correlation and consistency in clinical use. These findings reduce the sample volume and turnover time of PCT detection in clinical labs. However, different hematocrit (HCT) percentages of whole blood samples may affect the final results, especially abnormal hematocrit (HCT) percentages. To overcome this problem, we established a mathematical model to modify the whole blood test results and evaluated the effects of HCT correction. METHODS: First, we prepared a preliminary experiment - various hematocrit (HCT) percentages (15% - 65%) of whole blood samples with different PCT concentrations and established a mathematic model to correct the effects of PCT detection. Then, in this paper, we evaluated the consistency with Pearson's correlation and Kappa analysis between whole bloods detected by the i-Reader S system and plasma detected by the Biomerieux system. Besides, we prepared different HCT values about 15%, 40%, 60% of 9 samples with different PCT concentrations to evaluate the effects of HCT correction Results and Conclusions: Pearson's correlative studies and Kappa analysis indicated that PCT levels measured by i-Reader S (plasma & whole blood samples) were comparable to results from the VIDAS system, and HCT correction could improve consistency of PCT detection between whole blood and plasma. Analysis of samples with abnormal HCT values showed that the mathematical correction model could offset the influences of various HCT values.

Cerebrovascular reactivity measurements using simultaneous 15O-water PET and ASL MRI: Impacts of arterial transit time, labeling efficiency, and hematocrit.

Cerebrovascular reactivity (CVR) reflects the capacity of the brain to meet changing physiological demands and can predict the risk of cerebrovascular diseases. CVR can be obtained by measuring the change in cerebral blood flow (CBF) during a brain stress test where CBF is altered by a vasodilator such as acetazolamide. Although the gold standard to quantify CBF is PET imaging, the procedure is invasive and inaccessible to most patients. Arterial spin labeling (ASL) is a non-invasive and quantitative MRI method to measure CBF, and a consensus guideline has been published for the clinical application of ASL. Despite single post labeling delay (PLD) pseudo-continuous ASL (PCASL) being the recommended ASL technique for CBF quantification, it is sensitive to variations to the arterial transit time (ATT) and labeling efficiency induced by the vasodilator in CVR studies. Multi-PLD ASL controls for the changes in ATT, and velocity selective ASL is in theory insensitive to both ATT and labeling efficiency. Here we investigate CVR using simultaneous 15O-water PET and ASL MRI data from 19 healthy subjects. CVR and CBF measured by the ASL techniques were compared using PET as the reference technique. The impacts of blood T1 and labeling efficiency on ASL were assessed using individual measurements of hematocrit and flow velocity data of the carotid and vertebral arteries measured using phase-contrast MRI. We found that multi-PLD PCASL is the ASL technique most consistent with PET for CVR quantification (group mean CVR of the whole brain = 42±19% and 40±18% respectively). Single-PLD ASL underestimated the CVR of the whole brain significantly by 15±10% compared with PET (p<0.01, paired t-test). Changes in ATT pre- and post-acetazolamide was the principal factor affecting ASL-based CVR quantification. Variations in labeling efficiency and blood T1 had negligible effects.

Preoperative low hematocrit is an adverse prognostic biomarker in ovarian cancer.

OBJECTIVE: The study aimed to investigate the prognostic value of preoperative hematocrit (HCT) on the survival of epithelial ovarian cancer (EOC) patients. METHODS: Patients who underwent primary debulking surgery (PDS) in our institution, from January 2010 to December 2015, were enrolled. The preoperative HCT, hemoglobin (Hb), tumor stage, ascites volume, age, albumin, BMI, ASA score, diabetes and other factors were collected and analyzed to find the risk factors for poor prognosis of EOC patients using Cox regression. Survival analysis was conducted with Kaplan-Meier method and log-rank test. RESULTS: 192 patients met the inclusion criteria. HCT < 35% (P = 0.031, HR: 1.715, 95% CI 1.050-2.802) was an independent risk factor for poor overall survival in patients. The mean survival time was 83.7 months in patients with preoperative HCT ≥ 35% and 61.7 months in patients with HCT < 35% (P = 0.002). Patients with low HCT (< 35%) had a poor prognosis compared with patients with normal HCT, specifically in the patients of stage III/IV, age ≥ 65 years, BMI ≥ 25.0 kg/m2, ascites volume ≤ 500 mL, ASA score < 3, albumin ≥ 35 g/L and nondiabetic. Low HCT was more likely to occur in patients with advanced stage (III/IV), anemia (Hb < 110 g/mL), low albumin (< 35 g/L), high ASA score (≥ 3) and platelet > 400 × 109/L. CONCLUSIONS: Preoperative low HCT was a valuable predictor for EOC patients' poor prognosis, specifically in obese, nondiabetic, elder, advanced stage but having relatively good performance status patients.

Comparison of hemoglobin and hematocrit levels at 1, 4 and 24 h after red blood cell transfusion.

Previous studies have shown that equilibration following a red cell transfusion had occurred by 24 h. A shorter time to follow the hemoglobin (Hb) and hematocrit (Hct) after transfusion may help physicians to provide earlier and more pertinent treatment. This was a prospective study conducted from December 2014 to August 2015. This research aimed to determine the equilibration time point of the level of Hb and Hct after one unit red blood cell (RBC) transfusion. Patients were randomized into three groups and Hb level and Hct were assessed at one, four or 24 h after transfusion. The mean differences in Hb level and Hct before and after transfusion were compared between each group. Sixty patients were eligible for enrollment onto this study; 20 patients were therefore allocated to each group. The median age was 51 years old, male predominating (83.33%). The most common indication for transfusion was post-operative anemia (88.33%). There were no significant differences between the baseline characteristics baseline Hb, Hct and volume of RBC transfusion in each group. The mean differences in Hb (g/dl)/Hct (%) level at the different time points of one, four and 24 h were 1.21/3.62, 1.19/3.63, and 0.95/3.09 respectively (P = 0.109 and P = 0.398, respectively). The equilibration of Hb and Hct did not differ between one, four and 24 h after a RBC transfusion. The target Hb and Hct can be determined at one hour after transfusion.

Optimizing management of replacement fluids for therapeutic plasma exchange: Use of an automated mathematical model to predict post-procedure fibrinogen and antithrombin levels in high-risk patients.

BACKGROUND: Therapeutic plasma exchange (TPE) utilizes an extracorporeal circuit to remove pathologic proteins causing serious illness. When processing a patient's entire blood volume through an extracorporeal circuit, proteins responsible for maintaining hemostatic system homeostasis can reach critically low levels if replacement fluid types and volumes are not carefully titrated, which may increase complications. METHODS: The charts from 27 patients undergoing 46 TPE procedures were reviewed to evaluate the accuracy of our predictive mathematical model, utilizing the following patient information: weight, hematocrit, pre- and post-TPE factor levels (fibrinogen, n = 46, and antithrombin, n = 23), process volume and volumes of fluids (eg, plasma, albumin, and normal saline) administered during TPE and adverse events during and after TPE. RESULTS: Altogether, 25% of patients experienced minor adverse events that resolved spontaneously or with management. There were no bleeding or thrombotic complications. The mean difference between predicted and measured post-TPE fibrinogen concentrations was -0.29 mg/dL (SD ±23.0, range -59 to 37), while percent difference between measured and predicted fibrinogen concentration was 0.94% (SD ±10.8, range of -22 to 19). The mean difference between predicted and measured post-TPE antithrombin concentrations were 0.89% activity (SD ±10.0, range -23 to 14), while mean percent difference between predicted and measured antithrombin concentrations was 3.87% (SD ±14.5, range -25 to 38). CONCLUSIONS: Our model reliably predicts post-TPE fibrinogen and antithrombin concentrations, and may help optimize patient management and attenuate complications.

Systematic comparison of four point-of-care methods versus the reference laboratory measurement of hemoglobin in the surgical ICU setting: a cross-sectional method comparison study.

BACKGROUND: Transfusion decision during the perioperative period mostly relies on the point-of-care testing for Hb measurement. This study aimed systematically compared four point-of-care methods with the central laboratory measurement of hemoglobin (LHb) regarding the accuracy, precision, and assay practicality to identify the preferred point-of-care method during the perioperative period. METHODS: This cross-sectional method comparison study was conducted in the surgical intensive care unit at Ramathibodi Hospital, Thailand, from September 2015 to July 2016. Four point-of-care methods, i.e., capillary hematocrit (HctCap), HemoCue Hb201+, iSTAT with CG8+ cartridge, and SpHb from Radical-7 pulse co-oximeter were carried out when LHb was ordered. Pearson correlation and Bland-Altman analyses were performed to assess the accuracy and precision, while the workload, turnaround time, and the unit cost were evaluated for the method practicality. RESULTS: Thirty-five patients were enrolled, corresponding to 48 blood specimens for analyses, resulting in the measured hemoglobin of 11.2 ± 1.9 g/dL by LHb. Ranking by correlation (r), mean difference (bias) and 95% limit of agreement (LOA) showed the point-of-care methods from the greater to the less performance as followed, iSTAT-LHb pair (r = 0.941; bias 0.15 (95% LOA; - 1.41, 1.12) g/dL), HemoCue-LHb pair (r = 0.922; bias - 0.18 (95% LOA; - 1.63, 1.28) g/dL), SpHb-LHb pair (r = 0.670; bias 0.13 (95% LOA; - 3.12, 3.39) g/dL) and HctCap-LHb pair (r = 0.905; bias 0.46 (95% LOA; - 1.16, 2.08) g/dL). Considering the practicality, all point-of-care methods had less workload and turnaround time than LHb, but only HemoCue and HctCap had lower unit cost. CONCLUSION: This study identified HemoCue as the suitable point-of-care method for the sole purpose of Hb measurement in the surgical ICU setting, while iSTAT should be considered when additional data is needed.

Influence of measurement principle on total hemoglobin value.

BACKGROUND: Total hemoglobin (tHb) measurement is indispensable for determining the patient's condition (hemorrhagic vs. ischemic) and need for blood transfusion. Conductivity- and absorbance-based measurement methods are used for blood gas analysis of tHb. For conductivity-based measurement, tHb is calculated after converting blood conductivity into a hematocrit value, whereas absorbance measurement is based on light absorbance after red blood cell hemolysis. Due to changes in plasma electrolytes and hemolysis, there is a possibility that conductivity- and absorbance-based measurement methods may cause a difference in tHb. METHODS: In this study, test samples with controlled electrolyte changes and hemolysis were created by adding sodium chloride, distilled water or hemolytic blood to blood samples collected from healthy volunteers, and tHb values were compared between both methods. RESULTS: Conductivity-based measurement revealed reduced tHb value (from 15.49 to 13.05 g/dl) following the addition of 10% sodium chloride, which was also reduced by the addition of hemolysate. Conversely, the addition of distilled water significantly increased tHb value than the expected value. In the absorbance method, there was no significant change in tHb value due to electrolyte change or hemolysis. CONCLUSIONS: We have to recognize unexpected conductivity changes occur at all times when tHb is measured via conductivity- and absorbance-based measurement methods. The absorbance method should be used when measuring tHb in patients with expected blood conductivity changes. However, when using this method, the added contribution of hemoglobin from hemolytic erythrocytes lacking oxygen carrying capacity must be considered. We recognize that discrepancy can occur between conductivity- and absorbance-based measurement methods when tHb is measured.

Haematocrit differences modify the association of cardiopulmonary bypass reoxygenation with acute kidney injury after paediatric Tetralogy of Fallot repair.

BACKGROUND: Little is known regarding the potential impact of haematocrit differences in the association between cardiopulmonary bypass reoxygenation and acute kidney injury following Tetralogy of Fallot repair. METHODS: We investigated the association of perfusate oxygenation during aortic occlusion associated with acute kidney injury between 204 normal and 248 higher haematocrit children with Tetralogy of Fallot, aged 1 month-18 years, who were surgically repaired in 2012-2018. Normal and higher haematocrit children were defined as having a preoperative haematocrit within and above age- and sex-specific reference intervals, respectively. Acute kidney injury was determined as a binary variable according to the Kidney Disease Improving Global Outcomes criteria. RESULTS: After adjusting for baseline and clinical covariates, a significant interaction between the haematocrit and continuous perfusate oxygenation on acute kidney injury was found (pinteraction = 0.049): a higher perfusate oxygenation was associated with a greater acute kidney injury risk among higher haematocrit children (adjusted odds ratio = 1.50, 95% confidence interval = [1.02, 2.22] per SD, p = 0.038) but not among normal haematocrit children (adjusted odds ratio = 0.91, 95% confidence interval = [0.51, 1.63] per SD, p = 0.73). After a similar adjustment, there was a marginal interaction between tertiles of perfusate oxygenation and haematocrit on acute kidney injury (pinteraction = 0.09): the middle and top tertiles of perfusate oxygenation were associated with a trend towards increased acute kidney injury risks among higher haematocrit children (adjusted odds ratio = 1.69, 95% confidence interval = [0.61, 4.66]; adjusted odds ratio = 2.25, 95% confidence interval = [0.84, 5.99], respectively) but not among normal haematocrit children (adjusted odds ratio = 1.16, 95% confidence interval = [0.46, 2.94]; adjusted odds ratio = 0.45, 95% confidence interval = [0.15, 1.36], respectively) compared with the bottom tertile. CONCLUSION: Preoperative haematocrit differences significantly modify the association of perfusate oxygenation with acute kidney injury, highlighting differential control of reoxygenation for different haematocrit children with Tetralogy of Fallot in the management of cardiopulmonary bypass.

Volume-localized measurement of oxygen extraction fraction in the brain using MRI.

PURPOSE: T2 -relaxation-under-spin-tagging (TRUST) is an MR technique for the non-invasive assessment of whole-brain cerebral oxygen extraction fraction (OEF), through measurement of the venous blood T2 relaxation time in the sagittal sinus. A key limitation of TRUST, however, is the lack of spatial specificity of the measurement. We sought to develop a modified TRUST sequence, selective localized TRUST (SL-TRUST), having sensitivity to venous blood T2 within a targeted brain region, and therefore achieving spatially localized measurements of cerebral tissue OEF, while still retaining acquisition in the sagittal sinus. METHODS: A method for selective localization of TRUST sequence was developed, and the reproducibility of the technique was evaluated in healthy participants. Regional measurements were achieved for a single hemisphere and for a 3D-localized 70 × 70 × 80 mm3 tissue region using SL-TRUST and compared to a global TRUST measure. An additional measure of venous blood T1 in the sagittal sinus was used to estimate subject-specific hematocrit. Six subjects were scanned over 4 sessions, including intra-session repeat measurements. RESULTS: The average T2 in the sagittal sinus was found to be 60.8 ± 8.9, 62.7 ± 7.9, 64.6 ± 8.4, and 66.3 ± 10.3 ms (mean ± SD) for conventional TRUST, global SL-TRUST, hemispheric SL-TRUST, and 3D-localized SL-TRUST, respectively. Intra-, inter-session, and inter-subject coefficients of variation for OEF using SL-TRUST were found to be comparable and in some cases superior to those obtained using TRUST. CONCLUSION: OEF comparison of 2 contralateral regions was achievable in under 5 min suggesting SL-TRUST offers potential for quantifying regional OEF differences in both healthy and clinical populations.

UBC-Nepal Expedition: Haemoconcentration underlies the reductions in cerebral blood flow observed during acclimatization to high altitude.

NEW FINDINGS: What is the central question of this study? The aim was to evaluate the degree to which increases in haematocrit alter cerebral blood flow and cerebral oxygen delivery during acclimatization to high altitude. What is the main finding and its importance? Through haemodilution, we determined that, after 1 week of acclimatization, the primary mechanism contributing to the cerebral blood flow response during acclimatization is an increase in haemoglobin and haematocrit. The remaining contribution to the cerebral blood flow response during acclimatization is likely to be attributable to ventilatory acclimatization. ABSTRACT: At high altitude, an increase in haematocrit (Hct) is achieved through altitude-induced diuresis and erythropoiesis, both of which result in increased arterial oxygen content. Given the impact of alterations in Hct on oxygen content, haemoconcentration has been hypothesized to mediate, in part, the attenuation of the initial elevation in cerebral blood flow (CBF) at high altitude. To test this hypothesis, healthy men (n = 13) ascended to 5050 m over 9 days without the aid of prophylactic acclimatization medications. After 1 week of acclimatization at 5050 m, participants were haemodiluted by rapid saline infusion (2.10 ± 0.28 l) to return Hct towards pre-acclimatization values. Arterial blood gases, Hct, global CBF (duplex ultrasound) and haemodynamic variables were measured after initial arrival at 5050 m and after 1 week of acclimatization at high altitude, before and after the haemodilution protocol. After 1 week at 5050 m, the Hct increased from 42.5 ± 2.5 to 49.6 ± 2.5% (P < 0.001), and it was subsequently reduced to 45.6 ± 2.3% (P < 0.001) after haemodilution. Global CBF decreased from 844 ± 160 to 619 ± 136 ml min-1 (P = 0.033) after 1 week of acclimatization and increased to 714 ± 204 ml min -1 (P = 0.045) after haemodilution. Despite the significant changes in Hct, and thus oxygen content, cerebral oxygen delivery was unchanged at all time points. Furthermore, these observations occurred in the absence of any changes in mean arterial blood pressure, cardiac output, arterial blood pH or oxygen saturation pre- and posthaemodilution. These data highlight the influence of Hct in the regulation of CBF and are the first to demonstrate experimentally that haemoconcentration contributes to the reduction in CBF during acclimatization to altitude.

Interplay of Coriolis effect with rheology results in unique blood dynamics on a compact disc.

We investigate the influence of rotational forces on blood dynamics in a microfluidic device. The special confluence of Coriolis force and blood rheology is brought forth by analyzing the flow at different hematocrit (volume fraction of red blood cells) levels and rotational speeds. We further study the effects of channel layout and alignment with regard to the axis of rotation to understand this intricate interplay. We provide a sound basis for efficient designing of a lab on a compact disc (lab on CD) platform by harnessing the effects of Coriolis force at relatively much lower rotational speeds, in sharp contrast with the reported findings where Coriolis effects have been considered to be effective only for exceptionally high rotational speeds. Our results show that over certain intermediate regimes of rotational speeds, the flow profiles for different hematocrit levels are noticeably different. This, in turn, could be harnessed as a possible diagnostic signature of the hematocrit (or equivalently, packed cell volume) level, without necessitating the deployment of chemical consumables, in an energy efficient paradigm.

Next-generation reference intervals for pediatric hematology.

Background Interpreting hematology analytes in children is challenging due to the extensive changes in hematopoiesis that accompany physiological development and lead to pronounced sex- and age-specific dynamics. Continuous percentile charts from birth to adulthood allow accurate consideration of these dynamics. However, the ethical and practical challenges unique to pediatric reference intervals have restricted the creation of such percentile charts, and limitations in current approaches to laboratory test result displays restrict their use when guiding clinical decisions. Methods We employed an improved data-driven approach to create percentile charts from laboratory data collected during patient care in 10 German centers (9,576,910 samples from 358,292 patients, 412,905-1,278,987 samples per analyte). We demonstrate visualization of hematology test results using percentile charts and z-scores (www.pedref.org/hematology) and assess the potential of percentiles and z-scores to support diagnosis of different hematological diseases. Results We created percentile charts for hemoglobin, hematocrit, red cell indices, red cell count, red cell distribution width, white cell count and platelet count in girls and boys from birth to 18 years of age. Comparison of pediatricians evaluating complex clinical scenarios using percentile charts versus conventional/tabular representations shows that percentile charts can enhance physician assessment in selected example cases. Age-specific percentiles and z-scores, compared with absolute test results, improve the identification of children with blood count abnormalities and the discrimination between different hematological diseases. Conclusions The provided reference intervals enable precise assessment of pediatric hematology test results. Representation of test results using percentiles and z-scores facilitates their interpretation and demonstrates the potential of digital approaches to improve clinical decision-making.

Analysis of the Heterogeneous Distribution of Amiloride and Propranolol in Dried Blood Spot by UHPLC-FLD and MALDI-IMS.

Dried blood spot (DBS) has lately experienced an increase in its use in bioanalysis due to its several advantages compared with traditional blood sampling methods. Nevertheless, the use of DBS with quantitative purposes is hindered by the heterogeneous distribution of some compounds in the supporting matrix and the dependence of the response on different factors, such as the hematocrit, blood volume, and sampling position. In this study the effect of those factors in the analytical response was investigated by ultra high performance liquid chromatography coupled to fluorescence detection, using amiloride and propranolol as model compounds. The results showed a heterogeneous and drug-dependent distribution of the compounds in the blood spot. While amiloride concentration was higher in the center, propranolol concentration was higher in the periphery of the spot. Besides, the influence of the hematocrit on the quantitative results was observed. MALDI mass spectrometry imaging (MALDI-IMS) has allowed study of the distribution of the two cardiovascular drugs when they were placed in the DBS card using water:methanol solutions, demonstrating that they followed a similar distribution pattern as in blood. This work has showed the potentiality of the MALDI-IMS technique to predict the distribution of the drugs in the DBS card.

Human umbilical cord blood relaxation times and susceptibility at 3 T.

PURPOSE: To characterize the magnetic susceptibility and relaxation times (T1 and T2 ) of fetal blood at 3 T as a function of the hematocrit (Hct) and oxygen saturation (sO2 ). METHODS: Susceptibility and relaxometry measurements were performed on cord blood specimens (N = 90, derived from six caesarean deliveries) with a range of hematocrits and oxygen saturations (0.09 < Hct < 0.82, 7 < sO2 < 100%). To obtain simple, analytic relationships between MRI properties and blood properties, data were fit to established two-compartment (plasma and erythrocytes) models. RESULTS: Two-compartment models effectively described the cord blood data. The root-mean-squared deviation between the model and the data was 6.3, 10.3, and 1.3% for fits to T1 , T2 , and susceptibility measurements. Relaxometry data and estimated T1 and T2 model parameters were generally consistent with those reported in cord blood at 1.5 T and comparable to published values for adult blood. Notably, the measured value of Δχdeo , the susceptibility difference between fully oxygenated (sO2 = 100%) and deoxygenated (sO2 = 0) cord blood was approximately 20% lower than the established adult blood value (Δχdeo,cord = 2.64 ppm, Δχdeo,adult = 3.4 ppm). CONCLUSIONS: The described models and associated parameter values can be used to inform acquisition parameters, and interpret fetal/neonatal blood susceptibility measurements and relaxometry data acquired at 3 T with respect to hematocrit and sO2 . Magn Reson Med 79:3194-3206, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Erythrocyte P2X1 receptor expression is correlated with change in haematocrit in patients admitted to the ICU with blood pathogen-positive sepsis.

BACKGROUND: Pore-forming proteins released from bacteria or formed as result of complement activation are known to produce severe cell damage. Inhibition of purinergic P2X receptors markedly reduces damage inflicted by cytolytic bacterial toxin and after complement activation in both erythrocytes and monocytes. P2X expression generally shows variation throughout the population. Here, we investigate correlation between P2X receptor abundance in blood cell plasma membranes and haematocrit during sepsis, in patients admitted to the emergency department (ED) or intensive care unit (ICU). METHOD: Patients admitted to the ED and successively transferred to ICU with the diagnosis sepsis (< 2 systemic inflammatory response syndrome (SIRS) criteria and suspected infection), were grouped as either blood pathogen-positive (14 patients) or blood pathogen-negative (20 patients). Blood samples drawn at ICU admission were analysed for P2X1 and P2X7 receptor abundance using indirect flow cytometry. RESULTS: Here, we find inverse correlation between P2X1 receptor expression and change in haematocrit (rs - 0.80) and haemoglobin (rs - 0.78) levels from admission to ED to arrival at ICU in patients with pathogen-positive sepsis. This correlation was not found in patients without confirmed bacteraemia. Patients with high P2X1 expression had a significantly greater change in both haematocrit (- 0.59 ± 0.36) and haemoglobin levels (- 0.182 ± 0.038 mg/dl) per hour, during the first hours after hospital admission compared to patients with low P2X1 expression (0.007 ± 0.182 and - 0.020 ± 0.058 mg/dl, respectively). CONCLUSION: High levels of P2X1 are correlated with more pronounced reduction in haematocrit and haemoglobin in patients with confirmed bacteraemia. This supports previous in vitro findings of P2X activation as a significant component in cell damage caused by pore-forming bacterial toxins and complement-dependent major attack complex. These data suggest a new potential target for future therapeutics in initial stages of sepsis.

Promoting a Restrictive Intraoperative Transfusion Strategy: The Influence of a Transfusion Guideline and a Novel Software Tool.

BACKGROUND: The effect of neither transfusion guidelines nor decision support tools on intraoperative transfusion has been previously evaluated. The University of Michigan introduced a transfusion guideline in 2009, and in 2011, the Department of Anesthesiology developed a transfusion decision support tool. The primary aim of this study was to assess the associations of the transfusion guideline and the optional use of the software transfusion tool with intraoperative behaviors; pretransfusion hematocrit assessment (whether or not a hematocrit was checked before each red cell unit) and restrictive red cell use (withholding transfusion unless the hematocrit was ≤21%). METHODS: This was a before-after retrospective study without a concurrent control group of patients transfused 1-3 units of red cells intraoperatively. Three phases were studied to provide data both before and after the implementation of the transfusion guideline and the intraoperative software tool. Within each phase, trends of checking hematocrits before transfusion and restrictive transfusion were charted against time. F tests were used to measure differences of slopes. The difference between means of each phase was measured using Mann-Whitney U tests. Independent associations were measured using mixed-effects multivariable logistic regression. A secondary outcome analysis was conducted for 30-day mortality, myocardial infarction, renal injury, and their combination. RESULTS: The transfusion guideline was associated with increased pretransfusion hematocrit evaluation (67.4%, standard deviation [SD] 3.9 vs 76.5%, SD 2.7; P < .001) and restrictive transfusion practice (14.0%, SD 7.4 vs 33.3%, SD 4.4; P = .001). After adjustment for confounders, the guideline phase was independently associated with increased hematocrit checking (odds ratio, 1.72; 95% confidence interval, 1.46-2.03; P < .001) and restrictive red cell transfusion (odds ratio, 2.95; 95% confidence interval, 2.46-3.54; P < .001). The software tool was not associated with either transfusion behavior. There was no significant change in the rate of renal injury (16.06%), myocardial injury (4.93%), 30-day mortality (5.47%), or a composite (21.90%). CONCLUSIONS: The introduction of a transfusion guideline was independently associated with increased intraoperative pretransfusion hematocrit assessment and restrictive transfusion. The use of a software tool did not further influence either behavior.