Hematocrit Range Research Articles

Biological Reference Ranges for Healthy Indian Blood Donors: Experience of a Tertiary Care Center Vis-à-Vis International Literature.

Complete blood count is the most common, basic test requisitioned in hematology. The normal reference ranges of hematological parameters are required owing to variable socioeconomic, environmental, and genetic factors in populations. The current study determines the reference ranges of the healthy Indian donor population of a high socioeconomic group. The study was conducted in the Department of Transfusion Medicine at a tertiary care hospital in India and included 4098 individuals, aged 18-65 years coming for voluntary blood donation from July 2021 to October 2022. Blood samples were collected in K2EDTA, analyzed on the Sysmex XN-31 hematology analyzer, and using statistical tools, the normal reference ranges were calculated. The reference ranges for hemoglobin (HB) (137-185 g/L), WBC (5.1-1.7 × 109/L), platelet count (115.6-370.0 × 109/L) were noted. No statistically significant changes were observed in different age groups. There were gender-wise differences noted in nearly all parameters. The HB and hematocrit (HCT) range was slightly higher in other Indian and other Asian populations with comparable values with the Chinese, Korean populations, and Western populations; RBC parameters were overall comparable with minor differences; the WBC count was higher than the other Indian and Asian populations particularly the upper limit of lymphocyte and monocyte; and the range of platelet counts had a comparable upper limit with all populations and had the lowest lower value in males in our study, which was comparable to only the Chinese population. It is concluded that reference ranges of common parameters were calculated with minor changes noted in all hematological parameters on comparing with other Indian, Asian population, and Western data.

Modeling of three-dimensional blood flow in microchannels using a two-fluid method

This work presents a novel two-fluid method based on our recently proposed viscosity model for red blood cells (RBCs)—for simulating three-dimensional (3D) blood flow in a microchannel of dimension comparable to the diameter of red blood cells and larger. Toward this, whole blood is assumed as a suspension of red blood cells in blood plasma, with each phase considered as interpenetrating continua having its separate mass and momentum conservation equations. The proposed approach-based performance study is presented after comprehensively validating it with experimental data for blood flow in a uniform, sudden expansion-constriction, and Y-shaped bifurcated rectangular microchannels over—an extensive range of size (25–330 μm), flow rates (11.8 μl/h–30 ml/h), and inlet hematocrit (0%–45%). The proposed approach effectively captures significant biophysical and biomechanical insights into blood flow. It highlights a migration of red blood cells toward the center of the microchannel and the formation of a cell-free layer near the wall. Notably, with the introduction of constriction and expansion in the microchannel, it predicts a fivefold enhancement of the cell-free layer. The Fahraeus and Fahraeus–Lindquist effects are also demonstrated in microchannels, with less than 300 μm characteristic dimensions. These findings are consistent with experimental evidence. In addition to experimentally evident phenomena, our simulations unveil several additional flow phenomena and features of blood flow in the microchannel. It is observed that the presence of confluence (merging flow) is more disturbing to the blood flow than the presence of diverging bifurcations (splitting flow). Furthermore, after the confluence, velocity profiles exhibit a local peak that persists up to the microchannel outlet. Primary contribution of this work lies in the proposal of a two-fluid method for simulating 3D blood flow in complex geometries. This approach provides a comprehensive understanding of blood flow dynamics in microchannels and can be applied to optimize dimensions and geometries during the initial phases of plasma separation microdevices development.

Hematocrit-Independent Sampling Enables White Blood Cell Counts from Patterned Dried Blood Spot Cards.

The accurate and efficient measurement of white blood cell (WBC) counts is vital for monitoring general patient health and can aid in the diagnosis of a range of possible infections or diseases. Even with their importance universally acknowledged, access to WBC counts is largely limited to those with access to phlebotomists and centralized clinical laboratories, which house the instruments that perform the tests. As a result, large populations of people (e.g., those that are home-bound or live in remote locations) lack facile access to testing. Dried blood spot (DBS) cards are often used to bridge these gaps in access to testing by offering the ability to collect blood at home for ambient shipping to laboratories. However, it is well understood that these cards, which are prepared from cellulose cardstocks without further modification, suffer from variabilities in accuracy and precision due to uncontrolled sample spreading and hematocrit effects, which have hindered their use to determine WBC counts. In this paper, we present a method to obtain an accurate WBC count using a patterned dried blood spot (pDBS) card, which comprises collection zones that meter volumes of dried blood. Using an input volume of 75 μL of whole blood, we demonstrate that, unlike the gold standard DBS card (Whatman 903), our pDBS design allows for the collection of replicate zones containing a reproducible, average volume of dried blood (12.1 μL, 7.8% CV) over the range of hematocrits from 25 to 55%. We then used qPCR to quantify the 18S rRNA gene to determine WBC counts from the volumes of blood that are metered in pDBS zones. We observe that WBC counts generated from our method are comparable to those measured with a HemoCue point-of-care WBC analyzer. Our approach to using pDBS cards as a blood collection device has the potential to support at-home sampling and other patient populations that need WBC counts but lack access to clinical facilities.

A Comparison of the Clinical Outcomes of Minimum and Maximum Hematocrit Levels During Cardiopulmonary Bypass (CPB) in Low-risk Patients Undergoing Coronary Artery Bypass Graft Surgery (CABG): A Cross-sectional Study

Abstract Background: This study investigated the clinical outcomes at the minimum and maximum levels of hematocrit (HCT) during cardiopulmonary bypass (CPB) in low-risk patients undergoing coronary artery bypass graft (CABG) surgery. Materials and Methods: In this cross-sectional study, 85 patients who underwent CABG with an ejection fraction of greater than 35% were selected. Based on the HCT range during CPB, patients were divided into two groups: minimum HCT: HCT = 16–18% and maximum HCT: HCT = 25–27%. Then the operation outcomes, amount of drainage, and transfusion were recorded and compared between these groups. Results: In the middle tube 8 h after surgery and left tube 24 h after surgery, the amount of drainage in the minimum HCT group with mean of 71.00 ± 130.9 and 60.65 ± 71.23, respectively, was significantly lower than the maximum HCT group with mean of 101.5 ± 246.50 and 123.76 ± 93.17, respectively (P value < 0.05). The incidence of cognitive disorders in the maximum HCT group was significantly higher than in the minimum HCT group (11.1% vs. 0%, P value = 0.041). Also, the mean transfusion of packed red blood cell (PRBC) and fresh frozen plasm (FFP) during CPB in the maximum HCT group, with mean of 346.7 ± 86.22 and 396.1 ± 21.05, respectively, were significantly higher than the minimum HCT group with mean of 178.8 ± 80.91 and 136.8 ± 46.77, respectively (P value < 0.05). After CPB, there was no significant difference in transfusion products (P value > 0.05). Conclusion: According to the results of this study, patients undergoing CABG surgery with maximum HCT level versus minimum HCT level during CPB, need more packed cells and fresh frozen plasma products transfusion, which will be associated with the complication of cognitive impairment.

Dean vortex-enhanced blood plasma separation in self-driven spiral microchannel flow with cross-flow microfilters

Point-of-care (POC) diagnostic devices have been developing rapidly in recent years, but they are mainly using saliva instead of blood as a test sample. A highly efficient self-separation during the self-driven flow without power systems is desired for expanding the point-of-care diagnostic devices. Microfiltration stands out as a promising technique for blood plasma separation but faces limitations due to blood cell clogging, resulting in reduced separation speed and efficiency. These limitations are mainly caused by the high viscosity and hematocrit in the blood flow. A small increment in the hematocrit of the blood significantly increases the pressure needed for the blood plasma separation in the micro-filters and decreases the separation speed and efficiency. Addressing this challenge, this study explores the feasibility of diluting whole blood within a microfluidic device without external power systems. This study implemented a spiral microchannel utilizing the inertial focusing and Dean vortex effects to focus the red blood cells and extract the blood with lower hematocrit. The inertial migration of the particles during the capillary flow was first investigated experimentally; a maximum of 88% of the particles migrated to the bottom and top equilibrium positions in the optimized 350 × 60 μm (cross-sectional area, 5.8 aspect ratio) microchannel. With the optimized dimension of the microchannel, the whole blood samples within the physiological hematocrit range were tested in the experiments, and more than 10% of the hematocrit reduction was compared between the outer branch outlet and inner branch outlet in the 350 × 60 μm microchannel.

Incorporating the complex rheological behavior of blood in microvascular network simulations: Two-phase modeling and a model reduction approach

Vessel flow resistance in microvascular network simulations is often computed using the single-phase approximation, where the no-slip boundary condition is imposed on the microvessel wall, and the "in vitro viscosity law" or "the relative hematocrit" relationships proposed by Pries et al. (1992) are utilized. However, these models have limitations due to their reliance on experimental data, which inherently contain measurement errors, thereby affecting their consistency and accuracy. To moderate these limitations, biphasic flow models can be employed, allowing for adaptable rheological descriptions of blood. Nevertheless, this approach presents challenges in terms of automation and computational cost. In order to address these challenges, we propose a monophasic steady-state model that consistently incorporates a wall-slip condition in place of the cell-free layer contribution. Model reduction is achieved by establishing an explicit relationship for the apparent slip length, which is calibrated through the regression of biphasic model results. Subsequently, simulations are conducted on microvessel network structures. The predictions of wall shear stress by the monophasic model exhibit deviations of less than 2 % from the expected values, within the range of vessel radii (10–75 μm) and discharge hematocrits (0.2–0.7). Furthermore, the computational time required is reduced by almost an order of magnitude compared to the biphasic model, rendering it suitable for multiscale biochemical simulations. The developed model closely approximates the flow resistance predictions of the biphasic model, while its modular nature allows for easy implementation of future modifications. Both models successfully reproduce experimental data by Lipowsky et al. (1978). Finally, we derive semi-analytical expressions for the apparent slip length and discuss why it is more appropriate to impose only the "relative hematocrit" relationship as a global constraint for calculating the hemodynamics in microvessels, rather than relying on the "in vitro viscosity law", which provides unreliable predictions at low values of the discharge hematocrit.

#3169 EXPERIENCE IN INTRAOPERATIVE AUTOLOGOUS BLOOD SALVAGE IN PEDIATRIC CARDIAC SURGERY

Abstract Background and Aims Due to the drastic reduction in the number of voluntary blood donors has led to the need for the development of alternative strategies for allogeneic blood transfusion, which include the use of different strategies for autologous transfusion. Display: a) the use of "Cell-Saver" pediatric cardiac surgery at the Department of Cardiothoracic Surgery, Institute for Health Protection of Mother and Child of Serbia" Dr Vukan Cupic"; b) to analyze the reduced use of allogeneic blood and /or chemo products using "Cell-Saver" pediatric cardiac surgery; c) to evaluate the "cost benefit" of this strategy (e.g. the ratio of prices "set", "Cell-Saver") and pretransfusion rates processing one unit of allogeneic blood; d) to identify increased intraoperative security in complex. reconstructive and redocardiac surgery using the "Cell-Saver" combined with ultrafiltration (conventional or modified), particularly in cyanogenic congenital heart defects, and e) to establish and improve the hemodynamic status of hemoreologic operated child. Method A retrospective study was conducted. Experimental group included 63 patients (aged 12 days - 16 years and 4 months, body weight of patients that ranged between 2.9 kg and 80 kg - the mean body weight was 28.3 kg). In the experimental group patients were performed following cardiac surgery: 46 patients underwent reconstructive surgery (most often reoperations for cyanogenic congenital heart defects); 3 patients who underwent cardiovascular belief, and 3 patients who underwent cardio-surgical procedures had hematological disorders. The control group included 60 patients of similar age and body mass who underwent the cardio-surgical procedure without the use of "Cell-Saver" with application of allogeneic blood and/or chemo products during transfusion care. The following laboratory parameters were accompanied: hematocrit, platelet count, fibrinogen, prothrombin time (PT) and activated partial thromboplastin time (aPTT), after 3, 6, and 12 hours postoperatively compared to the control group. We compared the volume of postoperative bleeding by patients of the experimental group with the control group (1h, 4h, 7h, 11h, 15h, 21h and 24h) and analyzed the amount of used allogeneic and autologous blood and/or hemoglobin products used in the transfusion care during hospitalization the experimental group compared with the control group. Results Postoperative administration of allogeneic blood and/or hemoproducts was statistically significantly lower in the experimental group using "CellSaver" than in the control group. The amount of salvaged blood after surgery ranged from 210 ml - 620 ml. Intraoperative hematocrit "rescued" autologous blood ranged between 0.32 l / l and 0.38 l / l. e range of values preoperative and postoperative hematocrit were lower in the experimental group than in the control group that used "Cell-Saver". The total volume of postoperative drainage content was significantly lower in the experimental group, which used "Cell-Saver" compared to the control group. The postoperative hematocrit was higher in the experimental group patients who used "Cell-Saver", compared with the same operating using allogeneic blood and/or hemoproducts patients in the control group. The mean platelet count, fibrinogen, PT and aPTT results showed no statistically significant difference between the experimental group of patients in whom we used "Cell-Saver" in comparison to the control group. Conclusion The results obtained by the retrospective analysis of above mentioned data indicate a positive therapeutic effect of the application of the "Cell Saver" that is most common in reoperations. With the introduction of the "bell" of small volume, the use of the Cell Saver has become an integral part of the pediatric cardiac surgery - perfusion, regardless of body weight, age and body surface area of the child. The performance of intraoperative "rescue" of autologous blood using the "Cell Saver", while the follow-up of pediatric patients in the perioperative and postoperative period has immeasurable significance of teamwork perfuser, expert specialist nursing, pediatrician, cardiac surgeon and transfusion.

Environmentally Resilient Microfluidic Point-of-Care Immunoassay Enables Rapid Diagnosis of Talaromycosis.

Point-of-care tests (POCTs) are increasingly being used in field settings, particularly outdoors. The performance of current POCTs─most commonly the lateral flow immunoassay─can be adversely affected by ambient temperature and humidity. We developed a self-contained immunoassay platform─the D4 POCT─that can be conducted at the POC by integrating all reagents in a capillary-driven passive microfluidic cassette that minimizes user intervention. The assay can be imaged and analyzed on a portable fluorescence reader─the D4Scope─and provide quantitative outputs. Here, we systematically investigated the resilience of our D4 POCT to varied temperature and humidity and to physiologically diverse human whole blood samples that span a wide range of physiological hematocrit (30-65%). For all conditions, we showed that the platform maintained high sensitivity (0.05-0.41 ng/mL limits of detection). The platform also demonstrated good accuracy in reporting true analyte concentration across environmental extremes when compared to the manually operated format of the same test to detect a model analyte─ovalbumin. Additionally, we engineered an improved version of the microfluidic cassette that improved the ease-of-use of the device and shortened the time-to-result. We implemented this new cassette to create a rapid diagnostic test to detect talaromycosis infection in patients with advanced HIV disease at the POC, demonstrating comparable sensitivity and specificity to the laboratory test for the disease.

LC-MS/MS Method for the Quantification of PARP Inhibitors Olaparib, Rucaparib and Niraparib in Human Plasma and Dried Blood Spot: Development, Validation and Clinical Validation for Therapeutic Drug Monitoring.

Poly (ADP-ribose) polymerase inhibitors (PARPis) are becoming increasingly meaningful in oncology, and their therapeutic drug monitoring (TDM) might be beneficial for patients. Several bioanalytical methods have been reported for PARPis quantification in human plasma, but advantages might be obtained using dried blood spot (DBS) as a sampling technique. Our aim was to develop and validate a liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for olaparib, rucaparib, and niraparib quantification in both human plasma and DBS matrices. Additionally, we aimed to assess the correlation between the drug concentrations measured in these two matrices. DBS from patients was obtained using Hemaxis DB10 for volumetric sampling. Analytes were separated on a Cortecs-T3 column and detected with electrospray ionization (ESI)-MS in positive ionization mode. Validation was performed according to the latest regulatory guidelines, in the range (ng/mL) 140-7000 for olaparib, 100-5000 for rucaparib, and 60-3000 for niraparib, within the hematocrit (Hct) range 29-45%. The Passing-Bablok and Bland-Altman statistical analyses revealed a strong correlation between plasma and DBS for olaparib and niraparib. However, due to the limited amount of data, it was challenging to establish a robust regression analysis for rucaparib. To ensure a more reliable assessment, additional samples are required. The DBS-to-plasma ratio was used as a conversion factor (CF) without considering any patient-related hematological parameters. These results provide a solid basis for the feasibility of PARPis TDM using both plasma and DBS matrices.

A novel quantitative method to evaluate the contribution of platelet products to white thrombus formation in reconstituted blood under flow conditions.

Currently, the quality of platelet (PLT) products is evaluated using a series of in vitro tests, which only analyse PLTs as an inspection material. However, it would be ideal to assess the physiological functions of PLTs under conditions similar to the sequential blood haemostatic process. In this study, we attempted to establish an in vitro system where the thrombogenicity of PLT products was evaluated in the presence of red blood cells (RBCs) and plasma using a microchamber under constant shear stress (600/s). Blood samples were reconstituted by mixing PLT products, standard human plasma (SHP) and standard RBCs. Each component was serially diluted keeping the other two components fixed. The samples were applied onto a flow chamber system (Total Thrombus-formation Analysis System [T-TAS]), and white thrombus formation (WTF) was assessed under large arterial shear conditions. We observed a good correlation between the PLT numbers in the test samples and WTF. The WTF of samples containing ≦10% SHP was significantly lower than those containing ≧40% SHP, and no difference was observed in WTF among samples containing 40%-100% SHP. WTF significantly declined in the absence of RBCs, whereas no change in WTF was observed in the presence of RBCs, over haematocrit range of 12.5%-50%. The WTF assessed on the T-TAS using reconstituted blood may serve as a new physiological blood thrombus test to quantitatively determine the quality of PLT products.

A Validated Method for the Determination of Hematocrit in Dried Blood Spots Using Image Analysis

Aim: To develop a nondestructive method for the estimation of hematocrit (HCT) in dried blood spots (DBSs). Materials & methods: Standards and controls were created (HCT range: 0.20-0.50l/l) and DBS scanned using a flatbed scanner. Gray values and pixel areas were analyzed with open-source software to estimate HCT and volume, respectively. HCT obtained in whole blood using hematological analyzer was compared with DBS scanner method (n = 50). Results: Between-run precision was 4.7-10.2% and between-run accuracy was 89.6-102.1%. In the hematological instrument comparison, 96% of the patient sample results were within ±15%. Conclusion: The nondestructive method can be used to exclude patient DBS samples with extreme HCT levels from further analysis and avoid bias on measured concentration.

Determination of the erythrocyte sedimentation rate using the hematocrit-corrected aggregation index and mean corpuscular volume.

Determination of the erythrocyte sedimentation rate (ESR) by measurement of erythrocyte aggregation is an alternative to the Westergren method and can be performed rapidly. However, its principle is opaque and the ESR values obtained can deviate from Westergren method values (WG ESR) due to hematocrit. Furthermore, WG ESR is affected by particle size, but no studies have examined the effect of individual mean corpuscular volumes (MCVs). Simultaneous measurement of the erythrocyte aggregation index (AI) over a 5-s interval and determination of the complete blood count in 80 μL blood from 203 patients were performed (hematocrit, 21.4%-52.3%; MCV, 62.7-114.1 fL). ESR values were calculated with the hematocrit-corrected AI (HAI) for comparison with WG ESR. We improved the calculation formula by using MCV. The sedimentation velocity of a single erythrocyte in the samples agreed well with an exponential function of HAI. ESR values calculated using HAI showed excellent correlation with WG ESR (r = 0.899, p < 0.001; Bland-Altman analysis: bias 2.76, limits of agreement (LOA) -24.5 to 30.0), but the difference between the calculated ESR and WG ESR increased with decreasing MCV. Calculation of ESR considering both HAI and MCV eliminated the MCV-dependent deviation and improved the correlation with WG ESR (r = 0.920, p < 0.001, bias -2.17, LOA -24.6 to 20.3). Calculation using HAI and MCV can rapidly provide ESR values that are highly correlated with WG ESR in clinical specimens over a wide range of hematocrit and MCV values.

The influence of blood composition and loading frequency on the behavior of embolus analogs

In cases of acute ischemic stroke (AIS), mechanical thrombectomy (MT) can be used to directly remove lodged thromboemboli. Despite improvements in patient outcomes, one of the key factors affecting MT success is the mechanical properties of the occlusive thrombus. Therefore, the goal of this study was to investigate the viscoelastic properties of embolus analogs (EAs) and determine the influence of EA hematocrit and loading frequency.Bovine blood EAs were created over a range of physiological hematocrits (0–60%) and cyclic uniaxial compression testing was performed at three loading frequencies to mimic in vivo loading conditions, followed by stress-relaxation testing. It was found that EAs exhibited behaviors typical of hyper-viscoelastic materials and that EA hematocrit played a large role in both EA stiffness and relaxation, with both parameters decreasing as hematocrit increased from 0 to 60%. The viscoelastic behavior of the EAs was also affected by the frequency at which they were loaded, with significant increases in peak stresses between the 0.5 and 2 Hz loaded EAs. Lower hematocrit EAs had very dense fibrin networks while the higher hematocrit EAs consisted of closely packed RBCs with little fibrin present. These results suggest that fibrin contributes to EA stiffness and relaxation behaviors while RBCs play a role in decreasing the overall viscous response and strain-rate dependency.An Ogden hyperelastic model was found to best reproduce the EA loading data while a 3-term Prony series was fit to the stress relaxation data. A hyper-viscoelastic modeling framework was then implemented combining the loading and stress-relaxation fits and the results could match the full cyclic loading data for EAs of varying hematocrit and loading frequency. The results of the experimental mechanical characterization and hyper-viscoelastic curve fitting can be incorporated in future modeling efforts to optimize mechanical thrombectomy for AIS patients.

Concentration Scaling on Linear Viscoelastic Properties of Cellular Suspensions and Effects of Equilibrium Phase Behavior.

Concentration scaling on linear viscoelastic properties of cellular suspensions has been studied by rheometric characterisation of Phormidium suspensions and human blood in a wide range of volume fraction under small amplitude oscillatory shear experiments. The rheometric characterisation results are analysed by the time-concentration superposition (TCS) principle and show a power law scaling of characteristic relaxation time, plateau modulus and the zero-shear viscosity over the concentration ranges studied. The results show that the concentration effect of Phormidium suspensions on their elasticity is much stronger than that of human blood due to its strong cellular interactions and a high aspect ratio. For human blood, no obvious phase transition could be observed over the range of hematocrits studied here and with respect to a high-frequency dynamic regime, only one concentration scaling exponent could be identified. For Phormidium suspensions with respect to a low-frequency dynamic regime, three concentration scaling exponents in the volume fraction Region I (0.36≤ϕ/ϕref≤0.46), Region II (0.59≤ϕ/ϕref≤2.89) and Region III (3.11≤ϕ/ϕref≤3.44) are identified. The image observation shows that the network formation of Phormidium suspensions occurs as the volume fraction is increased from Region I to Region II; the sol-gel transition takes place from Region II to Region III. In combination with analysis of other nanoscale suspensions and liquid crystalline polymer solutions reported in the literature, it is revealed that such a power law concentration scaling exponent depends on colloidal or molecular interactions mediated with solvent and is sensitive to the equilibrium phase behaviour of complex fluids. The TCS principle is an unambiguous tool to give a quantitative estimation.

Applicability of vancomycin, meropenem, and linezolid in capillary microsamples vs. dried blood spots: A pilot study for microsampling in critically ill children.

Therapeutic drug monitoring (TDM) has been shown to be clinically beneficial for critically ill patients. However, this is a burden for neonates or children with small circulating blood volumes. Here, we aimed to develop and validate a microsampling TDM platform (including dried blood spots (DBS) and capillary microsamples (CMS)) for the simultaneous quantification of vancomycin, meropenem, and linezolid. Paired DBS and CMS samples were obtained from an intensive care unit (ICU) to evaluate its clinical application. Estimated plasma concentrations (EPC) were calculated from DBS concentrations. Agreement between methods was evaluated using Deming regression and Bland-Altman difference plots. The microsampling methods validation showed excellent reliability and compatibility with the analysis of the sample matrix and hematocrit range of the studied population. The DBS and CMS accuracy and precision results were within accepted ranges and samples were stable at room temperature for at least 2 days and 8 h, respectively. Hematocrit had no impact on CMS, but sightly impacted DBS measurements. The CMS and DBS antibiotic concentrations correlated well (r > 0.98). The drug concentration ratio in DBS samples to that in CMS was 1.39 for vancomycin, 1.34 for meropenem, and 0.94 for linezolid. The EPC calculated from the DBS using individual hematocrit ranges presented comparable absolute values for vancomycin (slope: 1.06) and meropenem (slope: 1.04), with a mean of 98% and 99% of the measured CMS concentrations, respectively. This study provides a microsampling TDM platform validated for clinical use for a rapid quantification of three antibiotics and is suitable for real-time TDM-guided personalization of antimicrobial treatment in critically ill children.

Preoperative Hematocrit Level and Associated Risk of Transfusion for Myomectomy Based on Myoma Burden and Surgical Route

To determine the association between preoperative hematocrit level and risk of blood transfusion for laparotomic and laparoscopic myomectomy based on myoma burden and surgical route. A cohort study of prospectively collected data. American College of Surgeons National Surgical Quality Improvement Program participating institutions. A total of 26229 women who underwent a laparotomic or laparoscopic myomectomy from 2010 to 2020. The primary outcome assessed was the risk of transfusion based on preoperative hematocrit level. This was evaluated with respect to myoma burden and surgical route. There were 26229 women who underwent a myomectomy during the study interval, 2345 women (9%) of whom required a blood transfusion. Compared with patients who did not require transfusion, those who did had lower median preoperative hematocrit levels (34.7 vs 38.2). Patients were stratified by surgical approach (laparotomic vs laparoscopic) and myoma burden (1-4 myomas/weight ≤250 g or ≥5 myomas/weight >250 g) using Current Procedural Terminology codes (58140, 58146, 58545, 58546). In all categories, there was an inverse relationship between blood transfusion and preoperative hematocrit level with increasing risk depending on preoperative hematocrit range. The odds ratios comparing hematocrit level of 29% with 39% were 6.16 (95% confidence interval [CI], 5.15-7.36), 4.92 (95% CI, 4.19-5.78), 4.85 (95% CI, 3.72-6.33), and 5.2 (95% CI, 3.63-7.43) for patients with laparotomic (1-4 myomas/≤250 g, ≥5 myomas/>250 g) and laparoscopic myomectomy (1-4 myomas/≤250 g, 5 myomas/>250 g), respectively. Incremental increases in hematocrit result in a significantly decreased risk of blood transfusion at the time of myomectomy.

Microfluidics geometries involved in effective blood plasma separation.

The last two decades witnessed a significant advancement in the field of diluted and whole blood plasma separation. This is one of the common procedures used to diagnose, cure and treat numerous acute and chronic diseases. For this separation purpose, various types of geometries of microfluidic devices, such as T-channel, Y-channel, trifurcation, constriction–expansion, curved/bend/spiral channels, a combination of any of the two geometries, etc., are being exploited, and this is detailed in this review article. The evaluation of the performance of such devices is based on the several parameters such as separation efficiency, flow rate, hematocrits, channel dimensions, etc. Thus, the current extensive review article endeavours to understand how particular geometry influences the separation efficiency for a given hematocrit. Additionally, a comparative analysis of various geometries is presented to demonstrate the less explored geometric configuration for the diluted and whole blood plasma separation. Also, a meta-analysis has been performed to highlight which geometry serves best to give a consistent separation efficiency. This article also presents tabulated data for various geometries with necessary details required from a designer’s perspective such as channel dimensions, targeted component, studied range of hematocrit and flow rate, separation efficiency, etc. The maximum separation efficiency that can be achieved for a given hematocrits and geometry has also been plotted. The current review highlights the critical findings relevant to this field, state of the art understanding and the future challenges.

Addressing new possibilities and new challenges: Automated nondestructive hematocrit normalization for dried blood spots

In the past decade, the use of microsampling in combination with the drying of the blood has gained vast popularity. Thereby, small volumes of capillary blood (typically 10–20 μL) are collected and allowed to dry on an absorbent sample support (e.g. cellulose filter paper or polymer-based tips). The collection of dried blood microsamples is easier, less invasive, and cheaper than conventional whole blood sampling, as samples can be handled, shipped, and stored more easily. In addition, it can be done by untrained persons, including the study subjects themselves and in remote settings. The patient's hematocrit (HCT) level can adversely affect the analysis results when dried blood spots (DBS) are used as a sample matrix. Volumetric DBS sampling has been proposed to nullify the impact of HCT area bias (spreading area) on DBS by normalizing it to a known sample volume. However, this strategy ignores DBS-related parameters such as analyte properties (red blood cell to plasma ratio) and HCT recovery bias. With the recent release of fully automated HCT measurement systems for DBS analysis, a broad range of end-users are now able to measure and correct a sample's HCT level in a non-destructive manner. These novel tools permit a correction for all known HCT-related impacts on DBS, such as analyte properties, HCT recovery bias, HCT area bias, and venous blood–to-DBS ratio, supporting and accelerating future quantitative DBS applications. However, with these novel tools, new questions arise concerning the normalization of analytical results, the choice of technique (single-wavelength reflectance VS near-infrared spectroscopy), and the DBS card-handling process post sampling. We address the necessary considerations for end-users and present real-life examples for the correction of the DBS's HCT based on the model compound Phosphatidylethanol 16:0/18:1 (PEth). PEth is remarkably HCT dependent due to its incorporation into red blood cells. For PEth a successful implementation of DBS HCT correction is presented based on the analysis of blood from four PEth positive individuals over a wide HCT range (HCT from 20%–70%) using fully automated DBS-Online-SPE-LC-MS/MS analysis. Such a correction can make the necessity of volumetric sampling for quantitative DBS analysis obsolete. Furthermore, combining automated HCT correction in combination with fully automated DBS LC-MS/MS analysis, the novel tools permits high-throughput analysis in combination with HCT independence. The obtained data demonstrate that as soon as the HCT dependence of an analyte is known, a correction factor can be applied for the normalization of HCT levels. In the context of PEth, a linear increase in PEth concentration was observed with increasing HCT concentrations (y = 1.9219x+0.0998, R2 = 0.9333), as PEth is primarily located within the cellular fraction. Thereby, for every 1% change in HCT, a PEth concentration change by 1.92% was observed (95% confidence interval of 1.695%–2.149%). The observed HCT dependency is in agreement with the earlier reported increase by Beck et al., which determined an approximate increase in PEth between 1.3–2.0% for every 1% increase in HCT. Based on the obtained results, the use of a common correction factor for PEth, when measuring with DBS is possible. Thereby, one could reference the obtained DBS analyte concentration to a common HCT level for all samples (e.g., 40%). Although this strategy appears attractive due to its simplicity, it does not consider genderspecific HCT differences. For example, the normal HCT range is 40.7%–50.3% for male subjects and 36.1%–44.3% for female subjects. Therefore, the novel tools to correct HCT not only offer many new possibilities but also create new challenges that need to be addressed.

A rapid and accurate method for estimating the erythrocyte sedimentation rate using a hematocrit-corrected optical aggregation index.

Although both the erythrocyte sedimentation rate (ESR) and optically measured erythrocyte aggregation parameters are affected by the hematocrit, this interaction is not considered by the method used to estimate ESR that considers aggregation parameters. In this study, we investigated the relationship between the ESR obtained by the Westergren method and that obtained with an aggregation parameter, namely, the aggregation index (AI) of multiple hematocrit values and fibrinogen-spiked samples with an analysis time of 5–60 s, and attempted to develop a rapid and accurate ESR estimation method. The AIs obtained from 5- and 10-s optical measurements with a fixed hematocrit were highly correlated with the erythrocyte sedimentation velocity. Furthermore, the rate of the AI increase with an increasing hematocrit was not significantly affected by the fibrinogen concentration at these measurement times. On the basis of these results, we defined the hematocrit-corrected aggregation index (HAI). The exponential function of the HAI obtained from the 5-s measurement agreed well with the sedimentation velocity calculated to eliminate the effect of hindered settling, and the HAI and hematocrit could be used to calculate the time constant of the sedimentation curve with a linear regression equation. The ESR value at 1 h was calculated based on the modified Stokes’ law and the HAI obtained from the 5-s measurement and showed an excellent correlation (R = 0.966) with the ESR value obtained by the Westergren method over a wide range of hematocrit and fibrinogen concentrations.

Evaluation of a Point-of-Care Test for Bilirubin in Malawi.

BiliSpec is a low-cost spectrophotometric reader and disposable paper-based strip to quantify total serum bilirubin from several blood drops. This study was a prospective evaluation of BiliSpec in 2 neonatal wards in Malawi compared with a reference standard bilirubinometer over a large range of bilirubin and hematocrit levels. The accuracy of BiliSpec and a transcutaneous bilirubinometer were compared with the reference standard of spectrophotometry for 475 blood samples collected from 375 subjects across a range of total serum bilirubin concentrations from 0.0 to 33.7 mg/dL. The development of error grids to assess the clinical effects of measurement differences is reported. BiliSpec was found to have a mean bias of -0.48 mg/dL and 95% limits of agreement of -5.09 mg/dL to +4.12 mg/dL. Results show 90.7% of BiliSpec measurements would have resulted in the same clinical decision as the reference standard, whereas 55.0% of transcutaneous bilirubin measurements would have resulted in the same clinical decision as the reference standard. This evaluation supports use of BiliSpec to provide accurate, low-cost, point-of-care bilirubin measurements in low-resource hospitals. Future work is needed to evaluate BiliSpec among a larger number of users.