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The CARMEN-France registry is a prospective, multicenter registry in France including adult patients with a new diagnosis of immune thrombocytopenia or of autoimmune immune hemolytic anemia (2402 patients included in December 31, 2023). The recording of clinical, biological and treatment data allows detailed epidemiological and pharmacoepidemiological real-world studies. This review summarizes the CARMEN-France registry protocol, gives examples of studies conducted in the registry, and indicates future directions such as inclusion of patient reported outcomes, linkage with the French national health insurance database and linkage with other registries in Europe. [ABSTRACT FROM AUTHOR]

Purpose: To summarize the clinical and biochemical characteristics of patients with ceftriaxone-induced liver injury and guide the selection of safe medication. Methods: Retrieved domestic and foreign databases from inception to October 2023, collected case data conforming to ceftriaxone-induced liver injury, and statistically analyzed the data. Results: A total of 617 articles were retrieved, and 16 articles with 33 cases (10 children, 23 adults) were included. Males represented 60% (18/30), with a male-to-female ratio of 1.5:1. The age of onset ranged from 2 days to 96 years, with 15 of 23 adults (65%) over 55 years old. The time from ceftriaxone use to liver injury fluctuated between 0.5 and 47 days. Only 9 patients (27.3%, 9/33) had clinical symptoms, and the clinical classification was dominated by cholestatic injury (46.2%, 12/26). There was a significant difference in the clinical classification of ceftriaxone-induced liver injury between children and adults (P = 0.0126), with hepatocellular injury predominating in children and cholestatic injury predominating in adults. The severity of liver injury was mainly mild (66.7%, 12/18). Peak values of alanine aminotransferase ranging from 228.5 to 8098 U/L, aspartate aminotransferase ranging from 86.7 to 21575 U/L, alkaline phosphatase ranging from 143 to 2434 U/L, and total bilirubin ranging from 3.35 to 66.1 mg/dL. There was a significant difference in peak values of alkaline phosphatase between children and adults (P = 0.027), with a higher peak value of alkaline phosphatase in adults (1039 ± 716.4 U/L vs. 257 ± 134.9 U/L). Patients with normal imaging examinations accounted for the majority (61.5%, 7/13). The prognosis of 32 patients (97%, 32/33) was good, and one child with sickle cell anemia who developed immune hemolysis, progressive renal failure, and acute liver injury after using ceftriaxone died in the end. Conclusion: Ceftriaxone-induced liver injury can occur at any age, with a higher risk in the elderly, and age may be related to the clinical classification. Although the clinical manifestations are not specific, close monitoring of liver biochemical indicators during the use can detect liver injury early. Most cases have a good prognosis, but for people with concomitant sickle cell anemia, it is necessary to be vigilant about the occurrence of severe hemolytic anemia. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the effects of contamination of venous blood with a lipid-containing solution on parameters measured by a modern blood gas analyzer. We collected venous blood from 17 healthcare workers (46 ± 11 years; 53 % women) into three blood gas syringes containing 0 , 5 and 10 % lipid-containing solution. Blood gas analysis was performed within 15 min from sample collection on GEM Premier 5000, while triglycerides and serum indices were assays on Roche COBAS C702. Triglycerides concentration increased from 1.0 ± 0.3 mmol/L in the uncontaminated blood gas syringe, to 39.4 ± 7.8 and 65.3 ± 14.4 mmol/L (both p<0.001) in syringes with 5 and 10 % final lipid contamination. The lipemic and hemolysis indices increased accordingly. Statistically significant variation was noted for all analytes except hematocrit and COHb in the syringe with 5 % lipids, while only COHb did not vary in the syringe with 10 % lipids. Significant increases were observed from 5 % lipid contamination for pO2, SO2 and lactate, while the values of pH, pCO2, sodium, potassium, chloride, ionized calcium, glucose, hematocrit (10 % contamination), hemoglobin and MetHB decreased. All these changes except lactate and CoHb exceeded their relative performance specifications. Artifactual hyperlipidemia caused by contamination with exogenous lipids can have a clinically significant impact on blood gas analysis. Manufacturers of blood gas analyzers must be persuaded to develop new instruments equipped with serum indices. [ABSTRACT FROM AUTHOR]

Background Cedrol (CRL) is a sesquiterpene alcohol present in the essential oils of coniferous trees including Cupressus and Juniperus genera. CRL has shown potent anticancer activity by virtue of apoptosis. Red blood cells (RBCs), although devoid of mitochondria and nucleus, can undergo hemolysis and eryptosis which contribute to chemotherapy-induced anemia (CIA). In this work, we explored the hemolytic and eryptotic potential of CRL in human RBCs as a safety assessment of the sesquiterpene as an anticancer agent. Methods RBCs from healthy donors were treated with anticancer concentrations of CRL for 24 h at 37°C with varying experimental manipulations. Hemolysis was photometrically assessed by measuring hemoglobin release whereas flow cytometry was employed to detect phosphatidylserine (PS) exposure by annexin-V-FITC, intracellular Ca2+ by Fluo4/AM, cell volume by forward scatter (FSC), and oxidative stress by 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA). Results Significant, concentration-responsive hemolysis was noted upon CRL exposure with concomitant K+, LDH, and AST leakage. CRL also significantly increased annexin-V-positive cells and Fluo4 fluorescence and reduced FSC. Moreover, the cytotoxicity of CRL was significantly ameliorated in the presence of L-NAME, D4476, and PEG 8,000 but was aggravated by urea and sucrose. Conclusion CRL stimulates hemolysis and eryptosis characterized by PS exposure, Ca2+ overload, and cell shrinkage. The hemolytic activity of CRL was mediated through nitric oxide synthase and casein kinase 1a. Blocking either enzyme may attenuate the toxicity of CRL to RBCs and prevent undesirable side effects associated with its anticancer applications. [ABSTRACT FROM AUTHOR]

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease characterized by complement-mediated hemolysis and potentially life-threatening complications. Pegcetacoplan, an inhibitor of complement components C3 and C3b, was approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) in 2021. A recent expansion to its indication by the EMA has made pegcetacoplan available for the treatment of both complement inhibitor-naïve and -experienced patients with PNH who have hemolytic anemia, a similarly broad patient population as in the US. This approval was based on results from the Phase 3 PEGASUS study, where pegcetacoplan showed superiority over the C5 inhibitor eculizumab with regard to improving the hemoglobin level in patients with anemia despite eculizumab treatment, and the Phase 3 PRINCE study, where pegcetacoplan showed superiority over supportive care with regard to hemoglobin stabilization and improving the lactate dehydrogenase level in complement inhibitor-naïve patients. In light of this recent indication expansion by the EMA, this article describes how the strong efficacy of pegcetacoplan is linked to its mechanism of action, which provides broad hemolysis control over both intravascular and extravascular hemolysis to improve a range of disease markers and enhance patients' quality of life. Furthermore, additional data and learnings obtained from over 3 years of experience with pegcetacoplan are summarized, including long-term efficacy and safety results, real-world clinical experiences, pharmacokinetic characteristics, and extensive practical guidance for the first-to-market proximal complement inhibitor for PNH. [ABSTRACT FROM AUTHOR]

Intravascular hemolysis is a central feature of congenital and acquired hemolytic anemias, complement disorders, infectious diseases, and toxemias. Massive and/or chronic hemolysis is followed by the induction of inflammation, very often with severe damage of organs, which enhances the morbidity and mortality of hemolytic diseases. Galectin-3 (Gal-3) is a β-galactoside-binding lectin that modulates the functions of many immune cells, thus affecting inflammatory processes. Gal-3 is also one of the main regulators of fibrosis. The role of Gal-3 in the development of different kidney and liver diseases and the potential of therapeutic Gal-3 inhibition have been demonstrated. Therefore, the objective of this review is to discuss the possible effects of Gal-3 on the process of kidney and liver damage induced by intravascular hemolysis, as well as to shed light on the potential therapeutic targeting of Gal-3 in intravascular hemolysis. [ABSTRACT FROM AUTHOR]

Background: Megaloblastic anemia is a subtype of anemia with increased red blood cell volume. These megaloblastic cells can be easily destroyed in the bone marrow and spleen, leading to ineffective hematopoiesis. Insulindegrading enzymes (IDE) in erythrocytes can break down the insulin into amino acid fragments; thus, when hemolysis occurs, IDE can be released into the blood, resulting in low insulin measurement values. Methods: This article reports a case of false insulin test results due to the hemolysis resulting from megaloblastic anemia. Results: The patient's first fasting glucose results indicated that the glucose and C-peptide levels were within the normal range while her insulin level was abnormally low. After hemolysis was corrected, the relevant indicators were re-evaluated and all the results were normal. Conclusions: This article reports a patient diagnosed with megaloblastic anemia, whose dysmorphic erythrocytes cause severe extravascular hemolysis. It was the occurrence of hemolysis that the IDE released into the blood, leading to the abnormal insulin test result. [ABSTRACT FROM AUTHOR]

Over the last years computer modelling and simulation has emerged as an effective tool to support the total product life cycle of cardiovascular devices, particularly in the device preclinical evaluation and post-market assessment. Computational modelling is particularly relevant for heart valve prostheses, which require an extensive assessment of their hydrodynamic performance and of risks of hemolysis and thromboembolic complications associated with mechanicallyinduced blood damage. These biomechanical aspects are typically evaluated through a fluid-structure interaction (FSI) approach, which enables valve fluid dynamics evaluation accounting for leaflets movement. In this context, the present narrative review focuses on the computational modelling of bileaflet mechanical aortic valves through FSI approach, aiming to foster and guide the use of simulations in device total product life cycle. The state of the art of FSI simulation of heart valve prostheses is reviewed to highlight the variety of modelling strategies adopted in the literature. Furthermore, the integration of FSI simulations in the total product life cycle of bileaflet aortic valves is discussed, with particular emphasis on the role of simulations in complementing and potentially replacing the experimental tests suggested by international standards. Simulations credibility assessment is also discussed in the light of recently published guidelines, thus paving the way for a broader inclusion of in silico evidence in regulatory submissions. The present narrative review highlights that FSI simulations can be successfully framed within the total product life cycle of bileaflet mechanical aortic valves, emphasizing that credible in silico models evaluating the performance of implantable devices can (at least) partially replace preclinical in vitro experimentation and support post-market biomechanical evaluation, leading to a reduction in both time and cost required for device development. [ABSTRACT FROM AUTHOR]

Background: Malaria continues to wreak havoc on the well-being of the community. Resistant parasites are jeopardizing the treatment. This is a wake-up call for better medications. Folk plants are the key starting point for antimalarial drug discovery. After crushing and mixing the leaves of Coriandrum sativum with water, one cup of tea is drunk daily for a duration of three to five days as a remedy for malaria by local folks in Ethiopia. Additionally, in vitro experiments conducted on the plant leaf extract elsewhere have also demonstrated the plant's malaria parasite inhibitory effect. There has been no pharmacologic research to assert this endowment in animals, though. This experiment was aimed at evaluating the antimalarial efficacy of C. sativum in Plasmodium berghei infected mice. Methods: The plant's leaf was extracted using maceration with distilled water. The extract was examined for potential acute toxicity. An evaluation of secondary phytoconstituents was done. Standard antimalarial screening models (prophylactic, chemosuppressive, curative tests) were utilized to assess the antiplasmodial effect. In each test, thirty mice were organized into groups of five. To the three categories, the test substance was given at doses of 100, 200 and 400 mg/kg/day before or after the commencement of P. berghei infection. Positive and negative control mice were provided Chloroquine and distilled water, respectively. Rectal temperature, parasitemia, body weight, survival time and packed cell volume were ultimately assessed. Analysis of the data was performed using Statistical Package for Social Sciences. Results: No toxicity was manifested in mice. The extract demonstrated a significant inhibition of parasitemia (p < 0.05) in all the models. The inhibition of parasite load was highest with the upper dose in the suppressive test (82.74%) followed by the curative procedure (78.49%). Likewise, inhibition of hypothermia, weight loss hampering, improved survival and protection against hemolysis were elicited by the extract. Conclusions: The results of our experimental study revealed that the aqueous crude leaf extract of C. sativum exhibits significant antimalarial efficacy in multiple in vivo models involving mice infected with P. berghei. Given this promising therapeutic attribute, in depth investigation on the plant is recommended. [ABSTRACT FROM AUTHOR]

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common enzymopathies worldwide. Patients with G6PD deficiency are usually asymptomatic throughout their life but can develop acute hemolysis after exposure to free radicals or certain medications. Several studies have shown that serum miRNAs can be used as prognostic biomarkers in various types of hemolytic anemias. However, the impact of G6PD deficiency on circulating miRNA profiles is largely unknown. The present study aimed to assess the use of serum miRNAs as biomarkers for detecting hemolysis in the nonacute phase of G6PD deficiency. Patients with severe or moderate G6PD Viangchan (871G > A) deficiency and normal G6PD patients were enrolled in the present study. The biochemical hemolysis indices were normal in the three groups, while the levels of serum miR-451a, miR-16, and miR-155 were significantly increased in patients with severe G6PD deficiency. In addition, 3D analysis of a set of three miRNAs (miR-451a, miR-16, and miR-155) was able to differentiate G6PD-deficient individuals from healthy individuals, suggesting that these three miRNAs may serve as potential biomarkers for patients in the nonhemolytic phase of G6PD deficiency. In conclusion, miRNAs can be utilized as additional biomarkers to detect hemolysis in the nonacute phase of G6PD deficiency. [ABSTRACT FROM AUTHOR]

Introduction: Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer commonly used in blood bags. Despite its protective effects on red blood cell (RBC) storage, concerns about its reproductive toxicity exist. This study investigated the in vitro quality of RBC concentrates stored in bags using di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) as an alternative plasticizer. Methods: Using a pool-and-split study design, we produced 20 matched homogenous quintets of RBC concentrates in two DINCH bags and three DEHP bags with citrate phosphate dextrose adenine (CPDA-1) anticoagulant. RBC storage quality was assessed weekly for 35 days. Results: On day 35, the median hemolysis levels in the DINCH bags (0.297–0.342%) were marginally higher (p < 0.05) than the DEHP bags (0.204–0.240%). All DINCH bags showed <0.8% hemolysis. RBCs in the DINCH bags showed increased mean corpuscular volume and decreased eosin 5′ maleimide binding than in the DEHP bags. Higher pO2 and lower pCO2 levels in the DINCH bags indicated better gas permeability than in DEHP bags. Other metabolic parameters were comparable in both bags. Compared to DEHP, DINCH exhibited considerably lower levels of plasticizer leaching into blood bags. Conclusion: The quality of RBC concentrates stored for 35 days in DINCH-plasticized blood bags with CDPA-1 is generally comparable to those in DEHP bags. Hence, DINCH can be a viable alternative to DEHP in blood bags for nonleukoreduced RBC storage even without the use of next-generation additive solutions to improve RBC preservation quality. Plain Language Summary: A plasticizer is a chemical substance added to plastic to increase its flexibility. DEHP is a plasticizer that has been widely used in many products including plastic tubing and bags of medical devices. However, concerns about DEHP-related toxicity have been debated for many years. DEHP has been replaced with other plasticizers in many products, but it is still being used in blood bags due to its protective effect on RBC preservation. DINCH is an alternative plasticizer with a low toxicology profile. This study investigated the quality of RBC concentrates stored in blood bags using DINCH. Twenty sets of five RBC concentrates were produced using two DINCH bags and three DEHP bags with CPDA-1 anticoagulant, and the storage quality was assessed weekly for 35 days. On day 35, the median hemolysis levels in the DINCH bags (0.297–0.342%) were slightly increased than the DEHP bags (0.204–0.240%). However, all DINCH bags showed hemolysis lower than the regulatory limit of 0.8%. DINCH bags exhibited better gas permeability than DEHP bags. Compared to DEHP, DINCH exhibited considerably lower levels of plasticizer leaching into blood bags. Most of the other metabolic parameters were comparable in both bags. The quality of nonleukocyte-reduced RBC concentrates stored for 35 days in DINCH-plasticized blood bags with CDPA-1 is generally comparable to those in DEHP bags. Hence, DINCH can be a viable alternative to DEHP in blood bags for RBC storage, even without the use of next-generation additive solutions to improve RBC preservation quality. [ABSTRACT FROM AUTHOR]

Immune function shows intraspecific variation, with diet being a crucial factor that could explain such variation. Using the isotopic signature δ15N and C:N ratio, we evaluated the relationship between immune state (hemolysis and hemagglutination score) and natural variation in resource use in individuals of the species Diuca diuca. We found that some components of the immune state, specifically the hemagglutination score, correlated positively and significantly with the incorporation of animal material (high levels of δ15N), while the hemolysis score correlated positively with the C:N ratio. In this sense, we conclude that individuals of Diuca Finches that fed with a variety of prey exhibit a better immune state. [ABSTRACT FROM AUTHOR]

Cd (II), Mn (II), Zn (II), Cr (III), and Fe (III) complexes of a carbohydrazone ligand H4EBC, prepared by the reaction of ethyl acetate and carbohydrazide, have been prepared and fully characterized. The ligand H4EBC acted as a bidentate carbohydrazone with Cd (II) and coordinated through the nitrogen of both (‐NH) and (C=N)azomethine groups, while with Mn (II) and Zn (II), it acted as a neutral NN bidentate ligand. In complexes with Fe (III) and Cr (III), H4EBC acts a bi‐negative tetra‐dentate, coordinating through the oxygen atoms of both enolized (C=O)ester groups and the nitrogen of both (C=N)azomethine groups. To illustrate the proposed geometries and chemical reactivity of the compounds, we employed DFT calculations. Additionally, thermal studies provided insights into the stability of the isolated compounds. Interestingly, the prepared complexes demonstrated emission broad bands at various wavelengths, indicating ligand to metal charge transfer. Based on the inhibition of DNA destruction, the complexes can be ranked in the following order: [Cd(H4EBC)Cl2].2H2O] (1) > H4EBC > [Mn(H4EBC)Cl2)].(H2O)2] (2) > [Zn(H4EBC)Cl2].2H2O] (3) > [Fe(H2EBC)Cl(H2O)].H2O (5) > [Cr(H2EBC)Cl (H2O)].H2O (4). Regarding erythrocyte hemolysis, the order of effectiveness can be arranged as follows: (2) > (1) > H4EBC > (5) > (3) > (4). We further investigated the compounds for their potential in antitumor activity against two cell lines and antimicrobial behavior. [ABSTRACT FROM AUTHOR]

The ammonia/ammonium (NH3/NH4+, AM) concentration in human erythrocytes (RBCs) is significantly higher than in plasma. Two main possible mechanisms for AM transport, including simple and facilitated diffusion, are described; however, the driving force for AM transport is not yet fully characterized. Since the erythroid ammonium channel RhAG forms a structural unit with anion exchanger 1 (eAE1) within the ankyrin core complex, we hypothesized the involvement of eAE1 in AM transport. To evaluate the functional interaction between eAE1 and RhAG, we used a unique feature of RBCs to swell and lyse in isotonic NH4+ buffer. The kinetics of cell swelling and lysis were analyzed by flow cytometry and an original laser diffraction method, adapted for accurate volume sensing. The eAE1 role was revealed according to (i) the changes in cell swelling and lysis kinetics, and (ii) changes in intracellular pH, triggered by eAE1 inhibition or the modulation of eAE1 main ligand concentrations (Cl− and HCO3−). Additionally, the AM import kinetics was analyzed enzymatically and colorimetrically. In NH4+ buffer, RBCs concentration-dependently swelled and lysed when [NH4+] exceeded 100 mM. Cell swelling and hemolysis were tightly regulated by chloride concentration. The complete substitution of chloride with glutamate prevented NH4+-induced cell swelling and hemolysis, and the restoration of [Cl−] dose-dependently amplified the rates of RBC swelling and lysis and the percentage of hemolyzed cells. Similarly, eAE1 inhibition impeded cell swelling and completely prevented hemolysis. Accordingly, eAE1 inhibition, or a lack of chloride anions in the buffer, significantly decreased NH4+ import. Our data indicate that the eAE1-mediated chloride gradient is required for AM transport. Taken together, our data reveal a new player in AM transport in RBCs. [ABSTRACT FROM AUTHOR]

The antioxidant, anti-glycation and anti-protein denaturation potential of test extracts were assessed by hemolysis, antioxidant, antiglycation, and anti-protein denaturation assays. The cytotoxic effect of the tested extracts ranged from 6.18 ± 0.15 to 29.33 ± 1.47%. The highest effect was noted in C. carandas, H. cannabinus, T. chebula and H. indicum in antioxidant assay. The phenolic content ranged from 84.73 to 238.23 mg GAE g−1 of extract and the flavonoid was 36.05 to 184.26 mgRE g−1 of extracts. Antiglycation activity exhibited in M. longifolia, T. chebula, H. cannabinus and H. indicum (leaf). C. carandas, H. cannabinus and H. indicum showed significant IC50 value in protein denaturation. [ABSTRACT FROM AUTHOR]

Neuron-specific enolase (NSE) derived from neurons and peripheral neuroendocrine cells is a biomarker for neuroendocrine tumors and for prognostication in comatose cardiac arrest survivors. However, as platelets and erythrocytes contain NSE, hemolysis causes falsely elevated NSE. We used native serum and hemolysate derived from the same patients to make serial dilutions, and subsequently measured NSE (mNSE) and hemolytic index (HI) in each dilution. An algorithm suitable for the laboratory information system was developed based on the mNSE, HI and the estimated gradient of hemolytic interference from 30 patients. We estimated the associated uncertainty of the corrected NSE (cNSE) results based on the observed range of the gradient and derived an equation for cNSE for samples with limited hemolysis (i.e. 5 < HI ≤ 30): cNSE = mNSE − HI × (0.34 ± 0.23) µg/L. By semi-quantitatively grading the contribution from limited hemolysis, a texted result noting the hemolysis-associated degree of uncertainty can accompany the cNSE result. The major challenge of hemolysis when using serum NSE as a biomarker can be managed using an automated algorithm for correction of NSE results based on degree of hemolysis. However, laboratorians and clinicians should be aware of the limitations associated with in vivo hemolysis. [ABSTRACT FROM AUTHOR]

The study aims to determine how chitosan impacts pectin hydrogel's ability to attach peritoneal leukocytes, activate complement, induce hemolysis, and adsorb blood proteins. The hydrogels PEC-Chi0, PEC-Chi25, PEC-Chi50, and PEC-Chi75 were prepared by placing a mixture solution of 4% pectin and 4% chitosan in a ratio of 4:0, 3:1, 2:2, and 1:3 in a solution of 1.0 M CaCl2. Chitosan was found to modify the mechanical properties of pectin–calcium hydrogels, such as hardness and cohesiveness-to-adhesiveness ratio. Chitosan in the pectin–calcium hydrogel caused pH-sensitive swelling in Hanks' solution. The PEC-Chi75 hydrogel was shown to adsorb serum proteins at pH 7.4 to a greater extent than other hydrogels. PEC-Chi75's strong adsorption capacity was related to lower peritoneal leukocyte adherence to its surface when compared to other hydrogels, showing improved biocompatibility. Using the optical tweezers approach, it was shown that the force of interaction between pectin–chitosan hydrogels and plasma proteins increased from 10 to 24 pN with increasing chitosan content from 0 to 75%. Thus, the properties of pectin–calcium hydrogel, which determine interactions with body tissues after implantation, are improved by the addition of chitosan, making pectin–chitosan hydrogel a promising candidate for smart biomaterial development. [ABSTRACT FROM AUTHOR]

Background: Sickle cell disease is the most common genetic hemoglobinopathy globally and systemically affects body functioning, decreasing exercise capacity. Objective: To assess exercise capacity through the 6-minute walk test (6MWT) and biomarkers in children and adolescents with sickle cell disease. Materials and Methods: Cross-sectional study involving 20 children and adolescents from Brazil. Demographic and socioeconomic data were obtained. Baseline measurements included biomarkers (red blood cells, hemoglobin, hematocrit, white blood cells, platelets, reticulocytes, lactate dehydrogenase, creatine phosphokinase, C-reactive protein, interleukin 6, and fetal hemoglobin). The following data were obtained before, during, and after the 6MWT: heart rate, blood pressure, and peripheral oxygen saturation. Results: Eighteen children and adolescents ages 5–14 years old were analyzed, 61.1% boys, 100% black or brown, and 61.1% in primary education, with low household income. The average distance walked in 6MWT was 463.8 (137.7) m, significantly less than the predicted value (P <.001). The distance of 6MWT was associated positively with age (P =.042) and inversely with reticulocyte count (P =.42) and interleukin 6 (P =.00). Age modified the effect of interleukin 6 in younger children (P =.038). Conclusion: Our findings suggest increased baseline levels of biomarkers of hemolysis and inflammation impact on 6MWT performance. [ABSTRACT FROM AUTHOR]

Simple Summary: The metabolic profile implies simultaneous determination of carbohydrate, fat, protein, and mineral metabolism parameters as well as endocrinological parameters in the blood of cows. Blood is exposed to a variety of preanalytical factors during sampling, transport to the laboratory, and laboratory preparation for analysis, which may cause hemolysis of the sample. As hemolysis affects the values of the metabolic profile, the analyzed blood parameters may falsely increase or decrease, and the metabolic status of the cows may be misinterpreted. Preventing hemolysis is important because severe hemolysis requires discarding the sample and resampling, which is very resource-intensive. In this paper, three levels of hemolysis were determined for each blood parameter tested: (a) a hemolysis level that does not affect the values of the parameters and allows the results to be issued without restriction; (b) a hemolysis level that affects the values of the parameters but remains within the acceptable biological variability and permits the results to be issued along with a note in the form of a correction formula; and (c) a hemolysis level at which the obtained values of the parameters or the entire sample must be discarded. The results are presented graphically using interferograms, which can be easily implemented in every laboratory after validation. Hemolysis is a common cause of errors in laboratory tests as it affects blood parameters and leads to a positive or negative bias. This study aims to examine the relationship between the level of hemolysis (expressed as cell-free hemoglobin concentration, g/L) and the variability of metabolic and endocrine parameters and to determine the threshold level of hemolysis that causes an analytically and clinically significant bias for the twenty most frequently examined blood parameters in cows. Paired blood samples of 10 mL each were obtained from 30 cows. One was subjected to mechanical trauma and plasma was extracted directly from the other. Hemolyzed and non-hemolyzed samples from the same animal were mixed to obtain final samples with cell-free hemoglobin concentrations of 0, 1, 2, 4, 6, 8, and 10 g/L. Metabolic and endocrine parameters were measured in the samples and their deviation and the linear equation between the level of hemolysis and the deviation were determined. The following threshold values of hemolysis were determined, which correspond to the acceptable analytical (lower value) and clinical (upper value) levels of parameter variability: BHB 0.96 and 4.81; NEFA 0.39 and 3.31; GLU 0.38 and 3.90; ALB 1.12 and 6.11; TPROT 1.40 and 6.80; UREA 6.62 and 20.1; TBIL 0.75 and 5.65; AST 0.11 and 2.18; GGT 1.71 and 8.90, LDH 0.01 and 0.11, ALP 0.97 and 2.95; TGC 1.56 and 15.5; CHOL 1.29 and 8.56; Ca 5.68 and 25.7; P 0.57 and 8.43; Mg 1.10 and 8.47; INS 1.15 and 3.89; T3 8.19 and 15.6; T4 8.97 and 18.5; and CORT 2.78 and 11.22 g/L cell-free hemoglobin. Three decision levels are available for each metabolic and endocrine parameter: if hemolysis is below the lower (analytical) threshold value, results can be reported without restriction; if hemolysis is between the lower and upper thresholds, the results can be issued with guidance in the form of corrective linear equations; and if hemolysis is above the upper (clinical) threshold, the results and sample must be discarded. This method contributes to an optimal approach to hemolysis interference with metabolic profile parameters in blood samples from cows. [ABSTRACT FROM AUTHOR]

Background: Due to the distinctive nature of cardiac surgery, patients suffering from hereditary spherocytosis (HS) are potentially at a high risk of perioperative complications resulting from hemolysis. Despite being the most prevalent cause of hereditary chronic hemolysis, the standards of surgical management are based solely on expert opinion. Objective: We analyze the risk of hemolysis in HS patients after cardiac surgery based on a systematic review of the literature. We also describe a case of a patient with hereditary spherocytosis who underwent aortic valve repair. Methods: This systematic review was registered in the PROSPERO international prospective register of systematic reviews (CRD42023417666) and included records from Embase, MEDLINE, Web of Science, and Google Scholar databases. The case study investigates a 38-year-old patient who underwent surgery for an aortic valve defect in mid-2022. Results: Of the 787 search results, 21 studies describing 23 cases of HS undergoing cardiac surgery were included in the final analysis. Hemolysis was diagnosed in five patients (one coronary artery bypass graft surgery, two aortic valve bioprosthesis, one ventricular septal defect closure, and one mitral valve plasty). None of the patients died in the perioperative period. Also, no significant clinical hemolysis was observed in our patient during the perioperative period. Conclusions: The literature data show that hemolysis is not common in patients with HS undergoing various cardiac surgery techniques. The typical management of a patient with mild/moderate HS does not appear to increase the risk of significant clinical hemolysis. Commonly accepted beliefs about factors inducing hemolysis during cardiac surgery may not be fully justified and require further investigation. [ABSTRACT FROM AUTHOR]

Introduction: Prostate cancer (PCa) is the second most frequent cancer diagnosis in men and the fifth leading cause of death worldwide. Prostate Specific Membrane Antigen (PSMA) and Gastrin Releasing Peptide (GRP) receptors are overexpressed in PCa. In this study, we have developed iron oxide nanoparticles (IONs) functionalized with the Prostate Specific Membrane Antigen (PSMA) and Gastrin Releasing Peptide (GRP) ligands for dual targeting of Prostate cancer. Methods: IONs were developed with a thin silica layer on their surface with MPTES (carrying -SH groups, IONs-SH), and they were coupled either with a pharmacophore targeting PSMA (IONs-PSMA) or with bombesin peptide (IONs-BN), targeting GRP receptors, or with both (IONs-PSMA/BN). The functionalized IONs were characterized for their size, zeta potential, and efficiency of functionalization using dynamic light scattering (DLS) and Fourier-Transform Infrared Spectroscopy (FT-IR). All the aforementioned types of IONs were radiolabeled directly with Technetium-99m (99mTc) and evaluated for their radiolabeling efficiency, stability, and binding ability on two different PCa cell lines (PC3 and LNCaP). Results and Discussion: The MTT assay demonstrated low toxicity of the IONs against PC3 and LNCaP cells, while the performed wound-healing assay further proved that these nanostructures did not affect cellular growth mechanisms. The observed hemolysis ratio after co-incubation with red blood cells was extremely low. Furthermore, the 99mTc-radiolabeled IONs showed good stability in human serum, DTPA, and histidine, and high specific binding rates in cancer cells, supporting their future utilization as potential diagnostic tools for PCa with Single Photon Emission Computed Tomography (SPECT) imaging. [ABSTRACT FROM AUTHOR]

Tick-borne diseases account for a large proportion of vector-borne illnesses. They include, for example, a variety of infections caused by bacteria, spirochetes, viruses, rickettsiae, and protozoa. We aim to present a review that demonstrates the connection between the diagnosis, treatment, prevention, and the significance of certain emergency tick-borne diseases in humans and their clinical–epidemiological features. This review covers three diseases: anaplasmosis, ehrlichiosis, and babesiosis. The emergence of ehrlichiosis and anaplasmosis is become more frequently diagnosed as the cause of human infections, as animal reservoirs and tick vectors have increased in numbers and humans have inhabited areas where reservoir and tick populations are high. They belong to the order Rickettsiales and the family Anaplasmataceae, and the clinical manifestations typically coexist. Furthermore, prompt diagnosis and appropriate treatment are critical to the patient's recovery. Similar to malaria, babesiosis causes hemolysis. It is spread by intraerythrocytic protozoa, and the parasitemia dictates how severe it can get. Left untreated, some patients might have a fatal outcome. The correct diagnosis can be difficult sometimes; that is why an in-depth knowledge of the diseases is required. Prevention, prompt diagnosis, and treatment of these tick-borne diseases depend on the understanding of their clinical, epidemiological, and laboratory features. [ABSTRACT FROM AUTHOR]

BACKGROUND Hemolytic disease of the fetus and newborn (HDFN) is a type of anemia in the fetus or newborn, characterized by anemia, jaundice, hyperbilirubinemia, and brain damage. IgG is the only antibody that can cross the placenta. The IgG subtypes have a different ability to destroy red blood cells (RBCs). IgG1 and IgG3 can bind to Fc-phagocyte cell receptors and cause hemolysis, while IgG3 has more ability than IgG1. This study aimed to identify the antibody IgG subtype contributing to clinical manifestation differences in HDFN. METHODS This study used blood and umbilical cord blood samples from 30 pairs of mother-baby. The samples were grouped into control (not jaundice/normal bilirubin levels) and jaundice/hyperbilirubinemia groups. A self-developed IgG subtype enzymelinked immunosorbent assay protocol was performed on maternal samples, resulting in optical density. Statistical analysis was performed using SPSS software version 23. RESULTS Blood type was associated with total bilirubin expression (p = 0.005). IgG1 anti-A, IgG3 anti-A, IgG4 anti-A, IgG1 anti-B, IgG3 anti-B, and IgG4 anti-B significantly affected hyperbilirubinemia in newborns (p = 0.041, 0.013, 0.017, 0.028, 0.001, and 0.007, respectively). CONCLUSIONS IgG1 and IgG3 were more significant in causing clinical problems. IgG4 suppressed IgG activation, resulting in no destruction of the infant's RBCs. [ABSTRACT FROM AUTHOR]

Maternal isoimmunization occurs when a pregnant woman develops an immune reaction due to the inheritance of a red‑cell antigen, which is paternally derived and can result in fetal anemia, hemolysis, fetal death, and hydrops fetalis as the antibodies might travel through the placenta and get adhered to the antigens present in the erythrocytes of the fetus. This report highlights a rare case of Rh isoimmunization leading to fetal anemia in a 26‑year‑old female and evaluates the impact of intrauterine transfusion (IUT) in terms of the gestational age at delivery along with the mode of delivery, procedural complications, and overall survival rate of the fetus. In conclusion, the most frequent cause of fetal anemia is Rh alloimmunization, which should be taken into consideration while making a differential diagnosis throughout the assessment. Improvements in IUT procedures and earlier detection of the MCA‑PSV by Doppler ultrasonographic examination have also contributed to better results. [ABSTRACT FROM AUTHOR]

The co-occurrence of myasthenia gravis (MG) and paroxysmal nocturnal hemoglobinuria (PNH) is rare; only one case has been published so far. We report a 63-year-old Caucasian female patient who was diagnosed with MG at the age of 43. Thymoma was also detected, and so it was surgically resected, which resulted in reasonable disease control for nearly 20 years. Slight hemolysis began to emerge, and then myasthenia symptoms progressed, so immunosuppressive therapy was started. Due to progressive disease and respiratory failure, the patient underwent plasmapheresis, and ventilatory support was stopped. Marked hemolysis was present, and diagnostic tests confirmed PNH with type III PNH cells. Her myasthenia symptoms aggravated, mechanical ventilation had to be started again, and due to the respiratory acidosis, massive hemolysis occurred. After two plasmapheresis sessions, the patient received eculizumab at 600 mg, resulting in prompt hemolysis control. After the second dose of the treatment, the patient was extubated. Still, due to their inability to cough, she developed another respiratory failure and pneumonia–sepsis, resulting in the patient's death. This case highlights the rare association between these two serious diseases and similar immune-mediated pathophysiology mechanisms involving the complement system. [ABSTRACT FROM AUTHOR]

This research aims to develop the formulation of Dissolving Microneedle Piperine (DMNs PIP) and evaluate the effect of polymer concentration on characterisation and permeation testing results in ex vivo. DMNs PIP were prepared from varying concentrations of piperine (PIP) (10, 15, and 20% w/w) and polymers of polyvinyl alcohol (PVA): Polyvinyl pyrrolidone (30:60 and 60:25), respectively. Then the morphological evaluation of the formula was carried out, followed by mechanical strength testing. Furthermore, the density, LOD, and weight percentage of piperine in the dried microneedle were calculated and the determination of volume, needle weight and piperine weight and analysed. Ex vivo testing, X-Ray Diffraction, FTIR and hemolysis tests were carried out. PIP with PVA and PVP (F1) polymers produced DMN with mechanical strength (8.35 ± 0.11%) and good penetration ability. In vitro tests showed that the F1 polymer mixture gave good penetration (95.02 ± 1.42 μg/cm2), significantly higher than the F2, F3, F4, and F5 polymer mixtures. The DMNs PIP characterisation results through XRD analysis showed a distinctive peak in the 20–30 region, indicating the presence of crystals. The FTIR study showed that the characteristics of piperine found in DMNs PIP indicated that piperine did not undergo interactions with polymers. The results of the ex vivo study through DMNs PIP hemolytic testing showed no hemolysis occurred, with the hemolysis index below the 5% threshold reported in the literature. These findings indicate that DMNs PIP is non-toxic and safe to use as alternative for treating inflammation [ABSTRACT FROM AUTHOR]

Methoxychalcones containing the NMe2, 3,4-(OMe)2, 3,4,5-(OMe)3, and isobornyl substituents in the B ring were synthesized from 1,3-dihydroxy-4-(1,7,7-trimethylbicyclo-[2.2.1]hept-exo-2-yl)benzene and 1,4-dihydroxy-3-(1,7,7-trimethylbicyclo[2.2.1]hept-exo-2-yl)benzene. Oxidative cyclization of the new isobornylchalcones afforded flavones bearing the 1,7,7-trimethylbicyclo[2.2.1]hept-exo-2-yl moiety. The erythrotoxicity, membrane-protective, and antioxidant activity of the synthesized compounds were evaluated in in vitro models including the model of oxidative hemolysis of mammalian erythrocytes initiated by H2O2 or 2,2′-azobis-(2-amidinopropane) dihydrochloride. All the chalcones studied and most flavones possessed good hemocompatibility and high antioxidant activity. The promise of further research into the synthesis of effective pharmacological substances based on the title compounds was demonstrated. [ABSTRACT FROM AUTHOR]

Microfluidic devices promise to overcome the limitations of conventional hemodialysis and oxygenation technologies by incorporating novel membranes with ultra-high permeability into portable devices with low blood volume. However, the characteristically small dimensions of these devices contribute to both non-physiologic shear that could damage blood components and laminar flow that inhibits transport. While many studies have been performed to empirically and computationally study hemolysis in medical devices, such as valves and blood pumps, little is known about blood damage in microfluidic devices. In this study, four variants of a representative microfluidic membrane-based oxygenator and two controls (positive and negative) are introduced, and computational models are used to predict hemolysis. The simulations were performed in ANSYS Fluent for nine shear stress-based parameter sets for the power law hemolysis model. We found that three of the nine tested parameters overpredict (5 to 10×) hemolysis compared to empirical experiments. However, three parameter sets demonstrated higher predictive accuracy for hemolysis values in devices characterized by low shear conditions, while another three parameter sets exhibited better performance for devices operating under higher shear conditions. Empirical testing of the devices in a recirculating loop revealed levels of hemolysis significantly lower (<2 ppm) than the hemolysis ranges observed in conventional oxygenators (>10 ppm). Evaluating the model's ability to predict hemolysis across diverse shearing conditions, both through empirical experiments and computational validation, will provide valuable insights for future micro ECMO device development by directly relating geometric and shear stress with hemolysis levels. We propose that, with an informed selection of hemolysis parameters based on the shear ranges of the test device, computational modeling can complement empirical testing in the development of novel high-flow blood-contacting microfluidic devices, allowing for a more efficient iterative design process. Furthermore, the low device-induced hemolysis measured in our study at physiologically relevant flow rates is promising for the future development of microfluidic oxygenators and dialyzers. [ABSTRACT FROM AUTHOR]

Spontaneous bacterial peritonitis is a frequent severe complication in cirrhotic patients with ascites. Carbapenem antibiotics are currently the treatment of choice for patients with hospital-acquired or healthcare-related infections. However, there is limited evidence available on the efficacy of ertapenem in cirrhotic patients with spontaneous bacterial peritonitis. As a result, the pharmacokynetics and pharmacodynamics of this antibiotic are still unknown. The objective of this study was to develop and validate measurement procedures based on liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) to determine ertapenem concentrations in plasma and ascitic fluid. Samples were pretreated by acetronile protein-precipitation. Chromatographic separation is performed on a C18 reversed-phase Acquity®-UPLC®-BEHTM column (2.1 × 100 mm id, 1.7 µm) using a non-linear gradient of water/acetonitrile containing 0.1 % of formic acid at a flow rate of 0.4 mL/min. Ertapenem and its internal standard (ertapenem-D4) are detected by tandem mass spectrometry using positive electrospray ionization and multiple reaction monitoring, and using 476.2 → 346.0/432.2 as mass transition for ertapenem and 480.2 → 350.0 for its internal standard. No significant interferences or carry-over contamination were observed. Imprecisions, absolute relative bias, matrix effects and normalized recoveries were ≤14.5 %, ≤9.3 % (92.8–104.5) % and (98.8–105.8) %, respectively. Chromatographic measurement procedures were linear from (0.50–100) mg/L. The measurement procedures based on UHPLC-MS/MS developed and validated in this study could be useful in pharmacokynetic and pharmacodynamic studies in subjects with liver cirrhosis who develop spontaneous bacterial peritonitis treated with ertapenem. [ABSTRACT FROM AUTHOR]

Background: This study was conducted to confirm the reliability of an in vitro mechanically induced hemolysis test (ISO 10993-4:2017), which is essential for ensuring the safety of blood pumps. Methods: For appropriate anticoagulant selection, porcine blood was prepared in anticoagulant citrate dextrose solution A (ACD-A), heparin, and citrate phosphate dextrose adenine (CPDA-1), respectively, according to the ASTM F1830 standard. Anticoagulant-treated porcine and bovine blood were circulated in a mock circulatory loop (MCL) for 6 h to observe the rate of plasma-free hemoglobin (pfHb) and RBCs with morphological integrity. Results: A morphological loss of red blood cells (RBCs) was observed over time. While there were differences in morphological loss depending on the anticoagulant, no consistent trend could be identified. The pfHb concentration was significantly higher in bovine than in porcine blood. Conversely, the number of RBCs with morphological integrity decreased over time in both, but the ratio of RBCs with morphological integrity was similar across all timepoints. Conclusions: The percentage of RBCs with morphological integrity can be used as a reliable indicator for the interpretation of mechanically induced hemolysis results in different blood types. Furthermore, the reliability of the in vitro mechanically induced hemolysis test (ISO 10993-4:2017) was assessed. [ABSTRACT FROM AUTHOR]

Clostridium perfringens alpha toxin (CPA), which causes yellow lamb disease in sheep and gas gangrene and food poisoning in humans, is produced by all types of C. perfringens and is the major virulence determinant of C. perfringens type A. CPA induces hemolysis in many species, including humans, murines, sheep and rabbits, through its enzymatic activity, which dissolves the cell membrane. Recent studies have shown that some pore-forming toxins cause hemolysis, which is achieved by the activation of purinergic receptors (P2). However, the relationship between P2 receptors and non-pore-forming toxin hemolysis has not been investigated. In the present study, we examined the function of P2 receptors in CPA toxin hemolysis and found that CPA-induced hemolysis was dependent on P2 receptor activation, and this was also true for Staphylococcus aureus β-Hemolysin, another non-pore-forming toxin. Furthermore, we use selective P2 receptor antagonists to demonstrate that P2X1 and P2X7 play important roles in the hemolysis of human and murine erythrocytes. In addition, we found that redox metabolism was mainly involved in CPA-induced hemolysis using metabolomic analysis. We further demonstrate that CPA activates P2 receptors and then activates NADPH oxidase through the PI3K/Akt and MEK1/ERK1 pathways, followed by the production of active oxygen to induce hemolysis. These findings contribute to our understanding of the pathological effects of CPA, clarify the relationship between P2 activation and non-pore-forming toxin-induced hemolysis, and provide new insights into CPA-induced hemolysis. [ABSTRACT FROM AUTHOR]

Sickle cell disease (SCD) is a lifelong blood disorder affecting approximately 100,000 people in the United States and is one of the most common monogenic diseases. A serious complication of SCD is acute chest syndrome (ACS). ACS is a condition with a high rate of morbidity and mortality. The aim of the study was to assess hemolysis and lipid parameters in a cohort of confirmed SCD patients to predict ACS development in the following year. Standard lipid were performed (triglycerides, total cholesterol, high-density cholesterol, low-density cholesterol) panel to calculate of non-HDL-C, large buoyant LDL cholesterol (lbLDL-C) and small dense LDL cholesterol (sdLDL-C) with Sampson equation. Hemolysis and hematologic parameters were also evaluated. Among 91 patients included between September 2018 and June 2021, thirty-seven patients had history of ACS and 6 patients developed ACS during following year. In unadjusted logistic regression, total bilirubin was associated with ACS occurrence (RR: 1.2 [1.05–1.51] p = 0.013). Concerning lipid profile, non-HDL-C (RR: 0.87 [0.0.67–0.99] p = 0.04) and sdLDL-C (RR: 0.78 [0.49–0.96] p = 0.03) were associated with ACS occurrence decrease. C-reactive protein was associated with ACS occurrence (RR: 1.27 [1.065–1.85] p = 0.011). Based on these findings, this study demonstrated that several biomarker easily available can be used at steady state to predict ACS in the following year. The validation of these results are required to ensure the reproducibility of the findings. [ABSTRACT FROM AUTHOR]

A 66-year-old man presented with hemolytic anemia, which required frequent blood transfusion, 6 months after surgical repair of an ascending aortic pseudoaneurysm. Hemolysis was attributed to luminal stenosis caused by graft kinking by laboratory test, CT and four-dimensional magnetic resonance imaging. First, an Excluder cuff was placed at the stenotic site under rapid pacing, but it migrated distally. Thereafter a Palmaz XL stent was placed at the stenotic site, which led to resolution of anemia. In this case, a Palmaz XL stent was successfully used to treat hemolytic anemia caused by graft kinking following ascending aortic surgery. [ABSTRACT FROM AUTHOR]

Complement inhibitors are the mainstay of paroxysmal nocturnal hemoglobinuria (PNH) treatment. The anti‐C5 monoclonal antibody eculizumab was the first treatment to improve hemolysis, thrombotic risk, and survival in PNH although at the price of a life‐long intravenous fortnightly drug. Additionally, suboptimal response may occur in up to 2/3 of patients with persistent anemia due to incomplete control of intravascular hemolysis, development of upstream C3‐mediated extravascular hemolysis (EVH), or concomitant bone marrow failure. Ravulizumab, a longer half‐life anti‐C5 developed from eculizumab, administered every 8 weeks, improved patient convenience, and reduced pharmacokinetic breakthrough hemolysis (BTH) by establishing more stable anti‐C5 concentrations. More recently, several other anti‐C5 compounds (crovalimab, pozelimab, tesidolumab, cemdisiran, zilucoplan, and coversin) are on study in clinical trials. Upstream inhibition of complement cascade was also explored with the anti‐C3 pegcetacoplan, and with the alternative pathway inhibitors iptacopan (anti‐factor B) and danicopan (anti‐factor D). These drugs efficiently target EVH and are able to improve anemia and transfusion need in suboptimal responders to anti‐C5. The route and schedule of administration (twice weekly subcutaneously for pegcetacoplan and twice or thrice oral daily dosing for iptacopan and danicopan, respectively) are very convenient but pose novel issues regarding adherence. Additionally, both anti‐C5 and upstream inhibitors do not resolve the unmet need of pharmacodynamic BTH events due to complement amplifying conditions such as infections, traumas, and surgery. In this review, we will recapitulate PNH physiopathology, clinical presentation, and diagnosis and describe available and developing drugs that will lead to a precision medicine approach for this rare though heterogenous disease. [ABSTRACT FROM AUTHOR]

Cardiopulmonary bypass (CPB) is associated with intravascular hemolysis which depletes endogenous nitric oxide (NO). The impact of hemolysis on pulmonary arterial compliance (PAC) and right ventricular systolic function has not been explored yet. We hypothesized that decreased NO availability is associated with worse PAC and right ventricular systolic function after CPB. This is a secondary analysis of an observational cohort study in patients undergoing cardiac surgery with CPB at Massachusetts General Hospital, USA (2014–2015). We assessed PAC (stroke volume/pulmonary artery pulse pressure ratio), and right ventricular function index (RVFI) (systolic pulmonary arterial pressure/cardiac output), as well as NO consumption at 15 min, 4 h and 12 h after CPB. Patients were stratified by CPB duration. Further, we assessed the association between changes in NO consumption with PAC and RVFI between 15min and 4 h after CPB. PAC was lowest at 15min after CPB and improved over time (n = 50). RVFI was highest -worse right ventricular function- at CPB end and gradually decreased. Changes in hemolysis, PAC and RVFI differed over time by CPB duration. PAC inversely correlated with total pulmonary resistance (TPR). TPR and PAC positively and negatively correlated with RVFI, respectively. NO consumption between 15min and 4 h after CPB correlated with changes in PAC (−0.28 ml/mmHg, 95%CI −0.49 to −0.01, p = 0.012) and RVFI (0.14 mmHg*L−1*min, 95%CI 0.10 to 0.18, p < 0.001) after multivariable adjustments. PAC and RVFI are worse at CPB end and improve over time. Depletion of endogenous NO may contribute to explain changes in PAC and RVFI after CPB. • Pulmonary arterial compliance (PAC) gradually increases after cardiopulmonary bypass (CPB). • PAC inversely correlates with total pulmonary resistance (TPR) after CPB. • TPR and PAC positively and negatively correlate with right ventricle function after CPB, respectively. • NO consumption, which reflects changes in hemolysis, independently correlates with PAC and right ventricle function after CPB. • Hemolysis may contribute to changes in PAC and right ventricle function after CPB. [ABSTRACT FROM AUTHOR]

Background: The study of blood trauma, such as hemolysis in blood‐carrying devices, is crucial due to the high incidence of adverse events like alteration of blood function, bleeding, and multi‐organ failure. The extent of flow‐induced hemolysis, predominantly influenced by stress duration and intensity, is described by established model parameters based on the power law approach. In recent years, various parameters were determined using different Couette shearing devices and donor species. However, they have not been validated due to limited experimental data. Methods: This study provides hemolysis measurements in a Couette shearing device and evaluates the suitability of different power law parameters. The revised Couette shearing device generates well‐defined dynamic stress loads that are repeatedly applied to blood samples at a defined temperature. Human blood samples with an adjusted hematocrit of 30%, were tested with varying repetitions (20 to 80 times). The half‐sinusoidal stress loads had amplitudes of 73 to 140 Pa and exposure times of 24 msec per repetition. The parameters of five common power law hemolysis approaches were then compared with the experimental data. Results: The prediction with the power law model parameters C = 3.458 × 10−6, α = 0.2777 and β = 2.0639 showed a good agreement with the experimental results. Conclusion: The effect of multiple short‐time stresses on hemolysis was investigated to validate the power law hemolysis model with the Couette shearing device of this study. [ABSTRACT FROM AUTHOR]

Background: A percutaneous ventricular assist device (pVAD) is an effective method to treat heart failure, but its complications, mainly hemolysis and thrombus formation, cannot be ignored. Accurate evaluation of hemolysis and thrombus formation in pVAD is essential to guide the development of pVAD and reduce the incidence of complications. Methods: This study optimized the numerical model to predict hemolysis and thrombus formation in pVAD. The hemolysis model is based on the power law function, and the multi‐component thrombus prediction model is improved by introducing the von Willebrand factor. Results: The error between the numerical simulation and the hydraulic performance experiment is within 5%. The numerical results of hemolysis are in good agreement with those of in vitro experiments. Meanwhile, the thrombus location predicted by the numerical model is the same as that found in the in vivo experiment. Conclusion: The numerical model suggested in this study may therefore accurately assess the possible hemolytic and thrombotic dangers in pVAD, making it an effective tool to support the development of pVAD. [ABSTRACT FROM AUTHOR]

Although Vibrio parahaemolyticus (V. parahaemolyticus) is a pathogen frequently found in seafood, there is a possibility of its presence in other foods, such as dairy products. The main virulence factors of V. parahaemolyticus are thermostable direct hemolysins (TDHs) which are lethal toxins, so it is necessary to establish qualitative and quantitative methods for determining TDHs. HPLC-ESI-TOF was employed to establish a method for identifying TDHs. The identification and quantification ions of TDHs were confirmed by HPLC-ESI-TOF. The method was developed for detecting TDHs in milk powder using HPLC-ESI-TOF in this paper, and limits of detection (were between 0.20 and 0.40 mg/kg, limits of quantitation were between 0.5 and 1.0 mg/kg and recoveries of all TDHs were between from 78% to 94% with relative standard deviation lower than 10%. This research will provide a reference for developing methods of HPLC-MS/MS to detect TDHs in food samples, which can provide a tool for the government to monitor TDHs contamination in foods. [ABSTRACT FROM AUTHOR]

Iptacopan (FABHALTA®) is an oral complement Factor B inhibitor developed by Novartis Pharmaceuticals for the treatment of complement-mediated diseases. Acting upstream of complement 5 in the alternative pathway, iptacopan inhibits both terminal complement-mediated intravascular haemolysis and complement 3-mediated extravascular haemolysis. On 5 December 2023, iptacopan received approval in the USA for the treatment of adults with paroxysmal nocturnal haemoglobinuria (PNH). This article summarizes the milestones in the development of iptacopan leading to this first approval for PNH. [ABSTRACT FROM AUTHOR]

A patient presented with fever, severe pain and edematous tight due to hip trauma and was scheduled for urgent fasciotomy. Following physical examination, laboratory analyses were requested, and results revealed anemia and severe infection. As the patient's condition was serious, a new set of samples was sent to the laboratory four hours later. Following centrifugation, severely hemolyzed dark-colored serum and plasma samples were obtained and in vitro hemolysis was suspected. The collection of samples was repeated, but a new set of samples was also hemolyzed with a significant decrease in the hemoglobin value. At that point, in vivo hemolysis was suspected, and samples were processed according to standard laboratory procedures for hemolytic samples. Following confirmation of the gas gangrene diagnosis by clinicians, the cause of hemolysis was attributed to the cytotoxic activity of a-toxin produced by the anaerobic gram-positive bacterium Clostridium perfringens. An insight into the laboratory procedure that could help to narrow down the causes of hemolysis and single out C. perfringens as a cause of intravascular hemolysis was given. [ABSTRACT FROM AUTHOR]

Introduction: Uvaria chamae and Sida linifolia are plants traditionally used in Togo in diabetes treatment, an affection that often leads to several complications. This study aimed to evaluate the antihyperglycemic, anti-inflammatory, antioxidant activity and toxicity of these two plants extracts. Methods: A phytochemical analysis was carried out on extracts obtained either by decoction or maceration in ethanol of Uvaria chamae leaves and Sida linifolia whole plant. Evaluation of the antihyperglycemic activity consisted in glucose absorption test using yeast and rats' muscle and jejunum. DPPH test, total antioxidant capacity assay, hemolysis and egg albumin denaturation inhibition assays and evaluation of extracts acute toxicity were performed. Results: Hydroalcoholic extract of Uvaria chamae showed the strongest antihyperglycemic activity (p<0.05); the highest phenolic contents (147.93 ± 1.01 mg/g), the best total antioxidant capacity (153.33 ± 4.07), the lowest IC50 (µg/mL) for DPPH test (296.96 ± 91.69), a capacity of hemolysis (825.99 ± 29.24) and egg albumin denaturation (738.10 ± 92.26) inhibition assays. In the same way, hydroalcoholic extract of Sida linifolia, showed the strongest antihyperglycemic activity (p<0.05), the highest phenolic contents (71.60 ± 2.16 mg/g), the best total antioxidant capacity (146.98 ± 2.81), lowest IC50 (µg/mL) for DPPH test (788.28 ± 112.54), the hemolysis (882.03 ± 20.86) and egg albumin denaturation (1966.18 ± 35.94) inhibition assays. None of the extracts showed acute toxicity in rats. Conclusion: the hydroalcoholic leaves extract of Uvaria chamae and of the whole plant of Sida linifolia could be candidates in the treatment of diabetes and its complications. [ABSTRACT FROM AUTHOR]

Introduction: Dapsone forms the backbone of multi-drug therapy (MDT) in leprosy and many other dermatological disorders. Haemolysis is its common side effect which often necessitates drug stoppage. Currently, wide variation in data of haemolysis with dapsone exists in literature ranging from 24.7% to 83% and none of the studies point towards the timing of onset of haemolysis/timing of maximal haemolysis which is important in therapeutic decision making regarding continuing or stopping the drug. This study aimed to answer such unanswered questions. Objectives: Primary: To estimate the fall in haemoglobin (Hb) levels after administering MDT for 3 months in patients with leprosy. Secondary: To determine factors associated with Hb change -- age, glucose-6-phosphate dehydrogenase (G6PD) status, pole of leprosy and duration of MDT taken (if any). Materials and Methods: All freshly diagnosed cases of Hansen's disease were studied for 3 months. At baseline, demographic data (age, sex), skin biopsy, slit skin smear and G6PD were taken. Haemoglobin (Hb), serum glutamate oxaloacetate transferase (SGOT), serum glutamate pyruvate transferase (SGPT), serum bilirubin, lactate dehydrogenase (LDH), reticulocyte count, peripheral blood smear (PBS) along with clinical photography was done at baseline, 1, 2 and 3 months. Results: Out of the 48 patients who completed the study: Mean Hb (g/dL) decreased from 13.37 at baseline to a minimum of 12.08 at 2 months, and then increased to 12.34 at 3 months. Of 42 patients (87.5%) with a fall in Hb, 13 (27.1%) had severe (fall >20%), 17 (35.4%) had moderate (fall 10--20%), 12 (25%) had mild fall (fall <10%) and in 6 (12.5%), there was no haemolysis. Reticulocyte count, LDH, SGOT and SGPT were significantly associated with haemolysis. Severe haemolysis occurred more frequently in the lepromatous spectrum. Conclusion: Dapsone causes maximal fall of hemoglobin by 1.29 g/dl at two months following which it increases. The fall of hemoglobin is reversible and hemoglobin starts to increase by 3 months of therapy making cessation of the drug unnecessary in most of the patients. [ABSTRACT FROM AUTHOR]

Background: Hemolysis is a common reason for specimen rejection in the laboratory. Our experience suggested that hemolysis (H) flag limits are too strict for some analytes leading to unnecessary specimen rejections. This study summarizes H flags for commonly rejected analytes on the Beckman Coulter DxC 700 AU analyzer. Methods: We evaluated analytes with low-limit H flags and high rejection rates. These included: aspartate aminotransferase (AST), alanine aminotransferase (ALT), iron (IRN), potassium (K), direct bilirubin (DBIL), magnesium (Mg), amylase (AMY), sodium (Na), gamma-glutamyltransferase (GGT), phosphorus (PHOS), albumin (ALB), alkaline phosphatase (ALKP), and lactate dehydrogenase (LDH). Five patient plasma pools without hemolysis were made from 50 patient specimens. Neat pools were analyzed to establish baseline analyte concentrations. A hemolysate was created by diluting whole blood with distilled water. Each analyte was tested after spiking each pool with the hemolysate to specific hemoglobin concentrations corresponding to manufacturer's H flags. Percent differences were calculated between baseline pool means and each flag's pool mean. Acceptance limits were based upon the average of the 2019 CLIA and the method precision limits. Calculated percent differences greater than the acceptance limits were considered significant. Results: Manufacturer-defined hemolysis flags can be updated to greater than 1+ for Na, K, and AST, greater than 3+ for ALKP, and greater than 4+ for AMY and Mg. No changes were noted for the remaining analytes. Conclusions: The hemolysis criteria set for ALKP, AMY, AST, Mg, K, and Na were updated in the Remisol Advance middleware, which led to a 56% reduction in rejected hemolyzed specimens. [ABSTRACT FROM AUTHOR]

Introduction: Sanquin donor medicine department is informed when donations or their components are rejected. This can occur isolated or frequently. It is undesirable because the donations cannot be used and there may be an underlying medical cause. Based on regional approaches, a uniform procedure was developed. Methods: Information about whole blood, plasma‐ plateletpheresis donations from which one or more components were rejected for filtration time (>2 h), hemolysis or clots were extracted from blood bank information system. After rejection of two successive components or donations or total ≥3 the donor is contacted. Depending on the medical history and investigation by the family doctor, the donor carrier is re‐evaluated. We looked for the causes of the discarded products and performed a survey among blood services regarding polices with discarded products. Results: One or more components from 1742 of about 2.2 million successful donations (0.08%) were rejected. The highest percentage of rejection was seen in plateletpheresis (1.5%), all for clots. No underlying medical causes were found. 24 whole blood donors were found to have sickle cell trait (SCT) and were permanently deferred. The policies for follow‐up after discarded products or acceptance of SCT donors vary between the 16 blood banks. Six organizations do not follow‐up donors and seven accept SCT for blood or plasma donation. Conclusion: Informing donors with repeated discarded products avoids the non‐use of donations. Causes of repeated discarded products can be found by follow‐up of donors. The results of the survey indicate a large discrepancy in policies applied worldwide. [ABSTRACT FROM AUTHOR]

Although the toxic effects of bee venom (BV) in humans are known, there are only a few systematic studies are available in literature. Here, we have evaluated the potential toxicity of BV from Apis mellifera L. (Hymenoptera: Apidae) by studying acute toxicity in mice receiving subcutaneous injections of high (120 mg/kg), medium (60 mg/kg) and low (8 mg/kg) doses of BV. General toxicity symptoms and histopathological changes were recorded for 14 days. The results indicated that highdose BV could be fatal. The mental state, appetite, and respiration of mice in the medium- and high-dose groups changed in varying degrees; higher doses led to more prominent symptoms (LD50, 119.7 mg/kg). BV in medium- and high-dose groups significantly inhibited weight gain in mice within 2 days, which did not significantly differ between the dose groups and control at the later stage. The hemolysis rate was significantly higher in the low-dose, while in the medium- and high-dose groups, the coagulation time significantly prolonged in male mice. Histopathological changes showed that medium- and high-dose groups exhibited toxicity to tested organs. Our study showed that BV exhibited strong toxicity at higher concentration and is relatively safe when the BV concentration is lower than 8 mg/kg. [ABSTRACT FROM AUTHOR]

Background Hemolysis is a common reason for nonreporting results in biochemistry and is measured using the hemolysis index (HI), with nonreporting limits set for analytes by manufacturers. Objective To verify the nonreporting HI limit for potassium, phosphate, magnesium, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), iron, CA19-9, and vitamin D on the Beckman Coulter AU5800/DxI800 analyzers. Method Hemolysate was created from EDTA-lined tubes of whole blood using an osmotic shock procedure. The hemolysate underwent serial dilutions with saline and was spiked in paired serum. The delta changes in HI and analyte concentration were measured, assessed using regression analysis, and compared against calculated reference change values. Results A linear relationship between increasing HI and increasing analyte concentration (R 2 > 0.9) was observed for potassium (y = 0.8864x), phosphate (y = 0.1079x), magnesium (y = 0.0678x), AST (y = 29.035x), and LDH (y = 350x). Increasing HI values did not have a linear effect on iron (y = −0.2544x), CA19-9 (y = 2.7019x), or vitamin D (y = 8.036x) concentrations. Conclusion The results from this experiment support increasing the HI nonreporting limit to 100 mg/dL for potassium; 200 mg/dL for magnesium; and 300 mg/dL for phosphate, CA19-9, and vitamin D. The iron assay is not affected by hemolysis as high as 500 mg/dL. The current HI nonreporting limit of 50 mg/dL is appropriate for LDH. [ABSTRACT FROM AUTHOR]

Background: Herbal products and traditional remedies are commonly used by individuals worldwide for the management of common ailments, even though most are not without risks. Acalypha indica is a popular medicinal plant consumed in some Asian countries. Case presentation: This case report presents a 40-year-old previously unevaluated Sri Lankan female and her 8-year-old son who presented with severe glucose-6-phosphate dehydrogenase (G6PD) deficiency related acute intravascular oxidative haemolysis and methaemoglobinaemia precipitated by Acalypha indica consumption, successfully managed with supportive care and blood transfusion. Conclusions: This case highlights the potential hemolytic and methaemoglobinaemic effects of ingesting oxidant herbal products and the importance of considering such exposures in patients presenting with hemolysis and multiorgan involvement, particularly in communities where herbal product intake is popular. Healthcare providers should be aware of the risks associated with traditional remedies and maintain a high index of suspicion to ensure prompt recognition and appropriate management. [ABSTRACT FROM AUTHOR]

Objective: Knowledge of proper collection, storage, preservation, and processing techniques is critical to ensuring proper handling and analysis of fluid cytology specimens. This study was conducted to determine the effect of anticoagulation, pre-smearing acetic acid treatment technique, and saline rehydration technique on morphological assessment, reproducibility, and reporting in fluid cytology. Material and Methods: The study was carried out in the cytopathology laboratory over 2 months (April–May 2022), where 100 effusion samples were analyzed. At least 20–40 mL of fluid was collected in heparinized and non-heparinized containers for each patient. Samples were processed in cytospin and stained with Giemsa and Papanicolaou stains. For 70 hemorrhagic specimens, an extra smear was prepared from the sediment and subjected to the saline rehydration technique as per the Indian Academy of Cytologists (IAC) guidelines. Seventy-three hemorrhagic specimens whose quantity received was more than 35 mL were subjected to the pre-smearing technique. These smears were evaluated for (a) the presence or absence of blue background/any other background staining, (b) cellularity, (c) cell morphology and (d) the presence/absence of microclots. Results: Heparinized samples showed no compromise in cellular morphology or cellularity although a blue background was observed in an occasional case. The pre-smearing technique had less background hemorrhage and preserved cell characteristics. The post-smearing saline rehydration technique did not compromise the cellularity but distorted morphology and showed background staining. Conclusion: The pre-smearing acetic acid treatment showed better-preserved cellularity and cytomorphology with the absence of background staining when compared to the post-smearing saline rehydration technique. [ABSTRACT FROM AUTHOR]

Pathologies such as malaria, hemorrhagic stroke, sickle cell disease, and thalassemia are characterized by the release of hemoglobin degradation products from damaged RBCs. Hematin (liganded with OH−) and hemin (liganded with Cl−)—are the oxidized forms of heme with toxic properties due to their hydrophobicity and the presence of redox-active Fe3. In the present study, using the original LaSca-TM laser particle analyzer, flow cytometry, and confocal microscopy, we showed that both hematin and hemin induce dose-dependent RBC spherization and hemolysis with ghost formation. Hematin and hemin at nanomolar concentrations increased [Ca2+]i in RBC; however, spherization and hemolysis occurred in the presence and absence of calcium, indicating that both processes are independent of [Ca2+]i. Both compounds triggered acute phosphatidylserine exposure on the membrane surface, reversible after 60 min of incubation. A comparison of hematin and hemin effects on RBCs revealed that hematin is a more reactive toxic metabolite than hemin towards human RBCs. The toxic effects of heme derivatives were reduced and even reversed in the presence of albumin, indicating the presence in RBCs of the own recovery system against the toxic effects of heme derivatives. [ABSTRACT FROM AUTHOR]