Red Cell Loss Research Articles

Impact of elevated direct factor Xa inhibitor plasma levels on perioperative blood loss in patients undergoing urgent surgery.

Data on the perioperative bleeding risk associated with elevated plasma levels of direct factor Xa inhibitors (FXa inhibitors) are limited. This study examines perioperative red blood cell (RBC) loss in patients undergoing urgent surgery with a residual FXa inhibitor level exceeding 100 mcg/L and without preoperative FXa inhibitor reversal. This retrospective analysis includes data from 32 patients who underwent urgent noncardiac surgery between 2018 and 2022. This study aims to analyze perioperative RBC loss in patients undergoing urgent surgery with a residual FXa inhibitor level exceeding 100 mcg/L and without preoperative FXa inhibitor antidote-based reversal or unspecific treatment with 4-factor prothrombin complex concentrate (PCC). All patients were managed using a watch-and-wait strategy. The last determination of FXa inhibitor plasma concentration prior to surgery showed a median of 245 mcg/L (IQR 144-345), with a median time interval of 3.8 h (IQR 2.4-7.2) before incision. Median RBC loss during surgery was 49 mL (IQR 0-253), 189 mL (IQR 104-217) until POD1 and 254 mL (IQR 58-265) until POD3. Only one patient required intraoperative treatment with 4-factor-PCC and none required reversal with andexanet alfa. Linear regression models found no significant influence of FXa inhibitor plasma levels on intraoperative RBC loss. Rivaroxaban was associated with higher RBC loss until postoperative Day 1 compared with apixaban. No thromboembolic events were observed. Despite markedly elevated plasma concentrations of residual direct FXa inhibitors, perioperative RBC loss was limited in patients undergoing urgent noncardiac surgery. The intraoperative watch-and-wait strategy with selective intraoperative FXa inhibitor reversal or treatment only when required appears to be an appropriate approach.

Разработка интеллектуальной системы поддержки принятия врачебных решений для прогнозирования хронической болезни почек у детей.

Introduction. Chronic kidney disease is often diagnosed too late. Currently, the diagnostic accuracy is 44.1%, which highlights the urgent need to improve diagnostic methods. The purpose of the study: to develop a model – a system of support of medical decisions to predict chronic kidney disease in children. Materials and methods. А one-center retrospective cohort study (2011–2022) of children with chronic kidney disease of 1–4 stages in the age from 1 to 17 years. To construct a predictive model for diagnosing chronic kidney disease in children, an ensemble learning method was used, using which the models obtained by machine learning algorithms were combined: multi-factor logistic regression and decision tree. The models use five variables: asthenic physique in a child, loss of protein and red blood cells with urine, ESR and blood serum sodium. Results. The study involved 158 patients. The main group includes 128 children with chronic kidney disease of stage 1–4 aged 1–17. The comparison group was 30 children with no diagnosed kidney pathology aged 1 to 17. The children of the two groups did not differ statistically by sex and age. A model has been obtained to predict chronic kidney disease in children on a test sample with an accuracy of 93.5% [87.1; 100.0]%; a sensitivity of 92.0% [82.1; 100.0]; a specificity of 100.0% [100.0; 100.0.0]; ROC-AUC = 98.7%;100.0].0. Obtained model of excellent quality (>90%). The model describes 90.3% [83.8; 96.1]% variance. Conclusion. The proposed model demonstrates excellent predictive ability and may be of important clinical importance for predicting the chronic process in primary health care, where symptoms associated with the risk of chronic kidney disease, may be overlooked. Predicting and developing early nephroprotective strategies can lead to better treatment outcomes and prolong life.

Effectiveness, safety and indications of acute normovolemic haemodilution in total knee arthroplasty

Total knee arthroplasty (TKA) is the most cost-effective, and potent method for the treatment of end-stage knee osteoarthritis. Acute normovolemic haemodilution (ANH) can effectively replace the need for allogeneic transfusions due to the high amount of bleeding during TKA. However, more studies are needed to prove the efficacy and safety of ANH and to clarify its indications in the field of knee replacement. Medical records from June 1, 2019 to June 1, 2021 were searched and grouped according to inclusion and exclusion criteria. PART I: 58 patients with ANH during TKA were selected as the ANH group (n = 58), and 58 patients with allogeneic transfusion were chosen as the control group (n = 58). PART II: Patients with anaemia were divided into the ANH group (n = 18) and the control group (n = 12). PART I: The postoperative inflammatory index and serum albumin in the ANH group were significantly lower than those in the control group. No significant difference was observed in the theoretical loss of red blood cells, postoperative renal function, liver function, cardiac function and biochemical ion index between the two groups. The effective rate of ANH in the normal haemoglobin group was significantly lower than that in the anaemia group. PART II: In patients with anaemia, the theoretical loss of red blood cells in patients with ANH was less than that in the control group. The postoperative inflammation, renal function, liver function and cardiac function in the ANH group were better than those in the control group, and no significant difference was noted in biochemical ions and nutritional status indicators. This paper shows that ANH not only can replace allogeneic transfusion in TKA, especially in patients with anaemia, but also has lower inflammatory indicators than allogeneic transfusion. From a security perspective, the body’s tolerance to ANH is within the body’s compensation range.

Autoimmune Haemolytic Anaemia and Anastomosing Haemangioma: A Possible Relationship

This study presents the case of a patient with autoimmune haemolytic anaemia and an anastomosing haemangioma. The main dilemma is whether or not there is a relationship between the two processes and how both issues should be managed. The diagnostic methods used were analytical and imaging techniques, which proved to be inconclusive for the diagnosis of anastomotic haemangioma. Preoperative treatment with corticosteroids did not prevent anaemia, platelets, and elevated levels of total reticulocytes in the postoperative period. Surgical indication was based on with reference to the progression of proliferative activity, with tumour enlargement and the compression of the vena cava over time. The procedure involved the total surgical resection of the tumour. The indication for surgical treatment of the anastomosing haemangioma and the decrease in alpha-fetoprotein after tumour resectioning are the most relevant data, although alpha-fetoprotein increased again after a few weeks. Angiogenesis resulting from the formation of erythroblastic islands in the tumour periphery, and clonal expansions may be a compensatory mechanism of haemolysis caused by autoimmune haemolytic anaemia. In conclusion, erythropoietic clonal proliferation in anastomosing haemangioma may be secondary to autoimmune haemolytic anaemia and compensates for the loss of red blood cells in bone marrow affected by senescence. Therefore, a possible causal relationship between autoimmune haemolytic anaemia and anastomosing haemangioma is proposed.

Part II: Blood Transfusion and Donor Exposure in the Surgical Management of Trigonocephaly Patients: A Protocol From Alder Hey Craniofacial Unit.

Trigonocephaly is a craniofacial malformation caused by premature fusion of the metopic suture. Surgical correction frequently results in the need for blood transfusion. Transfusion complications include transfusion-transmitted infections (TTIs), immune-mediated reactions, and volume overload. Donor exposure (DE) describes the number of blood products from unique donors with increasing DE equating to an increased risk of TTI. We evaluate data on 204 trigonocephaly patients covering 20 years of practice with respect to blood transfusions and DE. This represents the largest series from a single unit to date. A protocol based on our experiences has been devised that summarizes the key interventions we recommend to minimize blood transfusions and DE in craniofacial surgery. Patients operated on between 2000 and 2020 were included. DE and a range of values were calculated including estimated red cell loss (ERCL) and estimated red cell volume transfused (ERCVT). Groups were established by relevant interventions and compared using the Mann-Whitney U test. Mean DE fell from 1.46 at baseline to 0.85 ( P <0.05). Median allogenic transfusion volume fell from 350mL at baseline to 250mL ( P <0.05). Median ERCL fell from 15.05mL/kg at baseline to 12.39mL/kg and median ERCVT fell from 20.85 to 15.98mL/kg. Changes in ERCL and ERCVT did not reach statistical significance. DE can be minimized with the introduction of key interventions such as a restrictive transfusion policy, preoperative iron, cell saver, tranexamic acid, and use of a matchstick burr for osteotomies.

Mechanism of Actions, Efficacy, and Long-term Use of Steroids in Autoimmune Hemolytic Anemia (AIHA)

Autoimmune hemolytic anemia (AIHA) is a rare condition in which autoantibodies cause the loss of red blood cells. Steroids have been used to treat several illnesses, including AIHA. For now, steroids remain as the first line of treatment for AIHA. In AIHA, especially warm AIHA (wAIHA), steroids suppress autoantibody production and downregulate Fcγ receptors' expression on monocytes to prevent hemolysis. The type of steroids chosen for first-line therapy for wAIHA in pediatrics and adults are Prednisone (Prednisolone) and Methylprednisolone. At the same time, Dexamethasone is used as an alternative treatment in AIHA. Steroids show better therapeutic outcomes in the first 2-3 weeks of administration, but the proportion of patients who remain in remission after steroid discontinuation are still quite low. Long-term administration of steroids may affect bone, blood glucose metabolism, and hypothalamic-pituitary-adrenal axis (HPAA). However, steroids which have a linear pharmacokinetic profile, intermediate-acting glucocorticoids such as Prednisone (Prednisolone) or Methylprednisolone, and also tapering dose of steroids after 2-4 weeks administration will be safe for long term use as AIHA treatment.Keywords: steroids, glucocorticoid, corticosteroid, autoimmune hemolytic anemia, AIHA, mechanism of action, efficacy

Relevance of haemoglobin monitoring in apheresis plasma donors: A retrospective cohort study in Québec, Canada.

Systematically measuring pre-donation haemoglobin (Hb) levels might be overly cautious for apheresis plasma donation, since plasmapheresis entails a small loss of red blood cells. We explored the association between the frequency of apheresis plasma donation and capillary blood Hb levels. This retrospective cohort study included donors who gave apheresis plasma at least twice between 24 October 2020 and 23 October 2022 in Québec, Canada. Results were stratified by sex and analysed with linear repeated-measure mixed models with random intercepts. In total, 9535 men (mean age = 46.7 years) and 9409 women (mean age = 41.1 years) made ≥2, but no more than 16 apheresis plasma donations. Over an average of 9.2 months of observation, men maintained Hb levels well above the Hb deferral threshold, and their Hb levels decreased by only 0.17 g/dL between the 1st and 15th donation return (p < 0.0001). Over an average of 9.0 months of observation, women also maintained adequate Hb levels, and their Hb levels decreased by 0.08 g/dL between the 1st and 15th donation return. The frequency of apheresis plasma donation was not associated with clinically meaningful changes in Hb levels, neither in men nor in women. This evidence questions the relevance of systematically monitoring Hb for apheresis plasma donation, at least for donation frequencies of ≤7-8 times per year. However, an adverse impact of plasmapheresis on Hb levels cannot be ruled out for individuals donating more frequently or for longer than ~9 months.

Does the accelerometer-based navigation system reduce blood loss and transfusion in one-stage sequential bilateral total knee arthroplasty? A randomized double-blind controlled trial

BackgroundTotal knee arthroplasty (TKA) is associated with significant blood loss and postoperative transfusion. The accelerometer-based navigation (ABN) system guides the bone cutting plane without breaching the intramedullary canal, which may reduce bleeding. This study aimed to investigate blood loss and transfusion compared between the ABN system and the conventional procedure in patients undergoing one-stage sequential bilateral TKA (SBTKA).MethodsA total of 66 patients scheduled for SBTKA were randomly allocated to either the ABN or conventional group. Postoperative hematocrit (Hct) level, drainage blood loss, transfusion rate, and amount of packed red cell transfusion were collected. Total red blood cell (RBC) loss was then calculated for the primary outcome.ResultsThe mean calculated total RBC loss in the ABN and conventional group was 669.7 and 630.0 mL, respectively (p = 0.572). There was no significant difference between groups for other evaluated outcome parameters, including postoperative Hct level, drainage blood loss, or packed red cell transfusion volume. All patients in the conventional group required postoperative blood transfusion while 96.8% of patients in the ABN group were transfused.ConclusionsThe total RBC loss and volume of packed red cells transfusion were not significant difference between interventions, which suggest no benefit of the ABN system in reducing blood loss and transfusion in patients undergoing SBTKA.Trial registrationThe protocol of this study was registered in the Thai Clinical Trials Registry database no. TCTR20201126002 on 26/11/2020.

Plateletpheresis donor deferral patterns at a tertiary care hospital in North India: A need for rethink of haemoglobin cutoff.

The donor deferral criteria for blood or apheresis donations are established for two main reasons: (i) to ensure the safety of the blood donor (non-maleficence); (ii) to obtain safe blood of standard quality that has therapeutic benefit for the patient (beneficence). This study was planned to assess the various causes and patterns of plateletpheresis donor deferral in our hospital and to subsequently assess whether any evidence based changes can be done in the current plateletpheresis donor deferral criteria in India to maximize the platelet donor pool without compromising donor safety. The present study was conducted from May 2021 till June 2022 in the department of transfusion medicine of a tertiary care hospital in North India. The first part of the study was conducted from May 2021 till March 2022 to assess the various causes of donor deferral by analysing the plateletpheresis donor deferral data during the corresponding period. The second part of the study was conducted from April 2022 till June 2022, to assess: (i) average decrease in haemoglobin after plateletpheresis procedure; (ii) red blood cell loss during plateletpheresis procedure; (iii) to determine whether any correlation exists between donor haemoglobin and platelet yield. During the study period, a total of 260 donors were screened for plateletpheresis, out of which 221 (85%) donors were accepted and 39 (15%) donors were deferred for various reasons. Out of the 39 deferred donors, 33 (84.6%) were temporary deferrals, while 6 (15.4%) were permanent deferrals. Low haemoglobin (Hb<12.5g/dl) was a cause of deferral in 12.8% (n=5) of the deferred donors. 192 (73.9%) out of the 260 donors were replacement donors. The calculated mean decrease in haemoglobin as a result of plateletpheresis procedure was 0.4g/dl. No correlation was seen between donor pre-donation haemoglobin and platelet yield (p=0.86, r=0.06, R2=0.003). The calculated mean red cell loss as a result of plateletpheresis procedure was 28ml. Low haemoglobin (<12.5g/dl) is a significant cause of temporary plateletpheresis donor deferral in India. In view of the advancement in plateletpheresis technology, which has resulted in minimal red cell loss with the current generation apheresis devices, haemoglobin cutoff of 12.5g/dl needs to be reconsidered. Perhaps, after performing a multi-centric trial, a consenscus can be reached for revision of haemoglobin cutoff for plateletpheresis donations.

TLR2/6 agonist treatment after total body irradiation in mice and nonhuman primates induces proliferation of hematopoietic progenitor cells

Abstract Exposure to high doses of radiation, whether intentional or accidental, may cause injury or death. Therapeutics are urgently needed for mitigating injuries caused by radiation exposure. Previously, we identified a synthetic lipopeptide agonist of TLR2/6, namely fibroblast-stimulating lipopeptide (FSL-1), that prolonged survival of mice exposed to lethal ionizing radiation and mitigated hematopoietic acute radiation syndrome. Here, this agent was tested in several mouse models as well as in nonhuman primates given total body irradiation followed 24 hours later with a single subcutaneous injection of FSL-1. These studies revealed the mitigation of radiation-induced loss of platelets and red blood cells, as well as the promotion of bone marrow progenitor cell recovery. These beneficial hematopoietic outcomes were accompanied with a lack of toxicity, showcasing the safe, efficacious application of a single dose of FSL-1 for mitigating hematopoietic dysfunction resulting from radiation. By investigating the mechanism of action of FSL-1 in response to radiation, we confirmed that FSL-1 radio-mitigation activity was mediated through a TLR2/MyD88-dependent process. In FSL-1 treated irradiated mice, we found enhanced numbers of proliferating Ki67 +bone marrow cells. Finally, examination of cellular pathways in mice and nonhuman primate bone marrow cells indicated FSL-1 induced the activation of NF-kB and MAPK signaling. These data suggest that FSL-1 promotes hematopoietic progenitor cell proliferation through the activation of cell survival and activation pathways downstream of TLR2/6 stimulation, and thus may serve to mitigate the injurious consequences of radiation. Supported by grants from NIH (AI067798) and DOD Congressionally Directed Medical Research Program grant W81XWH-15-1-0574 (JMC).

Review and assessment of the donor safety among plasma donors.

Review and assessment of the donor safety among plasma donors.

Clinical and Physiological studies of jaundice in the newborn infants and novel design and diagnostic method for neonatal hyperbilirubinemia determination

Today, jaundice is one of the most common problems in newborns. Loss of Red Blood Cells (RBC) is the cause of jaundice. RBC rupture is known as hemolysis, and if hemolysis occurs faster than the liver excretes, bilirubin levels in the body rise and leading to jaundice. Bilirubin is directly soluble in water and is transported to the liver and excreted in stages, most of which is excreted in the feces and a small amount is excreted in the urine. Measuring bilirubin levels in infants is one of the essential tests after birth. In measuring the amount of jaundice in infants, complex components such as the formation of body organs, compounds on the skin of the infant, and other parameters are involved. Making a device to measure the amount of jaundice. The difference in the methods of measuring and treating jaundice in infants depends on the condition of the infant with jaundice. Non-invasive methods are used in infants with low bilirubin levels, but in acute and critical cases, invasive and direct methods are used. Jaundice tests are performed on both infected and healthy infants and are not limited to sick infants.

THE CORRELATION OF INFORMATION MEDIA ABOUT ADOLESCENT ANEMIA WITH INTEREST IN COMPLEMENTARY OR PHARMACOLOGY THERAPY

Background: Factors that cause anemia are diet, blood loss, chronic infection, micronutrients, or congenital abnormalities of red blood cells or Hb. Iron deficiency is a common cause of anemia, iron deficiency occurs when there is inadequate intake and absorption of iron even though iron is very important for the growth of human cells, especially during adolescence. This study aims to analyze the relationship between information media and interest in choosing complementary therapies or pharmacology if symptoms occur or anemia is diagnosed. Methods: This was a cross-sectional analytic research. The research population was all Midwifery Students of the Nahdlatul Ulama Institute of Health Tuban 2nd semester Age 18-23 years, data collection was carried out in April 2022. The sample size was calculated using the slovin formula, obtained 46 samples, side technique using simple random sampling. The instrument used is a questionnaire via google form which has been tested for validity and reliability. Analysis of the data used was the Contingency Coefficient with an alpha value of 0.05 using SPSS. Results: Almost half of the respondents (26.1%) who received information about anemia from electronic media were interested in using pharmacological therapy for anemia and almost half of the respondents (30.4%) who received information from print and electronic media were interested in choosing pharmacological therapy for anemia. Data analysis using contingency coefficients showed an insignificant relationship p = 0.938 (&gt; 0.05) between information media about adolescent anemia and interest in complementary or pharmacology therapies,. Conclusion: possible environmental factors that could influence a person's behavior of interest in choosing complementary or pharmacology therapies. Keywords: Anemia, complementary, information media, pharmacological therapy

Iron Deficiency Anemia: Efficacy and Limitations of Nutritional and Comprehensive Mitigation Strategies.

Iron deficiency anemia (IDA) has reached epidemic proportions in developing countries and has become a major global public health problem, affecting mainly 0–5-year-old children and young women of childbearing age, especially during pregnancy. Iron deficiency can lead to life-threatening loss of red blood cells, muscle function, and energy production. Therefore, the pathogenic features associated with IDA are weakness and impaired growth, motor, and cognitive performance. IDA affects the well-being of the young generation and the economic advancement of developing countries, such as India. The imbalance between iron intake/absorption/storage and iron utilization/loss culminates into IDA. However, numerous strategic programs aimed to increase iron intake have shown that improvement of iron intake alone has not been sufficient to mitigate IDA. Emerging critical risk factors for IDA include a composition of cultural diets, infections, genetics, inflammatory conditions, metabolic diseases, dysbiosis, and socioeconomic parameters. In this review, we discuss numerous IDA mitigation programs in India and their limitations. The new multifactorial mechanism of IDA pathogenesis opens perspectives for the improvement of mitigation programs and relief of IDA in India and worldwide.

Oxygen gradient ektacytometry does not predict pain in children with sickle cell anaemia

SummaryThe loss of red blood cell (RBC) deformability in sickle cell anaemia (SCA) is considered the primary factor responsible for episodes of acute pain and downstream progressive organ dysfunction. Oxygen gradient ektacytometry (Oxygenscan) is a recently commercialised functional assay that aims to describe the deformability of RBCs in SCA at differing oxygen tensions. So far, the Oxygenscan has been evaluated only by a small number of research groups and the validity and clinical value of Oxygenscan-derived biomarkers have not yet been fully established. In this study we examined RBC deformability measured with the Oxygenscan in 91 children with SCA at King’s College Hospital in London. We found a significant correlation between Oxygenscan-derived biomarkers and well-recognised modifiers of disease severity in SCA: haemoglobin F and co-inherited α-thalassaemia. We failed, however, to find any independent predictive value of the Oxygenscan in the clinical outcome measure of pain, as well as other important parameters such as hydroxycarbamide treatment. Although the Oxygenscan remains an intriguing tool for basic research, our results question whether it provides any additional information in predicting the clinical course in children with SCA, beyond measuring known markers of disease severity.

Macronutrient, nutritional status, and anemia incidence in adolescents at Islamic boarding school

Background: Anemia occurs due to the body's loss of red blood cells and decreased iron absorption. Globally, it is known that the prevalence of anemia is 1.62 billion, with the majority of anemia sufferers being a group of women who are not pregnant, as many as 468.4 million people. In addition, the highest prevalence of anemia in the group of school-age girls is 47.4%, while in men, only 12.7%.Objective: This study aims to determine the correlation between macronutrients and nutritional status with the anemia accident in adolescents at Islamic Boarding schools.Methods: This study used a case-control design with matching criteria aged 15-19 years, not menstruating, not fasting. Sampling with quota sampling of late adolescents with a population of 15-19 years 1,359 people, anemic case sample of 46 people and control without anemia 46 people, intake questionnaire using the SQ-FFQ, statistical test with Chi-Square.Results: There was a significant relationship between macronutrient intake [energy p=0.048; OR=3.3 (CI 0.965-11.28), protein p=0.036; OR=3.98 (CI 1.018-15.57)] and nutritional status [p=0.024; OR=5.35 (CI 1.088-26.32)] with anemia incidence. Less energy intake has a risk of 3.3 times anemia, lack of protein intake has a risk of 3.98 times, and malnutrition has a risk of anemia of 5.35 times.Conclusions: There was a significant correlation between energy, protein intake, and nutritional status with anemia incidents. Nutritional status has the strongest association with anemia. * Presented at the International Nutrition and Health Symposium (INHESION) on Sunday, November 15th, 2020, in Yogyakarta, organized by HIMAGIKA and the Department of Health Nutrition, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada

Comparison of a modified flow cytometry osmotic fragility test with the classical method for the diagnosis of hereditary spherocytosis.

Hereditary spherocytosis (HS) is the most common inherited hemolytic anemia. The flow cytometric test using eosin-5'maleimide (EMA) is a well-established diagnostic method. However, in order to improve HS detection, it is recommended that EMA and an osmotic fragility test (OFT) both be performed. OFT is time consuming and labor intensive. We used a flow cytometric (FOFT) adaptation of the classical OFT reported by Yamamoto. We compare the FOFT to the classical OFT including practical data and propose options for simplifying this method. Suspected and known HS patients and controls were tested by the following methods: EMA, OFT, and FOFT including some modifications. The FOFT method is robust and correlates to loss of red blood cells. OFT and FOFT gave similar results in healthy controls and four HS patients. Normal range for FOFT in 70 adults is shown and can be used as a reference value. Neonates should have their own normal range defined. Overnight sample incubation at 37°C did not add information to the FOFT results. Our modified Yamomoto FOFT can replace the classic OFT as the addition to EMA for the diagnosis of HS. The use of flow cytometry in both these methods requires small sample volume, is reproducible, simpler, and produces results more rapidly.

Methods of pathogen inactivation in whole blood and red blood cells: current state of knowledge

Although pathogen reduction technology was implemented for platelet concentrates and plasma, the risk of pathogen transmission has not been completely eliminated as no inactivation procedures were implemented for red blood cells and whole blood. Research was therefore focused on developing methods for effective pathogen inactivation in red blood cell components. Attempts were made to apply either chemical compounds (porphyrins and Sylsense compounds) or photosensitizers such as methylene blue (Theraflex MB Plasma System) and amotosalen hydrochloride (Intercept System) already in use for pathogen inactivation in plasma. None proved effective for pathogen inactivation in red blood cells. Approval was recently given to pathogen inactivation methods based on S-303 compound (for red blood cells) and with riboflavin (for whole blood). Clinical trials are ongoing. Pilot studies have shown that during storage of packed red blood cells subjected to pathogen inactivation with S-303 demonstrated slight loss of red blood cells, decrease in hemoglobin concentration, significantly lower lactate concentration, and lower pH. Pathogen inactivated whole blood stored at room temperature for up to seven days showed slight hemolysis (within the normal range). This paper presents several pilot clinical trials with pathogen inactivated red blood cells or whole blood. It focuses primarily on the recovery of red blood cells in the recipient's organism and on hemoglobin concentration.

Blood loss and transfusion rate compared among different dosing regimens of tranexamic acid administration in patients undergoing hip hemiarthroplasty for femoral neck fracture: A randomized controlled trial

BackgroundIntravenous tranexamic acid (TXA) administration is a proven safe and effective method for reducing both blood loss and transfusion in total joint arthroplasty. However, data specific to its efficacy in hip hemiarthroplasty (HHA) for femoral neck fracture are scarce. Furthermore, no study has investigated the efficacy of an additional dose of TXA administration. Accordingly, this study aimed to assess blood loss and the transfusion rate compared among different regimens of TXA administration in patients undergoing HHA for femoral neck fracture. MethodsBetween January 2019 to December 2020, 90 HHA patients were randomized into one of three groups (30 patients/group). Control group patients received intravenous normal saline solution (NSS) 20 mL before skin incision, and NSS 20 mL at 3 hours after surgery. one-dose (1D) group patients received 750 mg of intravenous TXA before skin incision, and NSS 20 mL at 3 hours after surgery. Two-dose (2D) group patients received 750 mg of intravenous TXA before skin incision, and 750 mg of TXA at 3 hours after surgery. The primary outcome was blood transfusion rate. Intraoperative blood loss, hemoglobin levels at 24- and 48-hours postoperation, and calculated total blood loss were compared among the three groups. ResultsThe mean age of the study population was 79.7 years, and 76.7% of participants were women. The transfusion rate in the control, 1D and 2D groups was 43.3%, 16.7%, and 3.3%, respectively. Total hemoglobin loss; total red blood cell loss; intraoperative blood loss; hemoglobin level at 24- and 48-hours postoperation; change in hemoglobin level between 0 and 24 hours, and between 0 and 48 hours; blood transfusion rate; and, the number of patients who did not require blood transfusion were all significantly improved in the 2D group compared to baseline. No parameters were significantly improved in the 1D group compared to controls. ConclusionsThe results of this study demonstrate both the efficacy of TXA administration in HHA, and the superiority of two-dose TXA administration over one-dose TXA administration in HHA for femoral neck fracture.

Influential Role of Macrophages in Hepcidin Regulation in Apo-Transferrin Treated β-Thalassemic Mice

Iron is a crucial component of the oxygen carrying molecules hemoglobin and myoglobin, and its recycling, primarily through macrophages, is essential to enable sufficient hemoglobin production to offset senescent red blood cell loss. The peptide hormone hepcidin, chiefly synthesized in the liver by hepatocytes, is the principle negative regulator of iron homeostasis and functions through binding and down-regulating ferroportin, the only known iron exporter on cells. IL-6 is an inflammatory cytokine secreted by macrophages, known to induce hepcidin expression via Stat3 signaling (Nemeth et al 2003; Wrighting and Andrews 2006). The disease β-thalassemia is characterized by a decrease in β-globin chain production that ultimately leads to a combination of anemia, ineffective erythropoiesis, and iron overload. We have shown that exogenous apo-transferrin (apoTf) treatment ameliorates ineffective erythropoiesis and reduces iron overload by increasing hepcidin expression in β-thalassemic mice (Li et al 2010). In addition to changes in MEK/ERK signaling (Chen et al 2016), our preliminary data reveals enhanced Stat3 signaling in hepatocytes from apoTf-treated mice. We hypothesize that apoTf functions in part through altering the function of macrophages and explore mechanisms of macrophage-induced hepcidin regulation in this setting. First, we examined the direct effect of apoTf on macrophages in vitro and demonstrate increased macrophage cell number and increasing IL-6, MCP-1, and IL-10 concentrations in supernatant of apoTf-treated macrophages. The addition of apoTf to cultured peritoneal macrophages from iron dextran treated mice resulted in increased iron mobilization to the supernatant without increasing ferroportin expression. Second, we explored the possibility that apoTf alters the polarization of macrophages or in another way influences the proportion of different types of macrophages. For example, two distinct macrophage populations have been identified in the peritoneal cavity, large peritoneal macrophages (LPM) and small peritoneal macrophages (SPM), that are functionally and developmentally distinct (Ghosn et al 2010). To assess the in vivo effect of exogenous apoTf on macrophages, we performed intraperitoneal apoTf injections of wild type and β-thalassemic mice and demonstrate a significantly increased proportion of SPM to LPM compared to PBS injected controls in both mice strains (Fig 1). Third, since apoTf upregulates hepcidin expression in vivo and shifts the population of peritoneal macrophages, we sought to test the role of macrophages in hepcidin regulation. To test the in vitro effect of macrophages on hepcidin expression, we co-cultured primary hepatocytes and macrophages. Peritoneal macrophages co-cultured with hepatocytes activated Stat3 signaling. Increasing the number of macrophages co-cultured with hepatocytes also correspondingly caused increased hepcidin expression. Furthermore, liver specific macrophages (Kupffer cells) and peritoneal macrophages both significantly upregulated hepcidin expression in hepatocyte co-culture and showed no difference in hepcidin induction ability between the two macrophage subsets (Fig 2). In addition, macrophages in co-culture with hepatocytes further increased hepcidin expression in the presence of additional apoTf, findings that were not recapitulated with addition of holo-transferrin in place of apoTf to co-culture (Fig 3). Lastly, mice were either treated with a low iron diet or intraperitoneally injected with iron dextran to induce iron loading to assess peritoneal macrophages' effect on hepcidin regulation in different iron conditions. Iron loaded macrophages induced the lowest hepcidin expression in hepatocyte co-culture while low iron diet macrophages caused the highest expression (Fig 4). IL-6 excretion was also highest in the low iron condition. Taken together, our data delineate the role of macrophages in hepcidin regulation in apoTf-treated, iron overloaded, and iron restricted conditions and suggest that apoTf functions through directly altering macrophage function and possibly sub-population to induce hepcidin expression in a paracrine manner in the liver. [Display omitted] DisclosuresFleming:Protagonist Therapeutics: Membership on an entity's Board of Directors or advisory committees.