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Homozygous familial hypercholesterolemia (HoFH), is a rare genetic disorder characterized by dual mutations in the low-density lipoprotein receptor (LDLR) gene, leading to dysfunctional or absent LDLRs, often accompanied by severe premature Atherosclerotic Cardiovascular Disease (ASCVD) and exhibiting refractoriness to aggressive pharmacological interventions. Double filtration plasmapheresis (DFPP), a form of lipoprotein apheresis (LA), has been effectively utilized as an adjunctive treatment modality to reduce serum LDL-C levels in refractory cases of HoFH. Here, we report a case of a 36-year-old female with HoFH who developed xanthomas on her limbs and waist at age 7. Despite maximum-tolerated doses of statins from age 32, combined with ezetimibe and evolocumab, her LDL-C levels remained critically elevated at 12–14 mmol/L. Her genetic testing confirmed a homozygous LDLR mutation. At 35 years old, she experienced exertional chest pain, and percutaneous coronary intervention revealed severe calcific left main stenosis, necessitating stent implantation. Subsequently, she initiated once every 1–2 months DFPP. Pre-DFPP, her LDL-C and total cholesterol (TC) levels were 13.82 ± 3.28 and 15.45 ± 0.78 mmol/L, respectively. Post-DFPP, her LDL-C and TC levels significantly decreased to 2.43 ± 0.33 mmol/L (81.76 ± 4.11% reduction) and 3.59 ± 0.41 mmol/L (76.76 ± 2.75% reduction), respectively. Lipoprotein (a) and triglycerides also decreased by 89.10 ± 1.39% and 42.29 ± 15.68%,respectively. Two years later, there was no progression of coronary artery disease, and her symptoms and xanthomas regressed significantly. Collectively, DFPP effectively reduces LDL-C levels in refractory cases of HoFH and contributes to delaying ASCVD progression, representing an efficacious adjunctive therapeutic modality. [ABSTRACT FROM AUTHOR]

Ultrasound‐guided cannulation (USGC) of a peripheral vein reduces the need for central vascular access device (CVAD) placement to perform a successful apheresis procedure. Effective training of healthcare professionals to acquire this skill is essential. Here, we report on the implementation of the USGC training across eight apheresis units in England. A 3‐h introductory training program was devised with theoretical and practical elements. This was followed by supervised USGC practices on any patient ≥ 18 years old, regardless of venous status. Data on all supervised USGC attempts were recorded and analyzed. Over an 11‐month period, 11 nurses were trained to USGC competency with another six nurses still in training, resulting in seven out of eight units having at least one USGC‐competent nurse. In one unit, USGC training has not started yet. Three hundred sixty‐one supervised USGC episodes on 168 patients and donors took place; of these, 178 were done for training purposes only on patients who had visible and palpable veins, 179 USGC were done on patients with difficult venous status and four were not recorded. The period from first supervised USGC to competency was a median of 45 days (Range: 17–166 days), with a median of 15 successful (Range: 10–30) and two unsuccessful (Range: 1–15) USGC being performed per trainee. The placement of 57 CVADs and 41 multiple cannulation attempts have been avoided. USGC is a useful tool to reduce the need for CVAD. Training across multiple apheresis units is a lengthy procedure, but it can be successfully implemented. [ABSTRACT FROM AUTHOR]

Apheresis is performed worldwide for an increasing number of indications. The development of common data elements (CDE) for apheresis related areas may facilitate conduct of new research, enhance quality initiatives including benchmarking, and improve patient care. This report describes the systematic development of the Uniform Apheresis Case Report Form (UACRF) as part of the Apheresis in the United States (ApheresUS) program. A consensus panel of 17 diverse experts in apheresis, related specialties, and electronic case report form (eCRF), and database development was assembled. The panel met via online conferencing from November 17, 2020 to December 1, 2021. A draft document was posted online for public comment from October 11, 2021 to November 10, 2021. Feedback was collected using an online survey tool. The consensus panel revised the UACRF. This version was converted to an eCRF with additional changes made to improve usability in this format. The final version of the UACRF was created on August 24, 2023. The UACRF contains 16 modules: procedure and subject eligibility, patient demographics, general procedure information, laboratory parameters, vascular access, common procedure elements, eight procedure specific modules (mononuclear cell collection and seven therapeutic modalities), outcomes, and site information. A total of 137 data elements were created, including 57 with one or more subelements. The UACRF is the first systematic attempt to develop CDE for therapeutic apheresis and white blood cell collections. Further validation of the UACRF is necessary to confirm the tool's ability to collect the relevant data elements and determine the usability of the form. [ABSTRACT FROM AUTHOR]

Evidence describing the use of plerixafor in the off‐label population of relapsed/refractory germ cell tumors (GCT) is limited. We aim to describe the effect of rescue versus preemptive plerixafor use on apheresis collection days, collection yields, and cost. We retrospectively collected data on 77 consecutive patients (at least 15 years of age) with GCT who underwent peripheral blood stem cell (PBSC) collection for autologous stem cell transplant between January 1, 2020 and May 1, 2022. Depending on insurance approval, plerixafor was given either as "rescue" (after a first apheresis collection of < 5 × 106 CD34+ cells/kg) or as "preemptive" on Day 4 of granulocyte‐colony stimulating factor (G‐CSF) prior to the first apheresis collection, if the Day 4 peripheral blood CD34+ count was < 40 cells/μL. A total of 66% of patients who received preemptive plerixafor completed collection in 1 day, similar to good mobilizers who only needed G‐CSF (71%, p = 0.366). In contrast, all poor mobilizers in the rescue group required at least 2 days of collection and had lower CD34+ cell yields than the preemptive group (7.15 vs. 9.81 × 106/kg, p = 0.0055). A cost analysis revealed that preemptive plerixafor may save approximately $7000 per patient compared with a rescue approach. Preemptive plerixafor in GCT patients undergoing PBSC collection allows relatively poor mobilizers to collect in fewer days and with lower overall cost. Fewer apheresis procedures result in less risk to the patient, increased patient satisfaction, and the ability to schedule more patients within the constraints of staffing. [ABSTRACT FROM AUTHOR]

Background and Objectives Materials and Methods Results Conclusion The post‐thaw shelf‐life of cryoprecipitate is 6 h, leading to high wastage. Storage of thawed cryoprecipitate at refrigerated temperatures may be feasible to extend the shelf‐life. This study aimed to evaluate the quality of thawed cryoprecipitate stored at 1–6°C for up to 14 days.Cryoprecipitate (mini‐ and full‐size packs derived from both apheresis and whole blood [WB] collections) was thawed, immediately sampled and then stored at 1–6°C for up to 14 days. Mini‐packs were sampled at 6, 24, 48 and 72 h, day 7 and 14; full‐size cryoprecipitate was sampled on day 3, 5 or 7. Coagulation factors (F) II, V, VIII, IX, X and XIII, von Willebrand factor (VWF) and fibrinogen were measured using a coagulation analyser. Thrombin generation was measured by calibrated automated thrombogram.FVIII decreased during post‐thaw storage; this was significant after 24 h for WB (p = 0.0002) and apheresis (p < 0.0001). All apheresis and eight of 20 WB cryoprecipitate met the FVIII specification (≥ 70 IU/unit) on day 14 post‐thaw. Fibrinogen remained stable for 48 h, and components met the specification on day 14 post‐thaw. There were no significant differences in VWF (WB p = 0.1292; apheresis p = 0.1507) throughout storage. There were small but significant decreases in thrombin generation lag time, endogenous thrombin potential and time to peak for both WB and apheresis cryoprecipitate.Whilst coagulation factors in cryoprecipitate decreased after post‐thaw storage, the thawed cryoprecipitate met the Council of Europe specifications when stored at refrigerated temperatures for 7 days. [ABSTRACT FROM AUTHOR]

This document contains summaries of various articles related to blood donation and transfusion. The articles cover topics such as efforts to improve ethnic minority blood donor numbers, collaborations to recruit blood donors for research programs, trends in malaria antibody testing, testing for Transfusion Related Acute Lung Injury (TRALI), and the accuracy of point-of-care testing methods. Other topics include restless legs syndrome and sleep disorders in blood donors, lookback investigations for transfusion-transmitted infections, and various parameters related to blood transfusion and testing. The document also discusses studies on red blood cell manufacturing methods, safe transfusion plans for patients with specific needs, predictors for red blood cell transfusion in pregnant women, and the appropriateness of blood transfusions in different hospital settings. Additionally, it covers initiatives to improve transfusion practices, patient safety, and the management of blood supply chain. The document emphasizes the importance of collaboration, education, and quality improvement in transfusion services. [Extracted from the article]

The Association for the Advancement of Blood and Biotherapies (AABB) has updated its Standards for blood banks and transfusion services in its 34th edition to ensure safety and standardization in transfusion practices. The new edition includes changes related to cold-stored platelets and the manufacture of Cryoprecipitated Antihemophilic Factor derived from PF24. These updates reflect advancements in technology, emerging infectious diseases, and feedback from AABB members, aiming to enhance safety and quality in blood collections, testing, and transfusions. [Extracted from the article]

Introduction: Phosphatidylethanol (PEth) is a long‐term marker of alcohol consumption used frequently in clinical scenarios such as liver transplant evaluation. Recent cases have demonstrated that packed red blood cell (pRBC) transfusion creates the potential for artificial elevation or decrease of observed PEth concentrations in recipients. Very little is known about the prevalence or stability of PEth in pRBCs. Methods: Apheresis and whole‐blood (WB) donations were tested for PEth using liquid chromatography – tandem mass spectrometry with limit of quantitation 10 ng/mL. Units were stored under routine blood bank conditions to evaluate the stability of PEth and the impact of irradiation. Results: Over 40% of apheresis and WB donors had PEth ≥10 ng/mL (maximum observed 587 ng/mL). As WB units were processed into component pRBCs, PEth concentrations increased and were higher than donor WB levels (EDTA sample) prior to collection (maximum observed 711 ng/mL). Storage for up to 5 weeks post donation resulted in mean 17.3% decrease in PEth‐positive units; in contrast to a prior report, we observed no PEth formation in units with negative (<10 ng/mL) baseline concentrations. Irradiation of pRBCs did not substantially affect PEth concentrations in either PEth‐positive or PEth‐negative units. Discussion: PEth concentrations in healthy blood donors may potentially confound alcohol use or abstinence assessment in pRBC recipients. Transfusion medicine services and clinical practices such as transplantation and behavioral medicine should recognize this phenomenon and collaborate on testing protocols to appropriately interpret PEth in pRBC recipients. [ABSTRACT FROM AUTHOR]

High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation is the standard of care for eligible patients with newly diagnosed multiple myeloma leading to prolonged progression free and overall survival. Successful engraftment following hematopoietic stem cell infusion requires adequate stem cell doses. Current mobilization regimens include granulocyte colony-stimulating factor (G-CSF) with or without plerixafor. Motixafortide is a recently approved agent that can be used in combination with G-CSF for mobilization. In the absence of any head-to-head trials comparing the two products, this article aims to outline the similarities and differences of these two agents. Though moxitafortide has a more favorable pharmacokinetic profile in comparison to plerixafor, in clinical trials, the agents demonstrated similar efficacy. In addition, the use of motixafortide in clinical practice may be limited by product cost as well as administration and monitoring requirements. [ABSTRACT FROM AUTHOR]

Introduction: Acute pancreatitis (AP) following drug-induced hypertriglyceridemia is a rare clinical phenomenon. Immune checkpoint inhibitors have revolutionized treatment for a variety of solid organ and hematological malignancies. Pembrolizumab is a programmed cell death receptor-1 (PD-1) inhibitor that has shown promising responses in many advanced cancers. However, a constellation of immune-related adverse events has also been described. There are reports of pembrolizumab-induced hypertriglyceridemia, but AP as a result of this side effect remains an exceedingly rare clinical sequela. Case report: We delineate a case of a patient with stage IVB non-small-cell lung cancer who developed progressive abdominal pain and nausea following administration of pembrolizumab for four months. Laboratory studies revealed increased serum lipase and triglyceride levels at 12,562 IU/L and 16,901 mg/dL, respectively. The diagnosis of AP was made based on the revised Atlanta classification criteria. After ruling out alternative causes, pembrolizumab-induced hypertriglyceridemia was considered the likely etiology of AP. Management and outcome: The patient was transferred to the medical intensive care unit for close monitoring. Treatment was initiated with intravenous fluids, pain medications, and an insulin infusion. However, her hypertriglyceridemia levels remained persistently elevated, necessitating therapeutic apheresis. She recovered well with no complications after triglyceride apheresis. Discussion: AP following pembrolizumab-associated hypertriglyceridemia remains a rare clinicopathologic entity. Given the widespread clinical use of immune checkpoint inhibitors, knowledge of such rare adverse events is crucial. Evaluation of serum triglyceride levels before and after initiating pembrolizumab therapy may be mandated, especially in patients with metabolic comorbidities. [ABSTRACT FROM AUTHOR]

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Background and Objectives Materials and Methods Results Conclusion In Japan, apheresis donation of plasma is allowed to a maximum of 24 times a year, and plateletpheresis are counted as two plasmapheresis donations. Diversion of the initial blood flow is conducted for all donations, and additionally, blood remaining in apheresis machine circuit is lost. Here, we aimed to investigate on the health impact of frequent apheresis donations, as measured by the serum ferritin (sFer).A total of 538 male apheresis donors and 538 age‐matched whole blood (WB) donors, who gave informed consent to join the study, were enrolled. sFer were compared, according to age. Another group of 19 apheresis donors were followed during four consecutive donations.About half (48%) of repeat male apheresis donors had iron deficiency (sFer < 26 ng/mL), compared with lower rates (13.9%) among male WB donors. It was evident in all age groups, except for teenagers, possibly because of the lower number of donations. Follow‐up of the 19 donors for 4 months revealed a progressive decrease in sFer.Blood remaining in the apheresis machine circuit and diversion of the initial blood flow have been implicated in iron deficiency for many years. Taking the present results, the manufacturer of apheresis equipment was requested to improve it to allow rinseback of the remaining blood, which was achieved only for plateletpheresis. Until further improvement, plasmapheresis frequency was reduced to 12 times a year. Additional measures, such as oral supplementation of iron, need to be considered. [ABSTRACT FROM AUTHOR]

Objectives: Hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for various diseases. The measurement of CD34+ cells is crucial to schedule the peripheral blood stem cell collection and assess the engraftment potential of the apheresis product. The AQUIOS STEM system has been introduced as a novel application on the AQUIOS CL, a fully automated flow cytometer, for the enumeration of CD34+ hematopoietic progenitor cells (HPCs) in accordance with the The International Society for Hematotherapy and Graft Engineering guidelines. This study aimed to assess the potential of the novel AQUIOS STEM system versus currently used systems including the FACSCanto‐II and the FACS Lyric flow cytometer in a multicenter study. Methods: A total of 91 samples were used for the validation of the AQUOIS STEM system, including an analytical performance evaluation by means of assessing precision, sample stability, intersample carryover, and linearity and a method comparison with the present FACS systems in use to assess analytical and clinical decision agreement. Results: Results showed excellent precision, with coefficient of variations <15% for dedicated quality control material and patient samples. There was no significant carry over. The fresh apheresis samples were stable when stored overnight at room temperature and at 4°C. Analytical comparison with the current systems demonstrated good correlation in peripheral blood, and minimal, clinically neglectable systematic and proportional bias in fresh apheresis products but a low correlation coefficient in cryopreserved products. Conclusions: The STEM system on AQUIOS CL allows automated enumeration of CD34+ stem cells, demonstrating good analytical performance and promising overall outcomes in peripheral blood and fresh apheresis products. [ABSTRACT FROM AUTHOR]

Background: Therapeutic apheresis (TA) is already used to treat various diseases in the field of nephrology. The aim of this study was to evaluate the frequency and types of complications that occur during TA in children with kidney disease. Methods: Records of children (≤ 18 years) who underwent TA between 2007 and 2022 were retrospectively reviewed. Children with missing data and those with a diagnosis of nonnephrological disease were excluded. Results: A total of 1214 TA sessions, including 1147 therapeutic plasma exchange (TPE) sessions and 67 immunoadsorption (IA) sessions, were performed on the 108 patients enrolled in the study. Forty-seven percent of the patients were male, and the mean age was 12.22 ± 4.47 years. Posttransplant antibody-mediated rejection (64.8%) and hemolytic uremic syndrome (14.8%) were the most common diagnoses indicating TA. Overall, 17 different complications occurred in 58 sessions (4.8%), and 53 sessions (4.6%) were not completed because of these complications. The distribution of complications among the patients was as follows: 41.4% had technical complications, 25.9% had allergic complications, and 32.7% had others. The most common technical complication was insufficient flow (37.5%). The incidence of complications was greater in patients aged 3–6 years than in patients in the other age groups (p = 0.031). The primary disease, type of vascular access, and rate of fresh frozen plasma/albumin use were similar between patients with and without complications (p values of 0.359 and 0.125 and 0.118, respectively). Conclusions: Our study showed that complications occurred in only 4.8% of TA sessions. The most common complication was technical problems. [ABSTRACT FROM AUTHOR]

With the success of chimeric antigen receptor T-cell (CAR-T) and similar cellular-based therapies, the demand for collection of autologous mononuclear cells by apheresis (MNC(A)) from blood by apheresis has increased. From an apheresis technical standpoint, the collection of MNC(A) is relatively straightforward, especially when compared with collection of hematopoietic progenitor cells (HPC(A)). Most of the collection for MNC(A) are performed for the commercial entities, who use the product for manufacturing cellular therapeutics. We have noticed discrepancies in the handling and apheresis processes required by different companies in obtaining essentially the same product (all companies in the study manufacture CAR-T-based products). We have analyzed the MNC collection requirements from all FDA-approved CAR-T cellular products and some investigational products collected at University of Nebraska Medical Center. We identified discrepancies in the process and suggested mitigation strategies. Step-by-step analysis of the collection requirements. Review of the current guidelines and recommendations on this issue. Multiple discrepancies in the collection process have been identified, even in the products collected for the same company. Practical approach of satisfying all the requirements based on University of Nebraska Medical Center experience has been suggested. The current recommendations from multiple sources were reviewed in discussion. [ABSTRACT FROM AUTHOR]

This article is a systematic review of the use of therapeutic plasma exchange (TPE) for acute complications of sickle cell disease (SCD). The review found that TPE may provide benefits by removing inflammatory cytokines and plasma-based acute phase proteins. The review analyzed studies on TPE for multi-organ failure, thrombotic microangiopathy, intrahepatic cholestasis, and other indications. More evidence is needed to fully understand the impact of TPE on patient outcomes. The text provides a series of case studies on patients with sickle cell disease who underwent TPE as a treatment. TPE was found to improve hemodynamic and respiratory status, resolve organ dysfunction, and lead to good outcomes in some cases. However, there were also instances where patients died or remained dependent on hemodialysis. The text also compares the outcomes of patients who received TPE with those who received red blood cell exchange (RBCX) alone and found similar mortality rates and hospital length of stay. This document provides information on TPE procedures and outcomes for patients with multi-organ failure (MOF) and thrombotic microangiopathy (TMA) related to sickle cell disease. For MOF, TPE was performed after RBCX, with an average plasma volume exchanged of 3.0 liters. The most common TPE outcomes were clinical improvement, hospital length of stay, and in-hospital mortality. For TMA, TPE was used in combination with other treatments, [Extracted from the article]

Background: The data to support chronic automated red cell exchange (RCE) in sickle cell disease (SCD) outside of stroke prevention, is limited, especially in adults. Study Design and Methods: A retrospective analysis was conducted of patients with SCD who were referred for chronic RCE at our institution over a 10‐year period. Data that were evaluated included patient demographics, referral indications, and procedural details (e.g., vascular access, adverse events, etc.). In a subanalysis, the number of annual acute care encounters during 3 years of chronic RCE was compared with that in the year preceding the first RCE. Results: A total of 164 patients were referred for chronic RCE: median age was 28 years (interquartile range [IQR] = 22–36) at referral and 60% were female. Seventy (42.6%) were naïve to chronic transfusion (simple or RCE) prior to referral. The leading indications for referral were refractory pain (73/164, 44.5%) and iron overload (57/164, 34.7%). A total of 5090 procedures occurred during the study period (median = 19, IQR = 5–45). Of the 138 patients who had central vascular access, 8 (6%) and 16 (12%) had ≥1 central‐line‐related thrombosis and/or infection, respectively. Of those who were not RBC alloimmunized at initiation of RCE, 12/105 (11.4%) developed new antibodies during chronic RCE. In those 30 patients who were adherent to therapy for 3 years, there was no significant difference in acute care encounters following initiation of RCE. Conclusion: Prospective clinical trials are needed to determine which patients are most likely to benefit from chronic RCE and refine selection accordingly. See editorial on page 1385–1387, in this issue [ABSTRACT FROM AUTHOR]

Introduction: Peripheral blood stem cell (PBSC) collection via apheresis requires the administration of granulocyte colony‐stimulating factor (filgrastim) to stem cell donors. Several reports have shown that filgrastim administration and apheresis procedure induce a hypercoagulable state across PBSC collection, which might predispose certain donors to thrombotic complications. Methods: We evaluated the hemostatic functions of healthy allogeneic stem cell donors by rotational thromboelastometry (ROTEM). Blood samples from healthy donors (n = 30) were collected at defined time points: before filgrastim (baseline), on the day of apheresis before and after the procedure, and 1 week after apheresis. Results: The results indicated that hemostatic changes are temporary since all parameters in both EXTEM and INTEM assays are restored to their initial values 1 week after the apheresis. Conclusion: We concluded that stem cell apheresis does not induce a hypercoagulable state in healthy donors. This is the first study evaluating the hemostatic functions of stem cell donors by ROTEM. [ABSTRACT FROM AUTHOR]

Background: Platelet inventory constraints necessitate ABO‐incompatible platelet transfusion. Many minimize the hemolytic impact by confirming low titre (LT) donor isohemagglutinins. This process is costly. Pathogen‐reduced platelets (PRP) in platelet additive solutions (PAS) will dilute plasma and decrease high‐titre isohemagglutinins (HT). We determined the proportion of HT platelets and incompatible transfusions for units suspended in plasma to reassess the need for titres following introduction of PRP/PAS. Study Design and Methods: Our titre method is manual tube (1:50) dilution of platelet supernatant from apheresis or whole blood derived buffy coat pools suspended in plasma, tested with A1/B red cells. Testing included 49,058 pooled and 11,738 apheresis platelets over 4 years. The HT proportion, rate of out‐of‐group transfusions, and hemolytic reactions were determined. The impact of PAS dilution was estimated. Results: Totally 60,796 platelet units were tested. Group O pooled and group B apheresis platelets had HT in 6.6% and 5.7%, respectively. Group A pooled and apheresis platelets included 2% with HT. Approximately 25% of platelets transfused were ABO‐incompatible and no hemolytic reactions were reported. Based on the proportions of PAS‐E and plasma for PRP platelets, plasma from each donor comprises 11 mL (6% of total volume) vs 20‐257 mL in untreated pools. PAS‐E will replace and dilute residual plasma by at least 50%. Discussion: Rare platelet pools may demonstrate HT. PRP platelets with PAS will reduce titres and may abrogate the need for titration. A strategy of group specific transfusion or transfusion of group A PRP platelet transfusions may be a safe alternative. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor-T (CAR-T) cell therapy is currently the best-known type of immune effector cells therapy. For CAR T-cell therapy, the determination of CD3+ T cells is necessary for the quality control of fresh leukapheresis product as starting material. The aim was to validate analytical method for quantification of percentage and absolute count of T lymphocyte subtypes (CD3+, CD4+ and CD8+ cells) in fresh apheresis products using single-platform method on flow cytometer BD FACS Canto II. Validation study included determination of precision, trueness (bias), assessment of linearity, carryover, comparison of results obtained with two different protocols on flow cytometer for CD3+ cells determination and stability study. For between-run precision coefficients of variation (CVs) were <20%, as well as bias for all T-lymphocyte subtypes. For within-run precision, CVs were <10%, except for low CD8+ cell (percentage 10.51% and viable absolute count 12.37%). Comparison of results obtained with two different protocols for CD3+ cells determination shows no statistically significant difference. Statistically significant differences between results of the analysis of CD4+ cells in fresh samples and results obtained after storage at 4 °C (p =.004) and at room temperature (p =.018) were found. In conclusion, method for enumeration of T-lymphocyte subtypes can be used in routine work on BD FACS Canto II instrument for quality assessment of fresh cell products collected by leukapheresis procedure. [ABSTRACT FROM AUTHOR]

To compare the increase in platelet count after the transfusion of apheresis and pooled platelet suspensions among patients in the internal medicine intensive care unit. Methods Patients who received platelet suspension transfusions and were followed up at the internal medicine intensive care unit at Mehmet Akif Inan Training and Research Hospital were evaluated. The patient’s platelet counts were administered apheresis, and pooled platelet suspensions were recorded before and after transfusion. The increase in platelet count was calculated. The two groups were statistically compared. Results: A total of 4,701 platelet suspension transfusions were performed at our hospital between January 1, 2020, and December 31, 2023. Of these transfusions, 2,990 belonged to pooled platelet suspensions and 1,711 to apheresis platelet suspensions. Conclusion: Platelet suspension transfusion is frequently used in patients receiving internal medicine intensive care. However, there is an ongoing debate concerning whether apheresis or pooled platelet transfusion is more effective in increasing platelet count. In this study, we found a significantly higher increase in platelet count among patients in the internal medicine intensive care unit after apheresis platelet suspension transfusion than pooled platelet suspension transfusion. [ABSTRACT FROM AUTHOR]

A freeze-dried, platelet-derived hemostatic agent (FPH) was developed for acute hemorrhage. The canine product (cFPH) was developed for use in preclinical models supporting human product (hFPH) investigations. A carotid artery bypass graft (CABG) study in dogs compared 3 dosages of cFPH to canine liquid stored platelets (cLSP) and vehicle (VEH) control groups. Histopathological analysis and blood loss assessments were completed. A separate ex-vivo synthetic graft study assessed thrombogenicity via blood from human and canine donors that was combined with species-specific FPH or apheresis platelets. Characterization of cFPH and hFPH included thrombin generation, total thrombus formation, and scanning electron microscopy. Blood loss was reduced in CABG dogs receiving standard of care (cLSP) or cFPH treatment compared to VEH control; a cFPH dose effect signal was observed. Further, cFPH dosing up to 5 × 109 cells/kg was not associated with increased mortality or occlusion of the anastomosis sites, and histopathologic evidence of off-target thrombosis was not detected. When passed through a synthetic graft (ex vivo), whole blood combined with species-specific FPH did not result in thrombosis beyond that of whole blood control. In vitro testing and imaging of cFPH and FPH were comparable. A single dose of cFPH or cLSP reduced blood loss in a pilot surgical study and was well tolerated with no related adverse events. Further, the hemostatic activity and characteristics of cFPH are comparable to that of hFPH, suggesting that research findings from the canine product are likely to inform the development of the human product. [Display omitted] • Canine freeze-dried platelet-derived hemostat reduced blood loss in a pilot cardiac surgical study. • Canine freeze-dried platelet-derived hemostat is a surrogate to evaluate the human product in surgical bleeding. • Canine freeze-dried platelet-derived hemostat does not induce off-target thrombosis. [ABSTRACT FROM AUTHOR]

Background and Objectives Plateletpheresis is the collection of platelets from a donor using an apheresis device. There are different types of apheresis devices used for plateletpheresis, and each device can have an impact on the quality of platelet concentrates produced. This review article aims to investigate the effect of plateletpheresis devices on the quality parameters of produced platelet units. Materials and Methods This article reviewed the effects of different apheresis devices on the quality of platelet units by searching keywords in PubMed, Google Scholar, Science Direct, and Scopus databases and used 83 related articles. Results To evaluate the quality of the plateletpheresis concentrates, various parameters such as platelet count and yield, WBC and RBC count, platelet aggregation, metabolic activity, platelet activity, and the number of platelets microparticles are evaluated. The platelet counts in platelet concentrates obtained from apheresis devices follow AABB and European standards. In examining the metabolic activity of apheresis platelets in most studies, the level of glucose and pO2 decreased, lactate and pCO2 increased, and pH was within acceptable limits. When comparing platelet aggregation with different agonists, the platelet unit from the Amicus device showed the lowest response, while Trima Accel showed the highest response. Moreover, Amicus reported a higher level of platelet activation and microparticle production, whereas the lowest level of both belonged to Trima Accel. Conclusions The quality of the plateletpheresis concentrate can be affected by the apheresis device. Although most available devices can provide platelet concentrates in accordance with the existing standards. According to the studies, the Trima Accel device provides a higher quality platelet concentrate than other devices (Haemonetics MCS+, Amicus, Cobe Spectra, Fresenius). [ABSTRACT FROM AUTHOR]

Primary objective of this examination is to discover hybridized nanofluid flowing and heat transport that flows between a rotatable cone positioned above an expandable disc. Hybridized nanofluid contains Cadmium telluride (CdTe) as first nanoparticle and Silicon carbide (SiC) as second nanoparticle in ethylene glycol as base fluid. Electromagnetic impact and Darcy-Forchheimer model are considered with thermal radiative fluxing. By using appropriate similarity transformation, physical phenomena may be illustrated by a collection of nondimensional equations. An in-depth analysis is conducted to examine how the expansion of the surface affects the motion and temperature layers, as well as the swirl angle from the disc surface, and heat transfers from the cone and disc walls. Results demonstrate that expanding the wall varies flowing and heat dynamics within the conical gap. Boost CdTe nanoparticles without SiC nanoparticles lower disc Nusselt numbers while increasing it in a cone. In absence of CdTe nanoparticles, SiC nanoparticles increase Nusselt numbers in disc and cone. Nusselt numbers peak for rotating cone and expanded disk at φ 1 = φ 2 = 0.04. When gap angles are modest, faster wall expansion rate cools disk surface and heats cone surface. These findings have important medical and pharmacological implications in blood component separation and drilling machine cooling. [ABSTRACT FROM AUTHOR]

Background: The COVID‐19 pandemic affected healthcare delivery across all specialties including apheresis. To describe the changes in apheresis service practices that occurred during the pandemic, the American Society for Apheresis (ASFA) Apheresis Medicine Attending Physician Subcommittee conducted a survey study. Study Design and Methods: A 32‐question survey was designed and distributed to 400 ASFA physician members on September 7, 2022. Attending physicians responded to questions about whether and how apheresis service practices changed during the COVID‐19 pandemic compared with the time period prior to the pandemic in terms of: (1) procedure types and volumes, (2) patient consultation workflow, and (3) the use of telemedicine. Descriptive analyses were reported as number and frequency of responses. Results: The survey response rate was 13.8% (55/400). Of these respondents, 96.4% (53/55) were attending physicians. The majority of respondents (42/53, 79.2%) indicated that the types of procedures performed during COVID‐19 compared to pre‐pandemic did not change. Most frequently for apheresis procedure volume, respondents reported: no change in their monthly inpatient volume (21/47, 44.7%) and a decrease in their monthly outpatient volume (28/46, 60.9%). Prior to COVID‐19, 75.0% (30/40) of respondents performed consultations at bedside for inpatients and 67.4% (29/43) performed consultations at bedside for outpatients. Bedside consultations decreased in both settings during the pandemic but were still most frequently performed by attending physicians. At the same time, the use of telemedicine increased for 15.4% of survey respondents during COVID‐19. Conclusion: Some, but not all, respondents observed or made changes to their apheresis service during the COVID‐19 pandemic. A subset of changes, such as increased utilization of telemedicine, may persist. [ABSTRACT FROM AUTHOR]

Introduction: A novel LDL (low‐density lipoprotein) apheresis therapeutic option, Rheocarna, has garnered attention as an alternative therapy for chronic limb‐threating ischemia (CLTI). Bradykinin‐mediated vasodilation is involved in the effects of LDL apheresis and a decrease in blood pressure (BP), but the changes in bradykinin concentration during Rheocarna therapy are unknown. Methods: The study involved patients with CLTI treated with Rheocarna at our hospital, from April 2022 to August 2023. Results: After Rheocarna therapy, skin ulcers improved in 80% of the patients. Circuit coagulation was observed in two patients with high fibrinogen levels. A decrease in BP was observed at approximately the same time when the bradykinin concentration peaked. The peak bradykinin concentration in a patient undergoing hemodialysis at the same time was considerably lower than that in the other patients. Conclusion: This is the first report on the changes in bradykinin concentration under Rheocarna therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Daratumumab is a CD38-targeting antibody that is being increasingly integrated into first-line multiple myeloma (MM) induction treatment, leading to an improved response depth and a longer progression-free survival. Autologous stem cell transplantation (ASCT) is commonly performed as a consolidation strategy following first-line treatment in fit MM patients. However, limited data on the short-term effects of daratumumab on the success and safety of stem cell mobilization and autologous stem cell transplantation are available to date. We analyzed the performance of stem cell mobilization and collection, as well as engraftment kinetics, in MM patients treated with daratumumab-containing induction regimens, compared to daratumumab-free therapy. Daratumumab is being increasingly integrated into first-line multiple myeloma (MM) induction regimens, leading to improved response depth and longer progression-free survival. Autologous stem cell transplantation (ASCT) is commonly performed as a consolidation strategy following first-line induction in fit MM patients. We investigated a cohort of 155 MM patients who received ASCT after first-line induction with or without daratumumab (RVd, n = 110; D-RVd, n = 45), analyzing differences in stem cell mobilization, apheresis, and engraftment. In the D-RVd group, fewer patients successfully completed mobilization at the planned apheresis date (44% vs. 71%, p = 0.0029), and more patients required the use of rescue plerixafor (38% vs. 28%, p = 0.3052). The median count of peripheral CD34+ cells at apheresis was lower (41.37 vs. 52.19 × 106/L, p = 0.0233), and the total number of collected CD34+ cells was inferior (8.27 vs. 10.22 × 106/kg BW, p = 0.0139). The time to recovery of neutrophils and platelets was prolonged (12 vs. 11 days, p = 0.0164; and 16 vs. 14 days, p = 0.0002, respectively), and a higher frequency of erythrocyte transfusions (74% vs. 51%, p = 0.0103) and a higher number of platelet concentrates/patients were required (4 vs. 2; p = 0.001). The use of daratumumab during MM induction might negatively impact stem cell mobilization and engraftment in the context of ASCT. [ABSTRACT FROM AUTHOR]

Background and Objectives: The Writing Committee of American Society for Apheresis released the ninth edition of guidelines for therapeutic apheresis in 2023. Categories have been a part of the guidelines since the first edition, and the grading system was introduced in the fifth edition, with updates in every new edition. In this study, we investigated the category and grade change trends through the latest five editions, focusing on therapeutic plasma exchange, to suggest future directions as part of evidence‐based medicine. Materials and Methods: Categories and grades for therapeutic plasma exchange (TPE) were collected and analysed from the fifth through ninth editions. We aligned classification changes to the ninth edition's clinical context and compared its categories and grades with those introduced in the guideline. Results: Among 166 total indications in the ninth edition, 118 included TPE procedure, either as a sole treatment or as one of the therapeutic apheresis techniques. The total number of indications changed, but Category III remained predominant throughout the editions. Similarly, Grade 2C consistently emerged as the most prevalent grade. Notably, 24 cases had grade changes. Of the 16 cases with evidence quality changes, the quality weakened in six and improved in 10. Evidence levels were not improved throughout the study period for 102 clinical conditions. Conclusion: To address gaps in evidence quality, international collaboration is imperative to establish comprehensive large‐scale studies or randomized controlled trials. This will refine the use of therapeutic apheresis, including TPE, to foster evidence‐based advancements in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Platelet concentrates (PCs) used for transfusion can be produced by apheresis or derived from whole blood (WB). The Reveos device is the first US Food and Drug Administration‐approved automated blood processing system that can produce PCs. In this work, we evaluated the quality and function of Reveos‐collected PCs stored for 7 days at room temperature. Study Design and Methods: WB was collected from healthy donors and componentized on the day of collection (Fresh) or after an overnight hold (Overnight). PCs were produced (n = 7 Fresh; n = 6 Overnight), stored at room temperature in plasma, and evaluated on days 1 and 7 for quality metrics, platelet activation, clot formation, and aggregation response. Results: Platelet count was comparable between Fresh and Overnight PCs. A drop in pH was reported in Fresh day 7 PCs (p <.001, vs. day 1) but not in Overnight. Overnight units displayed the lowest levels of P‐selectin expression (p =.0008, vs. day 7 Fresh). Reduced clot strength and increased lysis were observed in both Fresh and Overnight units on day 7 (vs. day 1). Overnight‐hold PCs resulted in the highest clot strength on day 7 (p =.0084, vs. Fresh). No differences in aggregation were reported between groups. Conclusion: Reveos‐processed PCs produced from overnight‐hold WB performed better in hemostatic function assays and displayed reduced activation compared to fresh WB‐derived PCs, although both PC groups maintained platelet quality throughout storage. Utilization of overnight WB for PC preparation with Reveos holds promise as an alternative method of producing platelets for transfusion purposes. [ABSTRACT FROM AUTHOR]

Objective To compare the efficiency of 3 different processing methods (Sepax, AutoXpress [AXP], and manual processing with hydroxyethyl starch [HES] sedimentation) used at Stemlab during a 10-year period. Methods Historical data were compiled and the analytical results obtained for the 3 different methods were compared. Results The manual processing (HES) method yielded the highest level of total nucleated cell recovery after processing, and the AXP system yielded the highest CD34+ cell number. The red blood cell reduction was also significantly higher with the HES method. Also, HES showed comparable results to Toticyte technology for umbilical cord blood (UCB) processing. Conclusion These results show that the HES method is as effective as automated technologies for UCB volume reduction; hence, it is a suitable methodology for private and public UCB banks. The HES method also proved to be superior to Toticyte technology for medical applications, with higher recovery yields of total nucleated cells after thawing and equivalent CD34+ cell recovery and functionality. [ABSTRACT FROM AUTHOR]

• Lp(a) level should be measured at least once in all adults. • Lp(a) levels represent a continuum of risk, not a risk threshold at a dichotomous cutpoint. • Risk classification by Lp(a) level ranges from low (<75 nmol/L) to high (≥125 nmol/L). • Lp(a) risk categories apply across races and ethnicities. • High Lp(a) levels warrant early and more-intensive risk factor management. Since the 2019 National Lipid Association (NLA) Scientific Statement on Use of Lipoprotein(a) in Clinical Practice was issued, accumulating epidemiological data have clarified the relationship between lipoprotein(a) [Lp(a)] level and cardiovascular disease risk and risk reduction. Therefore, the NLA developed this focused update to guide clinicians in applying this emerging evidence in clinical practice. We now have sufficient evidence to support the recommendation to measure Lp(a) levels at least once in every adult for risk stratification. Individuals with Lp(a) levels <75 nmol/L (30 mg/dL) are considered low risk, individuals with Lp(a) levels ≥125 nmol/L (50 mg/dL) are considered high risk, and individuals with Lp(a) levels between 75 and 125 nmol/L (30–50 mg/dL) are at intermediate risk. Cascade screening of first-degree relatives of patients with elevated Lp(a) can identify additional individuals at risk who require intervention. Patients with elevated Lp(a) should receive early, more-intensive risk factor management, including lifestyle modification and lipid-lowering drug therapy in high-risk individuals, primarily to reduce low-density lipoprotein cholesterol (LDL-C) levels. The U.S. Food and Drug Administration approved an indication for lipoprotein apheresis (which reduces both Lp(a) and LDL-C) in high-risk patients with familial hypercholesterolemia and documented coronary or peripheral artery disease whose Lp(a) level remains ≥60 mg/dL [∼150 nmol/L)] and LDL-C ≥ 100 mg/dL on maximally tolerated lipid-lowering therapy. Although Lp(a) is an established independent causal risk factor for cardiovascular disease, and despite the high prevalence of Lp(a) elevation (∼1 of 5 individuals), measurement rates are low, warranting improved screening strategies for cardiovascular disease prevention. [Display omitted] [ABSTRACT FROM AUTHOR]

Context: High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (AHSCT) is an established treatment for chemosensitive patients with relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL). Aims: We present the results of using different salvage chemotherapy plus granulocyte colony stimulating factor (G-CSF) for mobilization of peripheral blood stem cells in R/R lymphoma patients. Subjects and Methods: For salvage chemotherapy, 93 patients received platinum-containing regimens, 4 patients received cytarabine-containing regimens, and 5 patients received other regimens. Patient distributions were HL (n = 35) and NHL (n = 67). Results: In 87.2% of patients, first mobilization trial was successful (>2 × 106 CD34+ cells/kg). In 58.8% of patients, first apheresis season >5 × 106 CD34+ cells/kg collections was achieved. All 12.7% of patients were poorly mobilized at the first mobilization. There was no statistical difference between the previous chemotherapy numbers and failed mobilization (P > 0.05). Five patients who were poorly mobilized and 4 patients who were successfully mobilized underwent a previous radiotherapy (P < 0.05). Thirteen patients who were poorly mobilized in the first mobilization underwent a platinum-containing salvage regimen. At the time of the first mobilization, the average peripheral CD 34 counts in the successfully mobilized group were statistically higher than that in the poorly mobilized group (P < 0.01). Conclusions: We demonstrated that peripheral CD 34 cell count in the peripheral blood on the first apheresis day was a significant factor for more stem cell mobilization, fewer apheresis sessions, less volume, and earlier neutrophil engraftment for patients with R/R lymphoma and eligible for AHSCT. The history of the previous radiotherapy was a significant factor for poor mobilization. [ABSTRACT FROM AUTHOR]

Achieving successful hematopoietic stem cell transplantation (HSCT) relies on two fundamental pillars: effective mobilization and efficient collection through apheresis to attain the optimal graft dose. These cornerstones pave the way for enhanced patient outcomes. The primary challenges encountered by the clinical unit and collection facility within a transplant program encompass augmenting mobilization efficiency to optimize the harvest of target cell populations, implementing robust monitoring and predictive strategies for mobilization, streamlining the apheresis procedure to minimize collection duration while ensuring adequate yield, prioritizing patient comfort by reducing the overall collection time, guaranteeing the quality and purity of stem cell products to optimize graft function and transplant success, and facilitating seamless coordination between diverse entities involved in the HSCT process. In this review, we aim to address key questions and provide insights into the critical aspects of mobilizing and collecting hematopoietic stem cells for transplantation purposes. [ABSTRACT FROM AUTHOR]

Introduction: Primary human blood cells represent an essential model system to study physiology and disease. However, human blood is a limited resource. During healthy donor plateletpheresis, the leukoreduction system chamber (LRSC) reduces the leukocyte amount within the subsequent platelet concentrate through saturated, fluidized, particle bed filtration technology. Normally, the LRSC is discarded after apheresis is completed. Compared to peripheral blood, LRSC yields 10-fold mononuclear cell concentration. Methods: To explore if those retained leukocytes are attractive for research purposes, we isolated CD3+ T cells from the usually discarded LRSCs via density gradient centrifugation in order to manufacture CD19-targeted chimeric antigen receptor (CAR) T cells. Results: Immunophenotypic characterization revealed viable and normal CD4+ and CD8+ T-cell populations within LRSC, with low CD19+ B cell counts. Magnetic-activated cell sorting (MACS) purified CD3+ T cells were transduced with CD19 CAR-encoding lentiviral self-inactivating vectors using concentrated viral supernatants. Robust CD19 CAR cell surface expression on transduced T cells was confirmed by flow cytometry. CD19 CAR T cells were further enriched through anti-CAR MACS, yielding 80% CAR+ T-cell populations. In vitro CAR T cell expansion to clinically relevant numbers was achieved. To prove functionality, CAR T cells were co-incubated with the human CD19+ B cell precursor leukemia cell line Nalm6. Compared to unmodified T cells, CD19 CAR T cells effectively eradicated Nalm6 cells. Conclusion: Taken together, we can show that lymphocytes isolated from LRSCs of plateletpheresis sets can be efficiently used for the generation of functional CAR T cells for experimental purposes. [ABSTRACT FROM AUTHOR]

Background: Blood transfusion is a critical medical procedure essential for saving lives. However, the inappropriate use of blood transfusions poses risks to patients and strains healthcare resources. Recognizing the need for optimal blood utilization, this study evaluates the appropriateness of blood transfusions in a healthcare setting, emphasizing the need for implementation of stringent guidelines and judicious use of this scarce resource. Materials and Methods: A descriptive, observational retrospective study was conducted at a Blood Bank attached to a Teaching Hospital & Medical College, lacking a Blood Components Separation facility. The study analyzed 375 whole blood units transfused from January 1 to December 31, 2010, to assess the appropriateness of blood usage across various departments. The criteria for transfusion appropriateness were based on pre-established clinical guidelines, focusing on indications such as acute blood loss leading to hypovolemia and exchange transfusion in children. Results: Out of 375 whole blood units transfused, 144 (45.56%) were deemed appropriate, 162 (47.94%) avoidable, and 69 (6.49%) indeterminate. The study highlighted a significant portion of transfusions that could be classified as avoidable, with the highest appropriateness observed in the Department of Pediatrics (83.01%) and the lowest in the Department of Medicine (17.24%). The findings underscore the need for improved clinical practices and the potential benefits of blood components over whole blood transfusions. Conclusion: The study reveals a considerable case of avoidable blood transfusions, suggesting an urgent need for enhanced transfusion practices, adherence to clinical guidelines, and the establishment of a Hospital Transfusion Committee (HTC). Implementing a Maximum Surgical Blood Ordering Schedule (MSBOS) and promoting the use of blood components could significantly improve the rational use of blood in healthcare settings. [ABSTRACT FROM AUTHOR]

Homozygous familial hypercholesterolemia (HoFH) is a rare, autosomal semi-dominant lipid metabolism disorder characterized by extremely high low-density lipoprotein cholesterol (LDL-C) levels and premature cardiovascular disease. The objective of this study was to investigate sex-differences in the treatment and outcomes of patients with HoFH. We examined clinical characteristics, lipid-lowering therapy (LLT), and cardiovascular events using descriptive statistics of patients in the Canadian HoFH registry. Major adverse cardiovascular events (MACE) were defined as the composite of cardiovascular death, non-fatal myocardial infarction, and stroke. Sex differences between continuous and categorical variables were analyzed using Mann-Whitney U test and Fisher's Exact test, respectively. This study included 48 patients (27 (56%) female). The median age at diagnosis in females was 14.0 (interquartile range (IQR) 9.0–30.0) and in males was 8.0 (IQR 2.0–23.0) (p = 0.07). Baseline clinical characteristics were comparable between both sexes. The median baseline LDL-C was 12.7 mmol/L (10.0–18.3) in females and 15.3 (10.5–20.0) in males (p = 0.51). Follow up LDL-C levels were 7.6 mmol/L (IQR 4.8–11.0) in females and 6.3 (IQR 4.6–7.5) in males (p = 0.1). Most patients were taking 3 or more LLTs, with comparable proportions in both sexes (p = 0.26). Apheresis was similar in both sexes, 14 (51.8%) vs. 10 (47.6%) (p = 0.2). Over a mean of 10 years of follow-up, MACE occurred in 3 females (11.1%) and 4 males (19.1%) (p = 0.2). Lipid levels and treatment were similar between sexes. MACE occurred in similar proportions between sexes, indicating that HoFH offsets the inherently lower cardiovascular risk in pre-menopausal females. Further investigation into sex-differences in HoFH in larger sample sizes is warranted. [Display omitted] [ABSTRACT FROM AUTHOR]

• Serum VLCFAs and VLC-MUFAs were eluted at 57% after lipoprotein apheresis (LA). • Serum VLCFAs and VLC-MUFAs remained low for 7 days after LA. • LA induces an acute increase in the serum levels of anti-inflammatory BCFAs. • Long-term regular biweekly LA decreased the serum levels of VLC-MUFAs and n3 PUFAs. Lipoprotein apheresis (LA) is an extracorporeal treatment that transiently reduces lipoprotein (a) [Lp(a)] by 60% and leads to an 80–92% reduction in major adverse cardiovascular events. LA has a significant impact on lipid profile in serum of patients with atherosclerotic cardiovascular disease. To investigate the effects of LA on the composition of serum fatty acids (FAs), focusing on those which could have an impact on cardiovascular disease (CVD). This is a prospective study in the First Department of Cardiology of the Medical University of Gdansk, Poland. Serum samples were collected from 28 patients before LA, just after the procedure, and 7 days after LA. Additionally, in a smaller group of patients, the samples were collected after a second tour of LA (2 weeks later), as well as after 1 year from the first procedure. The serum FA profile was analyzed using gas chromatography-mass spectrometry. After the LA procedure, a substantial change in serum FA composition along with low-density lipoprotein cholesterol (LDL-C) and Lp(a) decrease were observed 7 days after procedure, but these parameters returned to the values similar to those before procedure after 14 days. Very long-chain FAs (VLCFAs) and very long-chain monounsaturated FAs (VLC-MUFAs) were eluted at 57% and remained low even 7 days after LA (p=0.027 and p < 0.001, respectively). We also observed an increase in the percentage of total branched-chain FAs (BCFAs) (p=0.004) and anteiso BCFAs (p=0.012) after LA. After 1 year of regular LA, a substantial decrease in serum VLC-MUFAs and n3 polyunsaturated LA (PUFAs) were noted. Decreased VLCFAs and VLC-MUFAs involved in CVD development remained low even 7 days after LA. An acute increase in the levels of anti-inflammatory BCFAs was observed. In turn long-term regular administration of LA substantially decreased VLC-MUFA and n3 PUFA. [Display omitted] [ABSTRACT FROM AUTHOR]

Many blood establishments are expanding plasmapheresis collection capacity to achieve increasing plasma for fractionation volume targets, driven by immunoglobulin product demand. Some adverse events occur in both apheresis and whole blood collection, such as venepuncture‐related trauma and vasovagal reactions. Others are specifically related to the apheresis procedure, such as citrate reactions, haemolysis, infiltration and air embolism. Whilst plasmapheresis procedures are generally well tolerated, theoretical longer term donor health considerations, such as the effects on donor plasma protein levels, bone mineral density, iron deficiency and malignancy also require consideration. An evidence‐based framework that supports a safe and sustainable increase in the collection of plasma is essential. Our review demonstrates a lack of high‐quality evidence on risks and outcomes specifically in plasmapheresis. Whilst conservative procedural controls and donor harm minimization policies will mitigate risk, high‐quality evidence is needed to facilitate practice change that is safe and sustainable and maximizes the potential of individual donor differences. [ABSTRACT FROM AUTHOR]

Understanding the apheresis principles for harvesting hematopoietic stem cells (HSCs) is critical for performing efficient procedures. However, despite significant advances in estimating the collection efficiency (CE) of aphereses, many confounding factors still need to be addressed in the classical calculations. The CE values are unrestricted, and many procedures exhibit CEs of a given cell population greater than 100%. This report introduces a simple equation that estimates the "crude" CE, which ranges from 0% to 100% and intrinsically considers the contribution of donor‐related variables such as the pre‐procedure mobilization and intra‐apheresis recruitment of CD34+ cells (as a convenient marker for HSCs), as well as the performance of the apheresis system itself. [ABSTRACT FROM AUTHOR]

BACKGROUND: Homozygous familial hypercholesterolemia is a genetic disease characterized by extremely high levels of lowdensity lipoprotein cholesterol (LDL-C) and a high risk of premature cardiovascular events. The proof-of-concept study ORION-2 (A Study of Inclisiran in Participants With Homozygous Familial Hypercholesterolemia) showed that inclisiran, a small interfering RNA that prevents production of the hepatic PCSK9 protein (proprotein convertase subtilisin/kexin type 9), could lead to durable reductions in LDL-C levels when added to statins and ezetimibe in patients with homozygous familial hypercholesterolemia. METHODS: ORION-5 was a phase 3, 2-part, multicenter study in 56 patients with homozygous familial hypercholesterolemia and elevated LDL-C levels despite maximum tolerated doses of LDL-C–lowering therapies with or without lipoprotein apheresis. Patients eligible for part 1 (double-blind, 6 months) were randomized 2:1 to receive either 300 mg of inclisiran sodium (equivalent to 284 mg of inclisiran) or placebo. Placebo-treated patients from part 1 were transitioned to inclisiran in part 2 (open-label, 18 months). The primary end point was the percentage change in LDL-C levels from baseline to day 150. RESULTS: The mean age of the patients was 42.7 years, and 60.7% were women. The mean baseline LDL-C levels were 294.0 mg/dL and 356.7 mg/dL in the inclisiran and placebo groups, respectively. The placebo-corrected percentage change in LDL-C level from baseline to day 150 was −1.68% (95% CI, −29.19% to 25.83%; P=0.90), and the difference was not statistically significant between the inclisiran and placebo groups. The placebo-corrected percentage change in PCSK9 levels from baseline to day 150 was −60.6% with inclisiran treatment (P<0.0001); this was sustained throughout the study, confirming the effect of inclisiran on its biological target of PCSK9. No statistically significant differences between the inclisiran and placebo groups were observed in the levels of other lipids and lipoproteins (apolipoprotein B, total cholesterol, and non−high-density lipoprotein cholesterol). Adverse events and serious adverse events did not differ between the inclisiran and placebo groups throughout the study. CONCLUSIONS: Inclisiran treatment did not reduce LDL-C levels in patients with homozygous familial hypercholesterolemia despite substantial lowering of PCSK9 levels. Inclisiran was well-tolerated, and the safety findings were consistent with previously reported studies and the overall safety profile. [ABSTRACT FROM AUTHOR]

Background: The heme oxygenase-1 (HO-1) enzyme pathway is of crucial importance in the removal of toxic blood components and regulation of neuroinflammation following hemorrhagic stroke. Although a circadian pattern dependency in the incidence and severity of hemorrhagic stroke exists, it is unknown whether the activity of the HO-1 system in the context of hemorrhagic injury also exhibits circadian dependency. We hypothesized that the circadian regulation of microglial HO-1 would determine the extent of neuroinflammation and neuronal injury in a murine model of subarachnoid hemorrhage (SAH). Methods: In vitro expression patterns of HO-1 and circadian rhythm genes were analyzed in the microglial BV-2 cell line and primary microglia (PMG) using Western blot and qPCR. PMG isolated from Hmox1fl/fl and LyzM-Cre-Hmox1fl/fl mice were used to evaluate the role of microglial HO-1. We further investigated the in vivo relevance in a murine subarachnoid hemorrhage (SAH) model using Hmox1fl/fl and LyzM-Cre-Hmox1fl/fl mice with myeloid cell HO-1 deficiency, inducing SAH at different zeitgeber (ZT) times and analyzing the expression of HO-1 and the circadian control gene Period-2 (Per-2), respectively. Furthermore, we measured the inflammatory cytokine Monocyte Chemoattractant Protein-1 (MCP-1) in the cerebrospinal fluid of SAH patients in correlation with clinical outcome. Results: HO-1 baseline expression and response to CO with blood exposure depended on ZT. In vitro expression of circadian control genes was de-synchronized in LyzM-Cre-Hmox1fl/fl PMG and did not respond to exogenous CO exposure. We found that circadian rhythm plays a crucial role in brain damage after SAH. At ZT2, we observed less phagocytic function, more vasospasm and increased microglial activation. CO reduced mortality at ZT12 in HO-1 deficient mice and reduced the difference between ZT2 and ZT12 in the inflammatory response. Induction of MCP-1 in the CSF from SAH patients was time-dependent and correlated with the expression of circadian control genes, SAH severity, functional impairment and delirium. Conclusions: Our data point towards a crucial role for the HO-1 enzyme system and circadian control in neuronal injury after a hemorrhagic stroke. [ABSTRACT FROM AUTHOR]

Background: This case report presents the clinical course and management of a 27-year-old male patient admitted with symptoms of fever, fatigue, diarrhea, and mild pallor. The patient exhibited signs of septic shock, including hypotension, tachypnea, and elevated inflammatory markers. Case presentation: Initial diagnosis revealed sepsis-associated thrombocytopenia and further investigations were conducted to exclude other infectious causes. The patient had a recent travel history to India. Blood culture results confirmed Salmonella infection, with the identified strain being resistant to fluoroquinolones but susceptible to ceftriaxone and meropenem. Imaging studies revealed findings consistent with typhlitis, and the patient exhibited pancytopenia and neutropenia, indicating immune compromise. Management and outcome: The patient received intravenous fluids and empirical antibiotics after culture collection and closely monitoring laboratory parameters. Norepinephrine administration was initiated to stabilize blood pressure, and intravenous steroids were given to reduce inflammation. Apheresis platelets were given due to low critical platelet count and associated lower gastrointestinal bleeding. Over the course of ten days, the patient showed positive progress, with decreased fever, cessation of diarrhea, and reduced inflammatory markers. Norepinephrine support was gradually tapered, and oral medications were initiated. Regular follow-up appointments were recommended for monitoring and adjustment of the treatment plan. Conclusion: This case highlights the challenges and multidisciplinary approach involved in managing septic shock associated with disseminated intravascular coagulation and thrombocytopenia, which was complicated by neutropenic enterocolitis (typhlitis). Prompt diagnosis, appropriate antibiotic therapy, supportive care, and close monitoring of laboratory parameters were crucial in optimizing patient outcomes. Further research and clinical studies are warranted to improve understanding and management of this complex condition. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to conduct a retrospective evaluation of clinical findings on patients undergoing autologous hematopoietic stem cell transplantation. Materials and Methods: A total of 167 consecutive patients who were diagnosed with multiple myeloma (MM) and lymphoma and then underwent autologous hematopoietic stem cell transplantation (AHSCT) between August 2010 and May 2013 were included in our study. Demographic, disease, mobilization, apheresis, and transplantation data were reviewed from patient files. Results: In 121 patients (72%), mobilization was achieved solely with granulocyte colony stimulating factor (G-CSF). There was no relationship between peripheral CD34+ cell count and age, disease type, or previous treatment features. The total CD34+ cell count post-apheresis was 3.3 ± 3.1 x 106/kg. Only nine patients could not achieve successful mobilization with any regimen. The median day of neutrophil and platelet engraftment among the entire patient group was 11 days. As the number of CD34+ cells infused into patients increased, neutrophil and platelet engraftment time decreased. Conclusion: Mobilization was achieved in most MM cases and at least two-thirds of lymphomas using G-CSF alone. Age and body weight did not affect mobilization success. Clinicians should increase successful mobilizations on the first day of the apheresis and prescribe AHSCT at appropriate times to avoid excessive cycles of chemotherapy. [ABSTRACT FROM AUTHOR]

Aim. The purpose of our study was to evaluate the effects of already existed and/or de novo generated DSAs in liver transplantation as predictors of graft rejection and to establish an interconnection between blood biochemical parameters (Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin level) with the level of DSA in patients with liver transplant. Methods. Blood for testing was collected to tubes without anticoagulant, centrifugated at 1500 rpm per 10 minutes [5] and processed immediately (for biochemical parameters measurement) or stored at –70 °C (for antibody detection). xMAP-Luminex next generation flow cytometry technology and LABScreen Single antigen beads reagent (Onelambda, USA) were used for antiHLA determination. Analysis of results with further calculation of PRA percentage for antibodies to Class I & II separately was performed on HLAFusion 4.6 software. Briefly: patient’s serum was centrifugated at 10 000 rcf during 10 min, treated with 100 mM EDTA (Invitrogene, USA) and incubated with LABScreen beads, covered with HLA Class I &II antigens. Positive reaction was detected with second anti-human phycoerythrin (PE)-labelled IgG. The presence of antibodies to specific HLA antigen was determined by the numerical value of the mean fluorescence intensity (MFI). Serum was considered positive when PRA value was higher than 0% (PRA > 0%) and the mean MFI was higher than 600 (MFI ≥ 600). Total bilirubin level was detected photometrically. The activity of ALT and AST was determined spectrophotometrically on the automatic analyzer COBAS C 111 (Roche, Switzerland) in accordance with the manufacture’s instruction. Results and Discussion. The group of examined participants consisted patients diagnosed with different liver diseases (hepatic cirrhosis and biliary atresia). Patients therapy consisted of plasmapheresis (removal of blood plasma components, in particular anti-HLA antibodies), immunosuppressive drug “Tacrolimus” (decreases T-lymphocytes production), “Solu-Medrol” pulse therapy (synthetic glucocorticoid anti-inflammatory drug). It should be noted, that multiple transfusions before transplantation were associated with an increase in DSA and PRA levels, which increases the probability of the formation of DSA in the recipient and subsequent rejection of the transplanted organ (Figure, A). The use of the above drugs in various combinations depending on the patient’s medical history led to changes in levels of antibodies to HLA antigens and blood biochemical parameters. Before graft rejection we observed high values of PRA, DSA and increased level of key biochemical parameters in bloodstream, which indicated start of liver disfunction development. It should be noted, that levels of PRA and DSA grew earlier than ALT and AST activity (Figure, В) and total bilirubin concentration (Figure, С). We can speculate, that PRA increase as well as de novo generated DSA can be the reason of graft rejection, which was confirmed by the changes of key biochemical markers of liver functioning (Figure 1, B, C). We observed directly proportional dependence between biochemical blood parameters and PRA and DSA. They have the same trend of growth and decline depending on the effectiveness of the therapy. After immunosuppression therapy, DSA were not detected, blood biochemical parameters returned to normal reference values (total bilirubin = 15 μmol/L; AST = 40 IU/L; ALT = 45 IU/L), however, general anti-HLA antibodies level was still present therefore antibody monitoring should be continued to prevent the possibility of graft rejection and to adjust immunosuppression protocols. Conclusions. The DSA and PRA levels as well as total bilirubin and ALT and AST activity corresponded to each other and could be used for comprehensive both pre- and post-transplantation screening of patients requiring liver transplantation or re-transplantation. Detection of DSA and PRA was important at the same level as measurement of classical biochemical parameters of liver function (ALT, AST etc.) for monitoring of graft status and prevention of acute or chronical rejection and choosing correct immunosuppression protocol. [ABSTRACT FROM AUTHOR]

Pregnancy in women with sickle cell disease (SCD) is a high-risk situation, especially during the third trimester of gestation and in the post-partum period, due to chronic hypoxia and vaso-occlusive phenomena occurring in the maternal–fetal microcirculation: as a result, unfavorable outcomes, such as intra-uterine growth restriction, prematurity or fetal loss are more frequent in SCD pregnancies. Therefore, there is a consensus on the need for a strict and multidisciplinary follow-up within specialized structures. Transfusion support remains the mainstay of treatment of SCD pregnancies, whereas more targeted modalities are still controversial: the benefit of prophylactic management, either by simple transfusions or by automated red blood cell exchange (aRBCX), is not unanimously recognized. We illustrate the cases of three SCD pregnant patients who underwent aRBCX procedures at our institution in different clinical scenarios. Moreover, we carried out a careful literature revision to investigate the management of pregnancy in SCD, with a particular focus on the viability of aRBCX. Our experience and the current literature support the use of aRBCX in pregnancy as a feasible and safe procedure, provided that specialized equipment and an experienced apheresis team is available. However, further research in this high-risk population, with appropriately powered prospective trials, is desirable to refine the indications and timing of aRBCX and to confirm the advantages of this approach on other transfusion modalities. [ABSTRACT FROM AUTHOR]

Objectives: The main objective of the present study was to evaluate whether the use of plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) or subsequent use of isolated G-CSF and then plerixafor following disease-specific chemotherapy, and whether it would allow for adequate peripheral stem cell collection in patients. Methods: The retrospective study evaluated 54 patients with previous mobilization failure who were administered plerixafor in 2 centers. In patients without any side effects, CD 34+ cell counts, the percentage of patients who were found eligible for autologous transplantation, the engraftment kinetics of the patients who underwent transplantation, and their overall survival results were compared between the two groups where G-CSF was used with plerixafor, or where plerixafor was used after isolated G-CSF following chemotherapy. Results: The median age of the patients was 49 years (range: 17-70), and 64.8% (n = 35) were males. It was identified that 31 (57.4%) patients underwent mobilization treatment with isolated G-CSF and plerixafor, and 23 (42.6%) patients underwent mobilization treatment with chemotherapy plus G-CSF and plerixafor. In all patients, mean hemoglobin level (11.3 ± 1.5 g/dL vs. 9.3 ± 1.3 g/dL; p < 0.001) and median platelet level (129.2 ×103/µL vs. 58.4 ×103/µL) were found to be higher, while febrile neutropenia rate (3.3% vs. 60.9%), the percentage of replacement patients (6.7% vs. 65.2%), and median days of G-CSF (6 vs. 9) were found to be lower on the day of plerixafor administration in the isolated G-CSF and plerixafor group compared to the chemotherapy and G-CSF and plerixafor group. Conclusions: In conclusion, our study demonstrated that administration of plerixafor is generally safe and well-tolerated. Regardless of the underlying disease, it offers an effective alternative for patients with previous failed mobilization attempts using conventional regimens, and allows stem cell collection with fewer apheresis sessions. [ABSTRACT FROM AUTHOR]

Background: Requirements of blood transfusions rise rapidly in China. Improving the efficiency of blood donation could help maintaining sufficient blood supplement. We conducted a pilot research to investigate the reliability and safety of collecting more units of red blood cell by apheresis. Methods: Thirty‐two healthy male volunteers were randomized into two groups: red blood cell apheresis (RA) (n = 16) and whole blood (WB) donation (n = 16). RA group donated individualized RBC volumes by apheresis according to the volunteers' basal total blood volumes and haematocrit levels, WB group donated 400 mL whole blood. All volunteers were scheduled seven visit times in 8 weeks' study period. The cardiovascular functions were assessed by laboratory examinations, echocardiography and cardiopulmonary functional tests. All results were compared between groups at the same visit time and compared between visit 1(before donation) and other visit times within the same group. Results: The average donated RBC volume in RA group and in WB group was 627.25 ± 109.74 mL and 175.28 ± 8.85 mL, respectively(p < 0.05); the RBC, haemoglobin and haematocrit levels changed significantly between times and between groups (p < 0.05). Cardiac biomarker levels such as NT‐proBNP, hs‐TnT and CK‐MB did not change significantly between times or between groups (p > 0.05). The echocardiographic and cardiopulmonary results did not change significantly between times or between groups during the whole study period(p > 0.05). Conclusions: We provided an efficient and secure method for RBC apheresis. By harvesting more RBC volumes at one single‐time, the cardiovascular functions did not change significantly compared with traditional whole blood donation. [ABSTRACT FROM AUTHOR]

Introduction: Bioactive substances of stored platelets change during the stored periods. Exosomes are reported to be increased during platelet storage. Circular RNAs (circRNAs) are one of the main components in exosomes. It is the purpose of this study to investigate the different expression of exosomal circRNAs during storage. Methods: Apheresis platelets were collected from 7 healthy volunteers and stored in platelet storage bags for 1 day or 5 days. We isolated exosomes by ultracentrifugation and characterized exosomes by transmission electron microscopy, nano-flow cytometry, and Western blot. We conducted microarray analysis to detect changes in the exosomal circRNAs from apheresis platelets during storage, and qRT-PCR to validate their expressions. To analyze the competing endogenous RNA (ceRNA) of circRNAs, microRNAs (miRNAs) targets were predicted based on interactions of circRNAs/miRNAs and miRNAs/mRNAs, using TargetScan and miRanda. A ceRNA network was constructed by Cytoscape. The targeted mRNAs were performed for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis by the DAVID. Results: Microarray analysis revealed that 61 differentially expressed circRNAs between day 1 and day 5. Thirty-one circRNAs of these are upregulated, while 30 circRNAs are downregulated. A ceRNA visualized network includes 9 circRNAs, 48 miRNAs, and 117 mRNAs. There were 117 mRNAs enriched in 203 GO terms and 9 KEGG pathways based on the GO and KEGG pathway enrichment analyses. Conclusion: We identified 61 dysregulated exosomal circRNAs from apheresis platelets during storage. The study provided insights into the underlying mechanisms of platelet storage lesion. [ABSTRACT FROM AUTHOR]

Introduction: In patients with a clinical indication for autologous hematopoietic stem cell transplantation (ASCT), sufficient mobilization of CD34+ precursor cells into peripheral blood is essential to ensure adequate hematopoietic stem cell (HSC) collection prior to intensive therapy. However, with standard granulocyte-colony stimulating factor (G-CSF)-based mobilization schemes, an important minority of patients fail to mobilize sufficient (e.g., >10/µL) CD34+ cell counts into the peripheral blood and are considered as poor mobilizers (PM). Because failure to achieve sufficient CD34+ cell mobilization can negatively affect important clinical treatment endpoints, the use of plerixafor (PLX) was approved to increase CD34+ mobilization in PM patients. Methods: The German non-interventional, multicenter, open-label, prospective OPTIMOB study evaluated HSC mobilization strategies prior to planned ASCT in adult patients with hematologic malignancies (lymphomas or multiple myeloma [MM]) focusing on PM patients. PM patients were defined as follows: (1) never achieving ≥20 CD34+ cells/µL before 1st apheresis, (2) receiving PLX at any timepoint of mobilization, (3) their initially planned stem cell yield had to be reduced, or (4) they had not received apheresis due to low CD34+ count in peripheral blood. Results: 168 of 475 MM patients (35%) participating in the OPTIMOB study were classified as PM, and 155 of them (92%) received PLX (PM+PLX) during the study. PM patients were 40–78 years old, slightly more often male (n = 97, 58%), mostly newly diagnosed (n = 146, 87%) and received highly individualized previous treatments. Ninety-four of the PMs underwent chemotherapy mobilization (65%), and 51 patients (35%) received steady-state mobilization with G-CSF only during 1st mobilization attempt. 92% of the total PM population (n = 155) underwent apheresis, 78% of them (n = 117) achieved >2.0 × 106 CD34+ cells/kg body weight on the 1st day of apheresis. PM+PLX had a higher median total collection result than those PM patients without PLX support (7.2 vs. 5.7 × 106 CD34+ cells/kg body weight). In total, ASCT was performed in 136 PM+PLX (88%) versus 8 PM−PLX patients (62%). Conclusion: The OPTIMOB study showed that a considerable proportion of adult MM patients in Germany are PMs. Even though most of PMs were supported with PLX in the OPTIMOB study, PM-PLX also successfully mobilized HSCs, allowing ASCT in majority of all PMs. However, further analyses are required for treatment optimization in PMs. [ABSTRACT FROM AUTHOR]