Apheresis Plasma Research Articles

Acoustofluidic-based therapeutic apheresis system

Therapeutic apheresis aims to selectively remove pathogenic substances, such as antibodies that trigger various symptoms and diseases. Unfortunately, current apheresis devices cannot handle small blood volumes in infants or small animals, hindering the testing of animal model advancements. This limitation restricts our ability to provide treatment options for particularly susceptible infants and children with limited therapeutic alternatives. Here, we report our solution to these challenges through an acoustofluidic-based therapeutic apheresis system designed for processing small blood volumes. Our design integrates an acoustofluidic device with a fluidic stabilizer array on a chip, separating blood components from minimal extracorporeal volumes. We carried out plasma apheresis in mouse models, each with a blood volume of just 280 μL. Additionally, we achieved successful plasmapheresis in a sensitized mouse, significantly lowering preformed donor-specific antibodies and enabling desensitization in a transplantation model. Our system offers a new solution for small-sized subjects, filling a critical gap in existing technologies and providing potential benefits for a wide range of patients.

Effect of apheresis plasma donation on plasma uric acid levels, the lipid profile, and major plasma proteins in plasma donors in China: A multicenter, prospective cohort study

Abnormal plasma uric acid (UA) levels, the lipid profile, and plasma proteins in blood are associated with a range of adverse health outcomes. This multicenter, prospective cohort study aimed to determine the possible effects of multiple apheresis plasma donations on plasma UA levels, the lipid profile, and major proteins in plasma donors. Participants were enrolled from 1 April 2021 to 31 August 2022. When their plasma UA (men: >420 µmol/L, women: >360 µmol/L) and/or lipid levels (total cholesterol [TC]: ≥6.2 mmol/L, triglycerides [TGs]: ≥2.3 mmol/L, low-density lipoprotein cholesterol: ≥4.1 mmol/L, or high-density lipoprotein cholesterol [HDL-C]: <1.0 mmol/L) were abnormal at their first plasma donation, the enrolled participants were followed up until they had completed 10 plasma donations. A total of 11485 participants were enrolled, of whom 1861 met the inclusion criteria. During the study period, 320 donors completed 10 plasma donations. None of the participants took any corrective medicine for their abnormal index. The measured parameters were significantly different from the first to the tenth plasma donations (donors with asymptomatic hyperuricemia: UA, P < 0.001; donors with asymptomatic hyperlipidemia: HDL-C, P < 0.001; TC, P = 0.025; TGs, P < 0.001; apolipoprotein B, P = 0.025; all of the plasma donors, immunoglobulin G, P < 0.001). The levels of HDL-C, TC, and apolipoprotein B were increased, and the levels of UA, TGs, and immunoglobulin G were decreased over this time. However, immunoglobulin G levels were still in the normal range. Moreover, the changes in these parameters were closely associated with the frequency of plasma donation during the study period. Repeated apheresis plasma donations can reduce plasma UA and TG levels and increase HDL-C levels; and further evaluation of the clinical significance with a larger sample size is required.

Increasing the time-to-freezing for clinical apheresis plasma meets quality specifications.

In Australia, the vast distances between blood collection centres and processing facilities make it challenging to align supply with demand. Increasing the time to freezing for clinical plasma beyond 6 h would alleviate supply issues. This study aimed to determine the quality of clinical apheresis plasma frozen within 12 h of collection. Apheresis plasma (n = 20) collected at donor centres was immediately transported to a blood processing facility, stored at 26°C and sampled aseptically at 6, 8 and 12 h post collection. Frozen samples were thawed, and coagulation factors (F) II, V, VII, VIII and XIII, von Willebrand factor (vWF) and fibrinogen were measured using a coagulation analyser. FVIII concentrations declined in plasma frozen at 6, 8 and 12 h post collection (1.22 ± 0.27, 1.21 ± 0.25 and 1.16 ± 0.24 IU/mL, respectively) but not significantly (p = 0.3338). Importantly, all components met the FVIII specification (>0.7 IU/mL) for clinical plasma. Fibrinogen concentrations were stable from 6 to 12 h (p = 0.3100), as were vWF concentrations (p = 0.1281). Coagulation factors II, V, VII and XIII were not significantly different (p > 0.05 for all factors). Clinical apheresis plasma can be frozen within 12 h of collection, allowing collections from donor centres further from processing centres and increasing supply.

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.

Initiation time of double-filtration plasma apheresis affects the risk of persistent organ failure in hypertriglyceridaemia-induced acute pancreatitis: a retrospective study

The effect of double filtration plasma apheresis (DFPP) on improving the outcomes of patients with hypertriglyceridaemia-induced acute pancreatitis (HTG-AP) remains unclear. The aim of this study was to evaluate the relationship between the initiation time of DFPP and the risk of persistent organ failure (POF) in an HTG-AP cohort in China. We retrospectively evaluated data from HTG-AP patients treated with DFPP 48 h after diagnosis between January 2017 and January 2022. Comparisons across tertiles of the interval from diagnosis to completion of one DFPP session (DTD) were analysed. Logistic regression models and restricted cubic splines (RCS) were used to determine the correlation between the DTD time and risk of POF. Of the 89 patients enrolled, 46 patients (51.69%) suffered POF in the first week of HTG-AP. DFPP was initiated at a median of 17 h after the diagnosis was confirmed. The patients in the highest tertile of DTD time had a significantly increased prevalence of POF. After multivariate adjustment, the logistic regression models found a significant decrease in the odds ratios (OR) of POF from the highest to the lowest DTD tertile (P for trend = 0.006). Moreover, the RCS curves showed a nonlinear relationship in the adjusted OR of POF and DTD time, which remained relatively low and flat during the early DTD time but increased sharply afterwards. Early initiation of DFPP treatment correlates with a reduced risk of POF in HTG-AP patients.

Consensus document on Lipoprotein(a) from the Italian Society for the Study of Atherosclerosis (SISA)

AimsIn view of the consolidating evidence on the causal role of Lp(a) in cardiovascular disease, the Italian Society for the Study of Atherosclerosis (SISA) has assembled a consensus on Lp(a) genetics and epidemiology, together with recommendations for its measurement and current and emerging therapeutic approaches to reduce its plasma levels. Data on the Italian population are also provided. Data synthesisLp(a) is constituted by one apo(a) molecule and a lipoprotein closely resembling to a low-density lipoprotein (LDL). Its similarity with an LDL, together with its ability to carry oxidized phospholipids are considered the two main features making Lp(a) harmful for cardiovascular health. Plasma Lp(a) concentrations vary over about 1000 folds in humans and are genetically determined, thus they are quite stable in any individual. Mendelian Randomization studies have suggested a causal role of Lp(a) in atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis and observational studies indicate a linear direct correlation between cardiovascular disease and Lp(a) plasma levels. Lp(a) measurement is strongly recommended once in a patient's lifetime, particularly in FH subjects, but also as part of the initial lipid screening to assess cardiovascular risk. The apo(a) size polymorphism represents a challenge for Lp(a) measurement in plasma, but new strategies are overcoming these difficulties. A reduction of Lp(a) levels can be currently attained only by plasma apheresis and, moderately, with PCSK9 inhibitor treatment. ConclusionsAwaiting the approval of selective Lp(a)-lowering drugs, an intensive management of the other risk factors for individuals with elevated Lp(a) levels is strongly recommended.

P-800 Autologous stem cell ovarian transplant induced long-lasting effects on the plasma proteome of women with premature ovarian insufficiency

Abstract Study question Does autologous stem cell ovarian transplant (ASCOT) induce any long-term modifications in the plasma proteomic profile of women with premature ovarian insufficiency (POI)? Summary answer Stem cell mobilization and infusion into the ovary elicit long-term proteomic changes in peripheral blood plasma composition in women with POI, reverting age-related proteomic changes. What is known already Patients with POI are challenging to treat, with oocyte donation remaining as the only feasible option to achieve pregnancy. Previous attempts to overcome the fertility problems of these patients have mainly been based on ovarian stimulation, and were likely unsuccessful due to the lack of stimulable antral follicles remaining in the ovaries. Our group described that ASCOT in patients with impaired ovarian function improves ovarian reserve biomarkers, follicle and oocyte quantity enabling pregnancy and delivery of healthy babies. Beneficial effects of ASCOT were associated with the presence of different stem-cell secreted factors in apheresis plasma. Study design, size, duration Experimental cohort study with plasma samples of POI women undergoing stem cell mobilization with granulocyte-colony stimulating factor (mobilization arm; N = 3) or stem cell mobilization and infusion into the ovarian artery (ASCOT arm; N = 3). Peripheral plasma samples were collected from all patients at recruitment (Pre), during bone marrow stem cell mobilization and collection by apheresis (Apheresis), and three months after mobilization or ASCOT (Post). Participants/materials, setting, methods Proteins were isolated from plasma samples and quantified by SWATHTM to compare the plasma proteomic profile of the different time points (Pre, Apheresis, Post), using an ElasticNet penalized linear regression method. To determine the biological processes affected by stem cell mobilization and infusion into the ovary, a Gene Ontology Enrichment Analysis for the differentially expressed proteins (DEPs) was performed, considering significantly enriched those GO Biological Processes with a False Discovery Rate &amp;lt;0.05. Main results and the role of chance Discriminant analysis highlighted clear distinctions between the plasma proteome at the three evaluated time points. Both the stem cell mobilization and ASCOT technique induced statistically significant modifications in the plasma composition, reversing some age-related protein expression changes. Specifically, differences between Apheresis and Pre samples were explained by fourteen DEPs, revealing the functional analysis an enrichment in processes related to the complement cascade, immune system, and platelet degranulation. When the link of these proteomic changes with aging was evaluated, we found three proteins that were upregulated in Apheresis [C1QC, LYSC, LYAM1] whose plasma levels decrease with aging, and one downregulated protein [CRP] whose expression rises with age. Regarding Post samples, twenty-four DEPs with respect to Pre condition were found within the mobilization arm, being two of them linked with aging [MMP2 and ALDOC]. These DEPs were related with immune response and platelet degranulation but also with processes associated with responses to oxygen-containing compounds and growth hormones, and blood vessel maturation. Within the ASCOT arm, Pre and Post samples were clearly differentiated by eleven DEPs, although any GO Biological Process were found. Nevertheless, among these DEPs, we found DIAC which increases in plasma with aging and was downregulated after ASCOT. Limitations, reasons for caution Considering the small sample size used in this study, further experimental studies will be needed to validate the results. Moreover, further research will be necessary to determine the extent of the regenerative effects of the identified DEPs within the ovaries, and their direct implications in ovarian aging. Wider implications of the findings Our findings highlight the potential proteins and biological processes that may promote the follicle activation and growth observed after ASCOT. Identifying plasma proteins that regenerate aged or damaged ovaries could lead to more effective, targeted and/or preventive therapies for affected patients. Funding: CIPROM/2021/058, PI21/00170, CP19/00141 and CD20/00116. Trial registration number NCT03535480

Mitigating the cryoprecipitate shortage by using apheresis plasma as a manufacturing source

TransfusionAccepted Articles LETTER TO THE EDITOR Mitigating the Cryoprecipitate shortage by using apheresis plasma as a manufacturing source Rugved Pattarkine MD, Corresponding Author Rugved Pattarkine MD [email protected] orcid.org/0000-0003-2961-3145 Wing-Kwai and Alice Lee-Tsing Chung Transfusion Service, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California Correspondence Rugved Pattarkine MD, Transfusion Medicine Fellow, UCLA health, 10833 Le Conte Ave. Los, Angeles, CA 90095, Email: [email protected]Search for more papers by this authorAida-Rae Manansala, Aida-Rae Manansala Wing-Kwai and Alice Lee-Tsing Chung Transfusion Service, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CaliforniaSearch for more papers by this authorAlyssa Ziman MD, Alyssa Ziman MD orcid.org/0000-0002-1814-9319 Wing-Kwai and Alice Lee-Tsing Chung Transfusion Service, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CaliforniaSearch for more papers by this authorDawn C. Ward MD, Dawn C. Ward MD orcid.org/0000-0003-1672-740X Wing-Kwai and Alice Lee-Tsing Chung Transfusion Service, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CaliforniaSearch for more papers by this author Rugved Pattarkine MD, Corresponding Author Rugved Pattarkine MD [email protected] orcid.org/0000-0003-2961-3145 Wing-Kwai and Alice Lee-Tsing Chung Transfusion Service, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California Correspondence Rugved Pattarkine MD, Transfusion Medicine Fellow, UCLA health, 10833 Le Conte Ave. Los, Angeles, CA 90095, Email: [email protected]Search for more papers by this authorAida-Rae Manansala, Aida-Rae Manansala Wing-Kwai and Alice Lee-Tsing Chung Transfusion Service, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CaliforniaSearch for more papers by this authorAlyssa Ziman MD, Alyssa Ziman MD orcid.org/0000-0002-1814-9319 Wing-Kwai and Alice Lee-Tsing Chung Transfusion Service, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CaliforniaSearch for more papers by this authorDawn C. Ward MD, Dawn C. Ward MD orcid.org/0000-0003-1672-740X Wing-Kwai and Alice Lee-Tsing Chung Transfusion Service, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CaliforniaSearch for more papers by this author First published: 27 March 2023 https://doi.org/10.1111/trf.17335 This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/trf.17335. AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Accepted ArticlesAccepted, unedited articles published online and citable. The final edited and typeset version of record will appear in the future. RelatedInformation

Magnetic blood purification-based soluble fms-like tyrosine kinase-1 removal in comparison with dextran sulfate apheresis and therapeutic plasma exchange.

Preeclampsia remains one of the most serious complications of pregnancy. Effective therapies are yet to be developed. Recent research has identified an imbalance of angiogenic and antiangiogenic factors as a root cause of preeclampsia. In particular, soluble fms-like tyrosine kinase-1 (sFlt-1) has been shown to bind the angiogenic factors vascular endothelial growth factor (VEGF) and placental growth factor (PlGF), reducing blood vessel growth. Increasing preclinical and clinical evidence suggests that removal of the sFlt-1 protein may benefit patients with early onset preeclampsia. sFlt-1 may be removed by conventional blood purification techniques, such as therapeutic plasma exchange (TPE) and dextran sulfate apheresis (DSA), or emerging technologies, including extracorporeal magnetic blood purification (MBP). We compare the performance and selectivity of TPE, DSA, and MBP for the therapeutic removal of sFlt-1. For MPB, we employ magnetic nanoparticles functionalized with either sFlt-1 antibodies or the sFlt-1-binding partner, vascular endothelial growth factor (VEGF). We demonstrate that sFlt-1 removal by MBP is feasible and significantly more selective than TPE and DSA at comparable sFlt-1 removal efficiencies (MBP 96%, TPE 92%, DSA 78%). During both TPE and DSA, complement factors (incl. C3c and C4) are depleted to a considerable extent (-90% for TPE, -55% for DSA), while in MBP, complement factor concentrations remain unaltered. We further demonstrate that the removal efficacy of sFlt-1 in the MBP approach is strongly dependent on the nanoparticle type and dose and can be optimized to reach clinically feasible throughputs. Taken together, the highly selective removal of sFlt-1 and potential other disease-causing factors by extracorporeal magnetic blood purification may offer new prospects for preeclamptic patients.

The safety of plasma apheresis from donors recovering from COVID-19 infection in Japan

PurposeSince 2020, the novel coronavirus infection (COVID-19) has spread globally. A few studies have investigated the safety of COVID-19 convalescent plasma (CCP) apheresis from COVID-19. This study was the first retrospective observational study of CCP in Japan. MethodsWe recruit donors from April 2020 to November 2021 and plasmapheresis in our center (NCGM: national center for global health and medicine). We set the primary endpoint as the Donors Adverse Event (DAE) occurrence at the time of the CCP collection. Variable selection was used to explore the determinants of DAE. ResultsMean and SD age was 50.5 (10.6) years old. Seventy-three (42.2 %) were female, and 87 (33.3 %) were multiple-times donors. Twelve (6.97 % by donors and 4.6 % in total collections) adverse events occurred. The DAEs were VVR (Vaso Vagal Reaction), paresthesia, hypotension, agitation, dizziness, malaise, and hearing impairment/paresthesia. Half of them were VVR during apheresis. DAE occurred only in first-time donors and more in severe illnesses such as using ventilation and ECMO. From the donor characteristics and variable selection, the risk factors are as follows: younger age, female, the severity of disease at the time of the disease, and lower SBP before initiation. Our DAE incidence did not differ from previous studies. DAEs were more likely to occur in CCP apheresis than in healthy donors. ConclusionWe confirm the safety of CCP apheresis in this study, although DAEs were more than healthy donors. More caution should be exercised in the plasma collection for future outbreaks of emerging infectious diseases.

Pregnancy-induced severe hypertriglyceridemia effectively treated with therapeutic plasmapheresis

IntroductionHypertriglyceridemia is associated with significant morbidity during pregnancy. Hypertriglyceridemia-induced pancreatitis (HTGP) is associated with genetically determined dyslipidemia or a secondary condition such as diabetes, alcohol, pregnancy, or medication use. The lack of data on the safety of drugs to be used to decrease triglyceride levels during pregnancy dictates that other strategies must be chosen. Patient and methodsWe describe a case of a pregnant woman with severe hypertriglyceridemia treated with two different techniques of plasmapheresis (Dual Filtration apheresis and Centrifugal Plasma Separation). ResultsThe patient could be treated throughout the pregnancy, with good control of the triglycerides, and a healthy baby was born. ConclusionHypertriglyceridemia is a major issue during pregnancy. The use of plasmapheresis is a safe and efficient tool in that clinical scenario.

FLAG Regimen and Bortezomib: A Study of Eight Cases with Relapsed Leukaemia

Historically, relapsed and refractory Acute Lymphoblastic Leukaemia (ALL) and Acute Myeloid Leukaemia (AML) have been associated with a dismal prognosis. Relapse-refractory ALL is associated with cure rates of &lt;10% in adults and 30% in the paediatric population. Similarly, the five-year survival rates for relapsed and refractory AML are only 10%. This case series describes eight patients with relapsed/refractory leukaemia (6 with ALL and 2 with AML) who received the FLAG-Bortezomib protocol from January 2021 to August 2022. In this case series, the authors investigated the remission rate and toxicity of the regimen, including Intensive Care Unit (ICU) admissions and the incidence of neutropenic sepsis. In the present study, the rates of culture-positive sepsis and High Dependency Unit (HDU) admission were 50% (4/8) and 37.5% (3/8), respectively, with no post-chemotherapy mortality in this cohort. Morphologic remission was documented in 87.5% (7/8) of cases, and negative minimal residual disease was achieved in 62.5% (5/8), with 100% (2/2) remission in those with AML. One patient with ALL experienced disease progression during treatment. The FLAG with Bortezomib protocol induces remission in relapsed and refractory ALL and AML patients with an acceptable toxicity profile. This protocol requires rigorous blood product support in the form of packed red blood cells, platelet-rich plasma, and single-donor platelet apheresis. It serves as a bridge to stem cell transplant.

Characteristics and trends in the work of the Blood Service of the Russian Federation in 2016–2020

Introduction. Ensuring a sustainable supply of safe donor blood is crucial for strategic issues and challenges. The evaluation of donor characteristics as well as the volume of components harvested and issued to medical organizations in the Russian Federation is a topical task for the national blood service.Aim — to analyze the performance indicators of the national blood service for the procurement and provision of donated blood and its components to medical organizations from 2016–2020.Methods. Data on over 6.5 million donors who donated blood in Russia during 2016–2020 were analyzed. Data were obtained from Blood Service report form No. 39 “Blood products and derivatives”. Descriptive statistics were used during analysis.Results. A decrease of the number of blood donors per thousand population was shown (from 9.68 to 8.26, р &lt; 0.0001). There was a decrease of the number of first-time donors and of the number of repeat donors (by 23 and 9.3 %, respectively) within studied period. Regular donor quantum increased from 71 to 76 %. The share of volunteer blood donors from 2016 to 2020 throughout the Russian Federation remained stable and amounted to 97.7–98.0 %. The total number of donations decreased by 6.0 % due to a significant decrease in the number of donations of automatic apheresis plasma (from 507,396 in 2016 to 388,742 in 2020, p &lt; 0.001), at the same time, a significant increase in the number of donations platelets was noted (from 83,285 donations in 2016 to 126,574 in 2020, p &lt; 0.001). During the follow-up period, there was an increase from 2.0 in 2016 to 2.21 in 2020 (10 %) in the average number of donations of blood components made by donors per year. Despite the decrease in the total number of donations in the analyzed period, the volume of blood components transferred for clinical use increased. The largest increase in blood components transferred at the request of medical organizations was noted for the concentrate of donor platelets (from 702,732 units in 2016 to 1,072,830 in 2020, by 34.5 %) and erythrocyte- containing blood components (from 491,791 liters in 2016 to 555,909 liters in 2020, by 13.5 %). A general trend was noted both towards a decrease in the frequency of detection of markers of bloodborne infections (from 16.8 to 7.7 %), and in individual infections. When analyzing the frequency of detection of infection markers, a significant difference was obtained in the group of newly registered and repeated donors (50,114 and 25,814, р &lt; 0,001).Conclusion. The decrease of the number of cases of detection of infection markers and the redistribution of blood collection in accordance with the changing demands of medical organizations demonstrates a targeted strategy for improving the safety of transfusions, improving the quality of recruiting activities, and improving the principles of lean production of blood components.

Wider perspectives: It's a changing world-The use of ABO-incompatible plasma for resuscitating massively bleeding patients.

Wider perspectives: It's a changing world-The use of ABO-incompatible plasma for resuscitating massively bleeding patients.

Elimination of Herpes Simplex Virus-2 and Epstein-Barr Virus With Seraph 100 Microbind Affinity Blood Filter and Therapeutic Plasma Exchange: An Explorative Study in a Patient With Acute Liver Failure

OBJECTIVES:Herpes simplex virus (HSV)-2 is a rare cause of hepatitis that can lead to acute liver failure (ALF) and often death. The earlier the initiation of acyclovir treatment the better the survival. With regard to ALF, controlled randomized data support the use of therapeutic plasma exchange (TPE) both as bridge to recovery or transplantation—possibly by modulating the systemic inflammatory response and by replacing coagulation factors. Seraph 100 Microbind Affinity Blood Filter (Seraph; Ex Thera Medical, Martinez, CA), a novel extracorporeal adsorption device, removes living pathogens by binding to a heparin-coated surface was shown to efficiently clear HSV-2 particles in vitro. Here, we tested the combination of Seraph with TPE to reduce a massive HSV-2 viral load to reach a situation in that liver transplantation would be feasible.DESIGN:Explorative study.SETTING:Academic tertiary care transplant center.PATIENT:Single patient with HSV-2–induced ALF.INTERVENTIONS:TPE + Seraph 100 Microbind Affinity Blood Filter.MEASUREMENTS AND MAIN RESULTS:We report Seraph clearance data of HSV-2 and of Epstein-Barr virus (EBV) in vivo as well as total viral elimination by TPE. Genome copies/mL of HSV-2 and EBV in EDTA plasma were measured by polymerase chain reaction every 60 minutes over 6 hours after starting Seraph both systemically and post adsorber. Also, HSV-2 and EBV were quantified before and after TPE and in the removed apheresis plasma. We found a total elimination of 1.81 × e11 HSV-2 copies and 2.11 × e6 EBV copies with a single TPE (exchange volume of 5L; 1.5× calculated plasma volume). Whole blood clearance of HSV-2 in the first 6 hours of treatment was 6.64 mL/min (4.98–12.92 mL/min). Despite much lower baseline viremia, clearance of EBV was higher 36.62 mL/min (22.67–53.48 mL/min).CONCLUSIONS:TPE was able to remove circulating HSV-2 copies by 25% and EBV copies by 40% from the blood. On the other hand, clearance of HSV-2 by Seraph was clinically irrelevant, but Seraph seemed to be far more effective of removing EBV, implicating a possible use in EBV-associated pathologies, but this requires further study.

PLASMA APHERESIS PROCEDURE

The present study investigates to prepare single donor Plasma Apheresis product in the blood center with the help of Fresenius Cell Separator for use in patientwho require coagulation factors, covid patients, dengue patients etc. Apheresis is a medical procedure that involves removing whole blood from a donor or patient and separating the blood into individual components so that one particular component can be removed.Apheresis is a medical procedure that involves removing whole blood from a donor or patient and separating the blood into individual components so that one particular component can be removed. The remaining blood components then are re-infused back into the bloodstream of the patient or donor. Apheresis is also called pheresis or hemapheresis. The terminology used may also reflect the component of blood that is being removed, such as: • Plasma (plasmapheresis) • Platelets (plateletpheresis) • Leukocytes (leukapheresis or leukopheresis) • Lymphocytes (lymphopheresis or lymphapheresis) • Red blood cells (erythropheresis) Total plasma exchange (removal of plasma and replacement with fresh frozen plasma) can also be performed using the apheresis procedure. It is also used for the collection of stem cells from the peripheral blood. KEYWORDS: Plasma Apheresis, medical procedure, hemapheresis, Leukocytes

Preparation and Storage of Cryoprecipitate Derived from Amotosalen and UVA-Treated Apheresis Plasma and Assessment of In Vitro Quality Parameters.

Cryoprecipitate is a plasma-derived blood product, enriched for fibrinogen, factor VIII, factor XIII, and von Willebrand factor. Due to infectious risk, the use of cryoprecipitate in Central Europe diminished over the last decades. However, after the introduction of various pathogen-reduction technologies for plasma, cryoprecipitate production in blood centers is a feasible alternative to pharmaceutical fibrinogen concentrate with a high safety profile. In our study, we evaluated the feasibility of the production of twenty-four cryoprecipitate units from pools of two units of apheresis plasma pathogen reduced using amotosalen and ultraviolet light A (UVA) (INTERCEPT® Blood System). The aim was to assess the compliance of the pathogen-reduced cryoprecipitate with the European Directorate for the Quality of Medicines (EDQM) guidelines and the stability of coagulation factors after frozen (≤−25 °C) storage and five-day liquid storage at ambient temperature post-thawing. All pathogen-reduced cryoprecipitate units fulfilled the European requirements for fibrinogen, factor VIII and von Willebrand factor content post-preparation. After five days of liquid storage, content of these factors exceeded the minimum values in the European requirements and the content of other factors was sufficient. Our method of production of cryoprecipitate using pathogen-reduced apheresis plasma in a jumbo bag is feasible and efficient.

Quality Assessment and Clinical Utility of Plasma Obtained Via Apheresis vs That Obtained from Whole Blood.

We studied the impact of storage of thawed plasma (TP) on the in vitro coagulation quality and posttransfusion outcomes of apheresis plasma (AP) vs whole blood plasma (WBP). One hundred units of each product were analyzed. In vitro assays were performed on TP on day 0, day 2, and after refreezing, evaluating international normalized ratio (INR), activated partial thromboplastin time (aPTT), fibrinogen, and factors V and VIII. Transfusion of TP on day 2 was studied in 70 patients with liver cirrhosis and 25 patients with thrombotic thrombocytopenic purpura (TTP). Refrozen specimens from both products showed a significant decline of all values, although AP had a considerably greater coagulation profile (P < .05).On day 0 and day 2, we observed significant decreases in coagulation values (except fibrinogen) with WBP, compared with AP (P < .05). The WBP, however, provided similar INR for patients with liver cirrhosis and TTP, as compared with AP. The AP resulted in a significant correction of aPTT following plasma exchange in TTP (P < .05). AP demonstrated considerably greater factor activity. This would be beneficial when manufacturing clotting factor concentrates. Large scale clinical trials are needed to further address the hemostatic outcomes of both products in massively transfused patients.

Anti-SARS-CoV-2 antibody responses in convalescent plasma donors with varying severity of COVID-19 illness

Background/Aim. Plasma containing a high titer of anti-SARS-CoV-2 antibodies, donated from individuals who recovered from COVID-19, has the potential to be used as initial therapy for patients who have been infected (passive immunization). It is a challenge to find suitable donors. The aim of the study was to successively monitor antibody titer in donations and to investigate the correlation between antibody titer and the severity of the clinical manifestations. Methods. The retrospective study was conducted from May 1 to October 31, 2020, at the Blood Transfusion Institute of Vojvodina. Donors had to meet certain criteria for inclusion in the study: proven SARS-CoV-2 infection, detected SARS-CoV-2 antibodies in the serum/plasma, fulfillment of general criteria for performing plasmapheresis, and adequate laboratory findings. Results. During the study, 651 apheresis plasma units were collected and divided into two equal doses. Plasma was donated by 311 COVID- 19 convalescents, including 208 (66.9%) men and 103 (33.1%) women. There were 15 (4.8%) plasma donors with asymptomatic infection, 235 (75. 6%) with a mild form of illness, 45 (14.5%) with a moderate form of illness, 16 (5.1%) with a severe form of illness, and none with a critical form of illness. Anti-SARS-CoV-2 IgG antibodies were present in the plasma of donors for more than 6 months after the disease. Plasma donors with a more severe clinical manifestation of COVID-19 had stable antibody levels for a longer period. However, the Pearson correlation of clinical severity and antibody titer did not confirm a statistically significant correlation between the variables. Conclusion. Anti-SARS-CoV-2 antibodies were present in the sample of recovered patients, plasma donors, for more than 6 months after the disease. Even though no statistically significant correlation was found between the anti-SARS-CoV-2 anti-body titer and the clinical severity of COVID-19, in patients with a more severe clinical manifestations of the disease, stable antibody levels were maintained for a longer period.

Characterization and first-in-human clinical dose-escalation safety evaluation of a next-gen human freeze-dried plasma.

BackgroundEarly plasma transfusion is life‐saving for bleeding trauma patients. Freeze‐dried plasma (FDP) provides unique formulation advantages for infusion in the prehospital setting. We describe characterization and clinical safety data of the first, next‐generation FDP stored in plastic bags with rapid reconstitution.Study design and methodsCoagulation and chemistry parameters on 155 pairs of fresh frozen plasma (FFP) and their derivative FDP units were compared. Next, a first‐in‐human, dose‐escalation safety evaluation of FDP, involving 24 healthy volunteers who donated either whole blood or apheresis plasma to create autologous FDP, was performed in three dose cohorts (270, 540, and 810 ml) and adverse events (AEs) were monitored. Cohort 3 was randomized, double‐blind with a cross‐over arm that compared FDP versus FFP using descriptive analysis for AEs, coagulation, hematology, and chemistry parameters.ResultsFDP coagulation factors, clotting times, and product quality (pH, total protein, and osmolality) post‐lyophilization were preserved. FDP infusions, of up to 810 ml per subject, were found to be safe and with no serious AEs (SAEs) related to FDP. The average time to reconstitute FDP was 67 s (range: 43–106). No differences in coagulation parameters or thrombin activation were detected in subjects infused with 810 ml of FDP compared with FFP.ConclusionThis first next‐generation FDP product preserves the potency and safety of FFP in a novel rugged, compressible, plastic container, for rapid transfusion, allowing rapid access to plasma in resuscitation protocols for therapy in acute traumatic hemorrhage.