Plasma Exchange Research Articles

Abnormal proteolytic activity profile in plasma of blood donors according to anti-SARS-CoV-2 IgG titer

This work aims to study whether there is a relationship between titer values of anti-SARS-CoV-2 IgG and changes in proteolytic processes. To confirm this hypothesis, we analyzed the content and activity of Matrix Metalloproteinases (MMPs) as well as the concentration and composition of circulating peptide pools in the plasma of blood donors divided into groups on the basis of anti-SARS-CoV-2 IgG titers. The results of gelatin zymography showed the presence of active MMP-2 in donors’ plasma who recovered from COVID-19. In contrast, collagenases and their complexes were detected in the plasma of donors with no anti-SARS-CoV-2 IgG, while their activity was undetectable in some groups of COVID-19 convalescent individuals. The content of MMPs also differed among the donors with different titers of anti-SARS-CoV-2 IgG. Plasma peptide content was identical among the donors' groups, but there were more peptide fractions in plasma peptide pools of COVID-19 convalescent individuals; furthermore, they all were characterized by the presence of peptides with molecular weights less than 920 Da and greater than 1530 Da. We hypothesized a link between proteolytic alterations and peptide fraction composition. Our data need further validation to confirm the relationship between the titer values of anti-SARS-CoV-2 IgG and the severity of the proteolytic imbalance.

Numerical simulation study on discharge characteristics of the Dual hollow cathode plasma source using magnetic mirror field

The Dual hollow cathode plasma source uses hollow cathode cylindrical sputtering and ionizing metal elements, which has a high material utilization rate and has potential application in the field of material modification. Its performance index requires the cooperation of electrode discharge parameters and the rational utilization of the inner surface of the hollow cathode. In this paper, a two-dimensional fluid model of a Dual hollow cathode structure is developed to simulate the basic distribution of the Dual hollow cathode discharge, which fills the central region of the Dual hollow cathode structure and the electrons oscillate on the axis. The effects of electrode parameters and hollow cathode radius on the discharge were investigated. The results show that the radial electron density of the hollow cathode increases with increasing heated cathode voltage, but as the hot cathode voltage continues to expand beyond 1200 V this trend becomes less obvious. The enhancement of the wall ion current by the heated cathode voltage is very pronounced, and the hollow cathode discharge is the result of the mutual enhancement of the heated cathode voltage and the hollow cathode voltage. Hollow cathode sputtering needs to reach a voltage threshold of 300 V, and the existence of an optimal radius (r = 4 mm−6 mm) to achieve a high plasma density and at the same time favor hollow cathode sputtering.

Effectiveness and safety of therapeutic plasma exchange in neurological diseases: An 11-year report from a tertiary care center.

Therapeutic plasma exchange has been a well-known treatment method for many years and is widely available. It leads to the improvement of neurological symptoms in autoimmune neurological diseases by the removal of antibodies. The aim of this study was to present therapeutic plasma exchange responses and procedure-related adverse events in patients with autoimmune neurological diseases based on our 11-year experience. A retrospective evaluation was conducted on adult patients who underwent a therapeutic plasma exchange procedure due to neurological diseases between January 2013 and January 2024. Data were gathered from electronic and written hospital and apheresis unit records. A total of 265 patients underwent 1274 procedures with a preliminary diagnosis of autoimmune neurological disease. Five patients were excluded from the analysis due to their final diagnoses. The most common clinical indications were Guillain-Barré syndrome (45.4%), myasthenia gravis (26.1%), and multiple sclerosis (19.2%). The overall response rate was 81.3%, with 21.7% exhibiting a complete response and 59.6% demonstrating a partial response. With the exception of one patient (hypertensive crisis), no complications necessitating the termination of the procedure were observed. The most prevalent complication was an easily manageable allergic reaction. Therapeutic plasma exchange has been demonstrated to be an efficacious and safe treatment option in autoimmune neurological diseases, with a favorable overall response rate and a manageable mild-to-moderate side effect profile.

Tracking myasthenia gravis severity over time: Insights from the French health insurance claims database.

Few data are available on the course of myasthenia gravis (MG) regarding disease severity and stability over time in real-world settings. This study used the French National Health Insurance Database (SNDS) to assess markers of disease severity in patients with MG longitudinally. All patients with MG-related claims in the SNDS between 2013 and 2020 were identified. Patients were followed for up to 8 years after the first claim. Intensive care unit (ICU) stays, treatment with intravenous immunoglobulin (IVIg) or plasma exchange (PE), and death were documented throughout the follow-up period. Standardized mortality rates were estimated, and mortality-related variables were identified using a Cox model. In all, 14,459 individuals constituted the full study population, including 6354 incident patients. In the incident population, 2199 (34.6%) were admitted to ICUs at least once, principally during the first year after the index date (N = 1477; 23.3%). This proportion decreased progressively to reach 3.0% in the seventh year. A total of 2817 patients received IVIg and 432 PE, again principally in the first year. In the full study population, the standardized mortality rate was 1.08 (95% confidence interval [CI] 1.03-1.13), being lower in men (0.95, 95% CI 0.89-1.02) than in women (1.15, 95% CI 1.07-1.23) and in patients aged >65 years (1.06, 95% CI 1.01-1.11) than in younger patients (1.50, 95% CI 1.24-1.76). Male gender, older age and higher comorbidity were independently associated with mortality. A subgroup of patients with MG require ICU admission and rescue therapy with IVIg or PE, indicative of poor disease control. New therapies are needed to improve disease control and reduce disease burden.

Apheresis therapies in MOGAD: a retrospective study of 117 therapeutic interventions in 571 attacks

BackgroundIncomplete attack remission is the main cause of disability in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Apheresis therapies such as plasma exchange and immunoadsorption are widely used in neuroimmunology. Data...

IgA Vasculitis (Henoch–Schönlein Purpura): An Update on Treatment

Objective: IgA vasculitis (IgAV), previously named as Henoch–Schönlein purpura, is the most frequent systemic vasculitis in children. In adults, IgAV is less common although it is associated with more severe disease. In fact, the frequency of glomerulonephritis (referred to as IgAV nephritis) in adults is higher than in children and tends to present more severely, with around 10–30% of those affected eventually progressing to end-stage renal disease. In this review, we describe the pathophysiology, main clinical features, diagnosis of the disease, and latest clinical data regarding IgAV therapy. Methods: A narrative literature review, primarily based on articles published in PubMed, was conducted. In addition to discussing the main aspects of glucocorticoids and conventional disease-modifying drugs used in the management of IgAV, this review focuses on the latest information reported regarding biologics and potential future therapies. Results: Glucocorticoids are the first-line therapy for IgAV, especially in adults with severe manifestations. Colchicine, dapsone, and methotrexate can be useful for controlling minor manifestations. Several immunomodulatory agents, such as cyclosporine A, tacrolimus, and mycophenolate mofetil, have shown favorable results as glucocorticoid-sparing agents. Leflunomide has shown promising results but requires further study. The use of rituximab has demonstrated efficacy in reducing relapse frequency, lowering the cumulative glucocorticoid burden, and achieving long-term remission of the disease in children and adults with IgAV. Immunoglobulins and plasma exchange therapy can also be useful in difficult and life-threatening situations. Other potential therapies with encouraging results include TRF-budesonide, B-cell-directed therapy, B-cell-depleting agents, sodium–glucose cotransporter-2 inhibitors, endothelin receptor antagonists, and complement pathway inhibitors. Conclusions: Glucocorticoids are the first-line therapy for IgAV, especially in adults with severe manifestations. The role of various immunomodulatory therapies, such as calcineurin inhibitors and mycophenolate mofetil, remains promising, while rituximab reduces the long-term side effects of glucocorticoids and can help achieve disease remission. Other potential therapies with encouraging results require further research.

Plasma exchange in Acute liver failure: The jury is still out!

Plasma exchange in Acute liver failure: The jury is still out!

Complex immunogenicity assessment in caplacizumab-treated patients with immune-mediated thrombotic thrombocytopenic purpura who have received plasma exchange

Complex immunogenicity assessment in caplacizumab-treated patients with immune-mediated thrombotic thrombocytopenic purpura who have received plasma exchange

Late use of Plasma Exchange in Acute Liver Failure: The Battle is Lost?

Late use of Plasma Exchange in Acute Liver Failure: The Battle is Lost?

How to make a decision for the use of plasma exchange in patients with acute liver failure?

How to make a decision for the use of plasma exchange in patients with acute liver failure?

Plasmapheresis for extracorporeal membrane oxygenation (ECMO)-induced hemolysis in infants

Background: Intravascular hemolysis is a known complication of extracorporeal membrane oxygenation (ECMO). Characterized by elevated plasma-free hemoglobin (PFH), intravascular hemolysis is associated with cytotoxic effects leading to renal replacement therapy (RRT), longer ECMO runs and mortality. Therapeutic plasma exchange (TPE) in tandem with ECMO was described as a therapy for various pathologic conditions, but there are no ELSO guidelines for the treatment of ECMO-induced hemolysis. We describe the use of TPE in the management of severe ECMO-induced hemolysis. Methods: Two term neonates receiving veno-arterial (VA) ECMO developed severe PFH, with peak values over 500 mg/dL. TPE was performed in tandem with the ECMO circuit. Packed red cells were used to prime the TPE circuit, and citrate anticoagulation was added to establish the interface, which could not be achieved with existing heparin in the ECMO circuit. Therapy was completed with saline solution as a decoy for citrate, to avoid hypocalcemia and intracranial bleeding. Plasma volume was replaced by fresh frozen plasma (FFP). Results: In one patient PFH fell to 120 mg/dL, but rebounded to close to 500 mg/dL, only to stabilize between 210 and 300 mg/dL after the second TPE. He was liberated from ECMO, but could not survive a respiratory decompensation. The other patient’s PFH improved to 360 mg/dL after one TPE and continued to decline to 120 mg/dL over the ensuing days. Despite that improvement, care was withdrawn. Conclusion: TPE is effective in decreasing the burden of PFH, is well tolerated in tandem with ECMO, and a database of infants with ECMO-induced hemolysis needs to be created to assess the current practice, and establish clinical guidelines for its most appropriate therapy.

Numerical Investigation of G–V Measurements of metal – A Nitride GaAs junction

In this study, a Schottky diode consisting of Au/GaN/GaAs was fabricated using a radiofrequency nitrogen plasma source. The voltage-conductance characteristics (G/ω-V) of this diode structure were investigated at room temperature. To interpret the changes in the electrical properties of the nitrided GaAs-based Schottky structure, we developed a simulation program. This program employs a numerical model to calculate the G-V characteristics, allowing us to validate the experimental measurements conducted on the Schottky diodes. The geometric model used in our simulation considers not only the GaN layer formed between the metal and GaAs substrate but also the density and distribution of trapped states within the band gap. The program utilizes the numerical resolution of the Poisson and continuity equations to calculate the electrostatic potential and the concentrations of both n and p mobile carriers. These parameters are then used to determine the electric charge, current, capacitance, and conductance. The simulation results were subsequently compared to the experimental measurements to ensure their accuracy.

Real-World Data on Effectiveness and Safety of First-Line Use of Caplacizumab in Italian Centers for the Treatment of Thrombotic Thrombocytopenic Purpura: The Roscapli Study

Background/Objectives: Immune thrombotic thrombocytopenic purpura (iTTP) is a thrombotic microangiopathy caused by the formation of anti-ADAMTS13 antibodies. Caplacizumab is approved for the treatment of acute episodes of iTTP in conjunction with plasma exchange (PEX) and immunosuppression. Real-world data for the use of caplacizumab in Italy have been recently published by a limited number of centers located in the northern and middle regions of the country only. Methods: A total of 38 patients with iTTP were enrolled in the study in six Italian centers spread over the entire territory of the country. The patients’ data were registered in eCRF. Results: All patients achieved normalization of platelet count (median 2.0 days, IQR: 2–4), within a time significantly shorter than in the absence of caplacizumab, as previously reported in other studies. As to the secondary aims, patients treated with caplacizumab had a few exacerbations (4/38 (10.5%)) and relapses (2/38, 5.3%). No deaths or refractoriness were observed in these patients. The total length of hospitalization was 12 days (IQR: 9–18) and only one patient required 2 days of stay in the intensive care unit. Interestingly, when caplacizumab was initiated within the first 3 days, the plasma exchange (PEX) duration was 9 days (IQR: 8–10), which was significantly lower than those reported in previous studies conducted in the absence of caplacizumab. No severe adverse event was described in the caplacizumab-treated patients. Conclusions: Caplacizumab reduced exacerbations and refractoriness compared with previously reported standard-of-care regimens. When administered in association with PEX and immunosuppressive therapy, caplacizumab provided rapid normalization of platelet count, which was responsible for lower overall hospitalization time, ICU stay, lower exacerbations and relapses compared to previously reported outcomes of studies carried out without caplacizumab.

Plasma exchange with albumin replacement for Alzheimer's disease treatment induced changes in serum and cerebrospinal fluid inflammatory mediator levels.

There is extensive literature indicating that inflammatory pathways are affected in Alzheimer's disease (AD). We examined whether plasma exchange with albumin replacement (PE-Alb) can impact the inflammatory status of AD patients and alter the relationship between inflammatory mediators and cognitive measures. Serum and cerebrospinal fluid (CSF) samples from 142 AD patients participating in the AMBAR trial (14-month schedule of PE-Alb treatment vs. placebo [sham PE-Alb]) were analyzed for changes from baseline for 19 inflammatory mediators (6 inflammatory cytokines, 9 chemokines, and 4 vascular injury indicators) at representative time points across the AMBAR study (lasting effects) as well as in pre- versus post-PE-Alb procedure (acute effects). Association between mediator changes and clinical outcomes reported in the AMBAR study (cognitive, functional, behavioral function, and global change tests) was assessed. PE-Alb significantly reduced IFN-γ, eotaxin, MIP-1α and ICAM-1 levels in serum, and eotaxin-3 and MIP-1β levels in CSF, at various time points during treatment (p < 0.05; false discovery rate-corrected). Vascular injury indicators were the mediators mostly affected by post- versus pre-PE-Alb level reduction. Increased serum MIP-1α levels were associated with worsening in ADAS-Cog, CDR-sb, and ADCS-CGIC scores in the placebo group, but not in the PE-Alb-treated group. Peripheral intervention could affect AD by reducing inflammatory mediators in both peripheral and central compartments. Changes in MIP-1α due to PE-Alb were associated with changes in clinical outcomes.

Securing commitment and control for the supply of plasma derivatives for public health systems. I: A short review of the global landscape.

The social market economies of the Western world considered the provision of plasma derivatives produced from publicly owned blood services as a legitimate state commitment and, until the last decades of the 20th century, many of the relevant jurisdictions maintained state-supported fractionation plants to convert publicly collected plasma into products for the public health system. This situation started to change in the 1990s, because of several converging factors, and currently, publicly owned/subsidized, not-for-profit fractionation activity has shrunk to a handful of players. However, the collection of plasma from publicly owned blood services has continued and recent developments have increased the interest of state authorities globally to increase the volume of plasma collected to increase the level of strategic independence in the supply of crucial plasma-derived medicines from commercial market pressures, particularly the global for-profit fractionation sector with its dominance of source plasma from paid donors in the United States. This paper reviews the development of the plasma industry and the evolution of the pressures on the supply of plasma, which has led to a situation of scarcity of key plasma-derived medicinal products (PDMPs).

Corrigendum: The use of plasma exchange with albumin replacement in the management of Alzheimer's disease: a scoping review

Corrigendum: The use of plasma exchange with albumin replacement in the management of Alzheimer's disease: a scoping review

Anticathode effect on electron kinetics in electron beam generated E×B plasma

Abstract Electron beam (e-beam) generated plasmas with applied crossed electric and magnetic (E×B) fields are promising for low damage processing of materials with applications to microelectronics and quantum information systems. In cylindrical e-beam E×B plasmas, radial confinement of electrons and ions is achieved by an axial magnetic field and radial electric field, respectively. To control the axial confinement of electrons, such e-beam generated plasma sources may incorporate a conducting boundary known as an anticathode, which is placed on the axially opposite side of the plasma from the cathode. In this work, it is shown that varying the anticathode voltage bias can control the degree to which the anticathode collects or repels incident electrons, allowing control of warm electron (electron energies in 10-30 eV range) and beam electron population confinement. It is suggested that the effect of the anticathode bias on the formation of these distinct electron populations is also associated with the transition between weak turbulence and strong Langmuir turbulence.

Prospective screening and proposed treatment algorithm for immune checkpoint inhibitor induced myositis in neoadjuvant-treated rectal cancer patients: data from the phase II CHINOREC trial

Abstract Background Myositis is an infrequent (&amp;lt;1%) but potentially life-threatening (case fatality rate 40-50%) immune-related adverse event (irAEs) of immune checkpoint inhibitors (ICI), such as ipilimumab (IPI) and nivolumab (NIVO). The true incidence is likely to be underestimated and may not be representative for curative neoadjuvant treatment approaches in gastrointestinal (GI) cancers, especially in combination with chemoradiotherapy (CRT). Currently, the summary of product characteristics (SmPC) does not suggest any pre-emptive screening or surveillance. Methods The CHINOREC study is an ongoing prospective, randomized, open-label, multicenter, phase II investigator-initiated trial (IIT). Patients with intermediate to locally advanced rectal cancer (LARC) receive either neoadjuvant CRT alone or in combination with a single dose of IPI and 3 cycles of NIVO, following surgical resection. Patients are monitored at baseline and throughout the whole study period for myotoxicity biomarkers, including cardiac troponin T (cTnT) and cardiac troponin I (cTnI). Findings From 06/2020 to 11/2023, 80 patients have been enrolled of whom 50 patients were randomized to the CRT+IPI/NIVO arm. Six patients (12%) developed biopsy-verified myositis. Myositis treatment was promptly implemented using a pragmatic step-up approach. Patients received glucocorticoids (GC) with concomitant intravenous immunoglobulin (IVIG). If myotoxicity biomarkers did not improve, patients received infliximab (INFLIXI) and/or plasma exchange (PLEX). Although all patients had strikingly elevated cTnT (median peak 284 ng/L, 95% CI 39-3097), cTnI levels remained largely normal, correlating with a negative cardiac magnetic resonance (CMR). All patients underwent successful tumor surgery without any major surgical complication. As of today, all patients' creatine kinase (CK) and myoglobin (MB) levels have normalized and they are tumor free without any major sequela. Interpretation Longitudinal biomarker screening (cTnT/cTnI) for ICI-induced myotoxicities is pivotal in curative neoadjuvant-treated cancer patients to initiate an early counter treatment in a holistic step-up approach, without compromising oncological principles.

On the in-situ determination of the effective secondary electron emission coefficient in low pressure capacitively coupled radio frequency discharges based on the electrical asymmetry effect

Abstract We present a method for the in-situ determination of the effective secondary electron emission coefficient (SEEC, γ) in a capacitively coupled plasma (CCP) source based on the γ-dependence of the DC self-bias voltage that develops over the plasma due to the Electrical Asymmetry Effect (EAE). The EAE is established via the simultaneous application of two consecutive radio-frequency harmonics (with a varied phase angle) for the excitation of the discharge. Following the measurement of the DC self-bias voltage experimentally, Particle-in-Cell/Monte Carlo Collision (PIC/MCC) simulations coupled with a diffusion-reaction-radiation (DRR) code to compute the argon atomic excited level dynamics are conducted with a sequence of SEEC values. The actual γ for the given discharge operating conditions is found by searching for the best match between the experimental and computed values of the DC self-bias voltage. The γ ≈ 0.07 values obtained this way are in agreement with typical literature data for the working gas of argon and the electrode material of stainless steel in the CCP source. The method can be applied for a wider range of conditions, as well as for different electrode materials and gases to reveal the effective SEEC for various physical settings and discharge operating conditions.

Inactivation Efficiency of Bacillus atrophaeus Spores on Seeds of Barley, Wheat, Lupine and Rapeseed by Direct Cold Atmospheric Pressure Plasma

The objective of this study was to evaluate the antimicrobial effect of direct cold atmospheric plasma (CAPP) treatment for pre-harvest application using four different crop species: Hordeum vulgare L. (barley), Triticum aestivum L. (wheat), Brassica napus L. (rapeseed) and Lupinus angustifolius L. (lupine). The model bacterium Bacillus atrophaeus served as a proxy for spore-forming plant pathogens on the seed surface. After semi-dry inoculation of spores onto the seeds, treatment with two different plasma sources, a volume-dielectric barrier discharge and a corona discharge, and different exposure times was carried out. Subsequently, recovery of viable spores from the seeds’ surfaces was performed. Moreover, seed viability was determined based on maximum germination, as well as water contact angle as a measure for seed surface hydrophilicity. Direct CAPP treatment was efficient in reducing viable spores of B. atrophaeus with no significant differences between the plasma sources, reaching a mean inactivation of 1 log10 CFU/mL across all treatment times and crops species. Maximum germination of seeds was not negatively affected under any treatment condition. Seed hydrophilicity was increased for both plasma sources tested. Overall, this study provides valuable information on the efficiency of direct CAPP treatment of seeds with the purpose of seed hygienization with the premise of unaltered seed vitality and evaluates the potential application in comparison with previous investigated CAPP methods.