Therapeutic apheresis in kidney transplantation: Emerging trends.

INTRODUCTION: The use of therapeutic apheresis (TA) either as stand-alone or adjunctive treatment in kidney transplantation has increased over the years to become a leading indication. This study shows recent trends in indications for TA related to kidney transplantation, adverse events, and patient outcome in this cohort. METHODS: This is a retrospective cohort review of adults who received TA for kidney transplant-related indications from January 1, 2017, to December 31, 2022, at the University of Virginia Medical Centre, Charlottesville, VA, USA. Data extracted include basic demographics, indication for apheresis, number of procedures, procedure characteristics, procedure-related adverse events (complications), and serum ionized calcium and serum creatinine. Data were analyzed using statistical package for social sciences (SPSS 2022 IBM Inc). RESULTS: Data from a total of 131 patients who received 860 TA procedures were analyzed. Indications for TA were antibody-mediated rejection (65.5%), recurrent focal segmental glomerulosclerosis (15%), thrombotic microangiopathy (5%), desensitization for ABO incompatibility (4.5%) and for HLA-incompatibility (4.5%), and recurrent IgA nephropathy (1%). Some adverse events were encountered in 16.7% of the procedures and include hypocalcemia (7%), vascular access malfunction (0.7%), hypotension (1.2%), arrhythmia (0.6%), and depletion coagulopathy (0.6%). The overall case mortality rate was 8.4% over the 6-year period. There was one death recorded on machine during TA resulting in a procedure-mortality rate of 0.12%. CONCLUSION: Antibody-mediated rejection was the most common indication for TA related to kidney transplantation. Adverse events were minor and patient survival over the time was within usual limits.

Clinical practice recommendations on lipoprotein apheresis for children with homozygous familial hypercholesterolaemia: An expert consensus statement from ERKNet and ESPN.

Homozygous familial hypercholesterolaemia is a life-threatening genetic condition, which causes extremely elevated LDL-C levels and atherosclerotic cardiovascular disease very early in life. It is vital to start effective lipid-lowering treatment from diagnosis onwards. Even with dietary and current multimodal pharmaceutical lipid-lowering therapies, LDL-C treatment goals cannot be achieved in many children. Lipoprotein apheresis is an extracorporeal lipid-lowering treatment, which is used for decades, lowering serum LDL-C levels by more than 70% directly after the treatment. Data on the use of lipoprotein apheresis in children with homozygous familial hypercholesterolaemia mainly consists of case-reports and case-series, precluding strong evidence-based guidelines. We present a consensus statement on lipoprotein apheresis in children based on the current available evidence and opinions from experts in lipoprotein apheresis from over the world. It comprises practical statements regarding the indication, methods, treatment goals and follow-up of lipoprotein apheresis in children with homozygous familial hypercholesterolaemia and on the role of lipoprotein(a) and liver transplantation.

A 3-step method for preparing cryopreserved samples of apheresis products for post-thaw analysis yields a higher percentage of viable cells.

BACKGROUND: Standard flow cytometry protocols for CD34+ cell enumeration designed for fresh samples are not appropriate for cryopreserved products. Special protocols have been developed to remove the cryoprotectant by quickly washing a freshly thawed sample. Exposing cells to a large volume of hypotonic solution and subsequent washing process was hypothesized to cause lab-induced cell death. Moreover, standard gating strategies must be altered to avoid reporting falsely high viabilities. STUDY DESIGN AND METHODS: We developed a novel method whereby thawed samples were diluted step-wise to 1:2 by 3 additions of 1/3 sample volume using 1% Human Albumin in Dextran 40 (10% Low Molecular Weight Dextran in 0.9% NaCl) separated by 5 min between each addition. An additional 1:10 dilution was required to obtain a desired cell concentration for flow cytometry testing resulting in a 1:20 dilution. RESULTS: Twenty samples were tested simultaneously in a method comparison; the new method demonstrated significant increases in mean cell viabilities for white blood cells, hematopoietic progenitor cells, and T cells as well as reduced standard deviations for each parameter. DISCUSSION: Slow, step-wise dilutions of freshly thawed samples of cryopreserved apheresis products to 1:20 yielded higher and more precise viability measurements compared to quickly washing samples to remove DMSO.

Stem Cells Collection and Mobilization in Adult Autologous/Allogeneic Transplantation: Critical Points and Future Challenges.

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.

Autologous peripheral blood stem cell mobilization and apheresis in pediatric patients with cancer: A single-center report of 64 procedures.

BACKGROUND: The published experience concerning autologous peripheral blood stem cell collection in children is very limited. METHODS: The data of pediatric patients who underwent autologous stem cell mobilization and apheresis between January 2011 and April 2020 were analyzed retrospectively. RESULTS: We studied retrospectively 64 mobilization and apheresis procedures in 48 pediatric patients (34 males, 14 females), mean age of 7.31 ± 5.38 (range, 1.5-19.7) years, the underlying disease was mostly neuroblastoma (NBL). The body weight of 21 patients (43.75%) was 15 kg or less. The targeted autologous peripheral stem cell apheresis (APSCA) was successfully achieved in 98% of patients. Neuroblastoma patients were younger than the rest of the patients and underwent apheresis after receiving fewer chemotherapy cycles than others and all of them mobilized within the first session successfully. Plerixafor was added to mobilization in nine heavily pretreated patients (18.7%), median two doses (range, 1-4 doses). 11 patients (22.9%) underwent radiotherapy (RT) before mobilization with doses of median 24 Gy (range, 10.8-54.0 Gy). Patients with RT were older at the time of apheresis and had received more chemotherapy courses than patients without RT. As a result, patients with a history of RT had significantly lower peripheral CD34+ cells and CD34+ yields than those without RT. In 17 patients (35.4%), 22 different complications were noted. The most common complications were catheter-related infections (n:10, 20.8%), followed by catheter-related thrombosis in eight patients (16.7%). CONCLUSIONS: Patients who had far less therapy before apheresis were more likely to mobilize successfully. Our study provides a detailed practice approach including complications during APSCA aiming to increase the success rates of apheresis in transplantation centers.

Apheresis practice variation during the COVID-19 pandemic: Results of a survey.

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.

Beyond traditional venous access: Midline catheter use in pediatric apheresis.

The objective of this study was to assess the use of midline catheters as venous access for apheresis procedures in pediatric patients. A retrospective analysis of medical records was conducted from September 2019 to June 2022 to evaluate the safety and efficacy of midline catheters for therapeutic pediatric apheresis. During the study period, a total of 121 procedures were inserted in 22 unique patients. The age of the subjects ranged from 2.7 to 21 years. The blood flow rates achieved with midline catheters met or exceeded the recommended rates for apheresis in children (40 mL/min), by the Wilcoxon signed-rank test (p < 0.0001). There was one episode of catheter-related thrombosis, but no cases of bloodstream infection or catheter dislodgement were reported. In conclusion, this study supports the use of midline catheters as a safe and effective alternative for venous access during therapeutic and donor apheresis procedures in pediatric patients.

Optimization of single-needle red cell exchange in patients with sickle cell disease.

The hypercoagulable state associated with sickle cell disease (SCD) can be challenging for apheresis procedures. Among 62 single-needle red cell exchanges (SN-RCEs) performed over a 15-month period, 4 patients experienced 6 hemolytic events with a discolored plasma layer, elevated plasma/RBC interface in the centrifuge, and accompanying alarms of "Cells were detected in plasma line from centrifuge" or "AIM system detected RBC at top of connector." The hemolysis originated from the apheresis instrument because samples from the apheresis belt but not the patients' peripheral blood were positive for hemolysis. Further analysis showed the alarms occurred more often in SN-RCEs (20.4%) than double-needle RCEs (2.7%), and the hemolysis was probably secondary to clumping. To optimize SN-RCE, we increased the anticoagulant dosage by changing Inlet/AC ratio from 13 to 8 and lowered the inlet rate to the level comparable to double-needle RCE. The adjustments were well-tolerated with no more hemolysis.

Using the daily rate of rise in hemoglobin S to manage RBC depletion/exchange treatment in sickle cell disease.

BACKGROUND: Red blood cell exchange is often used prophylactically in patients with sickle cell disease, with the goal to maintain hemoglobin S (HbS) below a target threshold level. We reviewed whether the daily "rate of rise" (RoR) in HbS that occurs between procedures can be used for patient management. For some patients not achieving their HbS goals despite efficient exchanges, the post-procedure hematocrit (Hct) target is increased to potentially suppress HbS production. This case series explores the utility of this approach, other clinical uses of the daily RoR in HbS, and the factors that influence it. STUDY DESIGN AND METHODS: A total of 660 procedures from 24 patients undergoing prophylactic RBC depletion/exchange procedures were included. Laboratory values and clinical parameters were collected and used to calculate the daily RoR in HbS. Factors such as Hct or medications that might influence the RoR in HbS were evaluated. RESULTS: The RoR in HbS varied widely between patients but remained relatively stable within individuals. Surprisingly, this value was not significantly influenced by changes in post-procedure Hct or concurrent hydroxyurea use. A patient's average RoR in HbS effectively predicted the pre-procedure HbS at the following visit (R2 = 0.65). DISCUSSION: The RoR in HbS is a relatively consistent parameter for individual patients that is unaffected by medication use or procedural Hct targets and may be useful in determining intervals between procedures.

Comparable bacterial growth in platelet concentrates suspended in plasma and platelet additive solution and improved detection of bacterial contamination using a new generation automated culture system.

BACKGROUND: Microbial screening of platelet concentrates (PC) with automated culture methods is widely implemented to reduce septic transfusion reactions. Herein, detection of bacterial contamination in PC was compared between units prepared in plasma and a mix of plasma and platelet additive solution (PAS) and between the BACT/ALERT 3D and next generation BACT/ALERT VIRTUO systems. STUDY DESIGN/METHODS: Double apheresis units were split into single units, diluted in either PAS (PAS-PC) or plasma (plasma-PC), and tested for in vitro quality and sterility prior to spiking with ~30 CFU/unit of Staphylococcus epidermidis, Staphylococcus aureus, Serratia marcescens, and Klebsiella pneumoniae or ~10 CFU/mL of Cutibacterium acnes. Spiked PC were sampled for BACT/ALERT testing (36 and 48 h post-spiking) and colony counts (24, 36, and 48 h post-spiking). Times to detection (TtoD) and bacterial loads were compared between PC products and BACT/ALERT systems (N = 3). RESULTS: Bacterial growth was similar in plasma-PC and PAS-PC. No significant differences in TtoD were observed between plasma-PC and PAS-PC at the 36-h sampling time except for S. epidermidis which grew faster in plasma-PC and C. acnes which was detected earlier in PAS-PC (p < .05). Detection of facultative bacteria was 1.3-2.2 h sooner in VIRTUO compared with 3D (p < .05) while TtoD for C. acnes was not significantly different between the two systems. DISCUSSION: Comparable bacterial detection was observed in plasma-PC and PAS-PC with PC sampling performed at 36-h post blood collection. PC sampling at ≤36 h could result in faster detection of facultative pathogenic organisms with the VIRTUO system and improved PC safety.

Extracorporeal Photopheresis in Dermatological Diseases.

Extracorporeal photopheresis (ECP) is an apheresis procedure that is conventionally used as a first-line treatment for cutaneous and leukemic subtypes of T-cell lymphoma, such as Sezary's syndrome and mycosis fungoides. Over the past three decades, its immunotherapeutic properties have been tested on a variety of autoimmune conditions, including many dermatologic diseases. There is ample evidence of ECP's ability to modify leukocytes and alter cytokine production for certain dermatologic diseases that have been refractory to first-line treatments, such as atopic dermatitis. However, the evidence on the efficacy of ECP for the treatment of these dermatologic diseases is unclear and/or lacks sufficient evidence. The purpose of this paper is to review the literature on the utilization and clinical efficacy of ECP in the treatment of several [autoimmune] dermatologic diseases and discuss its applications, guidelines, recommendations, and future implementation for dermatologic diseases.

[Apheresis Techniques for the Treatment of Hyperbilirubinemia in the Nephrology Unit].

Therapeutic apheresis is an important hematological and nephrological method for conditions with altered plasma composition. It is also indicated for the removal of protein-bound molecules, such as bilirubin. Several techniques can remove these compounds, such as the extracorporeal circulation molecular adsorption system (MARS), plasma exchange (PEX), and plasma adsorption and perfusion (PAP). Here we report our experience in the comparison between MARS, PEX and PAP, since current guidelines do not specify which method is the most appropriate and under which circumstances it should be used. The choice of technique cannot be based on the desired plasma bilirubin concentration, since these three techniques show similar results with a similar final outcome (exitus). In fact, PAP, PEX and MARS significantly reduce bilirubin levels, but the degree of reduction is not different among the three. Furthermore, the three techniques do not differ in the rate of cholinesterase change, while less reduction of liver transaminases was found by using PAP. MARS should be preferred in the case of renal involvement (hepatorenal syndrome with hyperbilirubinemia). PAP has the advantage of being simple and inexpensive. PEX remains an option when emergency PAP is not available, but the risk of using blood products (plasma and albumin) must be considered.

Comparing transfusion reactions between pre-storage and post-storage leukoreduced apheresis platelets: an analysis using propensity score matching.

Transfusion reactions induced by platelet transfusions may be reduced and alleviated by leukocyte reduction of platelets. Although leukoreduction of apheresis platelets can be performed either pre-storage or post-storage, seldom studies directly compare the incidence of transfusion reaction in these two different blood products. We conducted a retrospective study to compare the transfusion reactions between pre-storage and post-storage leukoreduced apheresis platelets. We reviewed the general characteristics and the transfusion reactions, symptoms, and categories for inpatients who received pre-storage or post-storage leukoreduced apheresis platelets. Propensity-score matching was performed to adjust for baseline differences between groups. A total of 40,837 leukoreduction apheresis platelet orders were reviewed. 116 (0.53%) transfusion reactions were reported in 21,884 transfusions with pre-storage leukoreduction, and 174 (0.91%) reactions were reported in 18,953 transfusions with post-storage leukoreduction. Before propensity-score matching, the odds ratio for transfusion reactions in the pre-storage group relative to the post-storage group was 0.57 (95% confidence interval [CI] 0.45-0.72, P < 0.01); the odds ratio after matching was 0.63 (95% CI 0.49-0.80, P < 0.01). A two-proportion z-test revealed pre-storage leukoreduction significantly decreases the symptoms of chills, fever, itching, urticaria, dyspnea, and hypertension as compared with those in post-storage leukoreduction. Pre-storage leukoreduced apheresis platelet significantly decreased febrile non-hemolytic transfusion reaction as compared with post-storage groups. This study suggests pre-storage leukoreduction apheresis platelet significantly decreases the transfusion reaction as compared with those in post-storage leukoreduction.

Results of clinical effectiveness of conventional versus Mirasol-treated Apheresis Platelets in Patients with Hypoproliferative Thrombocytopenia (MiPLATE) trial.

BACKGROUND: The Mirasol® Pathogen Reduction Technology System was developed to reduce transfusion-transmitted diseases in platelet (PLT) products. STUDY DESIGN AND METHODS: MiPLATE trial was a prospective, multicenter, controlled, randomized, non-inferiority (NI) study of the clinical effectiveness of conventional versus Mirasol-treated Apheresis PLTs in participants with hypoproliferative thrombocytopenia. The novel primary endpoint was days of ≥Grade 2 bleeding with an NI margin of 1.6. RESULTS: After 330 participants were randomized, a planned interim analysis of 297 participants (145 MIRASOL, 152 CONTROL) receiving ≥1 study transfusion found a 2.79-relative rate (RR) in the MIRASOL compared to the CONTROL in number of days with ≥Grade 2 bleeding (95% confidence interval [CI] 1.67-4.67). The proportion of subjects with ≥Grade 2 bleeding was 40.0% (n = 58) in MIRASOL and 30.3% (n = 46) in CONTROL (RR = 1.32, 95% CI 0.97-1.81, p = .08). Corrected count increments were lower (p < .01) and the number of PLT transfusion episodes per participant was higher (RR = 1.22, 95% CI 1.05-1.41) in MIRASOL. There was no difference in the days of PLT support (hazard ratio = 0.86, 95% CI 0.68-1.08) or total number of red blood cell transfusions (RR = 1.12, 95% CI 0.91-1.37) between MIRASOL versus CONTROL. Transfusion emergent adverse events were reported in 119 MIRASOL participants (84.4%) compared to 133 (82.6%) participants in CONTROL (p = NS). DISCUSSION: This study did not support that MIRASOL was non-inferior compared to conventional platelets using the novel endpoint number of days with ≥Grade 2 bleeding in MIRASOL when compared to CONTROL.

Expression of microRNAs during apheresis platelet storage up to day 14 in a blood bank in China.

BACKGROUND: Storage affects platelet microRNAs (miRNAs); discussing miRNA expression differences in apheresis platelets after varied storage periods is important for developing platelet quality measurement tools and identifying platelet storage lesion biomarkers. To our knowledge, the difference of MicroRNA expression profile in up to 14-day storage apheresis platelets has less relevant reports. STUDY DESIGN AND METHODS: Apheresis platelet bags from three donors were collected, divided into six groups, and stored for 1, 3, 5, 7, 9, and 14 days. miRNA expression was determined using quantitative reverse transcription polymerase chain reaction. Differentially expressed miRNAs were screened using RNA sequencing. RESULTS: MiRNA expression profiles showed that the six treatment groups generally highly expressed hsa-let-7 family, hsa-miR-26a-5p, hsa-miR-92a-3p, hsa-miR-199, and hsa-miR-103a-3p. A total of 15 miRNAs in the top 10 known miRNAs of the six groups were highly expressed. Time series analyses for the trend classification of 944 differentially expressed miRNAs indicated 43 genes with 14 trend changes. Hsa-miR-223-3p, hsa-miR-181a-5p, hsa-miR-4433b-5p, hsa-miR-22-3p, and hsa-miR-30c-5p were selected, and the qRT-PCR results also showed that they were significantly reduced under standard blood bank condition. DISCUSSION: Expression of microRNAs lays the foundation for further research on apheresis platelet storage lesions. Based on our results from information analysis and miRNA target gene prediction, we suggest hsa-miR-30c-5p as a biomarker of the quality and viability of apheresis platelets during storage in blood banks.

Plasma-reduction for Apheresis Granulocyte transfusions in pediatric patients.

Granulocyte transfusion (GT) may be used to treat and prevent infections in patients with severe neutropenia or nonfunctioning granulocytes. For pediatric patients, the volume of granulocyte unit transfused is a crucial consideration given smaller blood volume and increased risk of volume overload compared to adults. There is limited literature on the optimal dosing or the maximum amount of granulocytes that can be tolerated, especially in pediatric patients. Additionally, no consensus exists regarding granulocyte collection method, frequency, or timing of GT initiation. Previous studies have described splitting or limiting collection volume for GT in pediatric patients, but these methods yield lower absolute neutrophil count (ANC) increment. Our blood supplier provides high-volume (0.5-1 L/unit), high-dose apheresis-collected granulocytes from donors stimulated with both granulocyte colony-stimulating factor and steroids. Here, we report cases of two pediatric patients with active infection undergoing bone marrow transplant with dramatic ANC increments (median one-hour ANC increment 5524/µL, interquartile range (IQR) 4417-10087; median 24-hour ANC increment 3880/µL, IQR 2550-5263) after infusing 100 mL plasma-reduced, apheresis collected GT. Our cases indicate that pediatric patients can tolerate 4-6 × 109/kg plasma-reduced GT and have detectable ANC with GT every 3 days.

Collection efficiency and safety of large-volume leukapheresis for the manufacturing of tisagenlecleucel.

BACKGROUND: In patients with relapsed or refractory B cell acute lymphoblastic leukemia or B cell non-Hodgkin lymphoma (r/r B-ALL/B-NHL) with low CD3+ cells in the peripheral blood (PB), sufficient CD3+ cell yield in a single day may not be obtained with normal-volume leukapheresis (NVL). Large-volume leukapheresis (LVL) refers to the processing of more than three times the total blood volume (TBV) in a single session for PB apheresis; however, the efficiency and safety of LVL for manufacturing of tisagenlecleucel (tisa-cel) remain unclear. This study aimed to investigate the tolerability of LVL. STUDY DESIGN AND METHODS: We retrospectively collected data on LVL (≥3-fold TBV) and NVL (<3-fold TBV) performed for patients with r/r B-ALL/B-NHL in our institution during November 2019 and September 2023. All procedures were performed using a continuous mononuclear cell collection (cMNC) protocol with the Spectra Optia. RESULTS: Although pre-apheresis CD3+ cells in the PB were significantly lower in LVL procedures (900 vs. 348/µL, p < .01), all patients could obtain sufficient CD3+ cell yield in a single day with a comparably successful rate of final products (including out-of-specification) between the two groups (97.2% vs. 100.0%, p = 1.00). The incidence and severity of citrate toxicity (no patients with grade ≥ 3) during procedures was not significantly different between the two groups (22.2% vs. 26.1%, p = .43) and no patient discontinued leukapheresis due to any complications. CONCLUSION: LVL procedures using Spectra Optia cMNC protocol was well tolerated and did not affect the manufacturing of tisa-cel.

Trends in category and grade for therapeutic plasma exchange in the latest guideline on therapeutic apheresis by the American Society for Apheresis: Hurdles in pursuing evidence-based medicine.

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.

Lipoprotein apheresis affects the concentration of extracellular vesicles in patients with elevated lipoprotein (a).

Lipoprotein apheresis (LA) is a therapeutic option for hyperlipoproteinemia(a) (hyper-Lp(a)) and atherosclerotic cardiovascular disease (ASCVD). LA improves blood rheology, reduces oxidative stress parameters and improves endothelial function. The underlying molecular mechanisms of LA beneficial effects are unknown, but it has been suggested that LA exhibits multiple activities beyond simply removing lipoproteins. We hypothesized that LA removes not only lipoproteins, but also extracellular vesicles (EVs). To test this hypothesis, we performed a prospective study in 22 patients undergoing LA for hyper-Lp(a) and ASCVD. Different EVs subtypes were measured before and directly after LA, and after 7 days. We used calibrated flow cytometry to detect total particle concentration (diameter > ~ 100 nm), total lipoproteins concentration (diameter > 200 nm, RI > 1.51), total EV concentration (diameter > 200 nm, RI < 1.41), concentrations of EVs derived from erythrocytes (CD235a+; diameter > 200 nm, RI < 1.41), leukocytes (CD45+; diameter > 200 nm, RI < 1.41) and platelets (CD61+, PEVs; diameter > 200 nm, RI < 1.41). LA reduced the concentrations of all investigated EVs subtypes and lipoproteins. Lp(a) concentration was lowered by 64.5% [(58% - 71%); p < 0.001]. Plasma concentrations of EVs > 200 nm in diameter derived from platelets (CD61 +), leukocytes (CD45+) and erythrocytes (CD235a+) decreased after single LA procedure by 42.7% [(12.8-54.7); p = 0.005], 42.6% [(29.7-54.1); p = 0.030] and 26.7% [(1.0-62.7); p = 0.018], respectively, compared to baseline. All EV subtypes returned to the baseline concentrations in blood plasma after 7 days. To conclude, LA removes not only Lp(a), but also cell-derived EVs, which may contribute to LA beneficial effects.