Apheresis Techniques Research Articles

The Role of Early Hemoadsorption in Severe COVID-19 Treatment: A Pilot Randomized Controlled Trial

Introduction: Hemoadsorption, an extracorporeal apheresis technique, is reportedly used in severe COVID-19 patients. However, limited evidence from randomized clinical trials supports this practice. Methods: In this single-center study, severe COVID-19 patients requiring ICU admission were randomly assigned (1:1) to receive HA-330 hemoadsorption in combination with standard treatment or standard therapy alone. Both groups received tocilizumab intravenously if their clinical conditions worsened within 24–48 h. The primary outcome was mortality from any cause within 28 days after randomization. Secondary outcomes included mechanical ventilator-free days, daily C-reactive protein levels, oxygenation (defined by PaO2/FiO2 ratio), daily sequential organ failure assessment score, and severity score of lung infiltration on chest X-rays (CXR RALE score). Results: A total of 28 patients underwent randomization, with 14 (50%) receiving HA-330 hemoadsorption. Only 9 out of 14 patients (64.3%) in the control group experienced clinical worsening and were subsequently administered intravenous tocilizumab. At 28 days, the mortality rate was significantly lower in the intervention group (28.57% vs. 78.57%, p = 0.021), with a hazard ratio of death of 0.26 (95% CI = 0.08–0.81; p = 0.021). All of secondary outcomes were comparable in both groups. Conclusion: Based on our pilot randomized trial, the early application of HA-330 hemoadsorption in patients with severe COVID-19 may establish a favorable outcome in term of mortality. These data provide the initial proof of concept for conducting a large-scale study in the future.

#2875 Experience in the use of plasmapheresis as a therapeutic tool in acute pathologies in a tertiary level hospital

Abstract Background and Aims Apheresis is a therapeutic modality which purpose is the elimination from plasma of the pathogenic components of a disease or its clinical manifestations. Plasmapheresis is an apheresis technique used in the treatment of various diseases with varying degrees of proven clinical efficacy. The aim of our work is to describe the experience in the use of plasmapheresis in different acute pathologies in our center, and if there are factors that favor the clinical response to treatment. Method Retrospective cohort study. We included plasmapheresis performed in the years 2017-2022. Variables such as age, sex, etiology, type of replacement performed, number of sessions, and American Society for Apheresis (ASFA) classification, among others, were collected. We defined response to treatment as partial or total clinical remission. Results We included 72 patients who received plasmapheresis during 2017-2022. Mean age 54 ± 18 years. 56.9% male. Disease etiology was neurological in 56.9%, nephrological in 36.1% and hematological in 6.9%. Between 2017-2019, 39.7% of the plasmapheresis were performed, while the remaining 60.3% were between 2020-2022. The number of sessions was 5.3 ± 2. 59.6% were performed with albumin, 29.2% with fresh frozen plasma and 13.9% with albumin and fresh frozen plasma. The ASFA indication was category I in 68.1%. 23.6% presented some complication, the most frequent being febrile in 6.9%, systemic infection and allergic reaction in 5.6%. A response to treatment was observed in 75%. Antibodies were positive before starting plasmapheresis in 29.2%, decreasing to 16.7% 3 months after treatment. There was recurrence in 19.4%, 16.7% received more cycles of plasmapheresis and there was 11.1% mortality due to disease. In patients with response to treatment, a higher percentage of response was observed in those diseases of non-nephrological origin (70.4% vs. 29.6%, p 0.04), lower percentage of complications (16.7% vs. 83.3%, p 0.01) and lower mortality associated with the disease (3.7% vs. 96.3%, p 0.001). Conclusion Plasmapheresis is a therapeutic plasma exchange technique that is increasingly used in our hospital, with a greater increase in recent years. It is a therapeutic option that should be considered in many occasions as first line or adjuvant treatment, with a low rate of complications and clinical improvement in most patients. Despite this, studies with a larger number of patients are required to increase and consolidate the existing evidence on the use of these procedures.

#847 Experience with therapeutic apheresis in a tertiary level hospital over the last 25 years

Abstract Background and Aims The main purpose of therapeutic apheresis is the extraction and elimination from plasma of those components considered to be responsible for the pathogenesis of a disease, the replacement of deficient factors and the improvement of the function of the reticuloendothelial system and certain inflammatory mediators. Currently, it constitutes a good therapeutic alternative for the treatment of a wide variety of diseases of different specialties, where conventional treatment has not been successful or the desired response has not been obtained. In general, apheresis is a beneficial technique, well tolerated and with few complications. Requests for apheresis are increasingly frequent from different areas of daily clinical practice. Method Descriptive-retrospective cohort study, in which all the apheresis sessions performed in our department between January 1997 and February 2023 were analyzed. The aim of this study is to describe the experience with plasmapheresis performed by nephrologists in patients with different diseases. We analyzed the following variables: sex, age, underlying disease and indication according to the American Society for Apheresis (ASFA) classification, apheresis technique and number of sessions performed. In the last 5 years (2018-2023) we also evaluated: plasma replacement, vascular access and complications during the performance of the technique. Results During the period January 1997-February 2023 a total of 2483 sessions were performed. Of the sessions, 76% were plasmapheresis, 20.5% granulocytapheresis and 3% lipid apheresis. Apheresis was performed in 199 patients, 57% men (114), 42.5% women (85), with a mean age of 51 years. The average number of sessions per patient during the follow-up of their disease was 13 sessions. The main causes for which apheresis was performed were neurological diseases, 34.5% of the cases, including Myasthenia Gravis (41%), Guillain-Barré (29%). In second place, autoimmune nephrological diseases in 27%, rejection of transplanted organs in 27%, hematological diseases in 7.5% and metabolic diseases in 3.5%. Almost 70% of the indications corresponded to ASFA grade I and II evidence criteria. Focusing on the last 5 years, the services from which we were requested to perform the technique were mainly Neurology, Hematology, Digestive and Internal Medicine. The pathologies treated by apheresis were: 39% neurological diseases, 39% renal pathology (50% autoimmune diseases and 50% due to rejection of a transplanted organ) and 17% hematological diseases. According to ASFA criteria, the prevalent category was ASFA I (32%), followed by ASFA III (31%), ASFA II (24%), and finally ASFA IV (9.8%). Plasma replacement was performed with albumin in 63.4% of the cases, with fresh plasma in 22% of the cases and with both in 9.8% of the sessions. In relation to the technique, the complications observed were infrequent (14%), being fundamentally paresthesia, nausea, allergic reactions of a self-limited nature and with adequate control with premedication in subsequent sessions. Other less frequent complications were: hypotension or catheter dysfunction. Conclusion

#2917 Desensitization techniques in ABO-incompatible renal transplantation: efficacy and analysis of complications

Abstract Background and Aims Living donor transplantation is the best optimal choice for the vast majority of patients with terminal renal insufficiency. However, it is limited by the AB0/ HLA incompatibility between donor and receptor. The resolution of this inconvenient relies on desensitization of isoagglutinins (anti-AB0 immunoglobulins depletion); thus transplantation could be performed safely. For desensitization there are two techniques: specific adsorption (S) and non-specific (NS) techniques, including centrifugal therapeutic plasma exchange (cTPE) and membrane-based therapeutic plasma exchange (mTPE). The aims are to evaluate the efficacy of apheresis techniques: specific versus non-specific, and identify their complications. Secondary objectives include analyzing the acute rejection rate (RR), graft survival, and complications of each technique. Method A retrospective cohort study was conducted on AB0-incompatible living donor transplantation patients at our center (Bellvitge's Hospital) from 2014 to 2022. All patients (except 1) received rituximab and induction treatment by Thymoglobulin or Basiliximab, followed by maintenance treatment (Steroids, Mycophenolate, and calcineurin inhibitors). During follow-up, protocol renal biopsies (RB) were taken at one month and between 3-6 months post-transplantation. Complications were defined as significant haematological alterations, bleeding, or major infections requiring hospitalization. According to the technique used, two cohorts were identified: specific (Glycosorb®/Vitrosorb® columns) and non-specific: mTPE (prismaflex TPE2000) and cTPE (Spectra/Optia®). Both were anticoagulated with heparin or citrate randomly. An expert nurse supervised the technique. To calculate the efficacy we considered the percentual reduction of isoagglutinins in the first session. T-student test was used to calculate the percentage of complication and compare the results. Results A total of 50 patients were selected with a mean age (MA) of 49.5 ± 11.8. Four of these did not require apheresis due to lower title isoagglutinins (<1/8). Each cohort included 23 patients: specific with MA 49.5 vs non-specific 48.4, with a mean isoagglutinin titles in specific of 61.65 vs non-specific 11.8 (p = 0.05). Isoagglutinin clearance were higher in specific techniques with 73% vs 59% non-specific (p < 0.03). Due to the dispersion in the number of sessions, results are expressed with the median (4 sessions in specific vs 3 non-specific). Total renal graft survival rate is 93.4%. At one month, it was diagnosed by biopsy an acute renal rejection rate of 16.7% in non-specific vs 18.2% specific (p > 0.05). Considering complications, they are higher with non-specific 41.7% vs specific 18% (p < 0.05). Regarding infectious issues, there are no differences in cytomegalovirus or polyomavirus infections, but there are differences in urinary infections observing in non-specific 79.2% vs specific 63% (p < 0.05). Conclusion Specific techniques are more effective in reducing isoagglutinins, show a lower rate of complications and post-transplant infections, providing greater benefit to the patient.

#2107 Therapeutic apheresis for the management of lipid disorders: a case series

Abstract Background and Aims Hypertriglyceridemia (HTG) is defined as the plasmatic concentration of triglycerides above 150 mg/dl. With a current prevalence ranging from 15% to 20% in clinical practice, it's a prevalent condition that´s increasing alongside other cardiovascular risk factors such as diabetes mellitus, obesity and hypertension. In most patients HTG is asymptomatic, except in certain circumstances such as hereditary HTG, which can present with skin lesions such as eruptive xanthomas and xanthelasmas. Another exception is severe HTG, which can manifest with pancreatitis. Pharmacological treatment for HTG is typically initiated when serum triglyceride levels exceed 885 mg/dl or when patients with a previous episode of pancreatitis. However, in cases of severe HTG (triglycerides > 1000 mg/dl), conventional pharmacological therapies become less effective. Therefore, alternative therapeutic interventions, such as apheresis, become increasingly relevant for the management of severe HTG. Current guidelines from the American Society of Apheresis (ASFA) consider the use of therapeutic plasmapheresis in patients with acute pancreatitis secondary to severe hypertriglyceridemia as a category III/grade 1C recommendation and that in most cases it is an adjunct to medical treatment. Case series Below, we describe a series of cases in which we used this technique to control metabolic in our center during the last year. Case 1 A 30-year-old man with familial primary hypertriglyceridemia, schizophrenia, and sporadic drinking, was admitted from the Emergency Department with a 24h long severe abdominal pain with difficult management and vomiting. After complementary analysis, acute edematous pancreatitis without necrosis was diagnosed. Given the analytical values (Table 1), therapeutic plasmapheresis was decided, with a plasma volume of 3.5 liters calculated with the patient's weight and hematocrit and using albumin as the replacement fluid. As a complication, and despite administration of heparin, the filter required replacement halfway through the session due to problems with transmembrane pressure. Two sessions were completed on consecutive days until clinical and analytical control of triglycerides was achieved. Case 2 A 55-year-old man with a history of mild dyslipidemia controlled with diet and hypertension, was admitted from the Emergency Department with abdominal pain of 12 hours duration. After completing the study and diagnosis of acute pancreatitis of probable HTG origin, a plasmapheresis session was completed with a volume of 3 liters, albumin replacement fluid and heparinization during the technique, without complications, along with triglyceride control after the procedure maintaining medical treatment. Case 3 A 62-year-old man with a history of familial HTG, bronchial hyperreactivity, and occasional drinking, was admitted with abdominal pain of 72 hours duration accompanied by nausea and vomiting. Complementary studies confirmed acute severe pancreatitis with hemodynamic and respiratory failure. Given the analytical findings, a plasmapheresis session was performed with a volume of 2.5 liters per weight and hematocrit, with albumin replacement and heparin as per protocol. Subsequent HTG control with medical treatment was achieved without the need for further apheresis sessions. Conclusion Cardiovascular disease is responsible for the death of more than 4 million people in Europe each year, 2.2 million women (55%) and 1.8 million men (45%). Lipoprotein apheresis has preventive effects on the progression of atherosclerosis in addition to being an effective technique for reducing LDL, so its indication in groups of patients with severe and primarily familial hypercholesterolemia is well established. In our center, the recent start of the control of apheresis techniques from Nephrology in metabolic diseases, although still with limited experience and a limited number of patients, may constitute a new field of work in the specialty itself and collaboration with the different hospital specialties to improve the prevention, control, and treatment of patients with a high cardiovascular risk.

Comparison of double-filtration plasmapheresis (DFPP) versus heparin-mediated extracorporeal LDL-precipitation (HELP)-apheresis in early-onset preeclampsia

ObjectivesPreeclampsia (PE) is a major cause of maternal and fetal mortality, and preterm birth. Previous studies indicate that lipid-apheresis may prolong pregnancy, namely heparin-mediated extracorporeal LDL-precipitation (HELP)- and dextran sulfate cellulose (DSC)-apheresis. We now report on double membrane plasmapheresis (DFPP) in early-onset preeclampsia (eoPE). Study designOpen pilot study assessing the prolongation of pregnancy in PE by lipoprotein-apheresis (DRKS00004527). Two women with eoPE were treated by DFPP and compared to a historical cohort of 6 patients with eoPE treated by HELP-apheresis (NCT01967355). Main outcome measuresClinical outcome of mothers and babies and prolongation of pregnancies (time of admission to birth). ResultsPatient 1 (33y; 22 + 5/7GW) received 4 DFPP. Delivery day 19; birthweight 270 g; weight at discharge 2134 g on day 132. Patient 2 (35y; 21 + 4/7GW) received 2 DFPP. Delivery day 19; birthweight 465 g; weight at discharge 2540 g on day 104. DFPP was well tolerated by both patients. ConclusionsDFPP proved to be save and pregnancies remained stable as long as 19 days. Although babies were born very preterm both babies could finally be dismissed from hospital. No relevant clinical differences between DFPP and HELP-apheresis could be observed. Therefore, DFPP may extend the range of available apheresis techniques to prolong pregnancies in early-onset preeclampsia. However, further studies are necessary to gain more information. Register(DRKS00004527)

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.

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. 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. 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. 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.

The effect of thrombocytapheresis on hemogram and biochemistry parameters in patients with essential thrombocytemia.

Essential thrombocythemia is one of the chronic myeloproliferative neoplasms characterized by clonal proliferation of myeloid cells with variable morphological maturation and hematopoietic activity.It is characterized by excessive clonal platelet production with a tendency to thrombosis and bleeding. Thrombocytapheresıs is the removal of platelets by apheresis techniques. Thrombocytapheresıs is generally recommended in patients with essential thrombocythemia with acute, severe thrombotic or hemorrhagic events. The study included 39 patients who were diagnosed with essential thrombocythemia, started cytoreductive and aspirin therapy, and underwent thrombocytapheresıs due to the development of acute severe thrombotic or hemorrhagic events, diagnosed in the adult hematology clinic of İnönü University Turgut Ozal Medical Center. Hemogram and biochemistry values of the patients were scanned retrospectively. After thrombocytapheresıs, a statistically significant difference was found between the first and last measurements of hemoglobin, mean platelet volume, White blood cell, neutrophil, platelet, platelet distribution width, creatine, lactate dehydrogenase, fibronogen and calcium levels of the patients. The use of thrombocytapheresıs in patients with essential thrombocytosis causes a rapid decrease in platelet values as well as an effect on hemogram and biochemistry parameters. Other hemogram and biochemistry parameters such as platelet value should be monitored in patients.

Collection efficiency in apheresis

Significant advances in procedural information displayed by current apheresis machines have been made, but analyses of cell collection efficiency (CE) still rely on calculations done by apheresis professionals. Accordingly, understanding CE equations can support the optimization of apheresis techniques and identification of incidents that could impact the procedure’s effectiveness. This report summarizes classical and novel CE analyses applied to apheresis exemplified by an actual case of hematopoietic progenitor cell collection. In addition to the apheresis yield and most common CE1 and CE2 formulas, we present the instantaneous and corrected CE, fold enrichment, collection throughput, collection rate and its variants, average inlet rate, classical and adjusted captured cells, recruitment pool, recruitment factor, recruitment coefficient, blood component loss, predictive apheresis yield, and performance ratio calculations. Moreover, the mathematical relationship between these CE equations is also shown, which can be helpful in many apheresis procedures.

Therapeutic Plasma Exchange in Early-Onset Preeclampsia: A 7-Year Monocentric Experience.

Different therapeutic apheresis techniques have been clinically tested to delay preterm delivery in the case of eoPE (early-onset preeclampsia). Our study evaluated the feasibility of TPE (therapeutic plasma exchange) compared to standard-of-care treatment. Twenty patients treated with 95 TPE sessions were included in the final analysis and retrospectively matched with 21 patients with comparable placental dysfunction. Gestational age at admission was 23.75 ± 2.26 versus 27.57 ± 2.68 weeks of gestation (WoG) in the control group (p = < 0.001), mean sFlt-1/PlGF ratio was 1946.26 ± 2301.63 versus 2146.70 ± 3273.63 (p = 0.821) and mean sEng was 87.63 ± 108.2 ng/mL versus 114.48 ± 88.78 ng/mL (p = 0.445). Pregnancy was prolonged for 8.25 ± 5.97 days when TPE was started, compared to 3.14 ± 4.57 days (p = 0.004). The median sFlt-1/PlGF Ratio was 1430 before and 1153 after TPE (-18.02%). Median sEng fell from 55.96 ng/mL to 47.62 mg/mL (-27.73%). The fetal survival rate was higher in TPE-treated cases. NICU (Neonatal Intensive Center Unit) stay was in the median of 63 days in the TPE group versus 48 days in the standard-of-care group (p = 0.248). To date, this monocentric retrospective study, reports the largest experience with extracorporeal treatments in eoPE worldwide. TPE could improve pregnancy duration and reduce sFlt-1 and sEng in maternal serum without impairing neonatal outcomes.

Platelet Apheresis: Experience of the blood transfusion center of Avicenne military hospital in Marrakesh

Apheresis platelet concentrates (APC) are platelet suspensions obtained by apheresis from a cell separator. These techniques, which appeared a little more than 20 years ago, are currently the best way to obtain platelets in large quantities from a single donor. These separators, whether discontinuous or continuous flow, perform extracorporeal circulation from anticoagulated blood, which allows the collection of platelets, returning to the donor his red blood cells and a more or less important part of his plasma. The procedures used are all automated and often adaptable to the donor's parameters. Apheresis platelet concentrates are single-donor products and therefore limit the transfusion risks compared to standard platelet concentrate mixtures, which are derived from five to six donors on average. The objective of our work is to study platelet donations by apheresis technique, their advantage, indication, and description of the equipment used, during a period of 3 years, from July 2017 until July 2020. And during this period, 29 apheresis procedures were performed by HAEMONETICS' MCS+. The clinical hematology department is the first applicant of APC where acute leukemia and non-Hodgkin's lymphoma are the most treated pathologies by this substitution.

Therapeutic plasma exchange for myasthenia gravis, Guillain-Barre syndrome and other immune-mediated neurological diseases, over a 40-year experience

ABSTRACT Background Therapeutic plasma exchange (TPE) was first used in neurology in the 1980s for myasthenia gravis (MG) and Guillain-Barré syndrome (GBS). Indications have since grown. Fear of complications with this treatment modality limit its use. Research design & methods A study of patients undergoing TPE for neurological diseases (1981-2020) in a university hospital in Madrid, Spain. Clinical indications, complications, procedure number, apheresis technique and replacement fluids were prospectively recorded and retrospectively analysed. Historical trends were studied. Results Over 40 years, 159 patients (48.69±18.15 years, 54.3% females) underwent TPE using central-venous catheter and replacement fluid albumin. We performed 1207 procedures over 189 cycles (6.4±3.8 procedures/cycle). Most patients underwent TPE for category I-II indications, mainly GBS and MG (77.7%). Complication rate was low (3.9% procedures), mostly hypotensive/vasovagal reactions (55.3%) and vascular access-related complications (38.3%). Most were mild-moderate (92.9%), permitting TPE completion, and somewhat more frequent during the first procedure (38.3%) and after periods of little TPE use. GBS patients were more prone to complications than MG patients (6.5% vs. 1.2%,p<0.001) mainly hypotensive/vasovagal reactions (3.7% vs. 1.0%,p=0.008). Conclusions TPE is well-tolerated with low complication rate (<4% procedures), mainly hypotensive/vasovagal reactions. Patients with GBS seem more prone to them than MG patients. Acquaintance with this technique seems necessary.

Advances in Apheresis Techniques and Therapies in the Pediatric Setting

Advances in Apheresis Techniques and Therapies in the Pediatric Setting

Apheresis Technique for Acute Hyperlipidemic Pancreatitis: A Systemic Review and Meta-Analysis.

The apheresis technique is increasingly used in patients with hypertriglyceridemia-induced pancreatitis (HTGP), while its role in this context is still not well established. Thus, we aimed to evaluate the clinical outcomes of an apheresis therapy compared to usual care in such a patient population. We searched PubMed, Embase, and Cochrane library databases up to July 10, 2021. Studies were included if they focused on HTGP treated with or without apheresis technique. We used the Newcastle-Ottawa Scale to assess the quality of the included studies. The primary outcome was the mortality rate. We also explored the heterogeneity, sensitivity analysis, subgroup analysis, and publication bias. Sixteen observational studies with 1476 adults were included. The overall quality of included studies was moderate. Despite better TG level reduction with apheresis therapy (mean difference [MD], 12.27mmol/L, 95% CI, 3.74 to 20.81; I2 = 78%; P = 0.005), use of apheresis did not reduce the mortality (odds ratio [OR], 1.01; 95% CI, 0.65 to 1.59; P = 0.95) compared with usual care. This result was further confirmed by sensitivity analysis, subgroup analysis. The length of stay in hospital (MD, 0.96days; 95% CI, - 1.22 to 3.14; I2 = 70%; P = 0.39) and most complications were similar between the groups, while hospital cost was significantly higher in the apheresis group. The apheresis technique did not decrease the mortality in HTGP patients compared with usual care. Until the results of high-quality RCTs are known, these findings do not support the routine use of the apheresis technique in such a patient population.

Effect of Protein A-Immunoadsorption Therapy on Serum Cytokines in AAV Patients

Protein A-immunoadsorption (IA) is an extracorporeal apheresis technique used in patients with autoimmune diseases which aims to remove pathogenic autoantibodies. Apart from the adsorption of immunoglobulins (IgG), IA may influence cellular and humoral immunity. The aim of this study was to observe the effect of protein A-IA on cytokine networks in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients. A total of 12 newly diagnosed AAV patients received IA therapy on days 1, 3, and 5. Serum levels of inflammatory cytokines were measured before and after treatment including members of the interleukin family, PDGF-BB, TNF-α and IFN-γ. IL-1β, IL-9, IL-17A, PDGF-BB, IFN-γ, and TNF-α were elevated in AAV patients compared to healthy individuals. There were no changes in the levels of any cytokines after the first IA session but after 3 sessions, IL-9, PDGF-BB, and TNF-α dramatically decreased. Moreover, reductions in IL-9 levels were positively correlated with the changes of myeloperoxidase-ANCA (MPO-ANCA). Our observations suggest that protein A-IA therapy does not directly adsorb cytokines, but removes autoantibodies (MPO-ANCA) which indirectly leads to changes in cytokine networks linked to cellular or humoral immunity.

Study Protocol: A Randomized Controlled Prospective Single-Center Feasibility Study of Rheopheresis for Raynaud's Syndrome and Digital Ulcers in Systemic Sclerosis (RHEACT Study).

IntroductionRaynaud’s phenomenon (RP) and digital ulcers (DU) are frequent manifestations of Systemic Sclerosis (SSc). Despite being very common in SSc patients, both conditions have proven to be notoriously difficult to study. There are very few available approved drugs with varying efficacy. It has been shown that the presence of DU is associated with increased whole blood viscosity (WBV). Rheopheresis (RheoP) is an extracorporeal apheresis technique used to treat microcirculatory disorders by improving blood viscosity. Improved blood flow and wound healing after RheoP treatments have been reported in single case reports.Methods and AnalysisWe report the clinical trial protocol of “A randomized controlled prospective single-center feasibility study of Rheopheresis for Raynaud’s syndrome and Digital Ulcers in Systemic Sclerosis (RHEACT).” RHEACT aims to investigate the efficacy of RheoP on the Raynaud Condition Score (RCS) as the primary efficacy outcome measure after 16 weeks from baseline. Thirty patients will be randomized in a 1:1:1 ratio to one of two RheoP treatment groups or assigned to the standard of care (SoC) control group (intravenous iloprost). Secondary endpoints include changes in DU, changes in nailfold video capillaroscopy and patient-reported-outcomes (Scleroderma Health Assessment Questionnaire, FACIT-Fatigue, and the Disability of Arm, Shoulder, and Hand, quick version).DiscussionApheresis techniques have been investigated in SSc but mainly in observational, retrospective studies, or single case reports. RheoP is a pathophysiologically driven potential new therapy for heavily burdened patients with SSc-associated secondary RP with or without DU.Ethics and DisseminationThe study was registered at clinicaltrials.gov (Identifier: NCT05204784). Furthermore, the study is made publicly available on the website of the German network of Systemic Sclerosis “Deutsches Netzwerk Systemische Sklerodermie (DNSS).”

HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA IN CANADA

<h3>BACKGROUND</h3> Homozygous familial hypercholesterolemia (HoFH) is an orphan disease characterized by extremely high levels of plasma levels of LDL-C. Affected patients develop clinical atherosclerotic cardiovascular disease (ASCVD) in youth and survival > 30 years of age was unusual until the advent of medications (statins) and extracorporeal LDL filtration (apheresis) techniques. HoFH is an autosomal co-dominant condition defined as an LDL-C > 13 mmol/L in adults without treatment and homozygous or compound heterozygous mutations of the LDLR gene. HoFH has a genetic probability of ∼1/386,000 and the rare diseases inventory Orphanet estimates its worldwide prevalence at 1/1,000,000 individuals. Canada is known to have several regions with a founder effect for HoFH and we identified 79 cases across the country. Data from other countries show a median survival of HoFH patients at <40 years of age. Clinical outcomes in HoFH patients, especially ASCVD events (fatal and non-fatal myocardial infarctions, strokes and peripheral vascular disease) and severe calcific aortic stenosis, are difficult to capture, in part because of the rarity of the disorder and the lack of registry focusing on this disease. The objective of our project is to obtain a comprehensive registry of HoFH in Canada, estimate the cost to society caused by HoFH burden of disease in Canada, and implement changes to advocate access to specialized care for these patients. <h3>METHODS AND RESULTS</h3> Here, we present preliminary data (Table 1) on our Canadian HoFH registry, including medical history, levels of LDL-C, treatments and outcomes of 21 HoFH patients. <h3>CONCLUSION</h3> We plan to use this data at provincial and national levels, in help with the Canadian Organization for Rare Diseases (CORD) and the Réseau Québecois des maladies orphelines (RQMO), to provide HoFH patients access to care, including PCSK9 inhibitors, orphan drugs such as lomitapide and evinacumab, and treatment techniques such as extracorporeal LDL filtration (apheresis). This work will provide important new health-related knowledge about the determinants of ASCVD risk and phenotypic manifestations of HoFH in Canada and examine the quality of life and burden to the healthcare system.

Stem cell therapy in patients with nonischemic heart failure

Abstract Funding Acknowledgements None Background Advanced chronic heart failure, characterized by a functional NYHA class III/IV, low LVEF, elevated B-type natriuretic peptides and other criteria’s is a big epidemiological problem, and its prevalence is increasing every year. There are many treatment options for patients with chronic and advanced heart failure. Treatment options include optimal medical therapy, treatment with cardiac resynchronization devices, left ventricular assist devices, heart transplantation and from 2006 treatment with CD 34 + stem cells. Method Patient inclusion criteria for stem cell therapy include dilated cardiomyopathy with no valve disease, hypertension or substance abuse, with optimal medical management for 6 months and a decreased left ventricular ejection fraction of &amp;lt;40%. Patients are treated with autologous pluripotent CD 34+ cells, which are mobilized in the blood stream with a bone marrow stimulant Filgrastim, administered subcutaneously for 5 days. The patients are educated by the nurses to do administer the injections at home, and have a contact number of our department in case of side effects. On the day of the procedure, stem cells are collected using the apheresis technique and then delivered transendocardialy in the catheterisation laboratory using the system for electromechanical mapping. If no complications develop, the patients can go home the next day. Results During follow-up visits patients treated with stem cells have an increased left ventricular ejection fraction, lower levels of NT-proBNP, increased distance of 6-minute walk test and increased survival compared with the control group. They also report better physical performance. Conclusion Stem cell therapy is thus a viable option and could become a mainstream therapy for the treatment of advanced heart failure in the future.

Lipoprotein apheresis efficacy and challenges: single center experience

IntroductionLipoprotein apheresis (LA) is an extracorporeal therapy which removes apolipoprotein B-containing particles from the circulation. We evaluated techniques and efficiency of lipoprotein apheresis procedures applied to patients with familial and non-familial hypercholesterolemia (FH) at our center. MethodsWe retrospectively evaluated 250 LA procedures applied to 27 patients with dyslipidemia between March 2011 and August 2019. ResultsA total of 27 patients, of whom 19 (70.4%) were male and 8 (29.6%), female, were included. Eighteen (66.7%), 6 (22.2%) and 3 (11.1%) patients were diagnosed with non-FH, homozygous FH (HoFH) and heterozygous FH (HeFH), respectively. Two different apheresis techniques, direct adsorption of lipoproteins (DALI) (48.8%) and double filtration plasmapheresis (DFPP) (51.2%), were used. The change in the serum total cholesterol (TC) level was the median 302 mg/dl (171–604 mg/dl) (60.4%) in HoFH patients, 305 mg/dl (194–393 mg/dl) (60.8%) in HeFH patients and 227 mg/dl (75–749 mg/dl) (65.3%) in non-FH patients. The change in the serum low-density lipoprotein (LDL) level was the median 275 mg/dl (109–519 mg/dl) (64.2%), 232 mg/dl (207–291 mg/dl) (64.5%) and 325 mg/dl (22–735 mg/dl) (70.9%) in patients with HoFH, HeFH and non-FH, respectively. A significantly effective reduction in serum lipid levels, including TC, LDL and triglycerides, was achieved in all patients, regardless of the technique, p < .001. The decrease in the serum TC and LDL levels was significantly higher in the DFPP, compared to the DALI, being 220 mg/dl (−300 to 771) vs 184 mg/dl (64–415), p < .001 and 196 mg/dl (11–712) vs 157 mg/dl (54–340), p < .001, respectively. ConclusionsOur results showed that LA is a highly effective treatment in reducing serum lipid levels and safe, without any major adverse event.

The efficacy of therapeutic apheresis in patients with refractory neuromyelitis optica spectrum disorders: a single-center retrospective study.

Neuromyelitis optica spectrum disorders (NMOSD) are associated with recurrent episodes of optic neuritis and transverse myelitis, often resulting in high attack-related disability. Therapeutic apheresis has been recommended as a second-line treatment for steroid-refractory NMOSD. To assess the efficacy and safety of two apheresis techniques, lymphoplasmapheresis (LPE) and therapeutic plasma exchange (TPE), in refractory NMOSD and to provide a new treatment option for patients with refractory NMOSD. This retrospective study examined NMOSD patients who had undergone either LPE or TPE treatment between January 2015 and January 2018. The patients were monitored for improvements in disabilities, incidences of adverse reactions, and safety of the procedure over a one-year follow-up period. The primary outcome measures included changes in the visual outcome scale (VOS) score, the expanded disability status scale (EDSS), and the annualized relapse rate (ARR). Neurological function and objective response rates were significantly improved in 76.5% of patients treated with LPE and 83.3% of patients treated with TPE. There were no significant differences in the two treatment groups (P=0.392). Similarly, there were no differences in the reduction in the relative relapse rate between the two groups (P=0.494). Adverse reactions, mostly of mild or moderate intensity, were recorded in 9.3% of procedures in 38% of patients. The most commonly observed adverse events (AEs) were similar between the two treatment cohorts. Patients treated with LPE showed improved neurological function comparable to that reported with TPE treatment. No superiority was shown for either of the apheresis techniques.