Suspected autoimmune encephalitis: A retrospective study of patients referred for therapeutic plasma exchange.

INTRODUCTION: Autoimmune encephalitis (AE) comprises a heterogeneous group of autoantibody-mediated disorders targeting the brain parenchyma. Therapeutic plasma exchange (TPE), one of several first-line therapies for AE, is often initiated when AE is suspected, albeit prior to an established diagnosis. We sought to characterize the role of TPE in the treatment of suspected AE. METHODS: A single-center, retrospective analysis was performed of adults (≥18 years) who underwent at least one TPE procedure for "suspected AE." The following parameters were extracted and evaluated descriptively: clinicopathologic characteristics, treatment course, TPE-related adverse events, outcomes (e.g., modified Rankin scale [mRS]), and diagnosis once investigation was complete. RESULTS: A total of 37 patients (median age 56 years, range 28-77 years, 62.2% male) were evaluated. Autoimmune antibody testing was positive in serum for 43.2% (n = 16) and cerebrospinal fluid for 29.7% (n = 11). Patients underwent a median of five TPE procedures (range 3-16), with 97.3% (n = 36) via a central line and 21.6% (n = 8) requiring at least one unit of plasma as replacement fluid. Fifteen patients (40.5%) experienced at least one TPE-related adverse event. Compared with mRS at admission, the mRS at discharge was improved in 21.6% (n = 8), unchanged in 59.5% (n = 22), or worse in 18.9% (n = 7). Final diagnosis of AE was determined to be definite in 48.6% (n = 18), probable in 8.1% (n = 3) and possible in 27.0% (n = 10). Six (16.2%) patients were ultimately determined to have an alternate etiology. CONCLUSION: Empiric TPE for suspected AE is generally well-tolerated. However, its efficacy remains uncertain in the absence of controlled trials, particularly in the setting of seronegative disease.

The effect of donation frequency on donor health in blood donors donating plasma by plasmapheresis: study protocol for a randomized controlled trial.

BACKGROUND: The demand for plasma products is growing, necessitating an increase in plasma collection by plasmapheresis. While the 20th edition of the European Guidelines permits plasma donors in Europe to donate with 96-h donation intervals, the potential short- and long-term consequences of high-frequency plasma donations on donor health remain unknown. This study aims to measure the effect of plasma donation frequency on plasma protein composition, including total serum protein (TSP) and immunoglobulin G (IgG), in Norwegian male blood donors. METHODS: This randomized controlled trial (RCT) included 120 male blood donors who were randomized into two intervention groups and one control group: high-frequency plasma donors (HFPDs) who donated 650 mL of plasma 3 times every 2 weeks, whereas regular-frequency plasma donors (RFPDs) who donated 650 mL of plasma 1 time every 2 weeks. The control group consisted of whole blood donors. The primary outcomes are the concentrations of TSP and IgG. DISCUSSION: The findings from this study may have implications for recommendations related to donor health and plasma donation frequencies and may contribute to supporting the strategic independence of plasma products in Norway and Europe without compromising donor health. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05179200 . Registered December 20th, 2021.

Assessing the comparative efficacy of plasmapheresis and Intravenous immunoglobulin in myasthenia gravis treatment: A systematic review and meta-analysis.

BACKGROUND: Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by muscle weakness, posing significant challenges to patients' daily lives. Intravenous immunoglobulin (IVIG) and plasmapheresis are two prominent immunomodulatory therapies used in MG management, but the choice between them remains a clinical dilemma. This systematic review and meta-analysis aim to evaluate the comparative efficacy of IVIG versus plasmapheresis in MG management. METHODS: We adhered to PRISMA guidelines and prospectively registered the review protocol in PROSPERO. Systematic search across electronic databases identified 14 studies meeting inclusion criteria. Data from these studies were extracted, and assessed risk of bias. Primary outcomes included clinical efficacy, while secondary outcomes encompassed hospitalization, ventilation, antibody titers, and treatment-related complications. Statistical analysis was conducted using R software. RESULTS: The pooled results indicated that patients receiving plasmapheresis had higher odds of any improvement in MG symptoms compared to IVIG. However, change in severity scores did not significantly differ between the two treatments. Hospitalization durations were similar, but IVIG-treated patients tended to have shorter stays. Antibody titers, particularly anti-MUSK antibodies, favored plasmapheresis treatment. Complication rates were comparable between two groups. However, severe complications were more common in plasmapheresis. CONCLUSION: This comprehensive analysis suggests that plasmapheresis may offer superior short-term symptom improvement in MG compared to IVIG, while IVIG may lead to shorter hospital stays and lower complication rates. The choice between these treatments should be tailored to individual patient needs and disease characteristics. Further research is needed to explore long-term outcomes and mortality rates in MG management.

Effect of Plasmapheresis on the Efficacy of Rituximab in Antibody-Mediated Rejection Patients.

BACKGROUND: Rituximab and plasmapheresis (PP) suppress and eliminate antibody production in patients experiencing antibody-mediated rejection (AMR). Herein, we discuss a case where rituximab was less effective after PP for treating AMR. CASE: A 55-year-old male patient underwent kidney transplantation. His renal function remained normal for 1 year. Subsequently, renal function declined, and (donor-specific antibodies showed positive results. A biopsy of the transplanted kidney revealed AMR. On the day of the biopsy, the medical staff administered 200 mg of rituximab, followed by IV immunoglobulin (IVIg) and PP the next day. The time interval between PP + IVIg treatment and rituximab was 12 h. As a result, the B-cell markers CD19 and CD20 did not decrease sufficiently, and the patient's creatinine and glomerular filtration rate muscles did not recover adequately. CONCLUSION: We report a case in which PP was administered shortly after rituximab injection, resulting in insufficient B-cell inhibition due to the removal of rituximab.

Retrospective review of patients with myasthenia gravis switched from plasma exchange therapy to efgartigimod treatment.

INTRODUCTION/AIMS: Therapeutic plasma exchange (TPE) is sometimes used as maintenance therapy for the treatment of myasthenia gravis (MG). Efgartigimod is a newly approved monoclonal antibody targeting the neonatal Fc receptor, effectively reducing immunoglobulin G levels in the treatment of MG. The aim of this study was to describe the clinical experience of switching patients from maintenance TPE treatment to efgartigimod infusions. METHODS: A retrospective review of medical records was performed on patients previously treated with maintenance TPE for the diagnosis of MG and subsequently switched to efgartigimod infusions. Clinical characteristics and response to treatment switch were described. RESULTS: Five of seven patients demonstrated improvement on Myasthenia Gravis Foundation of America-post intervention status, one was unchanged and one was in pharmacological remission. This was reflected in pre- and postswitch MG activities of daily living and MG manual muscle testing scores. All patients have continued on efgartigimod therapy. The duration of treatment with efgartigimod at the time of this review ranged from 1 to 13 months. Recurrent uncomplicated infections were noted in two patients on efgartigimod therapy. Maintenance dosing regimens of efgartigimod varied based on clinical response to treatment and side effects. DISCUSSION: In this series, efgartigimod appeared effective and well tolerated in patients switched from TPE.

Use of Therapeutic Apheresis methods in ICU.

Apheresis is a modern medical approach in which plasma or cellular components are separated from the whole blood. Apheresis can be either diagnostic or therapeutic. Diagnostic apheresis is typically applied in hematology and cancer research. Therapeutic Apheresis (TA) includes a broad spectrum of extracorporeal treatments applied in various medical specialties, including Intensive Care Unit (ICU). Considering the complexity of the pathophysiologic characteristics of various clinical entities and in particular sepsis, apheresis methods are becoming increasingly applicable. Therapeutic Plasma Exchange (TPE) is the most common used method in ICU. It is considered as first line therapy for Thrombotic Thrombocytopenic Purpura (TTP) and Guillain Barre Syndrome, while the current data for sepsis are scarce. Over the last decades, technologic evolution has led to increasing application of new and more selective methods based on adsorptive techniques. In this review we will describe the current data of characteristics of different techniques, safety and clinical impact of apheresis methods used in ICUs.

Real-life experience with plasmapheresis in newly diagnosed multiple myeloma accompanied by acute kidney injury.

OBJECTIVES: The aim of this study was to retrospectively evaluate the effect of plasmapheresis treatment concomitant with chemotherapy and the number of sessions on renal improvement and survival in patients with newly diagnosed multiple myeloma (MM) presenting with acute kidney injury (AKI). MATERIAL AND METHODS: Retrospective analysis was performed on 55 newly diagnosed MM patients who were presented with AKI to the Hematology Clinic of University of the Health Sciences Antalya Training and Research Hospital between 2013 and 2021. RESULTS: The study included 55 patients between 39 and 91 years of age and comprised 22 (40%) women and 33 (60%) men. Forty-eight (87.3%) patients were treated with plasmapheresis and chemotherapy. Based on the median number of plasmapheresis sessions, the patients were grouped as ≤ 3 and > 3. A significant difference was observed in both groups between the mean values of repeated measurements at the time of diagnosis, after completion of plasmapheresis treatment, and at 1 month of plasmapheresis, when statistics of differences were evaluated for urea, creatinine, estimated glomerular filtration rate (eGFR) (ml/min), total protein, albumin, and globulin (p < 0.05); however, there was no difference between these parameters and the number of plasmapheresis sessions. The 1.16 (0.56-2.38) fold higher risk of ex found in patients with ≤ 3 plasmapheresis sessions compared to those with > 3 was not statistically significant (p > 0.05). CONCLUSION: It was observed that plasmapheresis is beneficial in the short term for renal recovery in the treatment of MM with AKI and that > 3 plasmapheresis sessions have no superior effectiveness in renal improvement or survival.

Serum immunoglobulin G level reduction is a predictor of short-term improvement in patients with myasthenia gravis undergoing plasmapheresis.

OBJECTIVES: The aim of the study was to investigate the serological factors in predicting symptom improvement in myasthenia gravis (MG) patients who underwent plasmapheresis (PP). METHODS: The relationship between symptom improvement and change in immunoglobin G (IgG) and acetylcholine receptor antibody (AchR-Ab) levels in 21 MG patients after PP was analyzed. RESULTS: Patients were divided into two groups: the favorable (n = 11) or unfavorable (n = 10) response groups around the median MG composite improvement rate (50 [29, 56]%) 2 weeks after a PP course. In all patients, the IgG reduction rate before and after PP was higher in the favorable than the unfavorable response group. In AChR-Ab-positive patients, IgG and AChR-Ab reduction rates were higher in the favorable than the unfavorable response group. CONCLUSION: IgG reduction rate is a predictor of symptom improvement in MG patients who underwent PP.

The role of plasmapheresis in severe acute disseminated encephalomyelitis with clinical findings of transverse myelitis.

INTRODUCTION: Acute disseminated encephalomyelitis is a rare acute demyelinating disease of the central nervous system (CNS). The pathogenesis remains unclear but is suspected to be autoimmune. High doses of methylprednisolone (HDMP) are currently considered standard of treatment. Plasmapheresis (PE) is typically given in steroid refractory cases. There is currently limited evidence supporting its use in ADEM. MATERIALS AND METHODS: We report a 16-year-old girl with ADEM who improved rapidly after initiating PE. RESULTS: The patient presented with acute onset of multifocal CNS symptoms, including encephalopathy, requiring intensive care unit management. Despite HDMP administration, her clinical condition continued to deteriorate. PE was therefore initiated on the same day as HDMP. Her clinical condition improved significantly following the first session. She was extubated and discharged from the intensive care unit the following day. CONCLUSION: HDMP combined with PE may be an effective first-line treatment in patients with fulminant ADEM.

A donor safety evidence literature review of the short- and long-term effects of plasmapheresis.

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

Divide et Vinces, Therapeutic Apheresis in Nephrological Clinical Practice.

Therapeutic plasma exchange (TPE) or plasmapheresis has been used in various life-threatening diseases as a primary treatment or in combination with other therapies. It was first successfully employed in the 1960s for diseases like Waldenström's disease and myeloma. Since then, TPE techniques using apheresis membranes have been introduced. Apheresis therapies separate plasma components from blood using membrane screening or centrifugation methods. TPE aims to remove substances involved in the pathophysiology of diseases. It selectively removes high-molecular-weight molecules, substances with prolonged half-life, and those associated with disease pathogenesis. TPE can be performed using membranes or centrifugation, with replacement of extracted plasma volume using albumin or fresh frozen plasma. TPE requires specific competencies in nephrology and can be prescribed and monitored by nephrologists and performed by dialysis nursing staff. TPE can be combined with adsorption-based therapies to enhance its effect, and this approach is called plasma filtration adsorption. Another variation is double plasma filtration, which selectively removes substances based on molecular size. TPE can also be combined with lipoprotein removal strategies for managing familial hypercholesterolemia. TPE is an affordable extracorporeal therapy that benefits patients with life-threatening diseases. It requires collaboration between nephrologists and other specialists, and our results demonstrate successful TPE without anticoagulation in general hospitalization or outpatient settings.

Risk prediction of iron deficiency for plasmapheresis donors in China: Development and validation of a prediction model.

BACKGROUND AND OBJECTIVES: The present study aims to evaluate the iron stores in plasmapheresis donors and develop and validate an iron deficiency (ID) risk prediction model for plasmapheresis donors with potential or existing ID. MATERIALS AND METHODS: We assessed plasmapheresis donors' serum ferritin (SF) and haemoglobin (Hb) levels. The candidate factors showing significant differences in the multivariate logistic regression analysis were used to establish a risk prediction scoring system. The participants were divided into a training cohort and an internal validation cohort in a 7:3 ratio. Additional plasmapheresis donors from a different station were recruited for external validation. RESULTS: The SF levels in both male and female donors in the high-frequency group were significantly lower than those of new donors (male: p < 0.001; female: p = 0.008). The prevalence of ID in female regular donors with a high frequency was significantly higher than that in new donors (33.1% vs. 24.6%; odds ratio = 1.209 [95% CI: 1.035-1.412]). Donation frequency, age, Hb, body mass index and being pre-menopausal were identified as independent risk factors for ID (p < 0.05). The developed model exhibited good discrimination ability (area under the receiver operating characteristic curve >0.7) and calibration (p > 0.05) in development, internal validation cohorts and external validation cohorts. CONCLUSION: A higher donation frequency has been associated with reduced SF levels and an increased risk of ID in women. The developed ID risk prediction model demonstrates moderate discriminative power and good model fitting, suggesting its potential clinical utility.

[Therapeutic Plasma Exchange in a Patient with Chronic Hemodialysis and a New Diagnosis of Myasthenia Gravis].

Case ReportC.S.T. (♂, 71 years old) is a patient with multiple and severe comorbidities, undergoing thrice-weekly chronic hemodialysis since 2008 due to the progression of post-lithiasic uropathy. Over the past 2 months, the patient had been experiencing progressive ptosis of the eyelids, muscle weakness, and ultimately dysphagia and dysarthria that emerged in the last few days. Urgently admitted to the Neurology department, electromyography (EMG) was performed, leading to a diagnosis of predominant cranial myasthenia gravis (with borderline anti-acetylcholine receptor antibody serology). Prompt treatment with pyridostigmine and steroids was initiated. Considering the high risk of acute myasthenic decompensation, therapeutic plasma exchange (TPE) with centrifugation technique was promptly undertaken after femoral CVC placement. TPE sessions were alternated with hemodialysis. The patient's condition complicated after the third TPE session, with septic shock caused by Methicillin-Sensitive Staphylococcus Aureus (MSSA). The patient was transferred to the Intensive Care Unit (ICU). Due to hemodynamic instability, continuous veno-venous hemodiafiltration (CVVHDF) with citrate anticoagulation was administered for 72 hours. After resolving the septic condition, intermittent treatment with Acetate-Free Biofiltration (AFB) technique was resumed. The patient completed the remaining three TPE sessions and, once the acute condition was resolved, was transferred back to Neurology. Here, the patient continued the treatment and underwent a rehabilitation program, showing significant motor and functional recovery until discharge. Conclusions. The multidisciplinary interaction among Nephrologists, Neurologists, Anesthesiologists, and experts from the Immunohematology and Transfusion Medicine Service enabled the management and treatment of a rare condition (MG) in a high-risk chronic hemodialysis patient.

Total arch replacement for an aortic arch aneurysm with cold agglutinin disease after rituximab and plasmapheresis.

BACKGROUND: Cold agglutinin disease can lead to significant complications, especially for patients undergoing arch repair requiring hypothermic circulatory arrest. Rituximab and plasmapheresis are treatments for cold agglutinin disease. However, its use in patients with Stanford type A dissection has not been reported. Therefore, after consultation with hematologists, we used rituximab and plasmapheresis before mild hypothermic aortic arch surgery to maintain the body temperature above the thermal altitude. CASE PRESENTATION: This report describes an 86-year-old male patient with acute type A aortic dissection who received outpatient treatment for rheumatoid arthritis and a 55-mm thoracic aortic aneurysm. The patient was scheduled to undergo urgent surgery for a type A intramural hematoma and progressive aortic aneurysm; however, laboratory test results indicated blood clotting and cold agglutinin. Consequently, urgent surgery was rescheduled. After consulting with hematologists, rituximab was initiated 3 months before surgery, and plasmapheresis was performed 2 days before surgery for cold agglutinin disease. Under mild hypothermia conditions, total arch replacement using the frozen elephant trunk technique was performed while maintaining cerebral and lower body perfusion. The postoperative course was uneventful. On postoperative day 42, the patient was discharged without any neurological deficits. CONCLUSIONS: This case involving total arch replacement with mild hypothermia for an aortic arch aneurysm with cold agglutinin disease after rituximab treatment and plasmapheresis resulted in a successful outcome.

The world apheresis association registry, 2023 update.

The WAA apheresis registry contains data on more than 140,000 apheresis procedures conducted in 12 different countries. The aim is to give an update of indications, type and number of procedures and adverse events (AEs). MATERIAL AND METHODS: The WAA-registry is used for registration of apheresis procedures and is free of charge. The responsible person for a center can apply at the site www.waa-registry.org RESULTS: Data includes reported AEs from 2012 and various procedures and diagnoses during the years 2018-2022; the latter in total from 27 centers registered a total of 9500 patients (41% women) that began therapeutic apheresis (TA) during the period. A total of 58,355 apheresis procedures were performed. The mean age was 50 years (range 0-94). The most common apheresis procedure was stem cell collection for which multiple myeloma was the most frequent diagnosis (51%). Donor cell collection was done in 14% and plasma exchange (PEX) in 28% of patients; In relation to all performed procedures PEX, using a centrifuge (35%) and LDL-apheresis (20%) were the most common. The main indication for PEX was TTP (17%). Peripheral veins were used in 56% as the vascular access. The preferred anticoagulant was ACD. AEs occurred in 2.7% of all procedures and were mostly mild (1%) and moderate 1.5% (needed supportive medication) and, only rarely, severe (0.15%). CONCLUSION: The data showed a wide range of indications and variability in apheresis procedures with low AE frequency.

Plasmapheresis Versus Intravenous Immunoglobulin in Patients With Autoimmune Neuromuscular and Neuro-immunological Conditions.

OBJECTIVES: Plasmapheresis (PLEX) and intravenous immunoglobulin (IVIg) are commonly used to treat autoimmune neuromuscular disorders, including myasthenia gravis, acute inflammatory demyelinating polyradiculoneuropathy, chronic inflammatory demyelinating polyradiculoneuropathy, and other autoimmune neurological disorders. The side effect profiles of these therapies vary, and concern has been raised regarding the safety of PLEX in the elderly population. In this study, we have examined the pattern of PLEX and IVIg use for autoimmune neurological disorders at a single facility and in a national database, focusing on the complications in elderly patients. METHODS: We performed a retrospective chart review of adult patients at our institution receiving PLEX or IVIg for any autoimmune neuromuscular or neuro-immunological disease. Next, we analyzed the National Inpatient Sample database to confirm the trend in IVIg and PLEX use from 2012 to 2018 for a set of neuromuscular and neuro-immunological primary diagnoses. RESULTS: IVIg was overall favored over PLEX. The adverse effects were similar among elderly patients (age ≥65 years) compared with younger patients (<65 years) in our institution, even after adequate matching of patients based on age, sex, and medical history. We examined the National Inpatient Sample dataset and noted increasingly higher frequency of IVIg use, consistent with the findings from our institution or facility. CONCLUSIONS: Both PLEX and IVIg are safe therapeutic choices in adult patients with autoimmune neuromuscular disorders and other neuro-immunological diseases and can be safely administered in the appropriate clinical setting.

Double filtration plasmapheresis combined with rituximab for donor-specific antibody desensitization in haploidentical haematopoietic stem cell transplantation.

Donor-specific anti-HLA antibodies (DSA) are a major cause of engraftment failure in patients receiving haploidentical haematopoietic stem cell transplantation (Haplo-HSCT). Double filtration plasmapheresis (DFPP) avoids the unnecessary loss of plasma proteins and increases the efficiency of purification. To investigate the effectiveness of the desensitization protocol including DFPP and rituximab, we conducted a nested case-control study. Thirty-three patients who had positive DSA were desensitized by the protocol and 99 patients with negative DSA were randomly matched as control. The median DSA mean fluorescence intensity values before and after DFPP treatment were 7505.88 ± 4424.38 versus 2013.29 ± 4067.22 (p < 0.001). All patients in DSA group achieved haematopoietic reconstitution and the median neutrophils and platelets engraftment times were 13 (10-21) and 13 (10-29) days respectively. Although the cumulative incidence of II-IV aGVHD (41.4% vs. 28.1%) and 3-year moderate to severe cGVHD (16.8% vs. 7.2%) were higher in DSA cohort than in the control, no statistical significance was observed. The 3-year non-relapse mortality and the overall survival were 6.39% and 72.0%, respectively, in the DSA cohort, which were comparable to the negative control. In conclusion, DFPP and rituximab could be effectively used for desensitization and overcome the negative effects of DSA in Haplo-HSCT.