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Background and Aims: Guillain‐Barré syndrome (GBS) is an acute, self‐limited, immune‐mediated peripheral neuropathy. Current treatments for GBS include intravenous immunoglobulin (IVIg) and plasma exchange, which may not sufficiently benefit severely affected patients. This study evaluated the efficacy and safety of eculizumab add‐on therapy to IVIg (standard‐of‐care treatment) in patients with severe GBS. Methods: This phase 3, multicenter, double‐blind, randomized, placebo‐controlled clinical trial (NCT04752566), enrolled Japanese adults (age ≥ 18 years) with severe GBS (Hughes functional grade [FG] score FG3 or FG4/FG5 within 2 weeks of onset of GBS). Participants were randomized 2:1 to receive intravenous infusion of eculizumab or placebo (once weekly for 4 weeks) with IVIg treatment with 20 weeks of follow‐up. Primary efficacy endpoint was the time to first reach FG score ≤1 (able to run). Key secondary endpoints were proportion of participants achieving FG ≤1 at weeks 8 and 24 and FG improvement ≥3 at week 24. Pharmacodynamic analysis of serum free C5 concentration over time was performed. Safety was evaluated. Results: The analysis included 57 participants (eculizumab, n = 37; placebo, n = 20). Primary endpoint was not achieved (hazard ratio, 0.9; 95% CI, 0.45–1.97; p =.89). Key secondary endpoints did not reach statistical significance. Serum C5 concentration was reduced by 99.99% at 1 h postdose and sustained to week 5 but returned to baseline at the end of follow‐up period. No new safety signals for eculizumab were identified. Interpretation: Although well tolerated, eculizumab treatment did not show significant effects on motor function recovery compared to placebo in patients with GBS. [ABSTRACT FROM AUTHOR]

Objective: Relapses of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis are important events that can cause organ dysfunction and reduce quality of life. Understanding the effects of the initial treatments for ANCA‐associated vasculitis on the subsequent risk of relapse may help guide monitoring and treatment. Methods: We performed a post hoc analysis of participants with severe ANCA‐associated vasculitis enrolled in an international two‐by‐two factorial randomized controlled trial comparing the effects of plasma exchange (PLEX) to no PLEX and a regimen of reduced glucocorticoid exposure to a standard regimen. We estimated the effects of treatments on relapses of any severity using three competing risk time‐to‐event models adjusted for patient and disease characteristics and other treatments. Each model was adjusted for disease manifestations in different ways. Results: Of 704 participants, 649 (92.2%) achieved remission and 147 (22.7%) experienced 204 relapses. The relapse rate was 10.3 (95% confidence interval [CI] 8.4–12.1) relapses per 100 patient‐years. Neither the use of PLEX (subhazard ratio 0.91–0.94; 95% CIs range from 0.66 to 1.31) nor a glucocorticoid regimen (subhazard ratio 0.93–0.94; 95% CIs range from 0.67 to 1.35) appreciably changed the risk of relapse. Proteinase 3–ANCA and the presence of nonhemorrhagic respiratory manifestations of the disease at trial entry were associated with increased risks of relapse. Receiving dialysis at baseline and administration of oral cyclophosphamide as induction therapy were associated with lower risks of relapse. Conclusion: In patients with severe ANCA‐associated vasculitis, relapses remain common; neither the use of PLEX nor an initial glucocorticoid tapering regimen impacted relapse risk. [ABSTRACT FROM AUTHOR]

In human leukocyte antigen (HLA)-mismatched allogeneic stem cell transplantation settings, donor-specific anti-HLA antibodies (DSAs) can independently lead to graft failure, including both primary graft rejection and primary poor graft function. Although several strategies, such as plasma exchange, intravenous immunoglobulin, rituximab, and bortezomib, have been used for DSA desensitization, the effectiveness of desensitization and transplantation outcomes in some patients remain unsatisfactory. In this review, we summarized recent research on the prevalence of anti-HLA antibodies and the underlying mechanism of DSAs in the pathogenesis of graft failure. We mainly focused on desensitization strategies for DSAs, especially novel methods that are being investigated in the preclinical stage and those with promising outcomes after preliminary clinical application. [ABSTRACT FROM AUTHOR]

Acute liver failure (ALF) is a life-threatening disorder characterised by rapid deterioration of liver function, coagulopathy, and hepatic encephalopathy in the absence of pre-existing liver disease. The cause of ALF varies across the world. Common causes of ALF in adults include drug toxicity, hepatotropic and non-hepatotropic viruses, herbal and dietary supplements, antituberculosis drugs, and autoimmune hepatitis. The cause of liver failure affects the management and prognosis, and therefore extensive investigation for cause is strongly suggested. Sepsis with multiorgan failure and cerebral oedema remain the leading causes of death in patients with ALF and early identification and appropriate management can alter the course of ALF. Liver transplantation is the best current therapy, although the role of artificial liver support systems, particularly therapeutic plasma exchange, can be useful for patients with ALF, especially in non-transplant centres. In this Seminar, we discuss the cause, prognostic models, and management of ALF. [ABSTRACT FROM AUTHOR]

A key aspect of preeclampsia pathophysiology is the reduced invasiveness of trophoblasts and the impairment of spiral artery remodelling. Understanding the causes of altered trophoblast function is critical to understand the development of preeclampsia. B7-H4, a checkpoint molecule, controls a wide range of processes, including T-cell activation, cytokine release, and tumour progression. Our previous findings indicated that B7-H4 levels are elevated in both maternal blood and placental villous tissue during the early stages of preeclampsia. Here, we investigated the function of B7-H4 in trophoblast physiology. Recombinant B7-H4 protein was used to treat human SGHPL-5 extravillous trophoblast cells. Biological functions were investigated using MTT, wound healing, and transwell assays. Signalling pathways were analysed by immunoblotting and immunofluorescence. The functionality of B7-H4 was further confirmed by immunoblotting and immunohistochemical analysis in placental tissues from control and preeclamptic patients following therapeutic plasma exchange (TPE) or standard of care treatment. This study showed that B7-H4 inhibited the proliferation, migration, and invasion capacities of SGHPL-5 extravillous cells while promoting apoptosis by downregulating the PI3K/Akt/STAT3 signalling pathway. These results were consistently confirmed in placental tissues from preterm controls compared to early-onset preeclamptic placental tissues from patients treated with standard of care or TPE treatment. B7-H4 may play a role in the development of preeclampsia by inhibiting essential functions of extravillous trophoblast cells during placental development. One possible mechanism by which TPE improves pregnancy outcomes in preeclampsia is through the elimination of B7-H4 amongst other factors. [ABSTRACT FROM AUTHOR]

Background: A recent Phase 2/3 study in Japanese patients showed that caplacizumab was effective in treating immune-mediated thrombotic thrombocytopenic purpura (iTTP), with a low rate of iTTP recurrence. ADAMTS13 activity is monitored weekly during caplacizumab treatment to guide discontinuation of caplacizumab and consequently avoid exacerbations or relapse. The aim of this study was to assess changes in ADAMTS13 activity/inhibitor levels during caplacizumab treatment in this patient population. Methods: A post hoc analysis of the Phase 2/3 study in Japanese patients was conducted. Patients ≥ 18 years old with confirmed iTTP received 10 mg of caplacizumab daily in conjunction with therapeutic plasma exchange (TPE) and immunosuppression for 30 days post-TPE. Outcomes included time to recovery of ADAMTS13 activity, ADAMTS13 activity level at treatment end, incidence of ADAMTS13 inhibitor re-elevation (ie, inhibitor boosting) during treatment, time to platelet count recovery, number of days of TPE, and safety. Outcomes according to presence of inhibitor boosting were also assessed. Results: Nineteen patients had confirmed iTTP and were included in this analysis. Median (95% confidence interval) time to recovery of ADAMTS13 activity to ≥ 10%, ≥ 20%, and ≥ 60% was 14.6 (5.9–24.8), 18.5 (5.9–31.8), and 47.5 (18.5–60.9) days, respectively. Median (range) ADAMTS13 activity level at caplacizumab treatment end was 62.0% (29.0–101.0). Nine patients had ADAMTS13 inhibitor boosting. Delayed response of ADAMTS13 activity was observed in patients with inhibitor boosting. The median time to platelet count response and median number of TPE days were shorter in patients with inhibitor boosting compared with patients without inhibitor boosting. Rituximab was administered to almost all patients with inhibitor boosting (88.9%), after completion of TPE. Patients without inhibitor boosting who were treated with rituximab received it prior to completion of TPE. Only one patient experienced a recurrence, which occurred shortly after caplacizumab discontinuation due to an adverse event. Conclusions: In patients with iTTP, caplacizumab with TPE and immunosuppression may reduce the risk of ADAMTS13 inhibitor boosting if rituximab is administered early in the iTTP treatment period. Early administration of rituximab in addition to caplacizumab may prevent iTTP recurrence with inhibitor boosting. Trial registration: NCT04074187. [ABSTRACT FROM AUTHOR]

This document is a comprehensive review of various topics in transfusion medicine, including advancements in red blood cell transfusion strategies, the impact of donor sex on transfusion outcomes, and the use of cryoprecipitate in trauma. It also discusses the use of hemostatic agents in trauma, such as 4-factor prothrombin complex concentrate and tranexamic acid. The text provides summaries of studies and trials on topics like prophylactic tranexamic acid after cesarean delivery, therapeutic apheresis, and gene therapies for sickle cell disease. It also addresses healthcare disparities and diversity in editorial positions, proposing solutions to address these issues. The document serves as a list of references to scientific articles and trials related to transfusion medicine and blood disorders, covering a wide range of topics. [Extracted from the article]

Background: Hemolytic uremic syndrome (HUS) is an important cause of acute kidney injury in children. HUS is known as an acute disease followed by complete recovery, but patients may present with kidney abnormalities after long periods of time. This study evaluates the long-term outcome of Shiga toxin-producing Escherichia coli-associated HUS (STEC-HUS) in pediatric patients, 10 years after the acute phase of disease to identify risk factors for long-term sequelae. Methods: Over a 6-year period, 619 patients under 18 years of age with HUS (490 STEC-positive, 79%) were registered in Austria and Germany. Long-term follow-up data of 138 STEC-HUS-patients were available after 10 years for analysis. Results: A total of 66% (n = 91, 95% CI 0.57–0.73) of patients fully recovered showing no sequelae after 10 years. An additional 34% (n = 47, 95% CI 0.27–0.43) presented either with decreased glomerular filtration rate (24%), proteinuria (23%), hypertension (17%), or neurological symptoms (3%). Thirty had sequelae 1 year after STEC-HUS, and the rest presented abnormalities unprecedented at the 2-year (n = 2), 3-year (n = 3), 5-year (n = 3), or 10-year (n = 9) follow-up. A total of 17 patients (36.2%) without kidney abnormalities at the 1-year follow-up presented with either proteinuria, hypertension, or decreased eGFR in subsequent follow-up visits. Patients needing extracorporeal treatments during the acute phase were at higher risk of presenting symptoms after 10 years (p < 0.05). Conclusions: Patients with STEC-HUS should undergo regular follow-up, for a minimum of 10 years following their index presentation, due to the risk of long-term sequelae of their disease. An initial critical illness, marked by need of kidney replacement therapy or plasma treatment may help predict poor long-term outcome. [ABSTRACT FROM AUTHOR]

Background: Therapeutic plasma exchange (TPE) is a highly effective rescue treatment for patients with acute exacerbation of neuroimmunological disease that removes circulating autoantibodies and inflammatory components from the bloodstream. The aims of this study are to explore the safety and the effectiveness of TPE in patients with autoimmune neurological disorders. Methods: We retrospectively evaluated the frequency of adverse events (AEs) and the effectiveness of TPE using the modified Ranking Scale (mRS) in patients with acute neurological flares who underwent TPE at the University Hospital of Palermo. Results: Of 59 patients, the majority underwent TPE due to multiple sclerosis (MS) relapse. In 23.7% of cases, TPE was performed before obtaining a definite diagnosis due to the severity of the clinical presentation. After TPE, the mRS score was globally reduced (p < 0.0001), and this effect was marked in patients with MS, Guillain–Barré syndrome, and myasthenia gravis crisis but not in those with paraneoplastic syndromes. Circulating pathogenetic antibodies, younger age, and the early use of TPE were factors strongly associated with TPE effectiveness. The overall safety profile of TPE was satisfactory with an AE frequency of 15%. Conclusions: These results highlight the early use of TPE in patients with circulating pathogenetic antibodies as well as its favorable safety profile. [ABSTRACT FROM AUTHOR]

Donor‐specific HLA antibody (DSA) has been recognised as an independent risk factor for graft failure in patients undergoing haploidentical haematopoietic stem cell transplantation (HID HSCT). Therapeutic plasma exchange (TPE), as a first‐line strategy for DSA desensitisation, can promptly reduce serum DSA levels. This study aimed to investigate DSA characteristics and identify a biomarker predicting the efficacy of DSA desensitisation in patients proceeding to HID HSCT. We retrospectively enrolled 32 patients with DSA from April 2021 to January 2024, and analysed the mean fluorescence intensity (MFI) value of DSA at the different time points of desensitisation treatment. Compared with baseline DSA level before TPE, the median MFI of HLA class I DSA was reduced from 8178.6 to 795.3 (p < 0.001), and HLA class II DSA decreased from 6210.9 to 808.8 (p < 0.001) after TPE. The DSA level in 1:16 diluted pre‐TPE serum correlated well with DSA value in post‐TPE serum (class I, r = 0.85, p < 0.0001; class II, r = 0.94, p < 0.0001), predicting TPE efficacy in 84.4% of patients. Based on the degree of DSA reduction after TPE, patients were divided into complete responders (decreased by >70%), partial responders (decreased by 30 to 70%) and non‐responders (decreased by <30%) and the percentages were 43.8%, 25% and 31.2%, respectively. Non‐responders receiving aggressive immunotherapy had longer overall survival compared to those receiving standard strategies (p < 0.05). The 1:16 diluted pre‐TPE serum may predict the efficacy of TPE and allow for more rational immunotherapy strategy for patients with DSA proceeding to HID HSCT. [ABSTRACT FROM AUTHOR]

Background: Primary focal segmental glomerulosclerosis (FSGS) frequently recurs after kidney transplantation and is associated with poor graft survival. Patients who do not achieve remission (nonresponders) have an especially poor graft survival. However, the characteristics that may affect graft survival in nonresponders are unknown. This study aimed to determine the clinical characteristics associated with graft survival in nonresponders. Methods: We retrospectively collected the clinical records of patients with FSGS and an age at onset <16 years who experienced posttransplant recurrence of FSGS at six hospitals in Japan from 1993 to 2018. Results: Eight nonresponders with recurrent FSGS were enrolled in this study. The median time to recurrence after kidney transplantation was 1 day (interquartile range, 1–2 days). All patients received therapeutic plasma exchange and methylprednisolone pulse therapy. Rituximab was used as an add‐on therapy in three patients. Five patients lost their graft within 2 years after kidney transplantation (rapid group). In contrast, three patients had much longer graft survival (nonrapid group). We compared the clinical characteristics of the rapid and nonrapid groups. Proteinuria tended to be lower in the nonrapid group at the third and subsequent months of therapy. The rapid group had persistent nephrotic syndrome. The rate of reduction in proteinuria was lower in the rapid group than in the nonrapid group. Conclusions: Our study suggests that persistent nephrotic syndrome and a low rate of reduction in proteinuria may predict rapid progression to graft failure in nonresponders. [ABSTRACT FROM AUTHOR]

Patients with acute liver failure (ALF) and acute on chronic liver failure (ACLF) have significant morbidity and mortality. They require extracorporeal blood purification modalities like continuous renal replacement therapy (CRRT) and therapeutic plasma exchange (TPE) as a bridge to recovery or liver transplantation. Limited data are available on the outcomes of patients treated with these therapies. This is a retrospective single-center study of 23 patients from 2015 to 2022 with ALF/ACLF who underwent CRRT and TPE. We aimed to describe the clinical characteristics and outcomes of these patients. Median (IQR) age was 0.93 years (0.57, 9.88), range 16 days to 20 years. Ten (43%) had ALF and 13 (57%) ACLF. Most (n = 19, 82%) started CRRT for hyperammonemia and/or hepatic encephalopathy and all received TPE for refractory coagulopathy. CRRT was started at a median of 2 days from ICU admission, and TPE started on the same day in most. The liver transplant was done in 17 (74%), and 2 recovered native liver function. Four patients, all with ACLF, died prior to ICU discharge without a liver transplant. The median peak ammonia pre-CRRT was 131 µmol/L for the whole cohort. The mean (SD) drop in ammonia after 48 h of CRRT was 95.45 (43.72) µmol/L in those who survived and 69.50 (21.70) µmol/L in those who did not (p 0.26). Those who survived had 0 median co-morbidities compared to 2.5 in non-survivors (aOR (95% CI) for mortality risk of 2.5 (1.1–5.7), p 0.028). Conclusion: In this cohort of 23 pediatric patients with ALF or ACLF who received CRRT and TPE, 83% survived with a liver transplant or recovered with their native liver. Survival was worse in those who had ACLF and those with co-morbid conditions. What is Known: • Pediatric acute liver failure is associated with high mortality. • Patients may require extracorporeal liver assist therapies (like CRRT, TPE, MARS, SPAD) to bridge them over to a transplant or recovery of native liver function. What is New: • Standard volume plasma exhange has not been evaluated against high volume plasma exchange for ALF. • The role, dose, and duration of therapeutic plasma exchange in patients with acute on chronic liver failure is not well described. [ABSTRACT FROM AUTHOR]

This article discusses a case report of a 9-year-old male with Duchenne muscular dystrophy (DMD) who developed immune-mediated myositis (IMM) after receiving gene therapy. The patient experienced weakness, angioedema, difficulty swallowing, and respiratory issues, and required therapeutic plasma exchange for treatment. Muscle biopsy showed inflammation attacking specific myofibers. The study suggests that the immune response against the transgenic protein may explain the inflammation. Further research is needed to understand the safety and risk factors of this treatment for patients with specific DMD gene mutations. [Extracted from the article]

The authors describe a case of bilateral diffuse paraneoplastic orbital myositis induced by a stage IA left testicular pure seminoma. The patient presented with findings typical of thyroid-associated orbitopathy (TAO) and was thought to have TAO until discovery of the malignancy. Treatment included an urgent orchiectomy, as well as 7 weeks of therapeutic plasma exchange. This is the fifth reported case of seminoma-associated orbitopathy, and the second to occur while cancer was in the occult phase. Although seminoma-associated orbitopathy is exceedingly rare, it can masquerade as TAO and should be considered in the differential diagnosis of any young male with atypical TAO findings. [ABSTRACT FROM AUTHOR]

Introduction: Serpiginous choroiditis presents with large yellow‐white exudative lesions that occur near the optic nerve papillae, that progresses slowly with repeated relapses and cures. Although infection and autoimmunity have been implicated, the cause is unknown. Methods: A man was diagnosed with serpiginous choroiditis on clinical and other examinations. He started treatment with oral corticosteroids, cyclophosphamide, adalimumab, azathioprine, rituximab, and mycophenolate mofetil. Only the steroids and cyclophosphamide had a therapeutic effect. Plasma exchange was initiated, and the lesions quickly resolved. Results: Disease control has been maintained by plasma exchange and cyclophosphamide during flare‐ups in the fall and winter, suggesting that plasma exchange is effective in the treatment of serpiginous choroiditis. Conclusion: The reproducible response with each recurrence suggests a strong association between the disease and autoimmunity. Furthermore, that some, as yet unknown, autoantibodies are involved in the pathogenesis of serpiginous choroiditis. [ABSTRACT FROM AUTHOR]

Background: Acute cerebellitis is a rare complication of pediatric infections. There are many reports that viral infections lead to neurological manifestations, including acute cerebellitis. Methods: A retrospective chart review was conducted for pediatric patients diagnosed with enterovirus cerebellitis between 2000 and 2024. The methods involved reviewing clinical and radiological records and assessing the treatment methods. Results: Case Report: We present the case of a 4‐year‐old immunocompetent child who initially presented with acute encephalopathy followed by truncal ataxia, and eventually received a diagnosis of postinfectious cerebellitis. Enterovirus real‐time polymerase chain reaction were positive in the nasopharyngeal swab. Therapeutic plasma exchange (TPE) was started due to neurological deterioration despite IVIG treatment. She improved significantly with TPE, and methylprednisolone treatment and was discharged in good health status. The patient is being followed up as neurologically normal. Conclusion: Acute cerebellitis associated with enterovirus is a rare pediatric disorder. Early diagnosis and treatment with TPE in this severe case is thought to be preventive for the potentially fatal complications. [ABSTRACT FROM AUTHOR]

Introduction: Apheresis practices in the United States (US) have not been comprehensively characterized to date. This study aimed to address this gap by evaluating apheresis therapy through a national survey. Methods: A multi‐institutional survey was conducted between April and July 2023. The survey, comprising 54 questions, focused on institutional demographics, procedures, equipment, staffing, training, and impacts of the Coronavirus Disease 2019 (COVID‐19) pandemic. Responses from 22 institutions, primarily academic medical centers, were analyzed. Results: Therapeutic plasma exchange (TPE) was the most common procedure, followed by hematopoietic progenitor cell collection (HPC‐A) and red blood cell exchange (RCE). CAR‐T cell collections were widespread, with some institutions supporting over 30 protocols concurrently. Most sites used the Spectra Optia Apheresis System, were managed by a transfusion medicine service, and employed internal apheresis providers. Insufficient staffing levels, exacerbated by the COVID‐19 pandemic, were common and most often addressed using overtime. Discussion: The survey highlighted the ubiquity of TPE, expanding cellular collections and staffing challenges. The role of apheresis in supporting cellular therapy, particularly in newly developing cell and gene therapies and clinical trials, was evident. Staffing issues during the pandemic emphasized the need for innovative recruitment strategies. Conclusion: This nationwide survey provides the most comprehensive analysis to date of apheresis practices in large US academic centers. [ABSTRACT FROM AUTHOR]

Background: Therapeutic plasma exchanges (TPE), which affect the humoral response, are often performed in combination with immunosuppressive drugs. For this reason, TPE may be associated with an increased susceptibility to infections. We aimed to describe blood stream infection (BSI) incidence in ICU patients treated with TPE and to identify associated risk factors. Methods: We retrospectively included patients that had received at least one session of TPE in the ICU of one of the 4 participating centers (all in Paris, France) between January 1st 2010 and December 31th 2019. Patients presenting with a BSI during ICU stay were compared to patients without such an infection. Risk factors for BSI were identified by a multivariate logistic regression model. Results: Over 10 years in the 4 ICUs, 387 patients were included, with a median of 5 [2–7] TPE sessions per patient. Most frequent indications for TPE were thrombotic microangiopathy (47%), central nervous system inflammatory disorders (11%), hyperviscosity syndrome (11%) and ANCA associated vasculitis (8.5%). Thirty-one patients (8%) presented with a BSI during their ICU stay, a median of 7 [3–11] days after start of TPE. In a multivariate logistic regression model, diabetes (OR 3.32 [1.21–8.32]) and total number of TPE sessions (OR 1.14 [1.08–1.20]) were independent risk factors for BSI. There was no difference between TPE catheter infection related BSI (n = 11 (35%)) and other sources of BSI (n = 20 (65%)) regarding catheter insertion site (p = 0.458) or rate of TPE catheter related deep vein thrombosis (p = 0.601). ICU course was severe in patients presenting with BSI when compared to patients without BSI, with higher need for mechanical ventilation (45% vs 18%, p = 0.001), renal replacement therapy (42% vs 20%, p = 0.011), vasopressors (32% vs 12%, p = 0.004) and a higher mortality (19% vs 5%, p = 0.010). Conclusion: Blood stream infections are frequent in patients receiving TPE in the ICU, and are associated with a severe ICU course. Vigilant monitoring is crucial particularly for patients receiving a high number of TPE sessions. [ABSTRACT FROM AUTHOR]

Background: Thrombotic microangiopathy is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ injury. The pathological features include vascular damage that is manifested by arteriolar and capillary thrombosis with characteristic abnormalities in the endothelium and vessel wall. Thrombocytopenia is one of the common adverse effects of interferon therapy. However, a more serious but rare side effect is thrombotic microangiopathy. Case presentation: We report the case of a 36-year-old Asian male patient with clinical manifestations of hypertension, blurred vision, acute renal failure, thrombocytopenia, and thrombotic microangiopathy. Renal biopsy showed interstitial edema with fibrosis, arteriolar thickening with vitreous changes, and epithelial podocytes segmental fusion. Immunofluorescence microscopy showed C3(+), Ig A(+) deposition in the mesangial region, which was pathologically consistent with thrombotic microangiopathy renal injury and Ig A deposition. The patient had a history of hepatitis B virus infection for more than 5 years. Lamivudine was used in the past, but the injection of long-acting interferon combined with tenofovir alafenamide fumarate was used since 2018. The comprehensive clinical investigation and laboratory examination diagnosed the condition as thrombotic microangiopathy kidney injury caused by interferon. After stopping interferon in his treatment, the patient's renal function partially recovered after three consecutive therapeutic plasma exchange treatments and follow-up treatment without immunosuppressant. The renal function of the patient remained stable. Conclusions: This report indicates that interferon can induce thrombotic microangiopathy with acute renal injury, which can progress to chronic renal insufficiency. [ABSTRACT FROM AUTHOR]

Introduction: Immune checkpoint inhibitors (ICIs) can cause a spectrum of adverse events known as immune-related adverse events (irAEs) that resemble autoimmune responses. Immune-mediated myasthenia gravis (MG) is a rare and serious neurologic adverse event that has been associated with ICIs requiring prompt treatment. In the Jehovah's Witness population, typical management of these adverse events may not be options, and alternative treatment choices would be needed. Case report: 73-year-old Jehovah's Witness patient with high-grade undifferentiated pleiomorphic sarcoma who developed immune-mediated MG approximately 4 weeks after initiation of pembrolizumab. On the day of admission, the patient presented with a three-day history of worsening ptosis, right greater than left. He was later found to be seronegative for MG. Management and outcome: The patient required therapy with pyridostigmine, steroids, and agreed to plasma exchange (PLEX) prior to discharge. He achieved near resolution of his neurologic symptoms, and pembrolizumab was discontinued. He later underwent radical resection of the left thigh soft tissue sarcoma and superficial inguinal lymph node dissection. He is now on active surveillance. Discussion: While neurologic adverse events typically present 6 weeks after initiation of ICIs, MG has been reported occurring as early as 4 weeks after initiation. This rare and serious adverse event requires prompt treatment, and clinicians need to be aware of the alternative treatment options in this unique patient population. Early conversations regarding blood products and factions must be had to develop a treatment plan in accordance with the patient's personal decisions. [ABSTRACT FROM AUTHOR]

Pregnancy‐associated atypical hemolytic uremic syndrome (P‐aHUS) is a rare disease. There are only few reports in the literature, and most are in the puerperium period. It is a thrombotic microangiopathy (TMA) characterized for microangiopathic hemolytic anemia, thrombocytopenia, and renal dysfunction. We report the case of a pregnant patient at 26.3 gestation weeks, who developed clinical features of TMA, neurological alterations, and septic shock; then after fetus and placental delivery, no clinical improvement was observed; a diagnostic protocol was performed due to suspicion of P‐aHUS, showing improvement after the plasma exchange sessions and eculizumab. We present here a brief review of the case since it is an entity that needs to be suspected during pregnancy when TMA features and requires an immediate diagnosis to provide timely treatment. [ABSTRACT FROM AUTHOR]

Severe cases of hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome requiring plasma exchange or dialysis should be differentiated from other thrombotic microangiopathy (TMA) and treated appropriately. To evaluate the prevalence and clinical characteristics of such cases in Japan, a questionnaire‐based survey was conducted among obstetricians who are members of the Perinatal Research Network Group in Japan. There were a total of 335 cases of HELLP syndrome over a 3‐year period in the 48 facilities that responded to the survey. Four patients required plasma exchange or dialysis, of which two were diagnosed with atypical hemolytic uremic syndrome and two with TMA secondary to systemic lupus erythematosus. Although such severe HELLP syndrome is rare, identifying the clinical features and making accurate differential diagnosis are critical for optimal clinical outcomes for mothers and neonates. [ABSTRACT FROM AUTHOR]

Background: Antibody‐mediated rejection (ABMR) poses a barrier to long‐term graft survival and is one of the most challenging events after kidney transplantation. Removing donor specific antibodies (DSA) through therapeutic plasma exchange (PLEX) is a cornerstone of antibody depletion but has inconsistent effects. Imlifidase is a treatment currently utilized for desensitization with near‐complete inactivation of DSA both in the intra‐ and extravascular space. Methods: This was a 6‐month, randomized, open‐label, multicenter, multinational trial conducted at 14 transplant centers. Thirty patients were randomized to either imlifidase or PLEX treatment. The primary endpoint was reduction in DSA level during the 5 days following the start of treatment. Results: Despite considerable heterogeneity in the trial population, DSA reduction as defined by the primary endpoint was 97% for imlifidase compared to 42% for PLEX. Additionally, imlifidase reduced DSA to noncomplement fixing levels, whereas PLEX failed to do so. After antibody rebound in the imlifidase arm (circa days 6–12), both arms had similar reductions in DSA. Five allograft losses occurred during the 6 months following the start of ABMR treatment—four within the imlifidase arm (18 patients treated) and one in the PLEX arm (10 patients treated). In terms of clinical efficacy, the Kaplan–Meier estimated graft survival was 78% for imlifidase and 89% for PLEX, with a slightly higher eGFR in the PLEX arm at the end of the trial. The observed adverse events in the trial were as expected, and there were no apparent differences between the arms. Conclusion: Imlifidase was safe and well‐tolerated in the ABMR population. Despite meeting the primary endpoint of maximum DSA reduction compared to PLEX, the trial was unsuccessful in demonstrating a clinical benefit of imlifidase in this heterogenous ABMR population. Trial Registration: EudraCT number: 2018‐000022‐66, 2020‐004777‐49; ClinicalTrials.gov identifier: NCT03897205, NCT04711850 [ABSTRACT FROM AUTHOR]

Background: Plasma exchanges (PEX) and immunosuppression are the cornerstone of management of anti-factor H (FH) antibody-associated atypical hemolytic uremic syndrome (aHUS), particularly if access to eculizumab is limited. The duration of therapy with PEX for anti-FH aHUS is empirical. Methods: We compared the efficacy of abbreviated PEX protocol (10–12 sessions) in a prospective cohort of patients diagnosed with anti-FH aHUS (2020–2022), to standard PEX protocol (20–22 sessions) in a historical cohort (2016–2019; n = 65). Efficacy was defined as 70% decline in anti-FH titers or fall to ≤ 1300 AU/ml at 4 weeks. Patients in both cohorts received similar immunosuppression with oral prednisolone, IV cyclophosphamide (5 doses) and mycophenolate mofetil. Outcomes included efficacy, rates of hematological remission and adverse kidney outcomes at 1, 3 and 6 months. Results: Of 23 patients, 8.2 ± 2.1 years old enrolled prospectively, two were excluded for significant protocol deviation. PEX was abbreviated in 18/21 (86%) patients to 11.5 ± 3.3 sessions. Abbreviation failed for lack of hematological remission by day 14 (n = 2) and persistent neurological manifestations (n = 1). All patients in whom PEX was abbreviated achieved > 70% reduction in anti-FH titers at day 28. The percentage fall in anti-FH titers was similar for the abbreviated vs. standard PEX protocols at 1, 3 and 6 months. At last follow-up, at median 50 months and 25 months for standard and abbreviated cohorts, the estimated GFR was similar at 104.8 ± 29.1 vs. 93.7 ± 53.4, respectively (P = 0.42). Conclusion: Abbreviation of the duration of PEX is feasible and efficacious in reducing anti-FH titers. Short-term outcomes were comparable in patients managed by abbreviated and standard PEX protocols. [ABSTRACT FROM AUTHOR]

Background: Anti‐neutrophil cytoplasmic antibody (ANCA)‐associated vasculitis (AAV) is a rare autoimmune disease which is managed by a range of specialities. There are limited data on treatment practices in Australia and New Zealand. Aims: To understand current patterns of acute AAV treatment in Australia and New Zealand. Methods: An online survey was conducted between July and October 2022 investigating physicians' views on the management of AAV, focusing on induction therapy. The survey contained questions pertaining to access to treatment and responses to clinical management scenarios. Eosinophilic granulomatosis with polyangiitis was not included. A chi‐squared test of independence was performed for statistical analysis. Results: From a total of 55 responses, plasma exchange was difficult to access for 44% of respondents, more so in rural centres, and they also had difficulty accessing infusion centres. New Zealand clinicians had more difficulty accessing rituximab, with only 44% reporting easy access compared with Australian clinicians (93%). With clinical management scenarios, there was variation in the dosing regimen of glucocorticoids and initiation of plasma exchange, with 42% of respondents prescribing a glucocorticoid regimen different from the standard of care, the 'reduced‐dose' arm of the Plasma Exchange and Glucocorticoids for the Treatment of ANCA‐Associated Vasculitis trial. The choice of cyclophosphamide or rituximab for induction therapy was based on patient characteristics and medical history. Conclusions: There is substantial variation in approaches to the acute management of AAV in Australia and New Zealand, including differences in resource availability. This variation in care demonstrates the need to implement current practice guidelines and institute contemporary monitoring of AAV management, to achieve best patient outcomes. [ABSTRACT FROM AUTHOR]

The Heidenhain variant of Creutzfeld-Jakob disease (CJD) is a rare form that initially presents with visual disturbances. In early stages, the presentation can mimic neuromyelitis optica spectrum disorders (NMOSD) and lead to unnecessary treatment modalities. Herein, we describe a case of a 66-year-old man who presented with bilateral vision loss and retro-orbital discomfort. In addition to immunosuppressive therapy, he received 4 rounds of therapeutic plasma exchange after his preliminary diagnosis of NMOSD. We were surprised to note that his condition did not show improvement but deteriorated, with severe neurocognitive symptoms. Eventually, CJD was suspected, and real-time quaking-induced conversion (RT-QuIC) was performed. By the time the diagnosis of Heidenhain variant of CJD was confirmed, the patient was discharged to hospice care and died shortly after. [ABSTRACT FROM AUTHOR]

Current treatment guidelines of myeloma cast nephropathy (MCN) recommend the institution of plasma cell‐directed therapy and consideration of therapeutic plasma exchange (TPE), with the goal of rapid reduction of the serum free light chain (sFLC). However, the role of TPE continues to remain a subject of debate. The goal of this retrospective bi‐institutional study was to evaluate the clinical outcomes of TPE in combination with systemic therapy. Eighty patients were included in this analysis, of whom 72.5% had ≥50% drop in their initial involved sFLC. At 3 months from TPE initiation, the overall hematologic response rate (ORR) was 67.5% with a very good partial response or better (≥VGPR) rate of 40%. At 6 months, ORR was 57.5%, with ≥VGPR rate of 49%. The renal response rate at 3 and 6 months was 47.5% and 43.75%, respectively; the overall renal response rate was 48.75%. On multivariable analysis, every one unit increase in baseline creatinine (odds ratio [OR] 0.76, p = 0.006), and achievement of ≥VGPR (OR 21.7 p < 0.0001) were significantly associated with renal response. Also, a ≥50% drop in sFLC was favorably associated with renal response (OR 3.39, p = 0.09). With a median follow‐up of 36.4 months, the median overall survival (OS) was 11 months. On multivariable analysis, achievement of renal response (hazard ratio [HR] 0.3, p < 0.0001) and newly diagnosed disease (NDMM; HR 0.43, p = 0.0055) were associated with improved OS. Among NDMM patients, those treated with daratumumab‐based regimens had a trend for better OS (p = 0.15), compared to other regimens, but the difference was not significant. At the end of follow‐up, an estimated 40.4% of patients who were on dialysis were able to become dialysis independent. In conclusion, our study highlights the poor survival of patients with MCN. Achievement of early renal response is crucial for prolonged OS, with daratumumab‐based therapies showing promise. [ABSTRACT FROM AUTHOR]

Background: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and glomerulonephritis is uncommon in children. We sought to characterize the histological and clinical features of the disease and report on risk factors for adverse outcomes in a pediatric cohort. Methods: Retrospective single-center cohort of all pediatric (< 20 years) patients diagnosed with ANCA-associated glomerulonephritis (AAGN) by kidney biopsy between 2002 and 2022 at Johns Hopkins University. Histological and clinical features were extracted from the medical record. Clinical, laboratory, and histological findings were analyzed to determine the association with kidney failure (KF) and/or death. Results: A total of 17 patients were identified (GPA n = 7, MPA = 10) with a median age of 15 years (IQR 12–17) at presentation, a slight female predominance (59%), with seven patients reaching the composite outcome of death (n = 1) or kidney failure (n = 6). There was no difference in presenting clinical symptoms or extra-renal manifestations between the two groups. Univariable Cox regression identified several factors associated with an increased hazard of endpoint including the degree of global or segmental sclerosis, interstitial fibrosis and tubular atrophy (IFTA), C3 and C1q staining, presence of subendothelial deposits, and proteinuria. Multivariable regression was not performed due to the small sample size. We saw a trend towards increased utilization of plasma exchange and a decrease in cyclophosphamide utilization in the more recent era. There was no association between treatment modality and outcome. Conclusions: Pediatric AAGN is a rare disease associated with significant morbidity. We identified glomerulosclerosis and IFTA on histology, and proteinuria on initial presentation as risk factors for KF/death. [ABSTRACT FROM AUTHOR]

Introduction: Therapeutic plasma exchange (TPE), an effective method to eliminate harmful soluble mediators associated with tissue injury, serves as a crucial intervention for systemic rheumatologic diseases (SRDs). However, its value in critically ill SRDs remains uncertain. This retrospective study aims to evaluate the efficacy of TPE in SRDs. Methods: Critically ill SRD patients admitted to the department of intensive care unit of a large tertiary hospital receiving TPE from January 2011 to December 2019 were included. Results: A total of 91 critically ill SRD patients received TPE were enrolled. Their mean age was 47.67 ± 16.35 years with a female predominance (n = 68). Significant decrease in SOFA score post‐TPE treatment was observed (p < 0.05). There were no TPE‐related fatalities. Improvement was observed in 64 (70.32%) patients. Conclusion: This study shows favorable clinical outcomes. TPE may be an acceptable treatment option for critically ill SRD patients. [ABSTRACT FROM AUTHOR]

Introduction: Therapeutic plasma exchange (TPE) is used in a wide spectrum of diseases in critically ill pediatric patients. We aim to review the indications, complications, safety, and outcomes of critically ill children who received TPE. Methods: All of the TPE procedures performed in a pediatric intensive care unit providing tertiary care during 19 years (January 2013–January 2023) were evaluated retrospectively. A total of 154 patients underwent 486 TPE sessions. Results: Median age was 6 years (2–12.5) and 35 children had a body weight of <10 kg (22.7%). Number of organ failure was 4 (2–6). Liver diseases were the most common indication for TPE (31.2%) followed by sepsis with multiorgan dysfunction syndrome (27.3%). Overall survival rate was 72.7%. The highest mortality was observed in hemophagocytic lymphohistiocytosis group. Non‐survivors had significantly higher number of organ failure (p < 0.001), higher PRISM score (p < 0.001), and higher PELOD score on admission (p < 0.001). Adverse events were observed in 68 (13.9%) sessions. Hypotension (7.8%) and hypocalcemia (5.1%) were the most frequent adverse events. Conclusion: TPE is safe for critically ill pediatric patients with experienced staff. Survival rate may vary depending on the underlying disease. Survival decreases with the increase in the number of failed organs. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to compare the efficacy of limited plasma exchange against supportive and standard treatments in treatment of Guillain-Barré syndrome (GBS). Method: A total of 90 GBS patients admitted to Yangon General Hospital, Yangon, Myanmar were recruited over 1.5-year-period from January 2017 to June 2018 and they were divided into 3 groups according to the treatment they received (convenience sampling method): supportive (n=36), limited plasma exchange (LPE) (n=35) and standard (therapeutic plasma exchange - TPE or IVIg) (n=19)). Their clinical features, electrophysiological subtypes and severity were compared at baseline, and outcome (change in GBS disability score (GDS) at 30 days after entry) was assessed and compared. Results: Baseline characteristics such as gender, GBS subtypes and respiratory involvement were comparable, but standard treatment group had older patients, and LPE group had shorter latency to nadir and more cases with antecedent diarrhea, which are poor outcome predictors. At 30 days from entry, mean GDS improvement was 0.9 + 0.6 in supportive, 1.4 + 0.6 in LPE and 1.2 + 0.8 in standard treatment groups respectively. The difference between LPE and supportive treatment was statistically significant (p 0.002) but there was no difference between LPE and standard treatment (p = 0.512). Regarding untoward effects, apart from one transient hypotension and 2 anemic cases, no other serious adverse effects were noted from LPE therapy. Conclusion: LPE may be superior to supportive treatment and may not be inferior to standard treatment. Therefore, LPE may be an alternative effective treatment for GBS patients who are not accessible to standard treatments especially in low income countries with limited resources. [ABSTRACT FROM AUTHOR]

Thrombotic thrombocytopenic purpura (TTP) is a life‑threatening disease present with the classic pentad of microangiopathic hemolytic anemia (MAHA), fever, neurologic changes, thrombocytopenia, and renal dysfunction. In a diagnostic dilemma, therapeutic plasma exchange (TPE) is a choice of life‑saving intervention. In this, we assess the efficacy of TPE in a suspected case of post‑partum TTP. A 27 years old female was admitted in an emergency on day 8 after a lower segment cesarian section (LSCS) with unresponsive behavior for 3 days and with TTP. She was normal 32 days back with her second, 7‑month pregnancy. Ultrasonography (USG) showed an umbilical cord around the neck of the baby. On the fifth post‑operative day, she was shifted to emergency with fever, generalized anasarca, gastrointestinal tract (GI) bleeding, low platelet count, and low Hb, with a poor Glasgow coma scale (GCS) of 6. On the bases of serum urea and serum creatinine, she presented acute kidney injury with encephalopathy. At emergency, she was unresponsive to mechanical ventilation and supportive treatment; hence, therapeutic plasma exchange was performed. After eight TPE cycles, the patient presented with an improved hematological and renal profile with good GCS. TPE is helpful and life‑saving for suspected TTP patients with AKI. [ABSTRACT FROM AUTHOR]

Background: Plasma exchange (PLEX) therapy is indicated for several disorders. The 5% albumin is often used as a sole replacement fluid during most PLEX. However, each 1.0 plasma volume exchange depletes coagulation factors by ~65%. Although most coagulation factors recover to hemostatic levels within 24 h post‐PLEX, fibrinogen requires 48–72 h to recover. Fibrinogen is the key coagulation protein for hemostasis. Therefore, fibrinogen is often monitored during the acute course of PLEX, and plasma is supplemented to prevent bleeding if fibrinogen is <100 mg/dL. Study Design and Methods: We conducted a prospective, single‐center, observational study to evaluate bleeding risk in adults who received an acute course of PLEX with a fibrinogen level of 80–100 mg/dL without plasma supplementation during the procedure or before central venous catheter removal. The study group was compared to patients with plasma fibrinogen >100 mg/dL. Results: Among the 275 patients who received 1406 PLEXes, 62 patients (23%) who underwent 323 PLEXes met the inclusion criteria, and only 2 (3%) patients had bleeding while on oral anticoagulants. In contrast, out of 275 patients, 143 (52%) with fibrinogen levels >100 mg/dL received 751 PLEX treatments, and bleeding occurred in 2 (1%) while on low‐molecular‐weight heparin. Conclusions: Our findings suggest that a pre‐procedure fibrinogen threshold of 80–100 mg/dL without plasma supplementation does not increase bleeding risk unless patients were on anticoagulation. See editorial on page 959–962, in this issue [ABSTRACT FROM AUTHOR]

Background: Antiphospholipid syndrome (APLS) is rarely complicated by catastrophic antiphospholipid syndrome (CAPS). Peripartum CAPS is rarer still and can masquerade as other obstetric disorders. A high degree of suspicion is critical for early diagnosis and specific management given the significant morbidity and mortality associated with this disorder. Case: We report a case of a 27-year-old at 22 week's gestation with a history of APLS found to have severe hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome, resulting in termination of pregnancy. Further workup revealed the diagnosis of CAPS followed by prompt treatment with triple therapy leading to clinical improvement. Conclusion: CAPS should be considered within the differential in an obstetric patient with a history of APLS who has evidence of multiorgan involvement with macro- or microvascular thrombosis. Although this may mimic alternative disorders, prompt diagnosis is imperative for appropriate therapy and reduction in maternal morbidity and mortality. [ABSTRACT FROM AUTHOR]

• ABO-incompatible liver transplantation often needs therapeutic plasma exchange (TPE). • Our patient experienced an anaphylactic reaction to fresh frozen plasma during TPE. • Successful management was achieved through a multidisciplinary approach. ABO-incompatible living donor liver transplantation (ABOi LDLT) is a complex procedure involving the reduction of anti-A and anti-B antibodies by therapeutic plasma exchange (TPE) to prevent acute antibody-mediated rejection. Fresh frozen plasma (FFP) is often used as replacement fluid during TPE. We report an ABOi LDLT case in which the patient experienced an anaphylactic reaction to FFP during TPE. Additional TPE was performed using 5% albumin as replacement fluid. ABOi LDLT was successfully performed by adapting the transfusion strategy to avoid FFP and cryoprecipitate and to administer washed platelets. This case highlights the importance of careful preoperative assessment, multidisciplinary coordination, and individualized approaches in ABOi LDLT, especially when the patient has an anaphylactic reaction to FFP. [ABSTRACT FROM AUTHOR]

Introduction: Therapeutic plasma exchange (TPE) is used for treating refractory Kawasaki disease (KD); however, there are few reports on its use in small children. Methods: Nine children with refractory KD who underwent TPE between January 2010 and December 2022 were retrospectively investigated. Data on patient demographics, inflammatory markers, coronary artery lesions (CALs), TPE settings and complications, and outcomes were examined. Results: A total of 37 TPE sessions were performed on nine patients, with 3–6 sessions per patient. The median body weight was 8.9 kg. C‐reactive protein, white blood cell (WBC), and interleukin‐6 levels significantly decreased (p < 0.05). Of the 33 coronary arteries with CALs before TPE, 44% and 3% had CALs at 1 month and 1 year after TPE, respectively. Minor complications, such as mild hypocalcemia and naturally recovering coagulopathy, occurred without serious complications. Conclusions: TPE for refractory KD may be safe and effective in preventing CALs. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to evaluate the safety and efficacy of therapeutic plasma exchange (TPE) in pediatric acute liver failure (PALF). Methods: All children aged 2‐18 years with PALF were included. The intervention cohort included a subset of PALF patients undergoing complete three sessions of TPE, whereas the matching controls were derived by propensity score matching from the patient cohort who did not receive any TPE. Propensity matching was performed based on the international normalized ratio (INR), grade of hepatic encephalopathy (HE), age, bilirubin, and ammonia levels. The primary outcome measure was native liver survival (NLS) in the two arms on day 28. Results: Of the total cohort of 403 patients with PALF, 65 patients who received TPE and 65 propensity‐matched controls were included in analysis. The 2 groups were well balanced with comparable baseline parameters. On day 4, patients in the TPE group had significantly lower INR (P = 0.001), lower bilirubin (P = 0.008), and higher mean arterial pressure (MAP) (P = 0.033) than controls. The NLS was 46.15% in the TPE arm and 26.15% in the control arm. The overall survival (OS) was 50.8% in the TPE arm and 35.4% in the control arm. Kaplan‐Meier survival analysis showed a significantly higher NLS in patients receiving TPE than controls (P = 0.001). On subgroup analysis, NLS benefit was predominantly seen in hepatitis A‐related and indeterminate PALF. Conclusion: TPE improved NLS and OS in a propensity‐matched cohort of patients with PALF. Patients receiving TPE had lower INR and bilirubin levels and higher MAP on day 4. [ABSTRACT FROM AUTHOR]

Objective: To determine the clinical characteristics, indications, technical aspects, complications, and outcomes of therapeutic plasma exchange (TPE) procedures performed in pediatric patients with neurologic and nonneurologic diseases at the Philippine Children's Medical Center during a 12‐year period (January 2010–March 2023). Materials and Methods: All TPE performed between January 2010 and March 2023 were retrospectively evaluated. The indications for TPE were classified according to the 2019 American Society for Apheresis (ASFA) categorization. Results: Fifty‐seven patients underwent a total of 297 TPE procedures. The median age was 12 years (2–18), with 51% male (n = 29) and 49% female (n = 28). The most common indication was N‐methyl‐d‐aspartate receptor antibody encephalitis, accounting for 54% of cases (n = 31), followed by Guillain‐Barré syndrome at 16% (n = 9), Hemolytic Uremic Syndrome at 7% (n = 4), and Sepsis with multiorgan failure at 7% (n = 4). Forty‐one patients (71.8%) were classified under ASFA category 1, seven (12.4%) as category II, and nine (15.8%) as category III. All TPE procedures were conducted using the centrifugation technique and citrate anticoagulation. Ninety‐nine percent of the procedures were performed through the internal jugular vein. Albumin was utilized as a replacement fluid in 88% of the procedures. Most complications were related to patient factors and occurred in 10% of cases (n = 31), while problems associated with the extracorporeal circuit were observed in only 4.37% of cases (n = 13). Overall response rate was 91% and there was no TPE‐related deaths. No clear association was found between clinical responses to TPE and specific diagnoses within ASFA categories. Conclusion: TPE is a safe and effective adjuvant treatment for pediatric patients with neurologic and nonneurologic diseases. The outcome in these patients requiring TPE is excellent. However, response varies with failed organs and the need for life‐sustaining therapies. [ABSTRACT FROM AUTHOR]

Background: Severe fever with thrombocytopenia syndrome (SFTS) is a zoonotic infectious disease caused by the severe fever with thrombocytopenia syndrome virus (SFTSV). Endemic in East Asia, SFTS is characterized by an exceptionally high mortality rate. Presently, there is no established treatment for SFTS, particularly for patients in critical condition. In this study, we collected and analyzed laboratory and clinical data from 92 critically ill patients with SFTS treated at Weihai Municipal Hospital between 2019 and 2022. We hope that our study will provide some hints for the treatment of critically ill patients with SFTS. Methods: A total of 92 critically ill patients with SFTS were included in this study. Of these patients, 45 received treatment with therapeutic plasma exchange (TPE) and ribavirin (referred to as the TPE group), while the remaining patients received only ribavirin (referred to as the non‐TPE group). Clinical and laboratory parameters were analyzed retrospectively. Results: The results showed significant improvements in multiple laboratory parameters following treatment with TPE and ribavirin, including white blood cell and neutrophil count, lactate dehydrogenase, creatine kinase isoenzyme‐MB, prothrombin time, activated partial thromboplastin time, D‐Dimer, serum sodium and copies of virus genomes. The combination of TPE with ribavirin demonstrated a significant reduction in mortality rates, with a mortality rate of 20.0% in the TPE group compared to 40.4% in the non‐TPE group (P = 0.033). Conclusions: Our findings suggest that critically ill patients with SFTS who received TPE and ribavirin experienced improvements in both clinical and laboratory parameters. These results indicate that TPE combined with ribavirin may represent a promising novel therapeutic approach for managing critically ill patients with SFTS. However, comparative studies of large sample size or randomized clinical trials are warranted to confirm the effectiveness of this combination therapy in the treatment of severe SFTS cases. [ABSTRACT FROM AUTHOR]

Anti‐PP1PK alloimmunization is rare given ubiquitous P1PK expression. Prevention of recurrent miscarriages and hemolytic disease of the fetus and newborn (HDFN) in pregnant individuals with anti‐PP1PK antibodies has relied upon individual reports. Here, we demonstrate the successful management of maternal anti‐PP1PK alloimmunization in a 23‐year‐old, G2P0010, with therapeutic plasma exchange (TPE), intravenous immunoglobulin (IVIG), and monitoring of anti‐PP1Pk titers. Twice‐weekly TPE (1.5 plasma volume [PV], 5% albumin replacement) with weekly titers and IVIG (1 g/kg) was initiated at 9 weeks of gestation (WG). The threshold titer was ≥16. Weekly middle cerebral artery‐peak systolic velocities (MCA‐PSV) for fetal anemia monitoring was initiated at 16 WG. PVs were adjusted throughout pregnancy based on treatment schedule, titers, and available albumin. Antigen‐negative, ABO‐compatible RBCs were obtained through the rare donor program and directed donation. An autologous blood autotransfusion system was reserved for delivery. Titers decreased from 128 to 8 by 10 WG. MCA‐PSV remained stable. At 24 WG, TPE decreased to once weekly. After titers increased to 32, twice‐weekly TPE resumed at 27 WG. Induction of labor was scheduled at 38 WG. Vaginal delivery of a 2950 g neonate (APGAR score: 9, 9) occurred without complication (Cord blood: 1+ IgG DAT; Anti‐PP1Pk eluted). Newborn hemoglobin and bilirubin were unremarkable. Discharge occurred postpartum day 2. Anti‐PP1Pk alloimmunization is rare but associated with recurrent miscarriages and HDFN. With multidisciplinary care, a successful pregnancy is possible with IVIG and TPE adjusted to PV and titers. We also propose a patient registry and comprehensive management plan. [ABSTRACT FROM AUTHOR]

Gemtuzumab ozogamicin (GO) is a CD33 monoclonal antibody‐drug conjugate currently in use to treat myeloid malignancies. A unique adverse effect of this medication is destruction of CD33 positive macrophages resulting in reduced clearance of free hemoglobin leading to grossly red plasma. This build‐up of free hemoglobin can potentially lead to end organ damage and prevent performance of clinically necessary laboratory evaluation. We present a case of a pediatric patient who developed this adverse effect and was successfully treated with therapeutic plasma exchange (TPE). We also present results from a systematic review of the medical literature and share data from a query of the United States Food and Drug Administration (FDA) Adverse Event Reporting system for GO‐related hemoglobin scavenging impairment. Among reported cases, patients undergoing TPE and those receiving steroids had improved outcomes. Practitioners should be aware of this rare drug side‐effect and the potential utility of TPE for these patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Acute liver failure (ALF) following yellow phosphorous (YP) ingestion is similar to acetaminophen‐induced ALF and it has become a public concern in our region. This study assessed low volume therapeutic plasma exchange (LV‐TPE) efficacy in improving the transplant free survival in YP poisoning. Methods: Adult patients with toxicology reports of YP and ALF requiring critical care were included in the study. LV‐TPE was planned for three consecutive days and three more if required. Performed 1.3 to 1.5 plasma volume replacing with 0.9% normal saline, 5% human albumin solution, and fresh frozen plasma based on ASFA 2019 criteria. MELD score, laboratory parameters, LV‐TPE details were captured. The study end point was clinical outcome of the patients. Results: Among 36 patients, 19 underwent LV‐TPE and 17 opted out of LV‐TPE and they were included as a control arm. The MELD score was 32.64 ± 8.05 and 37.83 ± 9.37 in both groups. There were 13 survivors in LV‐TPE group leading to a 68.42% reduction in mortality. The coagulation and biochemical parameters showed a significant percentage change after LV‐TPE. Refractory shock, delay in initiating procedure and acidosis were independent predictors of mortality. Conclusion: A well‐timed LV‐TPE improves the survival of patients with ALF due to YP poisoning. [ABSTRACT FROM AUTHOR]

Myasthenia gravis (MG) is an autoimmune disorder characterized by fluctuating muscle weakness. Severe patients may develop life-threatening respiratory failure and experience crisis. Plasma exchange or intravenous immunoglobulin (IVIg) is the first-line treatment option for myasthenia crisis, but some patients still poorly respond to them. Here, we first reported a generalized MG patient from China who was in a state of impending myasthenic crisis and did not respond effectively to IVIg but was successfully rescued by add-on efgartigimod. Especially, we also detected meaningful changes in T-cell and B-cell subsets after efgartigimod, promoting a potential role of efgartigimod in re-establishing immune homeostasis. [ABSTRACT FROM AUTHOR]

Background/aim: Therapeutic plasma exchange (TPE) is an extracorporeal treatment method that removes large molecular weight substances from plasma. In our study, we aimed to retrospectively examine the indications and procedural methods of the patients who had undergone TPE, and the complications that occurred during the procedure. Materials and methods: Forty-one patients who were monitored in thePICU of Gazi Yaşargil Training and Research Hospital and had indications for TPE between 2017 and 2021 were included in the study. Laboratory parameters were checked before and after the TPE procedure. In addition to these, patients’ diagnosis, weight, type of procedure and type of device, where the procedure was performed, duration of the procedure, amount of blood and plasma processed, complications, number of procedures, and death during the procedure or independent of the procedure were evaluated. Results: The median age was 93.0 (14.0–167.0) months. Hemolytic uremic syndrome (HUS) was the most common TPE indication with nine patients. The most common complication related to TPE was fever (11 patients), while no complication was observed in 18 patients. When laboratory results were evaluated according to American Society for Apheresis (ASFA) categories, a significant improvement was observed in the values of platelet, AST, ALT, LDH, urea, and creatinine in ASFA1 after TPE. No significant improvement was observed in ASFA2 (p > 0.05). In ASFA3, a significant improvement was observed in INR, AST, ALT, LDH, total bilirubin, creatinine, pH, and lactate values after TPE (p < 0.05). Five patients died from ASFA1, one from ASFA2, and three patients from ASFA3. Conclusion: Since significant adjustments are observed in clinical and laboratory values in sepsis-MOF, which is in the ASFA3 category, we believe that it should be evaluated in the ASFA2 or ASFA1 category in the early treatment of these diseases. In addition, we think that MIS-C cases, which have not been in any category according to ASFA, should be included in the ASFA2 or ASFA3 category, considering our TPE results. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and Aims: Acute‐on‐chronic liver failure (ACLF) is a serious illness associated with altered metabolome, organ failure and high mortality. Need for therapies to improve the metabolic milieu and support liver regeneration are urgently needed. Methods: We investigated the ability of haemoperfusion adsorption (HA) and therapeutic plasma exchange (TPE) in improving the metabolic profile and survival in ACLF patients. Altogether, 45 ACLF patients were randomized into three groups: standard medical therapy (SMT), HA and TPE groups. Plasma metabolomics was performed at baseline, post‐HA and TPE sessions on days 7 and 14 using high‐resolution mass spectrometry. Results: The baseline clinical/metabolic profiles of study groups were comparable. We identified 477 metabolites. Of these, 256 metabolites were significantly altered post 7 days of HA therapy (p <.05, FC > 1.5) and significantly reduced metabolites linked to purine (12 metabolites), tryptophan (7 metabolites), primary bile acid (6 metabolites) and arginine‐proline metabolism (6 metabolites) and microbial metabolism respectively (p <.05). Metabolites linked to taurine‐hypotaurine and histidine metabolism were reduced and temporal increase in metabolites linked to phenylalanine and tryptophan metabolism was observed post‐TPE therapy (p <.05). Finally, weighted metabolite correlation network analysis (WMCNA) along with inter/intragroup analysis confirmed significant reduction in inflammatory (tryptophan, arachidonic acid and bile acid metabolism) and secondary energy metabolic pathways post‐HA therapy compared to TPE and SMT (p <.05). Higher baseline plasma level of 11‐deoxycorticosterone (C03205; AUROC > 0.90, HR > 3.2) correlated with severity (r2 > 0.5, p <.05) and mortality (log‐rank‐p <.05). Notably, 51 of the 64 metabolite signatures (ACLF non‐survivor) were reversed post‐HA treatment compared to TPE and SMT(p <.05). Conclusion: HA more potentially (~80%) improves plasma milieu compared to TPE and SMT. High baseline plasma 11‐deoxycorticosterone level correlates with early mortality in ACLF patients. [ABSTRACT FROM AUTHOR]

Objective: To describe a case of bifenthrin toxicosis in a dog with a successful outcome following the use of therapeutic plasma exchange (TPE) and intralipid therapy. Case Summary: An 8‐month‐old female neutered poodle mix dog ingested an unknown amount of powered bifenthrin, which resulted in acutely altered mentation, cranial nerve deficits, and intractable tremors that persisted in severity despite aggressive medical management to include intravenous fluids, intravenous lipid emulsion, anticonvulsant medications, and methocarbamol. TPE was initiated after lack of significant clinical improvement 12 hours after initial presentation. The dog underwent cardiopulmonary arrest (CPA) following approximately 1 plasma volume equivalent exchange. The dog was successfully resuscitated and showed marked improvement 12 hours postarrest and post‐TPE treatment. Serum bifenthrin concentrations were analyzed prior to TPE (445.38 ng/mL) and ∼10 hours after TPE (51.18 ng/mL), which resulted in an 89% reduction in serum bifenthrin concentration. New Information: TPE may be a promising adjunctive therapeutic modality for bifenthrin toxicosis in dogs. [ABSTRACT FROM AUTHOR]

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