The Role of Plasmapheresis in Severe Leptospirosis Refractory to Standard Therapy: A Case Report and a Comprehensive Literature Review.

Leptospirosis, a zoonotic infection prevalent in Pakistan, presents diverse clinical manifestations ranging from mild flu-like symptoms to severe multiorgan failure known as Weil's disease. This case study reports on a 24-year-old woman with leptospirosis complicated by acute kidney injury and hyperbilirubinemia, unresponsive to standard therapies. Despite initial treatment with antibiotics and hemodialysis, her condition deteriorated. Following a single session of plasmapheresis, marked clinical and laboratory improvements were observed. Notably, plasma exchange effectively reduced bilirubin levels, underscoring its potential benefit in severe leptospirosis. This case highlights the role of plasmapheresis as rescue therapy in critically ill patients, demonstrating significant outcomes in cases resistant to conventional management. Further research is warranted to refine guidelines on the optimal timing and frequency of plasma exchange in such settings.

Bilateral Cerebellar Hemorrhages: An Atypical Presentation of Acute Hemorrhagic Encephalomyelitis.

Hurst disease, or Weston-Hurst syndrome, or acute hemorrhagic encephalomyelitis (AHEM), is an infrequent condition that usually gets provoked after a viral infection (respiratory tract infection) or, as reported in many case reports, post-vaccination. Hurst disease is a difficult-to-diagnose condition because it mimics common presentations such as stroke, decreased or loss of consciousness, brain abscess, and seizures, making clinical diagnosis challenging. Radiological imaging, such as magnetic resonance imaging (MRI) of the brain with diffusion-weighted imaging, now serves as the primary modality to identify such conditions, despite its lack of specificity. The treating doctor needs to do an in-depth analysis of the patient's history, as this carries a very high mortality rate. We hereby discuss a case that presented with seizures and deteriorating Glasgow Coma Scale (GCS) score, on imaging revealed posterior circulation acute hemorrhagic leukoencephalitis (AHLE)/AHEM, therein treated with steroids, plasmapheresis resulted in a good outcome implicating, early detection and timely management can reduce the mortality due to this condition.

A Case of Delayed and Persistent Carbamazepine Overdose Treated With Hemodialysis, Plasmapheresis, and Neostigmine.

Carbamazepine is utilized for various indications. Due to its pharmacokinetic profile and drug properties, toxicity can be delayed and persistent despite supportive care. We report a severe case of intentional carbamazepine toxicity in a carbamazepine naive individual mimicking brain death that was not diagnosed until three days after consumption of carbamazepine when the patient was comatose. Symptoms of overdose persisted for several days despite attempted treatment with activated charcoal and whole bowel irrigation, hemodialysis, and plasmapheresis. Symptoms only began to improve with bowel evacuation as a result of administration of neostigmine intravenously plus hemodialysis and plasmapheresis additionally. Despite previous literature that reported success with hemodialysis and/or plasmapheresis we did not find either to be overly effective in our case possibly due to lack of ability to perform multidose activated charcoal and whole bowel irrigation. To our knowledge this is one of the few cases of carbamazepine overdose utilizing both hemodialysis and plasmapheresis but without activated charcoal and the only case report in which neostigmine was administered as an attempt to remove drug via the gastrointestinal tract with success.

Management of Severe Pain in a Case of Sensory Guillain-Barre Syndrome.

Guillain-Barre syndrome (GBS) is an acute post-infectious polyradiculoneuropathy characterized by autoantibodies targeting host antigens, resulting in nerve fiber demyelination and axonal degeneration. While symmetric ascending weakness is typical, neuropathic pain is a common yet variable manifestation. We present a case of a 52-year-old man with progressive bilateral leg weakness and severe neuropathic pain following a flu-like illness. Despite conventional analgesics, his pain persisted, necessitating a unique pain management approach. The patient's examination revealed hyporeflexia and sensory deficits consistent with GBS. Diagnostic workup, including lumbar puncture, showed albuminocytologic dissociation. Plasma exchange therapy was initiated, but severe nocturnal neuropathic pain persisted, exacerbating during treatment. Conventional pain medications were ineffective, prompting a multimodal approach. Combining hydromorphone and lorazepam provided significant pain relief, enabling completion of plasmapheresis sessions. This regimen, supplemented with gabapentin, proved effective in managing both GBS-associated and treatment-induced pain. This case underscores the debilitating nature of GBS-related pain and the importance of tailored pain management strategies. While conventional agents may fail, a multimodal approach, including opioids and adjunctive medications, can offer relief, facilitating essential treatments like plasmapheresis. Careful monitoring is imperative to mitigate risks associated with potent analgesics. Our experience contributes to the armamentarium for managing GBS-related pain, emphasizing individualized care to improve patient outcomes.

Childhood Transverse Myelitis with Atypical Fever Presentation: A Case Report.

Transverse myelitis (TM) is a rare inflammatory spinal cord disorder, particularly uncommon in children. It is characterized by symptoms such as motor weakness, sensory disturbances, and autonomic dysfunction. This report describes a 10-year-old male presenting with bilateral lower limb weakness, urinary and fecal incontinence, and high-grade fever. Initial treatment at a local hospital with corticosteroids and antibiotics did not yield significant improvements, prompting advanced care at a tertiary facility. A magnetic resonance imaging (MRI) confirmed a longitudinally extensive TM lesion. Subsequent management with plasmapheresis led to satisfactory clinical improvement. This case highlights the importance of early consideration of TM in pediatric patients with acute neurological deficits and supports the use of aggressive therapeutic strategies for better outcomes.

Repeated apheresis donations cause important iron deficiency in male Japanese donors.

BACKGROUND AND OBJECTIVES: In Japan, apheresis donation of plasma is allowed to a maximum of 24 times a year, and plateletpheresis are counted as two plasmapheresis donations. Diversion of the initial blood flow is conducted for all donations, and additionally, blood remaining in apheresis machine circuit is lost. Here, we aimed to investigate on the health impact of frequent apheresis donations, as measured by the serum ferritin (sFer). MATERIALS AND METHODS: A total of 538 male apheresis donors and 538 age-matched whole blood (WB) donors, who gave informed consent to join the study, were enrolled. sFer were compared, according to age. Another group of 19 apheresis donors were followed during four consecutive donations. RESULTS: About half (48%) of repeat male apheresis donors had iron deficiency (sFer < 26 ng/mL), compared with lower rates (13.9%) among male WB donors. It was evident in all age groups, except for teenagers, possibly because of the lower number of donations. Follow-up of the 19 donors for 4 months revealed a progressive decrease in sFer. CONCLUSION: Blood remaining in the apheresis machine circuit and diversion of the initial blood flow have been implicated in iron deficiency for many years. Taking the present results, the manufacturer of apheresis equipment was requested to improve it to allow rinseback of the remaining blood, which was achieved only for plateletpheresis. Until further improvement, plasmapheresis frequency was reduced to 12 times a year. Additional measures, such as oral supplementation of iron, need to be considered.

Other Immunomodulatory Treatment for Cytokine Storm Syndromes.

Cytokine storm syndromes (CSS) include different entities such as macrophage activation syndrome, primary and secondary hemophagocytic lymphohistiocytosis (HLH), and multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19. An effective management strategy is critical in CSS. While biologics have become an essential part of CSS treatment, hematopoietic stem cell transplantation (HSCT) has changed the fate of primary HLH patients. This chapter will focus on the available alternative immunomodulatory therapies in CSS, which include corticosteroids, cyclosporine A, intravenous immunoglobulin, interleukin 18 binding protein, therapeutic plasmapheresis, HSCT, and mesenchymal stromal cell-based therapies.

HemoClear: A Practical and Cost-Effective Alternative to Conventional Convalescent Plasma Retrieval Methods.

Convalescent plasma has increasingly been used to treat various viral infections and confer post-exposure prophylactic protection during the last decade and has demonstrated favorable clinical outcomes in patients infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) during the recent COVID-19 pandemic. The pandemic has highlighted the need for cost-effective, accessible, and easy-to-use alternatives to conventional blood plasmapheresis techniques, allowing hospitals to become more self-sufficient in harvesting and transfusing donor plasma into recipients in a single setting. To this end, the use of a membrane-based bedside plasmapheresis device (HemoClear) was evaluated in an open-label, non-randomized prospective trial in Suriname in 2021, demonstrating its practicality and efficacy in a low-to middle-income country. This paper will review the use of this method and its potential to expedite the process of obtaining convalescent plasma, especially during pandemics and in resource-constrained settings.

Effects of Rheopheresis in dialysis patients with peripheral artery disease and diabetic foot ulcers: A multicentric Italian study.

BACKGROUND: Peripheral artery disease (PAD) in hemodialysis (HD) patients has a significant social impact due to its prevalence, poor response to standard therapy and dismal prognosis. Rheopheresis is indicated by guidelines for PAD treatment. MATERIALS AND METHODS: Twenty-five HD patients affected by PAD stage IV Lerichè-Fontaine and ischemic ulcer 1C or 2C according to the University of Texas Wound Classification System (UTWCS), without amelioration after traditional medical therapy and/or revascularization, were selected and underwent 12 Rheopheresis sessions in 10 weeks. Improvements in pain symptoms using Numerical Rating Scale (NRS), healing ulcers and laboratory hemorheological parameters have been evaluated. RESULTS: A clinically and statistically significant mean value reduction and of relative percentage differences between estimated marginal means (Δ), calculated at each visits, of NRS was observed, with a maximum value (-48.5%) between the first and last visit. At the end of the treatment period 14.3% of ulcers were completely healed, 46.4% downgraded, 53.6% were stable. Overall, no ulcers upgraded. A statistically significant reduction of the Δ, between the first and last visit, for fibrinogen (-16%) was also observed. CONCLUSION: Rheopheresis reduced overall painful symptoms; data suggest that it could heal or improve ulcers and hemorheological laboratory parameters in HD patients with PAD and ischemic ulcers resistant to standard therapies.

Effect of preoperative autologous platelet-rich plasmapheresis on postoperative bleeding in patients undergoing heart valve surgery.

Background: Cardiovascular surgeries often require deep hypothermic circulatory arrest and cardiopulmonary bypass (CPB), which can disrupt blood clotting and lead to excessive bleeding. Traditional treatments involve transfusing blood and blood products, which can have adverse effects and place significant strain on the global blood supply. Research suggests that autologous platelet-rich plasmapheresis (aPRP) may reduce the need for transfusions by preserving blood components. However, the impact of aPRP on postoperative blood loss and clinical outcomes in cardiovascular surgery remains controversial. This study aimed to examine the effects of aPRP on postoperative blood loss and recovery in patients undergoing heart valve surgery. Methods: A total of 183 patients were divided into either aPRP or control groups. The aPRP group received aPRP before CPB, whereas the control group did not. The primary endpoint was postoperative bleeding between the groups. The secondary endpoints were postoperative bleeding risk factors and clinical outcome assessment. Logistic regression analysis with covariate adjustment was used to calculate these risk factors. Results: A total of 76 patients (41.5%) in the aPRP group and 107 patients (58.5%) in the control group were included in the analysis. No significant difference was found in the occurrence of postoperative bleeding [odds ratio (OR) =0.53, 95% confidence interval (CI): 0.28-1.00, P=0.05], and the aPRP group had fewer complications than the controls (OR =0.28, 95% CI: 0.10-0.68, P=0.009). However, after adjusting for the New York Heart Association (NYHA) classification, diabetes, arrhythmology, mean activated clotting time (ACTmean), CPB, bleeding, thoracotomy, and body mass index (BMI), there was a significant difference in postoperative bleeding (adjusted OR =0.47, 95% CI: 0.22-0.98, P=0.04) and complications (adjusted OR =0.23, 95% CI: 0.07-0.64, P=0.008) between the two groups. Conclusions: Preoperative aPRP can improve postoperative outcomes and reduce complications in patients undergoing heart valve surgery.

An Unusual Case of Neurofascin 186 Neuropathy.

Among the diverse array of neuropathies, autoimmune neuropathy stands out as a distinctive subset, where the body's immune system mistakenly attacks its nerve tissues, triggering inflammation and nerve damage. NF 186, also known as neurofascin 186, is a cell adhesion molecule crucial for the integrity and functioning of the peripheral nervous system. This case report highlights the clinical presentation specific to NF 186-positive autoimmune neuropathy and also the treatment modalities.

Therapeutic plasma exchange for hyperviscosity syndrome in IgA multiple myeloma.

Hyperviscosity syndrome (HVS) is defined as the symptomatic presentation of increased blood thickness due to various clinical conditions such as hypergammaglobulinemia. HVS secondary to immunoglobulin (Ig)A multiple myeloma has been infrequently reported. Although the efficiency of IgM or IgG removal by therapeutic plasma exchange (TPE) is well described, the efficiency of IgA removal by TPE is not as well known. Here, we describe a case of HVS due to IgA myeloma in a patient who received 2 TPE treatments, with subsequent symptomatic improvement as well as decrease in IgA and viscosity levels.

A Case of Secondary Autoimmune Hemolytic Anemia Successfully Treated With Rituximab.

Secondary cold agglutinin autoimmune hemolytic anemia (AIHA) occurs most commonly due to infectious causes like Mycoplasma pneumonia and, more rarely, Epstein-Barr virus(EBV). Here we present a case of a 69-year-old female presenting with generalized weakness, who was found to have cold agglutinin hemolytic anemia. She unfortunately experienced some of the most severe complications of the disease including encephalopathy, hypoxia, and dry necrosis of peripheral extremities. Further investigation revealed an EBV infection, the rarest infectious cause of cold AIHA. She was started on steroids, the mainstay of treatment, but continued to worsen over the course of her extensive stay in the intensive care unit (ICU). Given the severity of the disease, the decision was made to use plasmapheresis and rituximab, the monoclonal antibody directed against CD20, as an experimental therapy. After adjunctive therapy was initiated, the patient began to clinically improve and ultimately made a full recovery. Rituximab is historically only effective in primary cold AIHA, but it appeared to elicit significant clinical improvement with our use in secondary cold AIHA. While there have been a handful of studies demonstrating its successful use in secondary cold AIHA, we propose that this medication be further studied to prevent the significant morbidity and mortality associated with the disease.

[Extracorporeal treatment in poisoning]. / Extrakorporale Verfahren bei Vergiftungen.

In rare cases, intoxicated patients may require an extracorporeal procedure for enhanced toxin elimination. The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup provides consensus- and evidence-based recommendations regarding the use of extracorporeal procedures in the management of critically ill, poisoned patients, with ongoing updates. Extracorporeal clearance is highest for low molecular weight substances with low volume of distribution, low plasma protein binding, and high water-solubility. To maximize the effect of extracorporeal clearance, blood and dialysate flow rates should be as high as possible, and the membrane with the largest surface area should be utilized. Intermittent hemodialysis is the most commonly employed extracorporeal procedure due to its highest effectiveness, while hemodynamically compromised patients can benefit from a continuous procedure.

ANCA-Associated Vasculitis.

ANCA-associated vasculitis (AAV) is a necrotizing, small-to-medium vessel vasculitis associated with significant morbidity and mortality. AAV is a systemic autoimmune disease affecting kidneys, eyes, sinuses, peripheral nerves, skin, and upper and lower respiratory tracts. AAV tends to present in characteristic phenotypes categorized clinically as granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic GPA (EGPA). Kidney involvement is a common feature of AAV, and has important implications on disease prognosis and management. Existing therapies have been refined and improvements in our understanding of the pathophysiology of AAV has led to approval of novel therapies. In this review, we provide an overview of epidemiology, disease mechanisms, clinical presentation and review therapeutic strategies for induction and maintenance of remission.

A Randomized Trial Comparing Imlifidase to Plasmapheresis in Kidney Transplant Recipients With Antibody-Mediated Rejection.

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.

Enhancing Success in the ABO-Incompatible Kidney Transplantation: A Case Report.

Kidney transplantation is the preferred treatment for end-stage renal disease (ESRD); however, ABO incompatibility (ABOi) poses challenges due to increased graft rejection risk. Desensitization strategies, including immunoadsorption (IA), aim to overcome ABOi barriers. The objective of this case report was to present the initial findings and patient outcomes of ABOi kidney transplantation (KT) using two different brands of IA columns (Glycosorb® ABO and SECORIM®-ABO) in reducing isoagglutinin titers to the desired target level. We present a case report of a 51-year-old male with ESRD secondary to diabetic kidney disease who underwent desensitization for ABOi KT, involving rituximab administration followed by IA using Glycosorb® and Vitrosorb SECORIM®-ABO columns and plasmapheresis (PP). Glycosorb® ABO column decreased anti-B titers from an initial level of 1:128/1:128 to 1:64/1:64 (target range ≤1:8); however, the titers rebounded to 1:64 following the fourth session of PP. Subsequent use of Vitrosorb SECORIM®-ABO column achieved target titers of 1:4, enabling successful transplantation with satisfactory graft function. Monitoring included anti-B IgG/IgM titer levels post IA columns, IA column reuse, kidney function, and adverse events. The IA columns were well tolerated. Desensitization using IA columns effectively reduced anti-B titers, facilitating successful ABOi KT.

Examination of drug removal profiles in patients undergoing therapeutic plasma exchange: A retrospective study.

INTRODUCTION: Therapeutic plasma exchange (TPE) eliminates disease-contributing substances but may also affect drug concentrations. This study aimed to assess the prevalence of prescription drugs removable via TPE by reviewing patient medication histories. METHODS: A retrospective, single-center study was conducted from January 1, 2021 to December 31, 2022. The study included 244 patients undergoing 1087 TPE sessions. Drugs prescribed to patients on TPE days were categorized as "yes" (probably removable), "maybe" (possibly removable), and "no" (unlikely removable) regarding their removability via TPE. RESULTS: Among 3966 prescriptions, 556 (14.0%) were analyzed, with 21.8%, 36.5%, and 41.7% falling into the "yes," "maybe," and "no" categories for removability. Although only 14.0% were categorized, 83.6% of patients received at least one analyzable drug. Among them, 83.8% had at least one potentially removable drug. CONCLUSION: Real-world data highlights the need for caution in drug treatments during TPE to ensure optimal therapeutic outcomes, particularly for specific drugs.

Antimicrobial management in patients undergoing therapeutic plasma exchange: A Cross-Sectional Nationwide Survey.

There is little evidence of antimicrobial elimination via therapeutic plasma exchange (TPE) and no guidelines for antimicrobial optimal dosing in patients undergoing TPE. We aimed to assess current practices and knowledge regarding antimicrobial management during TPE. A structured online survey was conducted from May to November 2023, and physicians were invited to participate through national scientific platforms and professional societies. One hundred five participants completed the survey, of whom 61% were infectious disease physicians, with 68.6% having more than 10 years of experience. That the TPE procedure could significantly affect plasma concentrations of antimicrobial agents was reported by 74.3% of the respondents. Among the physicians, 42.9% suggest antimicrobial dose adjustment, and 38.1% recommend temporarily discontinuing antimicrobial drug administration during TPE. Therapeutic drug monitoring was recommended by 33.3% of the respondents for certain antimicrobials, mainly glycopeptides and aminoglycosides, in patients undergoing concurrent TPE. Furthermore, 59.3% of physicians sometimes consult with another healthcare professional for treatment management, most commonly a pharmacist or a clinical pharmacist and an infectious diseases specialist. The core questions regarding potential drug-, procedure-, and patient-related antimicrobial elimination factors via TPE were responded to accurately by less than half of the physicians. It was clear that they had a lack of clinical practices and knowledge regarding antimicrobial management during TPE. To ensure the therapeutic efficacy of antimicrobials and avoid treatment failure, physicians should improve their practice strategies and consider antimicrobial elimination factors with TPE in this data-poor setting.

Outcomes of therapeutic plasma exchange for the treatment of patients with multiple myeloma cast nephropathy.

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.