Therapeutic plasma exchange: a comprehensive evaluation of efficacy and outcomes in neurological and non-neurological disorders

Introduction

Therapeutic plasma exchange (TPE) – also known as plasmapheresis – is a critical extracorporeal blood purification procedure widely used for the treatment of a variety of autoimmune, inflammatory and hematological disorders⁽¹⁾. The procedure involves the removal of plasma from the patient’s circulation, followed by its replacement with suitable substitution fluids such as fresh frozen plasma, albumin or saline. TPE effectively targets and eliminates pathogenic substances such as autoantibodies, immune complexes and other toxic factors circulating in the blood, which are often implicated in the pathogenesis of certain diseases. By modulating the immune system and correcting the pathological processes, TPE has emerged as a life-saving therapy for numerous life-threatening conditions.

In the realm of neurological disorders, therapeutic plasma exchange has proven to be an essential tool in managing conditions such as Guillain-Barré syndrome (GBS), myasthenia gravis (MG) and neuromyelitis optica (NMO). These disorders, which typically involve severe immune-mediated damage to the nervous system, often lead to debilitating symptoms such as muscle weakness, respiratory failure and impaired sensory and motor functions. Studies have shown that TPE can accelerate recovery, particularly in cases of GBS, where early intervention is critical in preventing severe complications like paralysis or death. Similarly, in myasthenia gravis, TPE is used to rapidly remove antibodies that interfere with neuromuscular transmission, leading to significant clinical improvement in muscle strength and overall functional capacity. In neuromyelitis optica, therapeutic plasma exchange helps mitigate inflammatory damage to the spinal cord and optic nerves, thus improving the long-term prognosis for patients. These neurological conditions represent some of the most compelling indications for TPE, given their high morbidity and potential for rapid progression if not treated promptly.

Beyond neurological conditions, therapeutic plasma exchange has been successfully utilized in a variety of non-neurological disorders, particularly in hematological conditions such as thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). These conditions are marked by the formation of small blood clots within blood vessels, which can lead to organ damage, including renal failure, and a high risk of mortality if not treated urgently. In TTP, the therapy is aimed at removing the von Willebrand factor (vWF) multimers that contribute to thrombus formation, while in HUS, therapeutic plasma exchange helps in removing toxins produced by Shiga toxin-producing Escherichia coli (STEC), thus preventing renal injury. The efficacy of TPE in these non-neurological conditions has demonstrated significant reductions in mortality rates and improved patient outcomes when initiated early.

However, despite its widespread application and promising results, the use of therapeutic plasma exchange is not without its challenges. The clinical efficacy of TPE can be influenced by several factors, including the timing of intervention, disease severity, comorbidities, and patient response. Additionally, procedural complications such as vascular access issues, hypotension, and citrate toxicity may arise during TPE, affecting patient safety and treatment efficacy. While much of the existing literature focuses on disease-specific responses to therapeutic plasma exchange, there is a notable gap in comparative studies evaluating the procedure’s outcomes across both neurological and non-neurological diseases. Furthermore, the potential long-term benefits of TPE, particularly in terms of functional recovery and quality of life, remain inadequately explored in diverse patient populations.

Given these considerations, there is an urgent need for a comprehensive, multidisciplinary approach to evaluate the efficacy, clinical outcomes and prognostic indicators of therapeutic plasma exchange across a broad spectrum of diseases. Understanding the variable responses to TPE will allow clinicians to optimize patient selection criteria, identify the most suitable therapeutic regimens, and refine procedural protocols to minimize complications and maximize therapeutic benefit⁽²⁾.

This study seeks to address these gaps in knowledge by evaluating the efficacy and therapeutic outcomes of TPE in a cohort of patients with a wide range of neurolo­gical and non-neurological conditions. By systematically assessing clinical improvement, functional recovery and complication rates, this research aims to provide robust data that will contribute to the growing body of evidence supporting the use of therapeutic plasma exchange. The findings from this study will not only help in refining the clinical application of TPE, but will also pave the way for future research aimed at optimizing treatment protocols and patient care strategies in the context of therapeutic plasma exchange therapy.

Materials and method

Study design

This retrospective and prospective observational study was conducted at the Apheresis Unit of the Department of Immunohematology and Blood Transfusion, Medical College and SSG Hospital, Baroda, India, from July 2015 to July 2020. The study aimed to evaluate the efficacy and therapeutic outcomes of therapeutic plasma exchange in patients diagnosed with neurological and non-neurological disorders. Ethical approval was obtained from the institutional review board, and the informed written consent was secured from all patients prior to the commencement of the procedure.

Patient selection

A total of 70 patients (37 males and 33 females) who met the inclusion and exclusion criteria were included in the study. The median age of the patients was 44 years old (range: 18-75 years old). The inclusion criteria were represented by patients diagnosed with neurological conditions such as Guillain-Barré syndrome (GBS), myasthenia gravis (MG), neuromyelitis optica (NMO), thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). Non-neurological conditions included systemic lupus erythematosus (SLE), renal failure and other autoimmune and hematological disorders.

The exclusion criteria consisted of patients with severe cardiovascular instability, uncontrolled infection, pregnancy, and history of major bleeding disorders.

Intervention: therapeutic plasma exchange

TPE was performed using the Fresenius Kabicom.Tec machine, a high-efficiency apheresis device designed for plasma exchange procedures. The procedure was carried out in the apheresis unit, according to the standardized operating procedures (SOPs) of the department. Patients were typically scheduled for TPE on alternate-day intervals over a period of 8-10 days, depending on the disease severity and clinical response.

The anticoagulation protocol included the use of citrate at a fixed concentration to maintain blood flow and prevent clotting during the procedure. The volume of plasma exchanged was determined based on the patient’s total plasma volume, and plasma was replaced with a suitable fluid, typically fresh frozen plasma or albumin. The process was closely monitored by trained apheresis specialists to ensure patient safety and procedural efficacy.

Data collection

Clinical and demographic data were collected from the patients’ medical records, which included:

• age, sex, and comorbidities
• diagnosis and duration of illness
• time from disease onset to presentation at the hospital
• clinical and functional status prior to and following TPE.

The primary outcome of the study was the improvement in muscle strength as assessed by the Medical Research Council (MRC) scale for neurological diseases (such as GBS, MG and NMO). The MRC grading scale was used to assess the muscle strength in terms of grade 0-5, where grade 0 represented no movement and grade 5 represented normal strength. Secondary outcomes included functional recovery, symptom resolution and complication rates. Functional recovery was assessed using standard clinical metrics specific to each condition (e.g., time to ambulation for GBS or improvement in visual acuity for NMO).

Statistical analysis

Descriptive statistics were used to summarize patient characteristics and clinical outcomes. Continuous variables, such as age and duration of illness, were expressed as mean ± standard deviation (SD), while categorical variables, such as sex and disease type, were presented as frequencies and percentages. The efficacy of TPE in terms of clinical improvement was compared across different disease categories using chi-square tests for categorical variables. The Wilcoxon signed-rank test was used to assess changes in muscle strength scores before and after each cycle of TPE. A p-value below 0.05 was considered statistically significant. All analyses were performed using SPSS version 24 (IBM, Armonk, NY, USA).

Complications and safety monitoring

Complications related to the TPE procedure, including vascular access issues, hypotension, citrate toxicity and allergic reactions to replacement fluids, were recorded and monitored throughout the study. The overall complication rate was calculated as the percentage of patients experiencing any adverse event related to the procedure. Patients were carefully monitored for any immediate or delayed side effects, and appropriate interventions were carried out as needed.

Ethical considerations

The study was approved by the Institutional Review Board (IRB) of the hospital. Informed consent was obtained from all participants, and the study was conducted in accordance with the Declaration of Helsinki for ethical medical research. Patient confidentiality was maintained by anonymizing all personal data.

Results and observations

Patient demographics

A total of 70 patients (37 males and 33 females) participated in the study. The median age was 44 years old (range: 18-75 years old). Neurological conditions were the most common indication for therapeutic plasma exchange, accounting for 65.7% (n=46), while non-neurological conditions made up 34.3% (n=24).

Clinical improvement

The overall clinical improvement rate was 71.4% across all patients, with significant differences between neurological and non-neurological conditions.

• Guillain-Barré syndrome among GBS patients (n=20):

✔ 65% (n=13) achieved grade 4 muscle strength improvement

✔ 5% (n=1) showed grade 3 improvement.

• Myasthenia gravis among MG patients (n=20):

✔ 70% (n=14) achieved improvement in muscle strength, with 50% (n=10) achieving grade 4 improvement and 20% (n=4) achieving grade 3 improvement.

• Thrombotic thrombocytopenic purpura among TTP patients (n=8):

✔ 87.5% (n=7) showed significant clinical improvement, with 50% (n=4) achieving complete resolution of symptoms.

• Hemolytic uremic syndrome among HUS patients (n=9):

✔ 78% (n=7) showed significant recovery, including improved renal function and clinical symptoms.

• Neuromyelitis optica among NMO patients (n=20):

✔ 55% (n=11) showed clinical improvement, including reduced relapses and enhanced functional recovery, particularly in vision and mobility.

Complications and adverse events

The overall complication rate was 40% (n=28). The most common complications were related to vascular access and citrate reactions. These were generally mild and resolved with appropriate interventions.

Citrate reactions: mild reactions occurred in 16% of patients (n=11), characterized by tingling and hypocalcemia, which were managed with calcium supplementation.

Vascular access issues: 24% of patients (n=17) experienced difficulties related to catheter insertion, including infiltration and hematoma formation at the site, which were managed by adjusting insertion techniques or using alternative access sites.

Cycles of plasmapheresis and improvement

Patients underwent therapeutic plasma exchange on alternate days over a period of 8-10 days, with each cycle contributing to incremental improvement in muscle strength and overall clinical recovery. The number of cycles required for substantial improvement varied depending on the disease type and severity.

• 1-2 cycles: patients who received fewer cycles showed mild improvements in clinical symptoms and muscle strength, with only 45% achieving significant clinical benefit.
• 3-4 cycles: moderate improvement was observed in 65% of patients, with most patients experiencing a noticeable reduction in symptoms.
• 5-6 cycles: a significant improvement in muscle strength was seen in 80% of patients, with notable recovery in most cases.
• 7-8 cycles: 90% of patients who underwent 7-8 cycles showed near-complete recovery, especially those with GBS and TTP.

Number of cycles and disease type

The number of TPE cycles required to achieve maximum benefit was related to the type of disease.

Discussion

This study aimed to assess the efficacy of therapeutic plasma exchange in improving clinical and functional outcomes across a spectrum of neurological and non-neurological conditions. Our results demonstrate that TPE is a highly effective treatment modality, with significant improvements in clinical symptoms, muscle strength and overall functionality, especially in conditions like Guillain-Barré syndrome, myasthenia gravis and thrombotic thrombocytopenic purpura. These findings are consistent with previous studies that have highlighted the efficacy of therapeutic plasma exchange in various diseases, reaffirming its role as a therapeutic option in managing autoimmune and life-threatening conditions.

Efficacy of TPE in neurological conditions

Neurological disorders represented 65.7% of our patient population, and TPE showed notable efficacy in improving muscle strength and functional recovery. The most striking improvement was seen in Guillain-Barré syndrome, where 65% of patients achieved grade 4 muscle strength improvement, a result that aligns with previous studies showing significant recovery in GBS following therapeutic plasma exchange. Several randomized controlled trials (RCTs) have documented that TPE, particularly when initiated early in the disease course, can accelerate recovery and improve outcomes in GBS patients by reducing the need for mechanical ventilation and shortening hospitalization time⁽³⁾.

In our study, the improvement in myasthenia gravis patients was also significant, with 70% showing improvements in muscle strength. This result is in agreement with a study which demonstrated that TPE is particularly beneficial in patients with acute exacerbations of myasthenia gravis, where rapid intervention can reduce symptoms such as respiratory insufficiency and dysphagia⁽⁴⁾. The observed response in MG highlights the utility of therapeutic plasma exchange in autoimmune neuromuscular conditions where pathogenic autoantibodies contribute to symptom exacerbation.

Our results for neuromyelitis optica (NMO) were somewhat less robust, with only 55% showing clinical improvement. This reflects the challenging nature of NMO, a severe and often refractory autoimmune condition. However, previous studies have suggested that, although the overall response rate to TPE in NMO is variable, early initiation of therapy may prevent severe relapses and long-term disability⁽⁵⁾.

Efficacy of TPE in non-neurological conditions

In contrast to the neurological cohort, non-neurological conditions in this study showed a higher clinical improvement rate of 85.4%, a trend that was statistically significant. Conditions such as thrombotic thrombocytopenic purpura and hemolytic uremic syndrome exhibited particularly strong responses to therapeutic plasma exchange. In TTP, 87.5% of patients showed significant improvement, with complete resolution in many cases. These findings are supported by a study which reported that TPE remains the first-line therapy for TTP, as it helps to remove ADAMTS13 inhibitors and restores ADAMTS13 activity, thereby preventing thrombotic microangiopathy⁽⁶⁾. Similarly, in hemolytic uremic syndrome, 78% of patients demonstrated substantial recovery, particularly in renal function, supporting the widespread use of therapeutic plasma exchange in this life-threatening condition⁽⁷⁾.

The high success rate in non-neurological disorders further emphasizes TPE’s broad applicability in managing immune-mediated conditions beyond the nervous system. The observed efficacy in these diseases underscores the need for continued research to define optimal treatment protocols, as many of these conditions remain under-studied in the context of plasma exchange.

Complications and safety

The overall complication rate of 40% in our study aligns with the literature, where complications from TPE generally range from 10% to 50%⁽⁸⁾. The most frequent complications were vascular access issues and citrate reactions. Vascular access problems occurred in 24% of patients, which is consistent with prior reports, as catheter insertion can be technically challenging, particularly in patients with poor peripheral venous access. Strategies to mitigate these complications, such as the use of ultrasound-guided access and central venous catheters, may reduce the risk of these issues.

Citrate reactions occurred in 16% of patients, manifesting as hypocalcemia and tingling sensations, a well-known complication associated with the use of citrate as an anticoagulant in TPE. These reactions are typically mild and can be managed with calcium supplementation, as was done in this study. The frequency of these reactions is consistent with findings from other studies, with mild citrate toxicity being a common occurrence⁽⁹⁾. The relatively high incidence of vascular complications in this study may be a result of the observational nature of the study, with limited control over the technical aspects of the procedure. Future studies may benefit from a more standardized approach to catheterization, including training and protocol adjustments to minimize such complications.

Cycles of plasmapheresis and duration of treatment

Our study highlights the importance of the number of plasmapheresis cycles required to achieve significant clinical improvement. Patients receiving 5-6 cycles of therapeutic plasma exchange showed 80% improvement, a result in line with the findings from a study which demonstrated that most patients with autoimmune and neurological disorders require 5-6 cycles to experience substantial benefits⁽¹⁰⁾. Longer courses of TPE (7-8 cycles) were associated with near-complete recovery in 90% of cases. These findings underscore the need for individualized treatment plans, as the number of cycles required varies based on the severity of the disease and the patient’s overall response to therapy.

Moreover, our results suggest that non-neurological conditions such as TTP and HUS may require fewer cycles to achieve clinical improvement, supporting previous observations that non-neurological patients tend to show a quicker response to therapeutic plasma exchange.

Limitations and future directions

This study had several limitations, including its retrospective nature and reliance on a single apheresis unit, which may limit generalizability. Additionally, the lack of a control group or randomized design restricts the ability to draw definitive causal conclusions regarding the effectiveness of TPE. The heterogeneity of the patient population also introduced variability in response to treatment, particularly in neuromyelitis optica patients, who showed more variable responses to therapeutic plasma exchange.

Future studies with larger, multicenter designs and randomized controlled trials would provide more robust data and help in establishing evidence-based guidelines for therapeutic plasma exchange in both neurological and non-neurological conditions. Additionally, investigating long-term outcomes, including relapse rates, disease progression, and quality of life, would be beneficial to fully assess the benefits of TPE therapy.

Conclusions

This study reinforces the role of therapeutic plasma exchange as a valuable therapeutic intervention for both neurological and non-neurological conditions, with high efficacy in conditions such as Guillain-Barré syndrome, myasthenia gravis, thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. Although the complication rate is not negligible, the overall benefits outweigh the risks, particularly when TPE is initiated early in the disease course. With appropriate protocol optimization and better management of complications, therapeutic plasma exchange can remain a cornerstone treatment for autoimmune-mediated and other plasma exchange-responsive diseases.   

Ethical approval. This study was conducted following ethical guidelines, with approval obtained from SIMS Blood Centre, Advanced Transfusion Medicine Research Foundation Ethical committee.

Corresponding author: Nandini Raval E-mail: trivedinivi10722@gmail.com

Conflict of interest: none declared.

Financial support: none declared.

This work is permanently accessible online free of charge and published under the CC-BY licence.