European Journal of Cardiovascular Medicine

Therapeutic Plasma Exchange (TPE) is an extracorporeal blood purification technique used to manage a variety of life-threatening conditions, including autoimmune diseases, thrombotic disorders, neurological diseases, and some hematological conditions. The process involves the removal of the patient’s plasma, which may contain pathological substances such as autoantibodies, immune complexes, or toxins, and replacing it with donor plasma or plasma substitutes. TPE has proven effective in treating diseases like myasthenia gravis, thrombotic thrombocytopenic purpura, and systemic lupus erythematosus (Hussain et al., 2020) [1]. Despite its clinical benefits, TPE is associated with a range of complications, some of which can significantly impact patient outcomes.

Complications of TPE can vary widely in severity, from mild symptoms such as hypotension and hypocalcemia to more severe events like infections, bleeding, and anaphylactic reactions (Gibson et al., 2018) [2]. The occurrence of these complications may depend on several factors, including the patient’s underlying condition, comorbidities, and the technical aspects of the procedure. In tertiary care hospitals, where patients with complex or critical conditions are often treated, the risk of complications may be heightened due to the increased severity of cases being managed (Chang et al., 2017) [3].

Although several studies have examined the complications associated with TPE, much of the existing literature is limited by small sample sizes or does not fully reflect the complexities of tertiary care environments (Franchini et al., 2017) [4]. Therefore, there is a need for further investigation into the specific complications occurring during TPE in such specialized healthcare settings. Understanding the frequency and nature of these complications can help inform clinical practice, improve patient safety, and optimize treatment protocols.

This study aims to analyze the types, frequency, and severity of complications associated with TPE in MGM Medical College and M Y hospitals Indore. By identifying patterns and risk factors, we seek to develop strategies to prevent and manage complications more effectively, ultimately enhancing the safety and efficacy of TPE in treating complex conditions (McClelland et al., 2019) [5]. In addition, this research could contribute to the broader body of knowledge surrounding TPE and its application in critically ill patients (Parker et al., 2016) [6].

This is a cross-sectional observational study conducted by the department of Transfusion Medicine at MGM Medical College and M Y HOSPITALS INDORE, a tertiary care hospital in central India from the period of December 2020 to December 2024.

This study covered patients of all ages and genders that needed TPE as part of their care. Participants in the study were those who met the requirements for TPE as outlined by the Drugs and Cosmetics Act, 2020, the Directorate General Health Services (DGHS), Ministry of Health and Family Welfare, Government of India.[7] Patients who did not provide informed consent for TPE were excluded. Institutional ethics committee approval will be obtained before commencement of the study. With a 95% confidence level (Z), 5% margin of error (d), and an estimated percentage of complications (P) of 53.4%, the sample size (n) was determined which came out to be nearly 400. A total of 400 plasmapheresis treatment sessions done on 160 patients were included in the study through consecutive non-probability sampling techniques.[8]

Therapeutic plasma exchange procedures were performed on COM. TEC, Fresenius Kabi, Germany®, by using TPE kit, it is a closed system, TPE Fresenius Kabi, Germany® and anticoagulant ACD Fresenius Kabi, Germany®. Normally the range of anticoagulant ACD ratio, will be use during the TPE cycle is 1:8 to 1:12. The range of the blood flow, will use during the TPE procedure is 30 to 50 ml/min. [9]

We observed the patient very carefully, recorded all the complications if it will be manifested after the procedure within 24 hour the procedure. Frequency, type, severity, and timing of complications during or after TPE were noted. Complications were categorized as mild, moderate, and severe. Mild reactions were without any clinical consequence. Whereas reactions that were of little clinical significance but required medical intervention and were resolved completely were considered Moderate. Life threatening complications were classified as Severe. The hospital serves as a major referral center, offering TPE services for a variety of clinical conditions.

The demographic profile of all patients including name, age, gender, medical record number, clinical indication for TPE and clinical parameters including vital signs, weight, and complications were entered in a predesigned Performa. Heart rate and blood pressure were measured during pre-treatment, post-treatment, and at 30-minute intervals during plasmapheresis. Temperature and saturation were recorded at the start and end of treatment. All clinical events described by the patient or observed by staff during the procedure were confirmed and documented by resident medicine on proforma. Data were analyzed using using IBM Statistical Package for the Social Sciences (SPSS) version 20. Descriptive statistics (mean, standard deviation, median, and interquartile range) were used to summarize continuous variables, while categorical variables were presented as frequencies and percentages. Associations between complications and patient or procedural characteristics were analyzed using chi-square tests for categorical variables and t-tests or Mann-Whitney U tests for continuous variables. A p-value <0.05 was considered statistically significant.

As can be seen in table 1, Majority of the patients were between 30–49 years (49.37%), followed by 10–29 years (43.75%). Patients aged 50–69 years and 70–89 years accounted for only 4.37% and 2.50%, respectively. The average age of the patients was 38.65 years, with a standard deviation of 14.3 years, indicating that most patients were middle-aged.

Table 1: Demographic characteristics of TPE patients

Figure 1 shows the gender distribution of TPE patients. Male patients constitute 55% (88 individuals) while female patients account for 45% (72 individuals).

This slight male predominance in the patient population undergoing therapeutic plasma exchange could reflect differences in disease prevalence or referral patterns requiring TPE.

Figure 1: Gender distribution of TPE patients

As can be seen in table 2, Overall complications were found in 37.75% of TPE sessions. Complications were most common during the procedure (93 cases, 61.59%), followed by within 1-hour post-TPE (43 cases, 28.48%), and least after 1 hour (15 cases, 9.93%). Most of the mild complications occurred during the procedure while severe complications occurred after the procedure. There was a statistically significant association between the timing and severity of complications (p-value = 0.004).

Table 2: Severity and Timing of Complications

Fever, pruritus and urticaria, and mild hypotension were the top three mild complications, each accounting for almost similar frequencies. Other notable mild issues included nausea/vomiting (12 cases, 11.3%), tachycardia (13 cases, 12.3%), and anxiety (10 cases, 9.4%). Dyspnoea (2 cases, 1.9%) was the least frequent mild complication.

Table 3: Mild Complications

Most Common Moderate Complications were Hypocalcemic symptoms (11 cases, ~30%), followed by allergic reactions (8 cases, ~22%) and catheter-related issues (8 cases, ~22%). Less common complications included severe hypotension (6 cases, ~16%), exit site infections (2 cases, ~5%), and rare events like hemoptysis and epistaxis (1 case each, ~3%).

Table 4: Moderate Complications

As far as severe complications were concerned, Deep vein thrombosis (3 cases, 37.5%) accounted as the most frequent severe complication. Rare but critical events included anaphylaxis, sepsis, severe bleeding, and arrhythmia (1 case each, 12.5% each).

Table 5: Severe Complications

Therapeutic Plasma Exchange (TPE) is a technique of blood purification by exchanging patient plasma with allogeneic or autologous plasma or albumin. This study highlights the spectrum of complications associated with TPE in a tertiary care hospital setting. The overall complication rate in this study is 37.75%, emphasizing the effectiveness and associated risks of therapeutic plasma exchange (TPE) in managing complex diseases. It is less than that observed by Afzali et al. [8] in Iran and more than observed by Ahmed N et al. [10] in his study in Pakistan. Nearly similar rate of complication was found by Bharti J et al. (33.33%) in her study in Lucknow.[11]

The findings of this study provide crucial insights into the types, frequency, and timing of complications associated with TPE in a tertiary care hospital. The complications identified—ranging from mild symptoms like hypotension to severe outcomes like deep vein thrombosis—mirror those described by Hussain et al. [1] and Gibson et al. [2].

Our observation of hypotension, pruritus, and fever as the most frequent complications corresponds with findings by Parker et al.[6], who noted that these events often result from anticoagulants or plasma substitutes. Furthermore, the role of patient-specific factors, including age and underlying diseases, in predisposing individuals to complications, has been reported by McClelland et al. [5] These events are often transient and manageable with immediate medical intervention as observed by Schwartz et al.[12]

The significant incidence of moderate complications, such as hypocalcemic symptoms and allergic reactions, reinforces the necessity for vigilant monitoring during TPE sessions, as highlighted by Franchini et al. (2017) [4]. The use of anticoagulants like ACD may explain the prevalence of hypocalcemia-related symptoms, which were observed in 7.2% of total complications. Previous study by Sternbach et al. [13], has identified this as a recurring issue during TPE, particularly in patients with prolonged procedures or high citrate exposure. Catheter-related issues, noted in 8 cases (5.3% of total complications) in this study, align with research by Cortese et al. [14] and Chang et al. [3], which emphasized the importance of aseptic techniques and meticulous catheter care to reduce infections and other mechanical complications. This highlights, the critical need for aseptic techniques and prompt intervention to mitigate these risks (Afzali et al.). [8]

Furthermore, severe events like deep vein thrombosis, sepsis, and arrhythmias, —though rare—have been similarly highlighted by Warkentin et al. as critical outcomes requiring heightened vigilance and prompt management.[15] Singh et al. also advocated the importance of careful patient selection and continuous training of healthcare professionals.[16]

Timing of complications was another critical aspect of this study. Interestingly, our data suggest that most complications occurred during the procedure, which is consistent with study by Gibson et al. [2] and Chang et al. [3] indicating that the dynamic nature of TPE introduces transient hemodynamic instability. This reflects the dynamic nature of TPE, where rapid fluid shifts and anticoagulant use can lead to hemodynamic instability. Severe complications occurring post-procedure, such as deep vein thrombosis and anaphylaxis, highlight the need for extended observation periods and follow-up, as advocated by Singh et al.[16] As suggested by Warkentin et al. [15] also, prolonged post-procedure supervision is necessary due to the strong association between the timing and degree of complications, with severe occurrences happening more frequently after the procedure.

The slightly higher incidence of complications in males compared to females in this study may reflect gender-based physiological differences or variations in disease prevalence, a finding echoed in earlier research by Vandenberghe and Peerlinck.[7] However, more extensive studies are required to validate this observation. Importantly, advancements in technology, such as the COM.TEC device used in this study, have improved the safety profile of TPE. Despite these advancements, challenges such as hypocalcemia and allergic reactions remain prevalent, as corroborated by recent reviews (Cortese et al.). [14] Continued innovation in equipment and protocols may further minimize these risks. This study adds to the growing body of evidence on TPE complications in tertiary care settings, where patients often present with severe co-morbidities. However, findings from our study emphasize the critical role of individualized treatment protocols and continuous monitoring to improve patient outcomes. A systematic approach to managing complications—rooted in evidence-based practices and supported by multi-disciplinary collaboration—can significantly enhance the safety and efficacy of TPE.[6] The role of advanced technology in minimizing complications cannot be overlooked. Devices like the COM.TEC system used in this study have improved procedural efficiency and safety. However, as noted by Johnson et al. (2019) [17], technology alone cannot eliminate all risks; adherence to evidence-based protocols and individualized patient management remains paramount. This study emphasizes the need for multidisciplinary teamwork, continuous monitoring, and preventive strategies to mitigate complications during TPE. It also aligns with the broader body of evidence suggesting that early identification and management of complications are critical to improving outcomes.[5]

This study identifies a 37.75% overall complication rate associated with Therapeutic Plasma Exchange (TPE) in a tertiary care setting, with mild complications such as hypotension and fever being the most frequent. Moderate complications, including hypocalcemia and catheter-related issues, and rare but severe events like deep vein thrombosis and sepsis, underscore the need for vigilant monitoring and extended post-procedure care. Patient-specific factors and adherence to aseptic techniques significantly influence outcomes. While technological advancements have improved safety, individualized protocols and multidisciplinary approaches remain essential. These findings provide critical insights to enhance patient safety and optimize TPE practices in complex healthcare environments.

Funding: No funding sources

Conflict of Interests: The authors declare no conflict of interest in this study.

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