Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 
  • Users Online:1200
  • Home
  • Print this page
  • Email this page

 Table of Contents  
Year : 2019  |  Volume : 4  |  Issue : 2  |  Page : 163-167

Adverse effects of intermittent flow therapeutic plasmapheresis in neurology patients in a resource constrained setting

Department of Transfusion Medicine and Haematology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India

Date of Submission05-Jan-2019
Date of Acceptance27-Mar-2019
Date of Web Publication17-Oct-2019

Correspondence Address:
Dr. Sukanya Baruah
Department of Transfusion Medicine and Haematology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/GJTM.GJTM_1_19

Rights and Permissions

Introduction: Therapeutic plasma exchange (TPE) aims at removing harmful substances from patient's plasma. It has become a treatment option in a variety of neurological disorders with good outcome. In the last decade, there has been an increase in the number and spectrum of indications for therapeutic apheresis. Aims and Objectives: To analyse the complications of plasmapheresis patients with varied neurological disorders in a tertiary care neurocentre to evaluate the safety of the procedure. Materials and Methods: A retrospective analysis of complications in all patients who underwent TPE for various neurological disorders in the Transfusion Medicine Department from April 2013 to May 2014 was carried out. Patient record files and TPE protocol forms were analysed to collect the data about various complications during the procedure. Results: A total of 1912 procedures were carried out on 399 patients. Guillain Barre Syndrome was the most common indication. A total of 145( 36.3%) patients had adverse reactions. Mild reactions like rash (40%), chill and rigor (21%), cramps (6.8%) were found in 98 cases (68%). Moderate reactions included hypotension (17.9%), access site pain and hematoma (7.5%), vasovagal attack (3.44%), seizure (1.37%) etc. Severe life threatning reactions were not seen in any of the cases. Conclusion: Our results advocate TPE as a safe and effective procedure in neurological disorders. Most complications are mild and can be managed effectively. Complications can be further reduced by careful patient monitoring, use of prophylactic calcium and use of albumin as replacement fluid.

Keywords: Complications, neurological cases, therapeutic plasma exchange

How to cite this article:
Baruah S, Periyavan S. Adverse effects of intermittent flow therapeutic plasmapheresis in neurology patients in a resource constrained setting. Glob J Transfus Med 2019;4:163-7

How to cite this URL:
Baruah S, Periyavan S. Adverse effects of intermittent flow therapeutic plasmapheresis in neurology patients in a resource constrained setting. Glob J Transfus Med [serial online] 2019 [cited 2022 Jan 25];4:163-7. Available from: https://www.gjtmonline.com/text.asp?2019/4/2/163/269379

  Introduction Top

Therapeutic plasma exchange (TPE) aims at removing harmful plasma constituents from patients and replacing the extracted plasma with replacement fluids.[1] Since being first employed way back in 1952 to control the hyperviscosity in multiple myeloma, it has evolved over the years to become a treatment option in a variety of neurological disorders.[2] The American Society for Apheresis (ASFA) has defined the categories of various indications of TPE in the “Guidelines for Therapeutic Apheresis.”[3] The 2016 ASFA guidelines (7th ed) contain 87 diseases and 179 indications.[4] In the last decade, there has been an increase in the number and spectrum of indications for therapeutic apheresis and frequency of procedures.[5] Apheresis is now performed for various neurological, renal, hematological, and rheumatological disorders with good outcome. Randomized controlled trials have demonstrated the efficacy of TPE in various neurological disorders such as Guillain–Barre syndrome (GBS), myasthenia gravis, chronic inflammatory polyneuropathy, and paraproteinemic polyneuropathy.[6] A variety of mechanisms for the actions of TPE has been proposed including removal of antibodies, immune complexes, toxins, cytokines, and the replenishment of specific plasma factors.[7] Despite TPE being a safe procedure in experienced hands, several studies have previously reported various side effects of the procedure.[8],[9],[10],[11],[12] In India, data related to TPE in neurological disorders are very less due to lack of this facility in smaller centers and lack of uniformity in performing the procedure. Various studies have already analyzed the efficacy of TPE in neurological disorders, but there are very few studies which have exclusively studied the complications of TPE. We have analyzed and evaluated the complications of TPE in neurological disorders and tried to find out the predictive factors to increase the safety of the procedure.


To analyse the complications of therapeutic plasmapheresis in patients with neurological disorders.


To evaluate the safety of therapeutic plasmaphersis in neurological disorders.

  Materials and Methods Top

Sample size and selection method

We have selected one year data without exception in our study. All the cases in the selected year were considered for analysis. Sample size was n = 1912 was considered adequate.

A retrospective analysis of all patients who underwent TPE for various neurological disorders in the transfusion medicine department of our institute was carried out from April 2013 to May 2014. ASFA guidelines were followed in assessing the eligibility status of all patients.[4] All the procedures were carried out under the direct supervision of the doctors and staff of transfusion medicine center. The cell separator used for all the procedures was Haemonetics MCS 3 plus which works on the principle of intermittent flow centrifugation. Standard instructions according to user manual were followed. The procedure was carried out through the peripheral venous access, preferably antecubital vein in majority of the cases. If there was no free flow of blood in the peripheral veins due to thrombosis or other causes, the procedure was done through the internal jugular or femoral vein. The procedures were performed on alternate days to reach a therapeutic plasma target of 150–200 ml/kg. All the patients were strictly monitored before, during, and after the procedure to detect any complications. Blood pressure (BP), heart rate, SpO2, respiratory rate, temperature, level of consciousness, vascular access site swelling, or redness was monitored in all cases. Laboratory tests including complete blood counts, coagulation profile, and serum electrolyte levels were repeated before and following the completion of TPE. Patient records and TPE protocol forms were analyzed to collect the data about various complications during the procedure. We have defined complication in our study as any side effect or untoward or unusual events which have happened contrary to the normal course of events associated with TPE. Hypotension was defined as a fall of baseline BP by more than 20%. The WHO definitions were taken into account to detect tachycardia or bradycardia. Below mentioned complications were described and categorized:

  1. Complications related to the procedure itself such as fall in BP, tachycardia, vasovagal attack, paraesthesia, muscle cramps, and other systemic side effects
  2. Complications related to vascular access such as hematoma and infection in the access site and inadequate blood flow
  3. Complications related to the usage of replacement fluids.

Complications were further subdivided into mild, moderate, and severe as described by Bramlage et al.[13] “Mild” complications were short lasting, hardly had clinical significance and did not cause delay in the procedure. They included skin rashes, paresthesia, restlessness, chills, and rigor. Complications which required medical attention but did not pose life risk were categorized as “Moderate.” They included fall in BP, tachycardia, nausea, vomiting, complications due to vascular access, minor type I allergic reactions, and breathing difficulty. Life-threatening events which necessitated stoppage of the procedure were classified as “severe.” They included anaphylactic shock and cardiopulmonary complications. All untoward events which occurred during or after the procedure were managed according to standard medical protocol by qualified medical and paramedical staff.

Statistical analysis

The main objective of this research work is to evaluate TPE. The objective of this study has been proved with simple percentage analysis. No comparison between groups has been made.


The study does not contain any patient identifiers and has been carried out as per ethical guidelines of the institute.

  Results Top

Patient characteristics

A total of 1912 procedures were carried out during the study on 399 patients. Among them, 54.6% (218) were male and rest were female. The median age of the patients was 37. Majority of the patients were in the age group of 21–30 years (24.3%) and two patients were above the age of 80 years [Table 1]. Among the females, there were two cases of a pregnant woman in the first trimester. About 9.7% (39) of cases were in the intensive care unit (ICU) on ventilator support.
Table 1: Age group distribution of patients

Click here to view

Among the indications of plasmapheresis, GBS constituted the overwhelming majority with a total of 259 cases followed by myasthenia gravis and neuromyelitis optica [Table 2].
Table 2: Indications of plasmapheresis

Click here to view

Plasma exchange variables

A total of 3–5 exchanges were performed on alternate days. An average of 1.5–2 L of plasma, i.e., approximately 30–40 ml/kg of plasma was removed per sitting. About 68.8% of patients underwent five sessions of TPE, and the rest underwent three sessions. The mean volume of plasma extracted was 1323.53 ml and 1441.33 ml in three and five sessions respectively. Since we have used intermittent flow apheresis machine in all the cases which has a higher extracorporeal volume compared to continuous flow machines, the volume of plasma extracted is less than one volume in some of the cases considering the hemodynamic status and weight of the patients to avoid complications during the procedure. However, the patients responded well, and further requests for increased volume extraction were not received by us. In our study, majority of the patients (90.4%) underwent TPE with fresh frozen plasma (FFP) as the replacement fluid. Albumin was used as replacement in only 9.5% of cases. The main reason for this is very high cost of albumin compared to FFP which especially in a third world country like ours is a major limiting factor. Vascular access in TPE was obtained by the cannulation of peripheral veins with 18 gauge needles in 93.8% of our cases. Internal jugular or femoral veins were used for vascular access in the rest 6.2% of cases. Acid citrate dextrose was the anticoagulant used for all cases in a ratio of 1:16. The ratio was adjusted in patients who complained of features of citrate toxicity during the procedure.

A total of 145 (36.3%) patients in our study had adverse reactions [Table 3]. Mild adverse effects were encountered in 98 (68%) cases, and these included rash, itching, chills and rigor, muscle cramps, paraesthesia, urticaria, and cephalgia. These were mild and transient and did not result in the termination of the procedure. Most adverse effects were moderate which included hypotension (17.9%), pain and hematoma in vascular access site (7.5%), allergic reactions to FFP and albumin, transfusion-related acute lung injury (0.02%), vasovagal reactions (3.44%), and seizure (1.37%). Severe adverse reactions were not seen in any of the cases. Mild-transient hypotension (systolic BP <100 mmHg with only minimal or no symptoms) was treated with reduction of the speed of inlet flow and/or by intravenous (IV) crystalloids. TPE was never stopped in these cases, and at the end, procedures were uneventful. Sustained hypotension (systolic BP <80 mmHg) during the procedure mandated stopping the procedure for some time and correction of hypotension by IV crystalloids. Whenever patients complained of pain at the access site thrombophlebitis was always looked into and in cases of even mild suspicion vascular access site was changed. Hematoma and redness in vascular access site were treated with anti-inflammatory drugs. The reactions to replacement fluids were managed with administration of antihistaminics. No patient in our study had developed severe complications to TPE. No mortality due to procedure-related complications was encountered.
Table 3: Complications of plasmapheresis

Click here to view

  Discussion Top

In India, there are very few centers which perform therapeutic plasmapheresis. Although various studies in literature have previously reported the efficacy and complications of TPE in neurological disorders, studies in this field from India are limited.[14],[15],[16],[17],[18],[19] We have analyzed 1912 plasmapheresis procedures involving 399 patients, among which 145 patients developed complications. To the best of our knowledge, our series is among the largest in literature, and it is one of the very few studies to exclusively study the complications of this procedure in neurological diseases.

The complication rate of 36.3% of patients in our study is more than previously published studies, for example, Sprenger (rate of complication 4.2%)[20] or Samtleben (17.5%).[21] In India, most of the patients of neurological disorders come to the tertiary care centers at a very late stage of the disease when complications are high. 39 (9.7%) patients were already on ventilator support in ICU by the time TPE was started in this study. In our study, the youngest patient was 10-year-old. We did not perform large volume plasma exchange in pediatric cases with body weight <24 kg as it is difficult to maintain extracorporeal blood volume <15% of the body weight using Hemonetics MCS 3 plus which works on the principle of intermittent flow centrifugation. Small volume plasma exchange was performed in such cases. Different technical equipment in addition to modification of the protocol and psychological issues pertaining to the patient needs to be addressed to perform the procedure in a safe and effective manner in children.[22] We included 37 patients above the age of 60 years in our study. Chances of hemodynamic alterations in TPE are higher in the elderly. The availability of data related to TPE in old population is very scarce. Basic-Jukic et al. reported an incidence of 11.5% in elderly compared to compared to 3.9% in the younger group.[23] All these factors have contributed to the overall incidence of complications in our series.

The most common complication in our study was rash and itching (40%) followed by chills and rigor (21%). Vikrant et al. reported 4.2% of chill and rigors in a retrospective study on 31 GBS patients.[16] In another Indian study, on 100 GBS patients, Gajjar et al. reported an incidence of 7% allergic reactions.[19] Higher incidence of allergic reactions in our study is related to the use of FFP as replacement fluid in majority of the cases. The main reason for this is cost constraints which in a country like India is always a major limiting factor. As per the recommendations of the French Cooperative Group on plasma exchange in GBS, albumin is the preferred replacement fluid instead of FFP.[24] In our study, only 9.5% of the patients could afford to use albumin. We have reported 6.89% of cases with paresthesias and muscle cramps which can be caused by large fluid volume shifts between the extra and intravascular compartments causing electrolyte imbalance and hypocalcemia resulting from the use of citrate. An incidence of 36.1% of paresthesias and/or cramps was reported by Gafoor et al. in a study on 230 patients undergoing plasmapheresis with neurological disorders.[14] while Gajjar et al. reported an incidence of 21% cases of citrate toxicity in a prospective study.[19] The incidence of citrate toxicity was less in our study compared to these studies. This could be due to the low ratio of citrate infusion (1:16) that we have used.

The incidence of hypotension (17.9%) is higher in our study than previous studies done in India by Sharma et al. which reported 2.6%–8.1% incidence[15] and Ahammed Nizar et al. which reported 7.8% incidence of hypotension.[17] We did TPE in exclusively neurological patients and majority of them comprised of GBS (67.67%) patients who are more prone to autonomic dysfunction. FFP usage as replacement fluid is also an independent risk factor for hypotension due to allergic reactions.[13] Bramlage et al. have previously reported neurological diseases as an independent risk factor for TPE complications.[13] Another Indian study by Gafoor et al. on TPE in neurological patients reported an incidence of 32.2% cases of mild hypotension and 5.2% cases of moderate-to-severe hypotension.[14] The higher incidence of hypotension and tachycardia may be a result of autonomic dysfunction in patients with neurological diseases although this is highly speculative. Other studies in literature have collected and analyzed data from apheresis registries of different countries for patients suffering from neurological as well as other diseases. However, in India, till date, we do not have a national apheresis registry. There was no life-threatening complication in our series which is an encouraging finding. There was also no procedure-related mortality. Nevertheless, the complication rates of TPE in our study are within acceptable limits if we compare with similar previous studies including a large study from India.[15] There are certain limitations in our study due to constrained resources in our set up. We have done all the procedures using an intermittent flow apheresis machine. FFP has been used as a replacement fluid instead of albumin in majority of the cases. We have not used prophylactic calcium gluconate during the procedure in any of the patients. These may be some of the reasons why our data relating to adverse effects may differ from other contemporary studies. Despite the limitations, we have achieved good results in the patients with no major life-threatening procedure-related complications.

  Conclusion Top

Our results advocate TPE as a safe procedure in experienced hands with benefits outnumbering the risks in neurological diseases. Most of the complications can be managed by competent treating staff. Regular monitoring during the procedure, treating at an early stage whenever indicated and using albumin as replacement fluid can further reduce the complications.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Winters JL. Hemapheresis. In: McPherson: Henry's Clinical Diagnosis and Management by Laboratory Methods. 22nd ed. Philadelphia: Saunders; 2011. p. 762-73.  Back to cited text no. 1
Strauss RG, Ciavarella D, Gilcher RO, Kasprisin DO, Kiprov DD, Klein HG, et al. An overview of current management. J Clin Apher 1993;8:189-94.  Back to cited text no. 2
Jones HG, Bandarenko N. Management of the therapeutic apheresis patient. In: McLeod B, Price TH, Weinstein R, editors. Apheresis, Principles and Practice. Maryland: American Association of Blood Banks Press; 2003. p. 253-74.  Back to cited text no. 3
Schwartz J, Padmanabhan A, Aqui N, Balogun RA, Connelly-Smith L, Delaney M, et al. Guidelines on the use of therapeutic apheresis in clinical practice-evidence-based approach from the writing Committee of the American Society for Apheresis: The seventh special issue. J Clin Apher 2016;31:149-62.  Back to cited text no. 4
Tiwari AK, Bhardwaj G, Aggarwal G, Arora D, Dara RC, Acharya DP, et al. Changing trends in therapeutic plasmapheresis: An Indian perspective. Ther Apher Dial 2017;21:500-6.  Back to cited text no. 5
Kes P, Basić-Kes V, Basić-Jukić N, Demarin V. Therapeutic plasma exchange in the neurologic intensive care setting recommendation for clinical practice. Acta Clin Croat 2012;51:137-53.  Back to cited text no. 6
Goto H, Matsuo H, Nakane S, Izumoto H, Fukudome T, Kambara C, et al. Plasmapheresis affects T helper type-1/T helper type-2 balance of circulating peripheral lymphocytes. Ther Apher 2001;5:494-6.  Back to cited text no. 7
Basic-Jukic N, Kes P, Glavas-Boras S, Brunetta B, Bubic-Filipi L, Puretic Z. Complications of therapeutic plasma exchange: Experience with 4857 treatments. Ther Apher Dial 2005;9:391-5.  Back to cited text no. 8
Wu MJ, Shu KH, Cheng CH, Lian JD. Complications of membrane-filtration plasma exchange. Zhonghua Yi Xue Za Zhi (Taipei) 1997;60:147-54.  Back to cited text no. 9
Koziolek MJ, Scheel A, Bramlage C, Groene HJ, Mueller GA, Strutz F. Effective treatment of hepatitis C-associated immune-complex nephritis with cryoprecipitate apheresis and antiviral therapy. Clin Nephrol 2007;67:245-9.  Back to cited text no. 10
Mokrzycki MH, Kaplan AA. Therapeutic plasma exchange: Complications and management. Am J Kidney Dis 1994;23:817-27.  Back to cited text no. 11
Sutton DM, Nair RC, Rock G. Complications of plasma exchange. Transfusion 1989;29:124-7.  Back to cited text no. 12
Bramlage CP, Schröder K, Bramlage P, Ahrens K, Zapf A, Müller GA, et al. Predictors of complications in therapeutic plasma exchange. J Clin Apher 2009;24:225-31.  Back to cited text no. 13
Gafoor VA, Jose J, Saifudheen K, Musthafa M. Plasmapheresis in neurological disorders: Experience from a tertiary care hospital in South India. Ann Indian Acad Neurol 2015;18:15-9.  Back to cited text no. 14
[PUBMED]  [Full text]  
Sharma RR, Saluja K, Jain A, Dhawan HK, Thakral B, Marwaha N, et al. Scope and application of therapeutic apheresis: Experience from a tertiary care hospital in North India. Transfus Apher Sci 2011;45:239-45.  Back to cited text no. 15
Vikrant S, Thakur S, Sharma A, Gupta D, Sharma S. Safety and efficacy of therapeutic membrane plasmapheresis in the treatment of Guillain-Barré syndrome: A study from a tertiary care hospital from India. Neurol India 2017;65:527-31.  Back to cited text no. 16
[PUBMED]  [Full text]  
Ahammed Nizar OT, Rai P, Rao SN, Shenoy MP. Plasmapheresis: A retrospective audit of procedures from a tertiary care center in Southern India. Indian J Crit Care Med 2017;21:857-60.  Back to cited text no. 17
Kumar AS, Latha B, Dhivya K. Therapeutic plasma exchange in neuroimmunological disorders. Int J Res Med Sci 2017;5:1550-3.  Back to cited text no. 18
Gajjar MD, Shah S, Shah M, Bhatnagar N, Soni S, Patil T. Efficacy and cost effectiveness of therapeutic plasma exchange in patients of Guillain-Barre syndrome – A prospective study. SEAJCRR 2013;2:218-28.  Back to cited text no. 19
Sprenger KB, Rasche H, Franz HE. Membrane plasma separation: Complications and monitoring. Artif Organs 1984;8:360-3.  Back to cited text no. 20
Samtleben W, Blumenstein M, Liebl L, Gurland HJ. Membrane plasma separation for treatment of immunologically mediated diseases. Trans Am Soc Artif Intern Organs 1980;26:12-6.  Back to cited text no. 21
Wong EC, Balogun RA. Therapeutic apheresis in pediatrics: Technique adjustments, indications and nonindications, a plasma exchange focus. J Clin Apher 2012;27:132-7.  Back to cited text no. 22
Basic-Jukic N, Brunetta B, Kes P. Plasma exchange in elderly patients. Ther Apher Dial 2010;14:161-5.  Back to cited text no. 23
Korach JM, Berger P, Giraud C, Le Perff-Desman C, Chillet P. Role of replacement fluids in the immediate complications of plasma exchange. French registry cooperative group. Intensive Care Med 1998;24:452-8.  Back to cited text no. 24


  [Table 1], [Table 2], [Table 3]


Similar in PUBMED
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  In this article
Materials and Me...
Article Tables

 Article Access Statistics
    PDF Downloaded109    
    Comments [Add]    

Recommend this journal