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 Table of Contents  
SHORT ARTICLE
Year : 2018  |  Volume : 3  |  Issue : 2  |  Page : 136-139

Therapeutic plasma exchange: A study of indications and efficacy


1 Department of Pathology, Himalayan Institute of Medical Sciences, Dehradun, Uttarakhand, India
2 Department of Medicine, Himalayan Institute of Medical Sciences, Dehradun, Uttarakhand, India

Date of Web Publication24-Oct-2018

Correspondence Address:
Dr. Rashi Ahuja
Department of Pathology, Himalayan Institute of Medical Sciences, Dehradun, Uttarakhand
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/GJTM.GJTM_26_18

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  Abstract 


Background and Objectives: Therapeutic plasma exchange has been in use to treat a variety of diseases and for the purpose of rational decision-making, the American Society for Apheresis has proposed guidelines for the same. The present study was undertaken to study various aspects of the plasma exchange facility in a tertiary care center at Uttarakhand, India. Methods: The relevant demographical details (age, sex, BMI), clinical history of patient (any previous illness, any chromic disease, medications etc.), relevant investigations performed (basic haematology and immunology tests), plasma exchange procedure notes (total time taken, any adverse reactions noted), and replacement fluids used (type and amount used) were recorded and analyzed. Results: A total of 157 plasma exchange procedures were performed on 47 patients. Of these, maximum procedures were done for patients with Guillain–Barre syndrome (GBS), myasthenic crisis, and disseminated intravascular coagulation (DIC). The other indications were multiple myeloma, plasma cell dyscrasia, thrombotic thrombocytopenic purpura, and DIC after scrub typhus and dengue. The most common adverse reaction noted was urticaria (8/19), followed by perioral tingling (3/19) and hypotension (7/19). Interpretation and Conclusions: Fifteen out of 17 patients suffering from GBS and all patients of myasthenic crisis showed recovery, however, one patient of myasthenia gravis did not show immediate improvement, but recovered after some delay. Among the patients with thrombotic thrombocytopenic purpura with neurological manifestations, 3 out of 5 patients showed significant improvement. Patients who presented with other indications of plasma exchange also showed clinical benefits and the procedure resulted in quick recovery.

Keywords: Indications, plasmapheresis, therapeutic plasma exchange


How to cite this article:
Negi G, Ahuja R, Gupta V, Gaur DS, Goel D, Kaushik R. Therapeutic plasma exchange: A study of indications and efficacy. Glob J Transfus Med 2018;3:136-9

How to cite this URL:
Negi G, Ahuja R, Gupta V, Gaur DS, Goel D, Kaushik R. Therapeutic plasma exchange: A study of indications and efficacy. Glob J Transfus Med [serial online] 2018 [cited 2018 Nov 20];3:136-9. Available from: http://www.gjtmonline.com/text.asp?2018/3/2/136/243924




  Introduction Top


The word “apheresis” is derived from the Greek word “aphairesis,” which means “to separate,” “to take away by force,” or “to remove.” This term was originally used by Abel, Rowntree, and Turner to describe manual plasma exchange.[1] Since this initial use, the term has been used more broadly to describe several procedures, all of which involve the separation of whole blood into its components with removal of one of these components. Therapeutic plasma exchange (TPE) is used to treat a variety of diseases through the bulk removal of plasma which is then replaced with some form of replacement fluid. TPE removes pathologic substances (pathologic antibodies, immune complexes, or cytokines), the removal of which renders clinical improvement. The procedure is being used in almost all the fields of medicine with indications covering a diverse range of diseases, some of which may prove to be even life-threatening and complications that may otherwise not be so as the morbid conditions. A wide variety of diseases can be treated with TPE and for the purpose of rational decision-making, the American Society for Apheresis (ASFA) has proposed the guidelines in which the indications for TPE were divided into four categories depending on the anticipated results.[1]

The present study was undertaken to study various aspects of the plasma exchange activities in a tertiary care center at Uttarakhand, India, which is the only center in the state that currently has a facility for TPE. The study was done with the aim of analyzing the usage, indications, procedure, and results of this procedure in a comprehensive manner.


  Materials and Methods Top


All patients with indications for therapeutic exchange, who were referred to the Blood Bank in a 4-year period between February 2012 and April 2016 were included in the retrospective analysis. Suitability for the procedure was ensured by detailed history, examination, and relevant investigations including hemogram, prothrombin time, activated partial thromboplastin time, serum albumin, and serum calcium levels. Besides, some other relevant demographical details of the patients were recorded.

The plasma exchange was performed on the MCS + haemonetics blood cell separator. A 12 French double lumen femoral catheter was used for venous access during the procedure. Detailed procedure notes including the amount of plasma volume exchanged, amount of anticoagulant volume, number of cycles, and adverse reactions, if any, were recorded in a predesigned format for the procedure. The volumes of replacement fluids that were used, that is, normal saline, human albumin solution, and fresh frozen plasma were also recorded.

A total of 157 TPEs were performed on 47 patients, the most of them were in an age group between 21 and 40 years, the youngest being a 9-year-old girl and the oldest one was a 78-year-old man.

Among the cases underwent the procedure, the number of patients with Guillain–Barre syndrome (GBS) were 17 and myasthenic crisis were 13. The other conditions include disseminated intravascular coagulation (DIC), multiple myeloma, plasma cell dyscrasia, thrombotic thrombocytopenic purpura (TTP), and DIC following the scrub typhus and dengue viral (DEV) infection. On an average, the patients underwent 1–8 cycles of TEP. Maximum number of cycles was given to the patients with GBS, that is, 4–5 cycles each and a patient with of myasthenia gravis, who had received 8 cycles.

The volume of plasma exchanged ranged from 1300 ml to 6814 ml depending on the patient's parameters (pulse, blood pressure, respiratory rate, and hemogram). The anticoagulant used was acid-citrate-dextrose adenine with its volume ranged from 100 ml to 655 ml for a single procedure; the average volume being 203 ml.

The procedures were mostly performed bedside in the intensive care unit and the adverse events, if any, were noted and handled bedside.


  Results Top


Observations

The most common adverse reaction noted was urticaria which occurred in 8 out of 19 patients. The other adverse reactions include perioral tingling (3/19) and hypotension (7/19).

A total number of 157 plasma exchange procedures were performed on 47 patients.

We had 17 cases of GBS, making it the most common indication for TPE in our study. Fifteen out of 17 patients suffering from GBS showed symptomatic improvement in neurological manifestations after the TPE.

Two of the 17 patients showed only mild improvement. The average number of procedures done on these patients was 4. All the patients with myasthenic crisis showed fast and significant improvement, though one patient with myasthenia gravis did not show an immediate improvement but did so after some delay. Among the patients with nonneurological conditions, such as multiple myeloma, plasma cell dyscrasia, TTP, and DIC, the procedure was beneficial to yield quick recovery.


  Discussion Top


According to the ASFA guidelines, the indications for TPE are divided into four categories, namely, Category I includes diseases in which TPE is considered as the first-line therapy, for example, myasthenia gravis, GBS, TTP; Category II, in which TPE is considered as stand-alone therapy or in conjunction with other modes of treatment, for example, cold-agglutinin disease, ABO-incompatible kidney transplant, multiple sclerosis, and systemic lupus erythematosus; Category III, wherein the optimum role of TPE is not established yet the treating physician may make his/her own judgment to go for the procedure; and Category IV, diseases in which the published evidence suggests TPE to be either ineffective or harmful, for example, inclusion body myositis, lupus nephritis, etc. Our cases in the present report belonged to Category I as per criteria laid down by the ASFA.

Devices used to perform TPE are based on two broad principles, namely, the one that separates the plasma from the cellular components as per their size and the other one that separates the blood components based on their density. In TPE, after ensuring a stable venous access through an intravenous catheter, the blood flow is directed to a spinning centrifuge bowl. The dense elements, such as RBCs, get settled at the bottom whereas the lesser dense elements such as leukocytes and platelets form a middle buffy coat layer, keeping the plasma on the very top. The plasma layer is collected into a collection bag and the remaining components are returned to the patient's blood circulation after mixing with the plasma substitute. Normal saline, fresh frozen plasma, or albumin serve as substitutes to replace plasma on required proportion depending on the disease condition of the individual patient.

Effectiveness of TPE depends on volume of plasma removed relative to total plasma volume that a patient has possessed; substances need to be removed that are distributed between intra-and extra-vascular compartments; speed at which the substance equilibrates between compartments and the rate at which substance is synthesized in the body. Routine practice is to exchange only 1–1.5 plasma volumes during a single TPE. Amount of plasma removed beyond 1.5 times of the existing plasma volumes gives rise to the removal of a smaller, less clinically important amounts of pathologic substance present in the plasma while prolonging the procedure and exposing the patient to more replacement fluid and anticoagulant. This may result in an increased risk of complications without increasing much benefit to the patient. In our study, most of the procedures involved an exchange of 1.5 times plasma volume safely.

Dada and Kaplan studied the response of TPE in comparison with treatment with intravenous immune globulin (IVIg), among the patients with GBS. In their study, 8/10 patients treated with TPE showed improvement in their neurological parameters. Of these, 4 patients had axonal involvement in the electromyogram and 3 of these 4 patients demonstrated an improvement with TPE, once they were failed to respond to IVIg treatment.[2]

In our study, all the four cases with plasma cell dyscrasias showed improvement, one of which had Waldenstrom's macroglobulinemia. The case with multiple myeloma and renal failure also showed a rapid reduction/removal of light chains by aggressive chemotherapy and/or plasmapheresis and that, it may prevent further complications like irreversible renal failure or the risk of renal damage.[3]

In our study, myasthenia gravis was another important indication for the need of TPE. Of 13 patients, 12 patients showed tremendous improvement following TPE and 10 of these were weaned off the ventilator by the 3rd day following the therapy. A 9-year-old patient did not show immediate improvement but slowly improved over a span of 2 months. Similar results were obtained among such patients and emphasized that the TPE reduces the hospital stay and thereby reducing an overall expenses in treatment.[4]

Of the 5 patients with TTP, 3 of them were improved, 1 patient died, and remaining 1 denied the consent and discontinued after initial treatment.

Shepard et al. carried out a multiapproach study on about 40 patients with TTP of which 17 patients were treated with plasma exchange, 15 with exchange transfusions, and 6 with both types of therapy. The complete response rates in each category were 88% for plasma exchange (15 patients), 47% for exchange transfusions (7 patients), and 67% for exchange transfusions and plasma exchange (4 patients).[5]

A few procedures were performed on the three patients with DIC having variable etiology. One of the patients with scrub typhus presented with DIC was an unusual condition that required TPE. All three cases showed marked improvement after TPE. Another case with the DEV infection presented with DIC underwent procedure of TPE as per request by the clinician but was not survived. Kandasamy et al.[6] analyzed the three children with dengue-associated hyperferritinemic multiple organ dysfunction syndrome had undergone TPE and concluded that TPE is an isolated immunomodulatory therapy in such cases and emphasized the need for further prospective studies. It was successfully performed on cases of MG, GBS, PCD, TTP, and scrub typhus.

Mokrzycki and Kaplan[7] noted urticaria to be the most common adverse reaction during plasma exchange procedures in their study. In our study, the procedure was found to be safe, with the majority of reactions and complications being mild, easily treated, and of limited duration. Since the procedures were done at bedside, the adverse reactions could immediately be noticed and treated. The most common adverse reaction noted was urticaria which occurred in 8 out of 19 patients. The other adverse reactions observed include perioral tingling and hypotension.

Thus, we endorse with our concluding note that plasma exchange is a safe therapeutic procedure to be used in treating a variety of diseases through the bulk removal of plasma.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Winters JL. Plasma exchange: Concepts, mechanisms, and an overview of the American society for apheresis guidelines. Hematology Am Soc Hematol Educ Program 2012;2012:7-12.  Back to cited text no. 1
    
2.
Dada MA, Kaplan AA. Plasmapheresis treatment in Guillain-Barré syndrome: Potential benefit over IVIg in patients with axonal involvement. Ther Apher Dial 2004;8:409-12.  Back to cited text no. 2
    
3.
Goldschmidt H, Lannert H, Bommer J, Ho AD. Multiple myeloma and renal failure. Nephrol Dial Transplant 2000;15:301-4.  Back to cited text no. 3
    
4.
Makroo RN, Raina V, Kohli A, Suri V, Kumar P. Effectiveness of therapeutic plasma exchange in myasthenia gravis. Apollo Med 2008;5:11820.  Back to cited text no. 4
    
5.
Shepard KV, Fishleder A, Lucas FV, Goormastic M, Bukowski RM. Thrombotic thrombocytopenic purpura treated with plasma exchange or exchange transfusions. West J Med 1991;154:410-3.  Back to cited text no. 5
    
6.
Vivekanand VV, Kandasamy S, Vijaya Kumar N, Sangaralingam T, Nedunchezhian. Effect of estimated glomerular filtration rate (eGFR) and fluid balance on clinical course and outcomes of children admitted with severe dengue. Pediatr Care Med 2014; 1-4.  Back to cited text no. 6
    
7.
Mokrzycki MH, Kaplan AA. Therapeutic plasma exchange: Complications and management. Am J Kidney Dis 1994;23:817-27.  Back to cited text no. 7
    




 

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