Article

Letter to the Editor

Ann Lab Med 2022; 42(6): 703-707

Published online November 1, 2022 https://doi.org/10.3343/alm.2022.42.6.703

Copyright © Korean Society for Laboratory Medicine.

Proposal of the Need for New Korean Guidelines on the Use of Therapeutic Apheresis in Clinical Practice

Yousun Chung, M.D.1 , Hyungsuk Kim, M.D.2 , and Dae-Hyun Ko, M.D.3

1Department of Laboratory Medicine, Kangdong Sacred Heart Hospital, Seoul, Korea; 2Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Korea; 3Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Correspondence to: Dae-Hyun Ko, M.D.
Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea
Tel: +82-2-3010-4504, Fax: +82-2-478-0884
E-mail: daehyuni1118@amc.seoul.kr

Received: January 24, 2022; Revised: March 13, 2022; Accepted: June 2, 2022

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Dear Editor,

Therapeutic apheresis is performed for numerous indications in various medicine fields [1-5]. The primary reference on the use of therapeutic apheresis are the evidence-based guidelines issued by the Writing Committee of the American Society for Apheresis (ASFA) [6]. These guidelines provide structured evidence for therapeutic apheresis and are offered for medical consideration worldwide. Recently, new guidelines were issued by the Japanese Society for Apheresis (JSFA) [7]. The main difference between the two guidelines lies in the primary modality used in each country and clinical indications for therapeutic apheresis. The primary apheresis modality used in Japan is the membrane separation method, whereas in the USA, the centrifugal separation method is mainly used. As the target diseases and their backgrounds differ between these countries, there was a need to develop new guidelines in Japan.

The most noticeable difference between the ASFA and JSFA guidelines is that various new techniques are suggested in the latter. New technologies and tools have been developed and applied in clinical apheresis in Japan, including hollow-fiber devices such as double filtration plasmapheresis (DFPP), adsorption devices such as polymyxin B-immobilized endotoxin adsorption columns, and selective plasma exchange devices. In the JSFA guidelines, out of four categories, plasma filtration with dialysis (PDF) for liver failure is classified as category II, implying that therapeutic apheresis can be applied as a second-line therapy, independent of plasma exchange and continuous hemodiafiltration (CHDF) for acute liver failure (category I). In the ASFA guidelines, plasma exchange is the only option suggested for acute liver failure. As for the diseases included in the two guidelines, 39 diseases are included only in the ASFA guidelines and 32 diseases only in the JSFA guidelines (Table 1). This likely reflects the variability in the prevalence of certain diseases according to country and ethnicity. Specifically, babesiosis, malaria, and sickle cell disease are included only in the ASFA guidelines as their prevalence in Asia is extremely low. Extracorporeal photopheresis (ECP) for graft-versus-host disease (GVHD) is classified into category II in the ASFA guidelines, whereas there is no mention of ECP for GVHD in the JSFA guidelines.

Table 1 . Diseases included in only one of the ASFA and JSFA guidelines and their modalities, indications, categories, and grades

GuidelinesDiseasesTherapeutic apheresis modalityIndicationCategoryGrade
ASFA onlyAge-related macular degeneration, dryRheopheresisHigh-riskII2B
Atopic (neuro-)dermatitis (atopic eczema), recalcitrantECP
IA
TPE/DFPP
III
III
III
2A
2C
2C
Autoimmune hemolytic anemia, severeTPE
TPE
Severe cold agglutinin disease
Severe warm autoimmune
II
III
2C
2C
BabesiosisRBC exchangeSevereII2C
Burn shock resuscitationTPEIII2B
Cardiac neonatal lupusTPEIII2C
Catastrophic antiphospholipid syndromeTPEIII2C
Erythropoietic protoporphyria, liver diseaseTPE
RBC exchange
III
III
2C
2C
Graft-versus-host diseaseECP
ECP
Acute
Chronic
II
II
1C
1B
Hemolysis, elevated liver enzymes, and low platelets (HELLP) syndromeTPE
TPE
Postpartum
Antepartum
III
IV
2C
2C
Hemophagocytic lymphohistiocytosis; hemophagocytic syndrome; macrophage activating syndromeTPEIII2C
Heparin-induced thrombocytopenia and thrombosisTPE
TPE
Pre-cardiopulmonary bypass
Thrombosis
III
III
2C
2C
Hereditary hemochromatosisErythrocytapheresisI1B
IgA nephropathy (Berger’s disease)TPE
TPE
Crescentic
Chronic progressive
III
III
2B
2C
Immune thrombocytopeniaTPE/IARefractoryIII2C
MalariaRBC exchangeSevereIII2B
Myeloma cast nephropathyTPEII2B
Nephrogenic systemic fibrosisECP/TPEIII2C
Pemphigus vulgarisTPE
ECP/IA
Severe
Severe
III
III
2B
2C
Peripheral vascular diseasesLAII1B
Post-transfusion purpuraTPEIII2C
Pruritus due to hepatobiliary diseasesTPETreatment resistantIII1C
Scleroderma (systemic sclerosis)TPE
ECP
III
III
2C
2A
Sickle cell disease, acuteRBC exchange
RBC exchange
RBC exchange
Acute stroke
Acute chest syndrome, severe
Other complications
I
II
III
1C
1C
2C
Sickle cell disease, non-acuteRBC exchange
RBC exchange
RBC exchange
RBC exchange
Stroke prophylaxis
Pregnancy
Recurrent vaso-occlusive pain crisis
Pre-operative management
I
II
II
III
1A
2B
2B
2A
Sudden sensorineural hearing lossLA/rheopheresis/TPEIII2A
ThrombocytosisThrombocytapheresis
Thrombocytapheresis
Symptomatic
Prophylactic or secondary
II
III
2C
2C
Thrombotic microangiopathy, coagulation mediatedTPETHBD, DGKE, and PLG mutationsIII2C
Thrombotic microangiopathy, drug-associatedTPE
TPE
TPE
Ticlopidine
TPE Clopidogrel
Gemcitabine/quinine
I
III
IV
2B
2B
2C
Thrombotic microangiopathy, transplantation associatedTPEIII2C
Thyroid stormTPEII2C
Transplantation, cardiacECP
ECP
TPE
TPE
Cellular/recurrent rejection
Rejection prophylaxis
Desensitization
Antibody-mediated rejection
II
II
II
III
1B
2A
1C
2C
Transplantation, hematopoietic stem cell, ABO incompatible (ABOi)TPE
TPE
RBC
TPE
Major ABOi HPC(M) II
Major ABOi HPC(A) II
Minor ABOi HPC(A) III
Major/minor ABOi with pure RBC aplasia
II
II
III
III
1B
2B
2C
2C
Transplantation, hematopoietic stem cell, human leukocyte antigen desensitizationTPEIII2C
Transplantation, liverTPE
TPE
ECP
ECP
Desensitization, ABOi living donor
Desensitization, ABOi deceased donor/antibody-mediated rejection
Desensitization, ABOi
Acute rejection/immune suppression withdrawal
I
III
III
III
1C
2C
2C
2B
Transplantation, lungECP
TPE
Bronchiolitis obliterans syndrome
Antibody-mediated rejection/desensitization
II
III
1C
2C
Vasculitis, IgA (Henoch–Schönlein purpura)TPE
TPE
Crescentic rapidly progressive glomerulonephritis
Severe extrarenal manifestations
III
III
2C
2C
Vasculitis, otherTPE
TPE
Adsorptive cytapheresis
TPE
Hepatitis B polyarteritis nodosa
Idiopathic polyarteritis nodosa
Adsorptive cytapheresis Behcet’s disease
Behcet’s disease
II
IV
II
III
2C
1B
1C
2C
Wilson’s disease, fulminantTPEI1C
JSFA onlyAcute autonomic sensory neuropathyTPEIII2C
Acute exacerbation of interstitial pneumoniaPMX-DHPIII2C
Acute pancreatitisCHDF, PDFII2B
Acute respiratory distress syndromeCHDFIII2C
Amyopathic dermatomyositis and polymyositis with complications of interstitial pneumoniaPMX-DHP, LCAPIII2B/3C
Arteriosclerosis obliteransLDL-AII1C
AscitesCARTII1C
Autoimmune autonomic ganglionopathyTPEIII2C
Autoimmune encephalitis/cerebellitis LGI1/Caspr2/GABAbR/ AMPAR/GAD/GlyR/NAETPE, IAPP, CAPIII2C
Bickerstaff brainstem encephalitisTPE, IAPPIII2C
CalciphylaxisLDL-A, TPE, cryofiltrationIII2C
Cholesterol crystal embolismLDL-AII or III2C
Chronic hepatitis CDFPPIII2C
Diabetic nephropathyLDL-AIII1C
Drug-induced lung damagePMX-DHPIII2C
Fisher’s syndromeTPE, DFPP, IAPPIII2C
HTLV-1-associated myelopathyTPE, IAPP, LCAPIII2C
Hypertrophic pachymeningitisLCAPIII2C
Isaacs’ syndromeTPE, DFPPIII2B
Neuropsychiatric SLEIAPP, TPE, DFPPII2C
Palmoplantar pustulosisGMAIII1C
PemphigoidTPE, DFPPII1C
Psoriatic arthritisGMAII1C
Pyoderma gangrenosumGMAIII2C
Rapidly progressive interstitial pneumonia associated with anti-MDA5 antibody-positive dermatomyositisPEIII2C
Refractory nephrotic syndromePE, DFPP, LDL-AIII/III–/2C
Renal failure with unstable hemodynamicsCHDFI
Severe sepsis and septic shockCHDF (without AN-69ST)
Sjögren’s syndromePE, DFPPIII2C
Tumefactive demyelinating diseasePEIII2C
Liver failurePDFII1C
Severe acute pancreatitisPDFIII2C

Abbreviations: ASFA, American Society for Apheresis; CART, cell-free and concentrated ascites reinfusion therapy; CHDF, continuous hemodiafiltration; DFPP, double filtration plasmapheresis; ECP, extracorporeal photopheresis; GMA, granulocyte and monocyte adsorption apheresis; HPC, hematopoietic progenitor cell; IA, immunoadsorption; IAPP, immunoadsorption plasmapheresis; JSFA, Japanese Society for Apheresis; LA, lipoprotein apheresis; LCAP, leukocytapheresis; LDL-A, LDL apheresis; PDF, plasma filtration with dialysis; PMX-DHP, polymyxin B-immobilized fiber column direct hemoperfusion; TPE, therapeutic plasma exchange; RBC: red blood cell.



Guidelines for therapeutic apheresis have yet to be developed in Korea. At present, medical decisions and national health insurance reimbursements for apheresis are based on the ASFA guidelines. Like in the USA, the main modality used for clinical apheresis in Korea is centrifugal separation. However, the target diseases are closer to those in Japan because of shared ethnic and geographical backgrounds. Due to the language barrier, literature published in Korean was not included in either of the guidelines. There is a need to develop Korean guidelines on therapeutic apheresis using both guidelines as a reference, while considering Korea’s unique demands. For example, severe fever with thrombocytopenia syndrome (SFTS) is uncommon in the USA and is therefore not included in the ASFA guidelines. Despite there being a few cases of SFTS in Japan, it is not included in the JSFA guidelines either. However, in Korea, the incidence of SFTS is relatively high, at 200–250 cases annually, and the clinical utility of therapeutic plasma exchange (TPE) for the treatment of SFTS has been suggested in case reports [8, 9]. In the guidelines published by the Korea Disease Control and Prevention Agency, TPE has been suggested as a treatment option for removing cytokines in SFTS [10]. New Korean guidelines should be introduced that enable the clinical application of therapeutic apheresis for diseases unique to the Korean population as well as the reimbursement from insurance for apheresis in such cases.

The frequency and modalities used for apheresis in different diseases vary among countries, as does the reimbursement from insurance [5]. Optimal guidelines for clinical apheresis should be established for each country’s unique population and could guide physicians in deciding whether to perform apheresis. There should be continuous academic and political efforts to establish clinical apheresis guidelines in Korea.

Chung Y: Investigation, Writing—original draft preparation; Kim Y: Writing—reviewing and editing; Ko DH: Conceptualization, Writing—reviewing and editing.

The authors have no competing interests to declare.

This study did not receive any grant from funding agencies in the public, commercial, or not-for-profit sectors.

  1. 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.
    Pubmed CrossRef
  2. De Silvestro G. The Italian registry of therapeutic apheresis-2015. Transfus Apher Sci 2017;56:75-81.
    Pubmed CrossRef
  3. De Silvestro G and Tison T; Italian Society of Apheresis and Cell Manipulation (SIdEM). Italian registry of therapeutic apheresis. Transfus Apher Sci 2018;57:143-7.
    Pubmed CrossRef
  4. Mörtzell Henriksson M, Newman E, Witt V, Derfler K, Leitner G, Eloot S, et al. Adverse events in apheresis: an update of the WAA registry data. Transfus Apher Sci 2016;54:2-15.
    Pubmed CrossRef
  5. Stegmayr B, Mörtzell Henriksson M, Newman E, Witt V, Derfler K, Leitner G, et al. Distribution of indications and procedures within the framework of centers participating in the WAA apheresis registry. Transfus Apher Sci 2017;56:71-4.
    Pubmed CrossRef
  6. Padmanabhan A, Connelly-Smith L, Aqui N, Balogun RA, Klingel R, Meyer E, 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 eighth special issue. J Clin Apher 2019;34:171-354.
    Pubmed CrossRef
  7. Abe T, Matsuo H, Abe R, Abe S, Asada H, Ashida A, et al. The Japanese Society for Apheresis clinical practice guideline for therapeutic apheresis. Ther Apher Dial 2021;25:728-876.
    Pubmed CrossRef
  8. Yoo JR, Kim SH, Kim YR, Lee KH, Oh WS, Heo ST. Application of therapeutic plasma exchange in patients having severe fever with thrombocytopenia syndrome. Korean J Intern Med 2019;34:902-9.
    Pubmed KoreaMed CrossRef
  9. Oh WS, Yoo JR, Kwon KT, Kim HI, Lee SJ, Jun JB, et al. Effect of early plasma exchange on survival in patients with severe fever with thrombocytopenia syndrome: a multicenter study. Yonsei Med J 2017;58:867-71.
    Pubmed KoreaMed CrossRef
  10. Korea Disease Control and Prevention Agency. Guidelines for treatment of severe febrile thrombocytopenia syndrome. http://www.mohw.go.kr/react/al/sal0301vw.jsp?PAR_MENU_ID=04&MENU_ID=0403&page=312&CONT_SEQ=333510 (Updated on Jul 2016).