Problem Solving in Apheresis Medicine

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Editor
Ilknur Kozanoglu
Adana Adult BMT Center
Baskent University
Adana, Türkiye
Acibadem Labmed Medical Laboratories
Hematology Laboratories
Istanbul, Türkiye

ISBN 978-3-031-74080-0    ISBN 978-3-031-74081-7 (eBook)

https://doi.org/10.1007/978-3-031-74081-7

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Contents

Part I Principles of Apheresis

1 History of Apheresis����������������������������������������������������������������������    3

Omur Kayikci and Emre Tekgunduz
2 The Basics of Apheresis ����������������������������������������������������������������    7
Kaatje le Poole, Marleen M. Neyrinck, and Hans Vrielink
3 Apheresis Mathematics������������������������������������������������������������������   19
Marleen M. Neyrinck and Hans Vrielink
4 Apheresis Team and Job Descriptions������������������������������������������   29
Nina Worel and Annika Malmborg Kisch

Part II ASFA Guide 2019

5 How to Read ASFA Guideline������������������������������������������������������   39

Bilgen Hulya
6 American Society for Apheresis Indication Categories
and Indications ������������������������������������������������������������������������������   47
Jeffrey L. Winters
7 Category IV Diseases for ASFA����������������������������������������������������   67
Kaya Ali Hakan

Part III Top Problems and Solutions in Apheresis

8 Vascular Access Problems During Apheresis������������������������������   75

David Barth
9 Problems During Apheresis in Children��������������������������������������   83
İkbal Ok Bozkaya and Namık Yaşar Özbek
10 Problems During the Usage and Dosage of Anticoagulants��������   91
Eylem Eliacik
11 Complications and How to Avoid Them During Apheresis��������   95
Ilknur Kozanoğlu

v
vi Contents

12 Complications During Adsorptive Cytapheresis Treatment��������� 105

Piero Vernia and Filippo Vernia
13 Basic Principles and Problems in Donor Lymphocyte
Collection���������������������������������������������������������������������������������������� 115
Meltem Kurt Yüksel

Part IV Complications During Plasma Exchange

and Plasmapheresis Therapy

14 Complications During Apheresis in Patients

with Hematologic Diseases������������������������������������������������������������ 137
Nihan Alkış and H. Atilla Özkan
15 Complications of Therapeutic Plasma Exchange
in Intoxication�������������������������������������������������������������������������������� 147
Murat Özkale and Yasemin Özkale
16 Complications During Apheresis in Patients with Sepsis ���������� 153
Sule Mine Bakanay Ozturk and Ankara Bilkent Şehir Hastanesi

Part V Problems During Red Cell Exchange Procedure

17 Managing Acute Complications of Sickle Cell Disease�������������� 163

Duygu Nurdan Avcı

Part VI Risk Evaluation in Double Filtration Plasmapheresis

18 Basic Principles of Double-­Filtration Plasmapheresis���������������� 173

Ilknur Kozanoğlu
19 Comparison of Double-Filtration Plasmapheresis
and Plasma Exchange�������������������������������������������������������������������� 179
Ilknur Kozanoğlu, Osman Sahin, and Cem Kis

Part VII Problems During Extracorporeal Photopheresis (ECP)

20 Extracorporeal Photopheresis in Patients with Acute

Graft-­Versus-­Host Disease������������������������������������������������������������ 185
Hakan Ozdogu and Çigdem Gereklioglu
21 Extracorporeal Photopheresis in Patients with Chronic
Graft-­Versus-­Host Disease������������������������������������������������������������ 191
Leylagül Kaynar and Yaşa Gül Mutlu

Part VIII What Should to Talk About for Apheresis

at the Future

22 Quality Control Principles in Apheresis�������������������������������������� 203

Songül Tepebaşı and İlknur Kozanoğlu
Contents vii

23 Current Developments and Research in Apheresis�������������������� 209

Robert W. Maitta
24 The Role of Therapeutic Plasma Exchange
(Plasmapheresis) in Aging ������������������������������������������������������������ 225
D. Kiprov, R. Rohe, M. Conboy, and I. Conboy
25 Apheresis and COVID-19�������������������������������������������������������������� 233
Funda Tanrikulu
 Part I
Principles of Apheresis
 History of Apheresis
1
Omur Kayikci and Emre Tekgunduz

1.1 Introduction increase of indications where apheresis can be

used as either a standalone or adjuvant treatment
The term apheresis is a Greek word, which means option.
to separate or remove. The idea of changing the Apheresis may be used for the separation of
blood composition and removing a presumed blood products like whole blood for transfusion
pathological substance from the blood to treat of components or for the treatment of patients
various diseases mainly through bloodletting (therapeutic apheresis). The former use of apher-
goes back to 1000 years BC [1]. Apheresis is a esis is closely associated with transfusion medi-
process or treatment modality by which blood is cine, whereas the latter has a wide range of
being removed from a patient/subject, desired clinical applications. History of apheresis reflects
component is collected, and the rest is returned to the development of instrumentation. It is not the
the donor [2]. Modern apheresis is a complex, scope of this review to discuss all the achieve-
technology-dependent field involved in the treat- ments regarding apheresis, but rather its mile-
ment of a broad spectrum of diseases belonging stones and current state will be summarized.
to various disciplines including but not restricted
to hematology, oncology, rheumatology, hemato-
poietic stem cell transplantation (HSCT), infec- 1.2 Early Efforts Regarding Cell
tious diseases, intensive care, cardiology, Separation
nephrology, neurology, and solid organ trans-
plantation. This fact is reflected by steady In 1914 Abel, Rowntree, and Turner used manual
apheresis in an animal model (performed in phle-
botomized dogs) where they separated plasma
O. Kayikci from whole blood through centrifugation [3]. The
Memorial Bahçelievler Hospital Adult Hematology return of red blood cells to the animal prevented
and BMT Clinic, Istanbul, Turkey undesirable effects of bleeding and was later
e-mail: [email protected]
found to be cost-effective in harvesting horse-­
E. Tekgunduz (*) derived antiserum [4]. Manual plasmapheresis
Memorial Bahçelievler Hospital Adult Hematology
was successfully used for the treatment of a
and BMT Clinic, Istanbul, Turkey
patient presenting with Waldenström
Division of Hematology, Department of Internal
macroglobulinemia-­associated hyperviscosity in
Medicine, Maltepe University Medical School,
Istanbul, Turkey 1952 [5]. Harvesting platelet concentrates by
e-mail: [email protected] using repeated manual plasmapheresis from

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2024 3

I. Kozanoglu (ed.), Problem Solving in Apheresis Medicine,
https://doi.org/10.1007/978-3-031-74081-7_1
4 O. Kayikci and E. Tekgunduz

blood donors was first described in 1961 [6]. 1.4 Red Blood Cell Procedures
Colman was the first to report on therapeutic
thrombocytapheresis decreasing the platelet Red blood cell (RBC) exchange, erythrocy-
count in a patient with myeloproliferative neo- tapheresis, and RBC depletion are different
plasm [7]. apheresis modalities used to decrease the RBC
mass in the donor/apheresis product or replace
patient RBSc with donor erythrocytes [11].
1.3 Blood Cell Separators Manual RBC exchange involves serial phleboto-
mies, followed by colloid/crystalloid infusions.
The basic principle behind the technology of Meanwhile, automated RBC exchange is per-
modern blood cell separator devices relied on the formed using apheresis instruments where donor
principle of Dr. Carl Gustaf Patrik De Laval, who RBCs are selectively removed and replaced with
invented a cream separator through continuous healthy donor RBC or colloid/crystalloid solu-
flow centrifugation [8]. In the early 1950s, Dr. tions. RBC exchange is frequently used to treat
Edwin Cohn developed a method for the purifica- acute/chronic complications of sickle cell disease
tion of plasma albumin from pooled human [12], to decrease the pathogen load in malaria
plasma that is used for the resuscitation of [13] and babesiosis [14], and to decrease acute
wounded soldiers. Dr. Cohn envisioned a device and long-term consequences in ABO-mismatched
to separate online donor plasma during whole allogeneic hematopoietic stem cell transplanta-
blood donation, which was actually more useful tion [15].
in deglycerolizing frozen red blood cells rather
than the intended purpose [9]. By improving the
design of the Cohn’s centrifugal element, Alan 1.5 Therapeutic Plasma
Latham developed Haemonetics model 30 as the Exchange
first apheresis device designed for intermittent-­
flow platelet donation and therapeutic apheresis Therapeutic plasma exchange (TPE) is the most
(TA) [10]. frequently used modality in therapeutic aphere-
An important step for the development of ther- sis. Acquired thrombotic thrombocytopenic pur-
apeutic apheresis technology came from the pura (aTTP) is the prototype disease indicating
National Cancer Institute. George Hudson, an the life-saving role of TPE, which is character-
IBM engineer, whose son was being treated for ized by autoantibody-associated inhibition of von
chronic myeloid leukemia (CML), worked with Willebrand cleaving protease (ADAMTS13).
Dr. Emil Freireich who envisioned a device The efficacy mechanism of TPE in aTTP depends
designed for collecting excess leucocytes from on the removal of autoantibody and restoration of
CML patient and the later use of these cells for normal enzyme activity. Rubinstein was the first
supporting neutropenic patients. The result of who successfully treated a child with aTTP with
this collaborative effort was the development of exchange transfusion in 1959 [16]. Similar obser-
Cobe Spectra instrument, which is widely used vations were made by Bukowski, who hypothe-
for therapeutic apheresis worldwide since the late sized that the success of plasma exchange was
1980s [9]. Herbert Cullis and Yoichiro Ito devised related to the removal of a soluble toxic substance
an independently sealless centrifuge mechanism in the plasma of aTTP patients [17]. Bukowski
designed for third-generation continuous flow has successfully treated two aTTP patients with
cell centrifugal separators [2]. TPE alone, which supported this hypothesis [18].
1 History of Apheresis 5

In their landmark study, Rock et al. showed the tic apheresis). (2) Correction (the pathology/
superiority of TPE over plasma infusion in the abnormality may be corrected with the proce-
treatment of aTTP, which made TPE a standard dure). (3) Clinal benefit (therapeutic apheresis
of care [19]. should confer clinical benefit to the patient) [25,
26]. Beginning with the fourth edition of
American Society for Apheresis (ASFA) guide-
1.6 Peripheral Blood Stem Cell line in 2007, ASFA regularly publish guidelines
Collection by using evidence-based approach in grading and
categorization of indications regarding therapeu-
HSCT is an established treatment modality with tic apheresis. The most recent ASFA guideline
a curative potential frequently used in patients was published in 2019 [27]. The development of
presenting with hematological malignancies, ASFA guidelines is an important step and valu-
inborn errors of metabolism, solid tumors, immu- able effort for the global standardization of
nodeficiency states, and collagen vascular disor- apheresis procedures regarding evidence-based
ders. There is a noted steady and global increase medicine.
in the use of HSCT for more than three decades.
[20, 21] The use of peripheral blood as a source Conflict of Interest Statement All authors declare that
of hematopoietic stem cells revolutionized the they do not have any potential conflict of interest that
could inappropriately influence the present study.
application of HSCT. Lansky was able to collect
sufficient number of pluripotent hematopoietic
cells from normal donors by apheresis in 1982
[22]. Kessinger showed the ability of peripheral References
blood-derived hematopoietic progenitor cells to 1. van Tellingen C. Bleeding—edge technology in
restore normal hematopoiesis after chemotherapy-­ cardiology—or the mixed blessings of phlebotomy
associated aplasia in breast cancer patients [23]. throughout the ages. Neth Heart J. 2010;18:2128–2.
Barlogie et al. used autologous bone marrow-­ 2. Corbin F, Cullis HM, Freireich EJ, et al. Development
of apheresis instrumentation. In: McLeod BC,
derived HSCT in refractory multiple myeloma Szczepiorkowski ZM, Weinstein R, Winters JL,
[24]. Due to faster engraftment kinetics, similar editors. Apheresis: principles and practice. 3rd ed.
efficacy, and not necessitating general anesthesia, Bethesda: AABB Press; 2010.
peripheral blood is found to be the preferred 3. Abell J, Rowntree L, Turner B. Plasma removal with
return of corpuscles (plasma-pheresis). J Pharmacol
source for almost 80% of HPCT procedures, Exp Ther. 1914;5:625–41.
especially in adults presenting with malignancies 4. Taft EG. Application history. In: McLeod BC,
[20, 21]. Szczepiorkowski ZM, Weinstein R, Winters JL,
editors. Apheresis: principles and practice. 3rd ed.
Bethesda: AABB Press; 2010.
5. Adams WS, Blahd WH, Bassett SH. A method of
1.7 Evidence-Based Application human plasmapheresis. Proc Soc Exp Biol Med.
of Apheresis 1952;80:377–9.
6. Kliman A, Gaydos LA, Schroeder LR, et al. Repeated
plasmapheresis of blood donors as a source of plate-
As therapeutic apheresis is not free of complica- lets. Blood. 1961;18:303–9.
tions, rational use of the procedure is of utmost 7. Colman RW, Sievers CA, Pugh
importance to provide clinical benefit without RP. Thrombocytapheresis: a rapid and effective
placing the patient at unnecessary risks. Before approach symptomatic thrombocytosis. J Lab Clin
Med. 1966;68:389–99.
evaluating a patient for therapeutic apheresis, 8. De Laval CGP. Inventor. US Patent 247,804. 1881.
every step of McLeod’s criteria should be consid- 9. McLeod BC. Therapeutic apheresis: history, clinical
ered: (1) Pathogenesis of the disease (there must application, and lingering uncertainties. Transfusion.
be a clear rationale justifying the use of therapeu- 2010;50:1413–26.
6 O. Kayikci and E. Tekgunduz

10. Tullis JL, Tinch RJ, Baudanza P, et al. Plateletpheresis 20. Passweg JR, Baldomero H, Chabannon C, et al.
in a disposable system. Transfusion. 1971;11:368–77. Hematopoietic cell transplantation and cellular ther-
11. Stussi G, Buser A, Holbro A. Red blood cells: apy survey of the EMBT: monitoring of activities
exchange, transfuse and deplete. Transfus Med and trends over 30 years. Bone Marrow Transplant.
Hemother. 2019;46:407–16. 2021;56:1651–64.
12. Kernoff LM, Botha MC, Jacobs P. Exchange trans- 21. Auletta JJ, Kou J, Chen M, et al. Current use and
fusion in sickle cell disease using a continuous-flow outcome of hematopoietic stem cell transplantation:
blood cell separator. Transfusion. 1977;17:269–71. CIBMTR summary slides; 2021. http://www.cibmtr.
13. Yarrish RL, Janas JS, Nosanchuk JS, et al. Transfusion org.
malaria. Treatment with exchange transfusion after 22. Lasky LC, Ash RC, Kersey JH, et al. Collection of
delayed diagnosis. Arch Intern Med. 1982;142:187–8. pluripotential hematopoietic stem cells by cytapher-
14. Cahill KM, Benach JL, Reich LM, et al. Red cell esis. Blood. 1982;59:822–7.
exchange: treatment of babesiosis in a splenectomized 23. Kessinger A, Armitage JO, Landmark JD, et al.
patient. Transfusion. 1981;21:193–8. Reconstitution of human hematopoietic function with
15. Rowley SD, Donato ML, Bhattacharyya P. Red blood autologous cryopreserved circulating stem cells. Exp
cell-incompatible allogeneic hematopoietic progeni- Hematol. 1986;14:192–6.
tor cell transplantation. Bone Marrow Transplant. 24. Barlogie B, Alexanian R, Dicke KA, et al. High-­
2011;46:1167–85. dose chemoradiotherapy and autologous bone mar-
16. Rubinstein MA, Kagan BM, MacGillivray MH, row transplantation for resistant multiple myeloma.
et al. Unusual remission in a case of thrombotic Blood. 1987;70:869–72.
thrombocytopenic purpura syndrome following 25. McLeod BC. An approach to evidence-based thera-
fresh blood exchange transfusions. Ann Intern Med. peutic apheresis. J Clin Apher. 2002;17:124–32.
1959;51:1409–19. 26. Schwartz J, Winters JL, Padmanabhan A, et al.
17. Bukowski RM, Hewlett JS, Harris JW, et al. Guidelines on the use of therapeutic apheresis in
Exchange transfusions in the treatment of throm- clinical practice-evidence-based approach from
botic thrombocytopenic purpura. Semin Hematol. the Writing Committee of the American Society
1976;13(3):219–32. for Apheresis: the sixth special issue. J Clin Apher.
18. Bukowski RM, King JW, Hewlett JS. Plasmapheresis 2013;28:145–284.
in the treatment of thrombotic thrombocytopenic pur- 27. Padmanabhan A, Connelly-Smith L, Aqui N, et al.
pura. Blood. 1977;50(3):413–7. Guidelines on the use of therapeutic apheresis in
19. Rock GA, Shumak KH, Buskard NA, et al. clinical practice-evidence-based approach from the
Comparison of plasma exchange with plasma infu- Writing Committee of the American Society for
sion in the treatment of thrombotic thrombocytopenic Apheresis: the eighth special issue. J Clin Apher.
purpura. N Engl J Med. 1991;325(6):393–7. 2019;34:171–354.
 The Basics of Apheresis
2
Kaatje le Poole, Marleen M. Neyrinck,
and Hans Vrielink

2.1 Introduction 2.2 History of Apheresis

Blood components from donors and patients can As early as 400 years BC, Hippocrates suggested
be collected via whole blood and apheresis dona- that a proper balance of the four bodily fluids
tion. The word apheresis is derived from the maintained the health of the human being. It was
Greek language, which means “to take away.” postulated that disease is an expression of mis-
However, apheresis does not only mean to take balance. Based on this hypothesis, he was con-
away. Apheresis is also described as a medical vinced that bloodletting could correct the balance
technology in which the blood of a donor or and therefore cure the disease. For many centu-
patient is separated into its component parts, the ries, this principle was followed. In the end of the
desired component is removed, and the remain- nineteenth century, the Swedish scientist Karl
ing components are returned to the donor or Gustaf Patrik de Laval developed the earliest
patient [1]. For this separation, specific blood continuous flow centrifugation device and pat-
separating machines are available. Usually, the ented this as centrifugal milk-cream separator.
apheresis procedure is named after the blood “Selective bloodletting” with the removal of
component that is collected, e.g., plasmapheresis plasma and return of blood cells to the person (=
when plasma is collected and HPC apheresis plasmapheresis) was described and practiced in
when human progenitor cells (HPCs) are the aim the USA in 1914 [2]. A unit of whole blood was
of the collection. drawn and mixed with citrate. With centrifugal
technique, cells were separated from the plasma
and returned to the donor. This can be interpreted
as a manual apheresis procedure during which
the unit of whole blood is collected in a bag. The
bag is disconnected from the needle after dona-
tion. The whole blood is separated into compo-
nents, and the not desired components are
K. le Poole · H. Vrielink (*)
Department of Transfusion Medicine, Sanquin Blood returned to the donor. At present, in the western
Supply, Amsterdam, The Netherlands world, this process is obsolete because of the risk
e-mail: [email protected]; [email protected] of mixing up collected units of cells of different
M. M. Neyrinck donors.
Department of Hematology, AZ Delta, To collect sufficient volumes of plasma for
Roeselare, Belgium wounded soldiers on the battle fields, selective
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2024 7

I. Kozanoglu (ed.), Problem Solving in Apheresis Medicine,
https://doi.org/10.1007/978-3-031-74081-7_2
8 K. le Poole et al.

bloodletting was used by Edwin Joseph Cohn and Table 2.1 An overview of apheresis procedures
colleagues during and after World War II. They Donor apheresis Patient apheresisa
started with the collection of whole blood glass Collection of components Therapeutic apheresis
bottles containing a citrate solution. After cen- – Plasma procedures
– Platelets – Reduction of cells
trifugation of the bottles, the cells were returned
– Lymphocytes – Platelets
to the donor, and the albumin fraction was iso- – Human progenitor cells – Leukocytes
lated from the plasma, or the plasma was stored (HPCs) – Erythrocytes
until use. Cohn also planned a device that would – Monocytes – Exchange of blood
– Granulocytes components
separate donor plasma—the desired compo-
– Erythrocytes – Plasma
nent—immediately and “online” during the – Erythrocytes
whole blood donation process. Allen Latham a
When a patient is donating for him/herself, the patient is
(inventor of the Latham centrifuge bowl and usually named (autologous) donor, e.g., autologous stem
founder of Haemonetics Corporation) thereafter cell donor
turned this idea into a working apheresis machine.
A second group of clinicians and scientists inter- • Therapeutic cells
ested in blood cells and the reduction of cells in –– Lymphocytes (lymphocytapheresis)
leukemia patients developed a second line of –– Monocytes (monocytapheresis)
apheresis equipment in the 1960s. The latter –– Granulocytes (granulocytapheresis)
equipment is the basis for the present apheresis • Hematopoietic progenitor cells (HPC
machines of Fresenius Kabi (Amicus Cell apheresis)
Separation Platform™) and Terumo BCT (Cobe 3. Multicomponent apheresis (apheresis proce-
Spectra® and Spectra Optia®) [3]. dure in which more than one blood compo-
Because of their work, de Laval and Cohn are nent is collected, e.g., platelets and red blood
considered as the founding fathers of the modern-­ cells (RBCs)).
day practice of apheresis science and medicine
and therefore honored by the World Apheresis In one apheresis procedure, one or more vol-
Association with an award. This award is given to umes of the total blood volume of a donor can be
recognize individuals who have made major con- processed to achieve the requested cell amount or
tributions to the discipline of apheresis [4]. plasma volume. Because of this, the apheresis
procedure can take several hours, depending on
the type of machine and the procedure to be per-
2.3 Background and Principle formed. The most performed apheresis proce-
of Apheresis dures in blood donors (plasmapheresis and
plateletpheresis) take approximately 30–90 min.
Apheresis procedures are performed in donors Besides donor procedures, apheresis proce-
and in patients as well (see Table 2.1). dures can also be of applied in patients as thera-
Based on the blood component requested, peutic procedure. In case a patient is donating
apheresis procedures for donors can be separated cells for further cellular therapy, e.g., CD34+
into as follows: cells, this is not a therapeutic apheresis proce-
dure, but a donor apheresis procedure. The aims
1. Plasmapheresis of these therapeutic apheresis procedures are to
2. Cytapheresis reduce the pathogenic substances in plasma (e.g.,
(a) Platelets (plateletpheresis) autoantibody removal and plasma exchange),
(b) Erythrocytes (erythrocytapheresis) remove A/B-antibodies in ABO-incompatible
(c) Cells for cellular therapies (leukocytes) organ transplants, and reduce myeloblasts in an
(it must be noted that when a patient is acute myeloid leukemia (AML) patient suffering
donating for him/herself, the patient is from leukostasis. In other situations, therapeutic
usually named (autologous) donor, e.g., apheresis is applied to “make space” for suffi-
autologous stem cell donor.) cient volume infusion of donor blood compo-
2 The Basics of Apheresis 9

nents, e.g., functional ADAMTS13 containing Most producers of apheresis machines have
plasma for patients with thrombotic thrombocy- patented single-use apheresis disposable collec-
topenic purpura (TTP) or exchange of red blood tion sets that fit only one type of machine. For
cells (RBCs) in sickle cell crisis. In a special most procedures, special disposal models are
issue of the Journal of Clinical Apheresis, on a available. The sterile disposable, incorporating
regular basis, indications for therapeutic aphere- collection bags, bacterial and/or separation filters
sis are reviewed [5]. and/or centrifuge chambers, etc., is placed in the
machine. To prevent clotting in the system and
collection bag, the patients/donors’ whole blood
2.4 Apheresis Procedures is mixed with an anticoagulant solution (usually
trisodium citrate) in a specific whole blood-to-­
As said above, in principle, manual and auto- anticoagulant ratio. To add these anticoagulation
mated apheresis procedures can be performed. solutions close to the needle, a port is available
on the inlet line. Since part of the anticoagulated
blood is returned to the donor/patient, trisodium
2.4.1 Manual Apheresis citrate will also be administered to the person on
the apheresis machine.
A standard whole blood donation is the starting For the collection or removal of the desired
point of a manual apheresis procedure. The col- blood component, the whole blood needs to be
lection bag with citrated whole blood is discon- separated in different components. Various sepa-
nected after the donation, but the needle remains ration techniques have been developed.
in situ. Clotting of the needle will be prevented
by maintaining a saline drip (0.9% NaCl). The 2.4.2.1 Filtration Techniques
collection bag with whole blood is centrifuged; In 1943, Willem Johan Kolff presented the first
the desired blood component is pressed into a hemodialysis machine (artificial kidney) using an
component collection bag, and the remainder of animal-derived membrane to filter plasma. The
the blood is returned intravenously to the donor. plasma of kidney patients contains a lethal
By repeating this process a few times, like amount of waste products and pathogenic sub-
mechanical/automated apheresis procedures, up stances due to kidney failure, which can be swept
to 750–850 mL of plasma can be collected in one via the filtering membrane and thus be removed
donation. If by accident the wrong blood compo- from the body of the kidney patient. Similar to
nents are returned to the donor, it can lead to fatal that principle, semipermeable filtration mem-
consequences. Therefore, in the developed world, branes are used for apheresis procedures. The
this technique has been abandoned. Currently, pore size of the membrane is used to separate
almost all apheresis procedures are performed blood components based on their size. Water and
with automated/mechanical apheresis small solutes can pass, but for larger blood pro-
equipment. teins and blood cells, the membrane acts as a
sieve. Filtration technique can be used solely for
plasmapheresis. A substantial part of the plasma
2.4.2 Mechanical Apheresis is pushed through the pores in the membrane and
guided to the waste collection bag. The remain-
Mechanical apheresis techniques are performed der of the plasma and the blood cells are returned
with specially developed machines. to the patient together with a volume of plasma-­
Plasmapheresis is the simplest apheresis proce- replacing fluids in an isovolumic way.
dure. Since plasmapheresis in donors is globally
the most frequently performed procedure, spe- 2.4.2.2 Centrifugal Techniques
cific plasmapheresis machines are produced by Anticoagulated whole blood flows into the cen-
most manufacturers to reduce costs. trifuge chamber of the apheresis machine. Here,
10 K. le Poole et al.

Table 2.2 Specific weight and size of various blood a specific elutriation chamber is placed in which
components the heavier cells are pushed to the centrifuge
Specific weight wall; meanwhile, with an opposite force caused
(kg/m3) Size (μm) by a fluid flow, a second separation of the blood
Plasma 1.026
cells based on the size of these cells is forced.
Platelets 1.040 1–4
The platelets are the smallest cells and will
Lymphocytes 1.050–1.061 6–10
Monocytes 1.077 10–30
leave the elutriation chamber prior to all other
Basophils 1.080 10–15 cells. The sequence of the various blood compo-
Eosinophils 1.082 9–15 nents with elutriation techniques is plasma—
Neutrophils 1.088 12–15 platelets—erythrocytes—lymphocytes—HPCs (if
Erythrocytes 1.100 6–8 present)—granulocytes—monocytes. Elutriation
in apheresis techniques is applied not only to
achieve leukoreduction of the collection of spe-
based on the specific weight of the various blood cific mononuclear cells (lymphocytes and mono-
cells and not the size of the cells, the blood is cytes) but also to reduce the donor’s platelet loss
separated into various blood components (see due to the apheresis procedure.
Table 2.2). Important in this are the time in the
centrifuge chamber, the radius of the centrifuge, 2.4.2.5 Adsorption Techniques
and the number of rotations per minute (G-forces The adsorption technique can be used to remove
in the centrifuge chamber). During the centrifu- substances out of the plasma (e.g., specific (auto)
gation process, various blood cells in the blood antibodies) by binding them to the surface of a
will be positioned in layers enriched with various solid-phase column (adsorber). During an apher-
blood components. The sequence in centrifugal esis procedure, plasma is separated by filtration
techniques of apheresis is always plasma—plate- or centrifugal techniques and led via an adsorber
lets—lymphocytes—HPCs (if present)—mono- before it is returned to the donor or patient with
cytes—granulocytes and finally the erythrocytes. the blood cells. With antigen-specific immunoad-
The apheresis machine is equipped with a soft- sorption, selected cells, lipids, or immunoglobu-
ware that allows the operator to decide which lins can be removed by binding to absorber fibers
components need to be collected and returned to in columns.
the donor.

2.4.2.3 Combination of Filtration 2.5 Apheresis Disposables

and Centrifugation Techniques
Besides the separation of blood components by As described earlier, product- and machine-­
centrifugation, a membrane separation is also specific apheresis disposables are used. Based on
employed. Usually, the membrane is located in the composition of the disposable, it can be cate-
the centrifuge chamber. Examples of this princi- gorized as an open or a closed system.
ple are the separation technology in the
Autopheresis C™ and Aurora™ plasmapheresis
system from Fresenius Kabi for the collection of 2.5.1 Closed Versus Open Apheresis
donor plasma. Disposables

2.4.2.4 Elutriation Techniques A closed apheresis disposable is one which is

In elutriation techniques, we make use of two completely assembled by the manufacturer and
opposite forces, the centrifugal force and the flow ready for use. Within the disposable, no connec-
of plasma. The centrifugal forces achieve a first tions need to be made. Connections between the
separation of the cells based on the specific machine and disposable (e.g., pressure lines) are
weight of the cells. In the product collection line, fitted with bacterial filters. Also, the anticoagu-
2 The Basics of Apheresis 11

lant solution is spiked using an inline bacterial apheresis machine and balanced to the drawn
filter. In a closed system only, the venipuncture is blood volume from the donor.
performed without a bacterial filter.
All other disposables are open systems.
Disposable systems may be delivered completely 2.6.1 Continuous
assembled by the manufacturer but are classed as and Discontinuous Flow
open systems when, for instance, there is no bac- Techniques
terial filter in the anticoagulant line incorporated.
More often, open apheresis disposables are not An apheresis procedure can be performed using a
completely assembled by the manufacturer. Prior continuous flow technique or a discontinuous
to use, the apheresis operator needs to connect flow technique. With continuous flow techniques,
one (e.g., the needle) or more parts, e.g., needle, the blood is drawn, processed, and returned at the
lines, centrifuge chamber, and collection bag(s). same time. In consequence, an inlet and a return
According to international guidelines, prod- line to the patient or donor are needed. Venous
ucts that are collected in open systems should be access can be obtained by placing two peripheral
used or processed within 24 h after donation. venous catheters or a double-lumen central
Usually, blood components that are applied for venous line. In donor procedures, the venipunc-
direct patient care (e.g., fresh frozen plasma ture is usually performed in the antecubital fossa
(FFP), platelets, RBCs, etc.) should be collected of both arms; hence, the donor is stalled for the
in closed systems, with one exception. Plasma duration of the apheresis procedure. Therefore, in
used to produce plasma-derived blood products some cases, for the return access, one of the veins
(e.g., intravenous immunoglobulin G (IVIG), in the forearm can also be used. In patients,
clotting factor VIII (FVIII), albumin, etc.) can double-­lumen central venous catheters placed in
be collected in sterile open systems. femoral, jugular, or subclavian veins are often
When a closed system is opened, (e.g., change used.
of needle, second venipuncture with the same In discontinuous flow techniques, only one
disposable), by definition, the system becomes an venipuncture is needed. During the draw period,
open system, and the collected blood component whole blood is drawn from the donor and enters
should be transfused within 24 h after donation. the separation part of the disposable set. Here, the
requested blood component is separated from the
other blood components and stored in a collec-
2.6 The Apheresis Procedure tion bag. The remaining blood components are
temporarily stored in a reservoir of the dispos-
The apheresis procedure is started by performing able. When the reservoir is full, the return phase
the venipuncture. Next to the needle, the donor’s of the procedure is then initiated, and the con-
blood is anticoagulated by adding an anticoagu- tents of the reservoir are returned to the donor/
lant solution. In donor apheresis, usually, triso- patient via the same needle. After this, the cycle
dium citrate is used as an anticoagulant, either as of draw, separation, and return is repeated until
a simple solution trisodium citrate solution or in the desired volume is reached.
mixtures such as acid citrate dextrose (ACD-A) In discontinuous techniques, two variants
solution or citrate phosphate dextrose (CPD) are seen: (1) return of the complete volume of
solution. Using the lines of the disposable set, the all components collected in the reservoir of the
anticoagulated whole blood is guided to the sepa- disposable, followed by an iteration of the
ration part. After separation, the requested blood entire procedure until the target volume of
component is stored in a collection bag, and the requested blood components is achieved, or (2)
remaining components are returned to the donor after fully filling the collection and separation
including a specific volume of the anticoagulant system, draw and return of small volumes of
used. During an automated apheresis procedure, blood is performed intermittently; thus, the sep-
the volume of anticoagulation is controlled by the aration of the blood components is performed
12 K. le Poole et al.

almost continuously. Usually, in the first vari- 3. The effect of the anticoagulant should have no
ant, the centrifuge is completely stopped or as little as possible activation of the plate-
(including loss of the separation); meanwhile, lets or clotting factors.
in the second variant, the centrifuge remains 4. The anticoagulant should be as safe as possi-
working at normal levels, or the number of rota- ble for the donor and patient.
tions per minute is slightly decreased. The ben-
efit of this technique is that the separation of Three important types of anticoagulation can
blood cells in the system remains intact, thus be distinguished:
reducing the procedure time to achieve a new
full separation. One of the advantages of con-
tinuous apheresis techniques versus the discon- 2.7.1 Local Anticoagulation
tinuous technique is a smaller extracorporeal with a Citrate Solution
volume.
Citric acid (Fig. 2.1) occurs naturally in citrus
fruits. In biochemistry, it is an intermediate in the
2.7 Anticoagulant citric acid cycle, which occurs in the metabolism
of all aerobic organisms and is present in all body
There are at least four requirements for antico- cells. The anticoagulation effect of citrate is
agulation solutions used in apheresis practice: based on the chelation of calcium, which is nec-
essary for the coagulation cascade (Fig. 2.2).
1. Blood should not clot during a procedure. With the binding of ionized calcium in the system
2. The effect of the anticoagulant should also be and the collection bag, there is no free calcium
sufficient to prevent clotting during storage for the calcium-dependent reactions in the clot-
and transfusion of the blood component. ting cascade resulting in clotting prevention.

Fig. 2.1 Elutriation in the leukoreduction process during platelet apheresis with Trima Accel® Automated Blood
Collection System (Terumo BCT)