Page 2010 - Hematology_ Basic Principles and Practice ( PDFDrive )

C H A P T E R 118

HEMAPHERESIS

Sandhya R. Panch and Harvey G. Klein

Therapeutic bloodletting is an ancient therapy, fashionable, albeit automated cell separators depends on the number of cells available,
unproved, and practiced well into the 19th century. About the time the volume of blood processed, the efficiency of the particular instru-
that scientific skepticism began to temper the widespread use of ment, and the separation characteristics of the different cells. Most
therapeutic phlebotomy, a new technique for blood removal, apher- commercially available instruments remove platelets and lymphocytes
1
esis, appeared in the research laboratory. The term apheresis, derived extremely efficiently. Granulocytes and other mononuclear cells,
from a Greek verb meaning “to take away or withdraw,” was coined including HPCs from peripheral blood, cannot be cleanly separated
to describe removal of one component of blood with return of the from other cells by standard centrifugal apheresis equipment (Fig.
remaining components to the donor. Like phlebotomy, apheresis was 118.3). Optimal harvesting of these cells requires special techniques
used first to treat patients but later became more important for col- such as stimulating the donor with corticosteroids or cytokines and
lecting blood components for transfusion. Increasingly, apheresis adding sedimenting agents to enhance cell separation.
techniques are used to collect cell populations from the peripheral Whereas this model accurately estimates removal of cells and large
blood of healthy donors and patients for purposes of hematopoietic proteins such as fibrinogen and immunoglobulin (Ig) M, removal of
stem/progenitor cell (HPC) transplantation and immune cell thera- smaller solutes such as IgG and albumin-bound drugs is less efficient.
pies. Annually in the United States, about 1.9 million units of red Transfer of these moieties from the extravascular to the intravascular
blood cells (RBCs), 2.5 million units of platelets, and 2500 granulo- compartment depends both on diffusion along a concentration gradi-
cyte doses are collected by apheresis and more than 50,000 units of ent and on active transport. The rate of clearance can be calculated
peripheral blood-hematopoietic stem and progenitor cells (PB-HSPC) using diffusion coefficients, sieving coefficients, and lymphatic flow
and therapeutic cellular therapy products are collected at hospital and rate, although in practice this degree of accuracy is rarely necessary.
blood center apheresis facilities. 2
TECHNOLOGY AND TECHNIQUES
PRINCIPLES OF APHERESIS
The plasmapheresis technique that originated in the animal labora-
The principal objective of apheresis is efficient removal of some cir- tory required manual resuspension of RBCs and posed a substantial
culating blood component, either cells (cytapheresis) or some plasma risk of microbial contamination of the components being reinfused.
solute (plasmapheresis). For most disorders the treatment goal is to With the introduction of sterile, disposable, interconnected plastic
deplete the circulating cell or substance directly responsible for the blood bags, plasmapheresis became relatively safe and easy. However,
disease process. Apheresis can also mobilize cells and plasma compo- manual apheresis proved too inefficient and labor intensive for col-
nents from tissue depots. For example, lymphocytes may be mobilized lecting large component volumes and raised concerns that the sepa-
from the spleen and lymph nodes of some patients with chronic rated units of RBCs might be reinfused accidentally into the wrong
lymphocytic leukemia (CLL), and low-density lipoproteins (LDLs) donor or patient. The introduction of automated online blood cell
can be removed from tissue stores in patients with familial hypercho- separators solved these problems. Automated apheresis instruments
+
lesterolemia. The apheresis procedure itself mobilizes CD34 cells use microprocessor technology to draw and anticoagulate blood,
from extravascular depots in peripheral blood-hematopoietic stem separate components either by centrifugation or by filtration, collect
and progenitor cells (PB-HSPC) donors, resulting in collection of the desired component, and recombine the remaining components
+
more than twice as many CD34 cells than estimated based on for return to the patient or donor. The equipment contains disposable
preapheresis peripheral blood cell counts (Fig. 118.1). Apheresis may plastic software in the blood path and uses anticoagulants containing
have other, less obvious effects. Lymphocyte depletion may modify citrate or combinations of citrate and heparin that do not result in
immune responsiveness in some disease states, possibly by disturbing clinical anticoagulation of the patient or donor. Most instruments
the control mechanisms of cellular immune regulation. Plasmapher- function well at blood flow rates of 30–80 mL/min and can operate
esis enhances splenic clearance of immune complexes in certain from peripheral venous access or from a variety of multilumen central
autoimmune disorders. When therapeutic effect is judged by clinical venous catheters. Newer therapeutic apheresis devices are smaller and
improvement rather than by efficiency of solute removal, apheresis is more automated, allowing for implementation of more safety func-
more often a helpful adjunct than a form of first-line therapy. tions and improved portability.
Several mathematical models formulated for different clinical Because the ideal method for treating disorders mediated by
conditions describe the kinetics of apheresis. Removal of most blood abnormal plasma components is to remove the offending substance
constituents follows a logarithmic curve (Fig. 118.2). This model selectively, a variety of online filtration and column adsorption
assumes that the substance removed is neither synthesized nor techniques have been introduced or proposed. Ligands bound to a
degraded substantially during the procedure, remains within the column matrix may be relatively nonspecific chemical sorbents, such
intravascular compartment, and mixes instantaneously and com- as charcoal or heparin, or specific ligands, such as monoclonal anti-
pletely with any plasma replacement solution. When the goal of bodies and recombinant protein antigens. Two such columns are
plasmapheresis is to supply a deficient substance, for example, the commercially available: one using staphylococcal protein A and the
cleavase ADAMTS13 in the treatment of thrombotic thrombocyto- other using negatively charged dextran sulfate cellulose beads. Staphy-
penic purpura (TTP), replacement follows logarithmic kinetics lococcal protein A has high affinity for the Fc portion of IgG1, IgG2,
similar to those developed for solute removal. From Fig. 118.2, it is and IgG4 and for immune complexes containing these IgG subtypes.
evident that removal of 1.5–2.0 volumes will reduce an intravascular This column is approved for use in therapeutic apheresis procedures
substance by approximately 80% and that processing larger volumes for patients with chronic immune thrombocytopenia and selected
results in little additional gain. Specific cell removal with centrifugal adult patients with rheumatoid arthritis. The dextran sulfate cellulose

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