Page 452 - Williams Hematology ( PDFDrive )

427

CHAPTER 28 (ASFA) categorizes the indications for apheresis (Table 28–1) accord-
ing to where apheresis fits into the management strategy for the condi-
THERAPEUTIC APHERESIS: tion under consideration. In addition, ASFA evaluates the individual
4
indications (clinical entities) and issues recommendations regarding
INDICATIONS, EFFICACY, the use of apheresis in their treatment according to the GRADE (Grad-
ing of Recommendations Assessment, Development and Evaluation)
system. Table 28–2 lists the covered indications most relevant to the
4,5
AND COMPLICATIONS practice of hematology. This chapter considers the various apheresis
approaches to hematologic disorders.
THERAPEUTIC PLASMA EXCHANGE
Robert Weinstein
Therapeutic plasma exchange (TPE) is the most commonly performed
therapeutic apheresis procedure in the United States and Medicare
6
claims for TPE have doubled over the past 10 years. The term plasma-
SUMMARY pheresis refers to the removal of plasma from the circulation by manual
or automated methods; the term plasma exchange refers to a therapeutic
Therapeutic apheresis refers to several blood processing methods that are used procedure in which plasmapheresis is combined with replacement of
in the treatment of diverse clinical conditions. In most cases, the disorders so the removed plasma by a substitute colloid fluid, most commonly a mix-
4,7
treated are characterized by a specific qualitative or quantitative abnormality ture of 5 percent human serum albumin and 0.9 percent saline. The
of the blood. In hematologic practice, apheresis procedures are used to mit- efficient extraction of the plasma from whole blood, and its replacement
igate hyperviscosity in monoclonal protein disorders or remove pathologic with a substitute colloid fluid, is predicated on the hypothesis that the
autoantibodies and replete important plasma proteins. Red cell apheresis is plasma substance targeted for removal (usually an immunoglobulin or
used to improve the ratio of normal to abnormal red cells in hemoglobinopa- other large molecule) does not escape to the extracellular space dur-
7
thies and protozoan disease, and to remove excess red cells, red cell-associated ing the time it takes to perform the plasma exchange procedure. This
hypothesis underlies the “one compartment model” that forms the basis
toxins, or excess iron from the body. Leukocyte apheresis is used to reduce the for our understanding of the physiology of plasma exchange and the
circulating blast count in acute leukemias with hyperleukocytosis and plate- depletion of plasma constituents (Fig. 28–1).
let apheresis is used to lower a very elevated platelet count in patients with If the “one compartment model” applies, then the intravascular
myeloproliferative neoplasms. Photopheresis is used in the treatment of cuta- mass of a substance to be removed is a function of its concentration in
neous T-cell lymphoma and chronic graft-versus-host disease. Adverse effects the plasma (y) and the patient’s plasma volume. Its clearance from the
of apheresis with current technologies are typically mild and, usually, do not plasma by plasmapheresis depends on the fraction of that plasma vol-
prevent completion of therapy. ume that is removed per unit of time during the exchange. The fraction
of the targeted substance remaining in the intravascular space at any
time (t) during the exchange procedure can be expressed as
DEFINITION AND HISTORY y = y e −x
0
t
where y is the concentration of targeted substance remaining in the
The term apheresis emerged in 1914 when John J. Abel, of the Johns t
Hopkins University Pharmacological Laboratory, demonstrated how intravascular space at time t, y is the concentration of targeted substance
0
large quantities of plasma could be removed from dogs by a process at the start of the procedure (time zero), e is the natural logarithm base
he called “plasmapheresis” (from the Greek apairesos or Roman apha- (a constant valued at approximately 2.718282) and x represents multiples
eresis, meaning take away by force). The treatment, by manual plas- of the patient’s plasma volume processed by time t. Figure 28–2 is a plot
1
mapheresis, of hyperviscosity syndrome in patients with Waldenström based on this formula that generates an asymptotic curve that predicts
macroglobulinemia during the 1950s supported the concept that a the disappearance of the intravascular target substance as a function of
disease state causally related to a substance in the plasma can be effec- plasma volumes processed (i.e., multiples of the patient’s plasma volume).
2,3
tively treated by removal of plasma. Today, a number of automated The curve is initially steep, and the processing of one plasma volume
apheresis, or blood processing, techniques are used in the treatment of removes approximately two-thirds of the substance of interest. Process-
a growing list of clinical disorders. The American Society for Apheresis ing of another half plasma volume lowers the remaining substance of
interest to approximately 22 percent of its initial level in the blood. But
the curve then rapidly flattens, with much less removal of the substance
of interest per volume of plasma processed. Thus the “sweet spot” for
Abbreviations and Acronyms: ADAMTS-13, von Willebrand factor cleaving plasma exchange procedures is the processing of between 1.0 and
7
metalloprotease; ARDS, acute respiratory distress syndrome; ASFA, 1.5 plasma volumes. The “one compartment model” is particularly rel-
American Society for Apheresis; CDC, United States Centers for Disease evant to the removal of large molecules, such as immunoglobulins, that
Control and Prevention; ECP, extracorporeal photochemotherapy; FCR, frac- have a predictable rate of synthesis and volume of distribution within
tion of cells remaining; GRADE, Grading of Recommendations Assessment, the intravascular space. Smaller molecules, that are synthesized and/or
metabolized in a less-predictable fashion, or are distributed within total
Development and Evaluation; HUS, hemolytic uremic syndrome; MHC, major body water, are less predictably removed according to the model. 7
histocompatibility complex; 8-MOP, 8-methoxypsoralen; PUVA, psoralen As shown in Table 28–2, most indications for plasma exchange
plus ultraviolet A; TPE, therapeutic plasma exchange; TTP, thrombotic throm- in hematologic disorders are weakly recommended based on low-
bocytopenic purpura; UVA, ultraviolet A light; VR, volume of red blood cells quality evidence. These indications are reviewed in detail elsewhere.
8,9
to be removed. The discussion herein is restricted to situations where plasma exchange
has an important impact on hematologic practice.

Kaushansky_chapter 28_p0427-0436.indd 427 9/17/15 6:05 PM