Page 699 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 42 Sickle Cell Disease 591

in an episodic fashion or in a chronic fashion. Therefore transfusion for patients with SCD, even those who do not have high risk char-
therapy in SCD is of the following types: episodic simple, episodic acteristics at the time of surgery, and preoperative transfusion should
partial exchange, or chronic partial exchange. In both simple and be considered. A caveat is that extended phenotyping of transfused
exchange transfusion, the target Hb level is 10–11 g/dL (hematocrit, red cells, should be performed, as discussed further subsequently.
30%). 71,72 Transfusing to a higher Hb or hematocrit level is avoided Chronic partial-exchange transfusion is indicated in primary and
because a hematocrit level greater than 30% is associated with secondary prevention of cerebral thrombosis as discussed in the
hyperviscosity if there is a substantial proportion of Hb S in the section on neurologic complications.
blood. In exchange transfusion, an additional objective is to achieve Transfusion complications include alloimmunization, delayed
an Hb S percentage of less than 30% (or sometimes <50%). In hemolytic transfusion reactions (discussed in Exacerbations of
partial-exchange transfusion, a proportion of the patient’s diseased Anemia), iron overload, and transmission of viral illness. The inci-
RBCs are removed before transfusion of normal donor RBCs; this dence of alloimmunization is between 19% and 30% and usually
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can be done manually through phlebotomy followed by transfusion occurs with fewer than 15 transfusions. Some patients seem to toler-
or concurrently using an automated device. In patients who need ate multiple transfusions without developing alloantibodies, but
chronic transfusions, partial exchange is recommended because of the others are readily allosensitized. The high rate of alloimmunization
reduced iron burden of this approach. Partial exchange is also indi- in transfused sickle cell patients is partly attributable to minor blood
cated if the baseline Hb level is more than 10 g/dL. Simple transfu- group incompatibilities between the recipient and donor pool, which
sion in this instance risks exacerbating the clinical condition through often differ in ethnicity. 76,77 Antibodies against the C and E antigens
increased viscosity. For critical illness, exchange transfusion is also of the Rh group, Kell (K) and Lewis, Duffy (Fya, Fyb), and Kidd
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preferred. Although the target Hb S level should be less than 30% in (Jk) are common. In the Stroke Prevention Trial in Sickle Cell
exchange transfusion, decreasing Hb S levels to less than 50% may Anemia, the routine use of WBC-reduced RBCs matched for E, C,
suffice depending on the severity of the complication being treated. and Kell decreased the allosensitization rate compared with historical
The volumes required for simple and exchange transfusions (Table data from 3% to 0.5% per unit transfused and decreased the rate of
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42.6) are particularly important for transfusing children. For normal- hemolytic transfusion reactions by 90%. Therefore the recom-
size adults, the general rule is that each unit of RBCs infused increases mended approach to preventing alloimmunization is to reduce leu-
the Hb level approximately 1 g/dL. 73 kocytes and perform limited phenotype matching for all patients
Episodic simple transfusion should be considered for blood (ABO, C, D, E, and Kell) and extended phenotype matching for
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volume replacement in aplastic crisis and splenic sequestration crises patients with alloantibodies. The management of a delayed hemo-
and for protection when there is a more than 20% decrease in Hb lytic transfusion reaction and transfusional iron overload are discussed
from baseline from severe illness such as septicemia or severe vasooc- under Exacerbations of Anemia, later.
clusive crisis or hyperhemolysis or Hb levels of less than 5 g/dL. Transmission of human immunodeficiency virus, hepatitis B and
Episodic simple or exchange transfusion should be considered for C, and human T-cell leukemia/lymphoma virus-1 has diminished
acute chest syndrome, priapism, and preoperatively. The choice of with improved screening of banked units but remains an issue. In
simple versus exchange transfusion is determined by the pretransfu- addition to better screening programs, the use of leukocyte-depleted
sion total Hb level and the severity of the illness. RBC transfusions can reduce this hazard. 79
In the preoperative setting, there is good randomized data to
support the use of preoperative transfusion to decrease the risk of
complications, including severe complications such as acute chest Stem Cell Transplantation
syndrome. 74,75 Preoperative transfusions can be categorized as follows.
(1) Top-up transfusions to a target Hb level of 10 g/dL. This is an At this time, allogeneic stem cell transplantation remains the only
appropriate intervention for patients with baseline Hb between curative option for SCD, and improvements in conditioning
6.5–9 g/dL undergoing low or medium risk surgeries (e.g., cholecys- approaches suggest both pediatric and adult populations are eligible.
tectomy, joint replacement). (2) Partial exchange transfusion to The largest series to date has been in a pediatric population with
achieve a target Hb level of 10 g/dL with an estimated Hb S percent- severely symptomatic SCD failing to respond to HU. Using myeloab-
age of <60%. This is an appropriate intervention for patients with lative conditioning and human leukocyte antigen (HLA)–matched
baseline Hb levels of >9.5 g/dL undergoing low- or medium-risk or one-mismatch (two cases) sibling donors, with bone marrow as
surgeries as per above. (3) Exchange transfusion to achieve a target the source of stem cells in the majority, there was a 10% mortality
Hb level of 10 g/dL with an estimated Hb S percentage of <30%. rate with 90% overall survival and 82% event-free survival at a
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This procedure should be considered for patients with SCD undergo- median follow-up of 54 months. Similar results were obtained when
ing high-risk surgeries (e.g., cardiothoracic surgery). In short, surgery, related, HLA-matched umbilical cord blood was used as the source
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even low- or medium-risk surgery, is a substantial physiologic stressor of stem cells. According to these results, stem cell transplant is a
therapeutic option for the severely symptomatic child with an HLA-
matched sibling donor.
TABLE Transfusion Formulas In adults, incorporation of rapamycin (to induce immunologic
42.6 tolerance) into nonmyeloablative stem cell transplant protocols
Dilutional effects of transfusion on Hb S: PRBC volume (PRBCV) (mL) has enabled stable mixed hematopoietic chimerism with associ-
ated full-donor erythroid engraftment and normalization of blood
= (Hct d − Hct i ) × TBV × Hct rp B counts. The attainment of tolerance may allow extension of this
a
Manual partial-exchange transfusion: Hb Sf = 1 − (PRBCV × Hct rp ) potentially curative approach to alternative donor sources, an
(TBV × Hct i ) + (PRBCV × Hct rp ) × Hb S i C active area of research. 82,83 The issue of the cost-effectiveness of
Automated exchange transfusion: Exchange volume (mL) = (Hct d − Hct i ) bone marrow transplantation (BMT) gains perspective from the
× TBVHct rp − (Hct i + Hct d )2D comparative costs in the United States of $150,000 to $200,000 for
an uncomplicated BMT versus up to $112,000 annually for con-
RBC volume (mL) = Hct i × TBV ventional medical care of a chronically transfused, iron-overloaded
a In these formulas, Hct and Hb S are fractions (e.g., 40% = 0.4). patient. 84
Hct d, desired hematocrit; Hct i, initial hematocrit; Hct rp, hematocrit of
replacement cells (usually 0.75); Hb S i, initial Hb S; Hb S f, final Hb S; PRBC,
packed red blood cells; TBV, estimated total blood volume in milliliters
(children, 80 mL/kg; adults, 65 mL/kg; nomograms are available). (From Education
Linderkamp et al, with permission. Copyright 1977, Springer-Verlag.)
From Nieburg and Stockman, with permission. Copyright 1977, American Education regarding the nature of the disease, genetic counseling, and
Medical Association.
psychosocial assessments of patients and their families are best