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522 Part VI: The Erythrocyte Chapter 35: Aplastic Anemia: Acquired and Inherited 523

on several factors, including the patient’s age and condition and the ABO-identical platelets because this enhances platelet survival and fur-
availability of a suitable allele-level HLA-matched hematopoietic ther decreases refractoriness to platelet transfusion. Single-donor HLA-
stem cell donor. In general, transplantation is the preferred treatment matched apheresis-harvested platelets may be necessary in previously
for children and most otherwise healthy younger adults. Early histo- pregnant or transfused patients who are already allosensitized or who
compatibility testing of siblings is of particular importance because it so become after treatment with leukoreduced platelets. The frequency
establishes whether there is an optimal donor available to the patient of either of these events is less than 10 percent. Chapter 139 discusses
for transplantation. The preferred stem cell source is a histocompatible approaches to chronic platelet transfusion.
sibling matched at the HLA-A, -B, -C, and -DR loci. Management of Neutropenia Neutropenic precautions should
be applied to hospitalized patients with a severe depression of the neu-
Supportive Care trophil count. The level of neutrophils requiring precautions is fewer
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The Use of Blood Products Although it has been recommended that than 500/μL (0.5 × 10 /L). One approach is to use private rooms, with
red cell and platelet transfusions be used sparingly in potential trans- requirements for face masks and handwashing with antiseptic soap.
plant recipients to minimize sensitization to histocompatibility anti- Unwashed fresh fruits and vegetables should be avoided as they are
gens, this has become less important since ATG and cyclophosphamide sources of bacterial contamination. It is uncommon for patients with
have been used as the preparative regimen for transplantation in aplas- aplastic anemia to present with a significant infection. When patients
tic anemia, as their use has markedly reduced the problem of graft with aplastic anemia become febrile, cultures should be obtained from
rejection. 146 the throat, sputum (if any), blood, urine, stool, and any suspicious
Cytomegalovirus (CMV)-reduced risk red cells and platelets lesions. Broad-spectrum bactericidal antibiotics should be initiated
should be given to a potential transplant recipient to minimize prob- promptly, without awaiting culture results. The choice of antibiotics
lems with CMV infections after transplantation. Once a patient is depends on the prevalence of organisms and their antibiotic sensitiv-
shown to be CMV-positive, this restriction is no longer necessary. Leu- ity in the local setting. Organisms of concern usually include Staphy-
kocyte-depletion filters or CMV serotesting are equivalent methods of lococcus aureus (notably methicillin-and oxacillin-resistant strains),
decreasing the risk of transmitting CMV. Staphylococcus epidermidis (in patients with venous access devices),
Red Cell Transfusion Packed red cells to alleviate symptoms of and Gram-negative organisms. Patients with persistent culture-negative
anemia usually are indicated at hemoglobin values below 8 g/dL (80 g/L), fevers should be considered for antifungal treatment (Chap. 24).
unless comorbid medical conditions require a higher hemoglobin con- In the past, leukocyte transfusions were used on a daily basis to
centration. These products should be leukocyte-depleted to lessen leu- reduce the short-term mortality from infections. It was unusual to
kocyte and platelet sensitization and to reduce subsequent transfusion detect more than 100 to 200 neutrophils per microliter for more than
reactions and radiated to reduce the potential for a transfusion-related a few hours after transfusion. The yield of neutrophils can be increased
graft-versus-host reaction. It is important not to transfuse patients with by administering granulocyte colony-stimulating factor (G-CSF) to the
153
red cells (or platelets) from family members if transplantation within donor, but most physicians avoid using white cell products because
the family is remotely possible, as this approach may sensitize patients present-day antibiotics are usually sufficient to treat a patient for an epi-
to minor histocompatibility antigens, increasing the risk of graft rejec- sode of sepsis. Notable exceptions include documented invasive asper-
tion after marrow transplantation. Following a marrow transplant, or in gillosis unresponsive to amphotericin (particularly in the posttransplant
those individuals in whom transplantation is not a consideration, family setting), infections with organisms resistant to all known antibiotics,
members may be ideal donors for platelet products. Because each unit and when blood cultures remain positive in spite of antibiotic treat-
of red cells adds approximately 200 mg of iron to the total body iron, ment. Leukocyte transfusion is more effective in children and adults
over the long-term transfusion-induced iron overload may occur. This with smaller body size, as transfused leukocytes have a smaller distri-
is not a major problem in patients who respond to transplantation or bution space, which results in higher blood and tissue concentrations.
immunosuppressive therapy, but it is an issue in nonresponders who
require continued transfusion support. In the latter case, consideration Specific Treatment
should be given to iron-chelation therapy. Newer oral agents make this Hematopoietic Stem Cell Transplantation Prompt therapy usually is
procedure easier to effect (Chap. 48). 147 indicated for patients with severe aplastic anemia. The major curative
Platelet Transfusion It is important to assess the risk of bleed- approach is hematopoietic stem cell transplantation from a histocom-
ing in each patient. Most patients tolerate platelet counts of 10,000/μL patible sibling. 154–156 Chapter 23 describes this treatment modality. Only
9
(10 × 10 /L) without undue bruising or bleeding, unless a systemic infec- 20 to 30 percent of patients in the United States have compatible sib-
tion is present or vascular integrity is impaired. 148,149 A traumatic injury ling donors (related to average family size). In the unusual case of an
or surgery requires transfusion to greater than 50,000/μL or greater identical twin donor, conditioning is required to obliterate the immune
than 100,000/μL, respectively. Administration of ε-aminocaproic acid, disease in the recipient, but it can be limited to cyclophosphamide. In
50 mg/kg per dose every 4 hours orally or intravenously, may reduce the this setting, an 80 to 90 percent survival is expected. Marrow stem cells
150
bleeding tendency. Pooled random-donor platelets may be used until seem to perform better than blood stem cells when used as a source for
sensitization ensues, although it is preferable to use single-donor plate- patients with aplastic anemia, although this is under continued study.
lets from the onset to minimize sensitization to HLA or platelet anti- The results of transplantation are best in patients younger than age 20
gens. Subsequently, single-donor apheresis products or HLA-matched years (80 to 90 percent long-term survival) but decrease every decade
platelets may be required. of increasing age thereafter. Posttransplant mortality is increased and
Platelet refractoriness is a major problem with long-term transfu- survival decreased with increasing age (Fig. 35–3). In patients older
151
sion support. This may occur transiently, with fever or infection, or than age 40 years, survival in matched sibling transplant is reduced to
as a chronic problem secondary to HLA sensitization. In the past, this approximately 50 percent. There are still uncertainties about the opti-
157
occurred in approximately 50 percent of patients after 8 to 10 weeks mal conditioning program in younger and older patients. ATG, cyclo-
of transfusion support. Filtration of blood and platelet concentrates to phosphamide, total-body radiation, fludarabine, and alemtuzumab are
remove leukocytes reduces this problem to approximately 15 percent among the agents being studied. 154,156–158 Alemtuzumab (Campath)-
of patients receiving chronic transfusions. 151,152 Patient’s should also get containing regimens appear to improve outcome by decreasing the

Kaushansky_chapter 35_p0513-0538.indd 522 9/19/15 12:24 AM