Page 652 - Hematology_ Basic Principles and Practice ( PDFDrive )

554 Part V Red Blood Cells

250 Deciding to Begin Transfusion Therapy in Patients With Thalassemia
Blood requirement (mL pure RBC/kg/y) 150 1.73 1.81 1.68 1.50 1.30 1.31 1.34 1.34 1.31 of patients with thalassemia. Regular RBC transfusions not only distin-
The decision to initiate regular RBC transfusions is one of the most
200
important—and sometimes most difficult—steps in the management
guish thalassemia major from thalassemia intermedia but also commit
the patient to long-term chelation therapy to control the transfusional
iron loading. The decision should include consideration of both clinical
and laboratory findings. Children who are growing poorly and develop-
ing disfiguring bone changes will benefit from regular transfusions
100
even if their hemoglobin levels are 8–9 g/dL. On the other hand,
children who are asymptomatic at hemoglobin levels of 7–8 g/dL may
have little to gain from transfusions. Hemoglobin levels below 7 g/
50
and the compensatory erythropoiesis. When the hemoglobin level is
consistently less than 7 g/dL, there is usually little to be gained from
delaying transfusion.
0 dL are usually associated with problems related to both the anemia
Before the first blood transfusion is given to a child with thalassemia
9.0−9.4 10.0−10.4 11.0−11.4 12.0−12.4 13.0−13.4 major, a complete RBC antigen profile should be obtained. This infor-
Mean hemoglobin (g/dL) mation is valuable for identifying minor blood group incompatibility if
alloimmunization develops later and helps to distinguish alloantibodies
Fig. 40.7 Relationship between transfusion requirements and mean hemo- from autoantibodies. The value of extended matching of donor RBCs
globin level maintained by patients with thalassemia major. Blue = splenec- has not been established in cases of thalassemia, but experience with
tomized patients, yellow = nonsplenectomized patients. RBC, Red blood cell. sickle cell disease suggests that matching for the full Rh system as well
(Adapted from Rebulla P, Modell B: Transfusion requirements and effects in patients as the Kell antigen may reduce the rate of alloimmunization.
with thalassemia major. Lancet 337:277, 1991.) In practice, the goal of maintaining the hemoglobin level above
9–10.5 g/dL is usually achieved by administration of approximately
15 mL/kg/mo or 1 to 2 units of donor RBCs every 2 to 5 weeks. Patients
same time that new donor RBCs are transfused. This approach has with heart disease may need smaller aliquots of RBCs at more frequent
been applied successfully to transfusion therapy for sickle cell disease. intervals to prevent problems related to volume overload. In general,
However, the goal of transfusion therapy in sickle cell disease is the patients can receive the entire unit of donor packed RBCs. However,
fractional units are appropriate for infants, small patients, and older
replacement of Hb S–containing RBCs with Hb A–containing RBCs patients with heart disease. With the use of current additive solutions,
irrespective of the total Hb level. In contrast, the goal of transfusion the duration of storage of donor RBCs has only a small effect on the
therapy in patients with thalassemia is to maintain a specific total Hb 24-hour recovery and the survival of the RBCs in each transfused unit.
level. Despite these different goals, studies of automated exchange However, for patients with thalassemia major who undergo transfusion
transfusion in patients with thalassemia have demonstrated a reduction every 2 to 5 weeks, these small differences may have a significant
in net RBC requirements of 30% to 50%, either by reducing the impact on the annual consumption of blood. Consequently, the use of
amount of blood administered at the usual transfusion interval or by donor RBCs that have been stored for less than 7 to 10 days strikes
prolonging the interval between transfusions. 118,119 The benefits of this a reasonable balance between the potential reduction in transfusion
approach are probably attributable to the removal of previously trans- iron loading and the efficient use of the blood bank inventory. The
use of volunteer blood donors remains the standard for patients with
fused RBCs from the patients and replacement with younger, recently thalassemia. Although some families of children with thalassemia
donated RBCs, reducing the overall age of the circulating RBC popula- prefer directed donations, this approach has not reduced the rate of
tion. Further clinical trials of automated exchange transfusion in thalas- transfusion-transmitted infections among blood recipients in general
semia are currently underway. and has not been shown to reduce the rate of alloimmunization in
The decision to initiate transfusion therapy should take into thalassemia. If directed donations are used, close relatives should be
account the overall clinical condition of the patient as well as the Hb avoided because stem cell transplantation may be a later therapeutic
level. Patients with severe and persistent anemia (Hb <6–7 g/dL) option.
usually also have failure to thrive, decreased activity level, and irrita- RBC, red blood cell.
bility. For these patients, transfusion therapy should begin after
confirmation of the diagnosis of thalassemia and after demonstration
that acute factors such as a febrile illness or folic acid deficiency are major, the rate of transfusional iron accumulation is approximately
not confounding the assessment of the severity of anemia. For patients 0.30–0.60 mg/kg/d. The massive IE associated with the intermedia
with higher Hb levels, the decision to begin transfusion depends on and major thalassemias leads to excessive gastrointestinal iron absorp-
the careful assessment of the child’s clinical findings. For example, tion that adds to the transfusional iron burden, although absorption
some children with thalassemia have early and pronounced facial is reduced when a Hb level above 9 g/dL is maintained. 120,121 Humans
bone deformities caused by BM expansion despite a Hb level of 8 g/ have no physiologic mechanism to induce significant excretion of
dL or higher. For such children, the benefits of transfusion therapy excess iron. Phlebotomy, the most efficient method of removing iron
may outweigh the risks. In contrast, some patients with thalassemia in other situations, is precluded in severely anemic patients with
have little or no clinical difficulty despite a persistent Hb level of thalassemia owing to transfusion dependence.
7–8 g/dL, and the benefits of transfusion therapy may be small. A pharmacologic approach using specific iron-chelating agents
Determination of genotype may provide some guidance by distin- remains the only strategy for removing excess iron in transfusion-
guishing patients with more severe defects in β-globin production dependent patients. Several drugs with chelating properties have been
from those with less severe defects, but the overlap between genotype synthesized or recovered from microorganisms. Many lack iron
and phenotype in thalassemia still requires reliance on clinical assess- specificity or are inefficient; others cause significant toxicity. To
ment (see box on Deciding to Begin Transfusion Therapy in Patients chelate iron, the chelating agent must complex with all of the iron
With Thalassemia). atom’s six available coordination sites. Three general classes of iron
chelators occur or have been synthesized: hexadentate (deferoxamine),
bidentate (deferiprone), and tridentate (deferasirox). Only one
Chelation Therapy hexadentate molecule is necessary to bind one atom of iron, but three
molecules of a bidentate iron chelator bind one iron atom and two
Each unit of packed RBCs contains approximately 200–250 mg of molecules of a tridentate chelator are required to bind one atom of
iron. Based on usual blood requirements in patients with thalassemia iron. Chelatable iron is thought to be derived from the intracellular