|
The expected benefits and rationale for the use of blood transfusions in SCD must be carefully weighed against the risks of infection, immunologic complications and iron overload. However, the indications for transfusing patients with SCD have expanded in recent years, leading to an increased incidence of iron overload [1]. Notably, the demonstrated 92% stroke risk reduction in children in the USA who receive transfusion therapy [2] has prompted more aggressive use of transfusion therapy. In addition, a follow-up study (STOP II) showed that when treatment was discontinued, a high rate of reversion to abnormal blood-flow velocities was observed, thus increasing the risk of stroke [3].
When transfusing patients with SCD, alloimmunization is an important concern due to differences in certain minor red blood cell antigens commonly encountered between the donor and recipient populations. Matching for C, E, Kell, JKB (Kidd), and Fya (Duffy) antigens can significantly reduce the risk of alloimmunization [4].
The introduction of hydroxyurea, which increases the concentration of fetal hemoglobin chains [5], as well as recent improvements in allogeneic bone-marrow transplantation, provides additional therapeutic options. In addition, the use of automated red blood cell exchange transfusions can, where available, reduce transfusional iron accumulation allowing corresponding reductions in iron chelation therapy [6].
The suggested indications that follow apply to the treatment of patients with homozygous SCD and sickle beta-zero thalassemia [7]; the role of transfusion in the treatment of patients with hemoglobin SCD and hemoglobin sickle beta-plus thalassemia is uncertain. Indications discussed include:
The only absolute indication for transfusing patients with SCD is in children with abnormal cerebral blood flow or a history of stroke. As shown in the STOP trial, preventive treatment with a program of chronic transfusions can reduce the yearly risk of stroke in children by as much as 92% [2].
Transfusions in anemic patients are usually simple (without exchange) and are most often provided to treat any of several symptoms of varying seriousness.
| Acute/episodic |
- Anemia
- Splenic sequestration
- Severe or long-lasting aplastic crises
- Stroke
- Acute chest syndrome
- Multiple-organ failure syndrome
- Preoperative (in select cases)
- Malaria-associated severe hemolytic anemia with impending cardiac decompensation
- Cerebral dysfunction
- Sudden drops in hemoglobin concentration, particularly during acute splenic or hepatic sequestration crises in which there is rapid enlargement of the spleen or liver and rapidly falling hematocrit levels
- Aplastic crisis may also be treated by infusion if anemic symptoms such as dyspnea or hypovolemia are present
|
| Chronic |
- Heart failure
- Prophylaxis against recurrent stroke
- Stroke prevention when transcranial doppler velocities are abnormal
- Chronic pulmonary hypertension (unresponsive to other approaches)
- Refractory congestive heart failure
- Severe recurrent vaso-occlusive crises
- Previous splenic sequestration in a child aged 2-3 years (in anticipation of later splenectomy)
- Chronic pain
- Fatigue and dyspnea, particularly in association with erythroid hypoplasia or aplasia, and with hemoglobin and hematocrit concentrations <5.0 g/dL and <15%, respectively
|
Exchange transfusions can be used to decrease the proportion of erythrocytes containing hemoglobin S and thereby improve tissue perfusion. This may be indicated in patients about to undergo general anesthesia or surgery to the posterior segment of the eye. A variety of acute and chronic conditions may also warrant the use of an exchange transfusion:
- Acute or suspected cerebrovascular accidents or transient ischemic attack.
- Multiorgan failure syndrome.
- Acute chest syndrome or other acute lung disease in which oxygen therapy fails to maintain arterial oxygen at near-normal levels, or in which antibiotics or other therapies fail.
- Acute priapism that is not responsive to therapy.
There are a number of events and situations in which transfusions have been used to provide symptomatic relief or as a preventive treatment. These include: intractable, frequent pain; rapid deterioration unresponsive to other treatment; prior to injection of hypertonic contrast media; leg ulcers; prevention of pregnancy complications; chronic organ failure; prevention of severe vaso-occlusive crisis in patients eligible for hydroxyurea therapy; loss of blood due to trauma; and extreme deterioration of performance status.
Several steps can be taken to maximize the benefits of transfusion therapy for patients with SCD:
- In patients who have had, or are at risk of having, a stroke, transfusions may be provided every 3-4 weeks, with the goal of maintaining hemoglobin A >50-70%, and hemoglobin S <30%. To avoid high viscosity, total hemoglobin is usually maintained <12 g/dL until hemoglobin S is brought down to ≤30% [10;11]
- In treating aplastic crisis in children, a red blood cell transfusion should be considered if the hematocrit level is 20-25% below baseline levels [12].
- Patients who have an episode of splenic sequestration should either have a blood transfusion, followed by splenectomy, or be placed on a program of chronic transfusions. Since splenectomy is not recommended in children under the age of 2 years, a chronic transfusion regimen to keep hemoglobin S levels <30% can be used until the child is old enough to undergo splenectomy.
- Patients who have received chronic or repeated red blood cell transfusions may be considered for iron chelation therapy.
  References
(1) Reed WF, Vichinsky EP: Transfusion practice for patients with sickle cell disease. Curr Opin Hematol 1999; 6(6):432-436.
(2) Adams RJ, McKie VC, Hsu L, Files B, Vichinsky E, Pegelow C, Abboud M, Gallagher D, Kutlar A, Nichols FT, Bonds DR, Brambilla D: Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography. N Engl J Med 1998; 339(1):5-11.
(3) Adams RJ, Brambilla D: Discontinuing prophylactic transfusions used to prevent stroke in sickle cell disease. N Engl J Med 2005; 353(26):2769-2778.
(4) Singer ST, Wu V, Mignacca R, Kuypers FA, Morel P, Vichinsky EP: Alloimmunization and erythrocyte autoimmunization in transfusion-dependent thalassemia patients of predominantly Asian descent. Blood 2000; 96(10):3369-3373.
(5) Steinberg MH, Barton F, Castro O, Pegelow CH, Ballas SK, Kutlar A, Orringer E, Bellevue R, Olivieri N, Eckman J, Varma M, Ramirez G, Adler B, Smith W, Carlos T, Ataga K, DeCastro L, Bigelow C, Saunthararajah Y, Telfer M, Vichinsky E, Claster S, Shurin S, Bridges K, Waclawiw M, Bonds D, Terrin M: Effect of hydroxyurea on mortality and morbidity in adult sickle cell anemia: risks and benefits up to 9 years of treatment. JAMA 2003; 289(13):1645-1651.
(6) Cohen AR, Martin MB, Silber JH, Kim HC, Ohene-Frempong K, Schwartz E: A modified transfusion program for prevention of stroke in sickle cell disease. Blood 1992; 79(7):1657-1661.
(7) National Heart, Lung, and Blood Institute. Clinical alert from the National Heart, Lung, and Blood Institute.http://www.nhlbi.nih.gov/health/prof/blood/sickle/clinical-alert-scd.htm2004.
(8) Stuart MJ, Nagel RL: Sickle-cell disease. Lancet 2004; 364(9442):1343-1360.
(9) Vichinsky E: Consensus document for transfusion-related iron overload. Semin Hematol 2001; 38(1 Suppl 1):2-4.
(10) Adams RJ, Ohene-Frempong K, Wang W: Sickle cell and the brain. Hematology (Am Soc Hematol Educ Program ) 2001;31-46.
(11) Ohene-Frempong K: Stroke in sickle cell disease: demographic, clinical, and therapeutic considerations. Semin Hematol 1991; 28(3):213-219
(12) Vichinsky EP: Current issues with blood transfusions in sickle cell disease. Semin Hematol 2001; 38 (1 Suppl 1):14-22.
 |
