Chapter 2 Aplastic Anemia
PATHOPHYSIOLOGY
Aplastic anemia occurs when bone marrow failure leads to the depletion of all marrow elements. The production of blood cells is decreased or lacking. Pancytopenia and hypocellularity of the marrow occur. The manifestation of symptoms is dependent on the extent of the thrombocytopenia (hemorrhagic symptoms), neutropenia (bacterial infections, fever), and anemia (pallor, fatigue, congestive heart failure, tachycardia). Severe aplastic anemia is characterized by a granulocyte count of less than 500/mm3, a platelet count of less than 20,000/mm3, and a reticulocyte count of less than 1%. Aplastic anemia can be acquired or inherited. Acquired forms can be caused by drugs (chloramphenicol and chemotherapeutic agents), chemicals (benzene), radiation, or viral infection (hepatitis virus, human parvovirus, Epstein-Barr virus), and in rare instances are associated with paroxysmal nocturnal hemoglobinuria. Fanconi’s anemia is the most common inherited type and is associated with various physical findings and renal and cardiac abnormalities. Diamond-Blackfan anemia is a hypoplastic anemia that only affects the erythrocyte cell line; it is diagnosed in early infancy.
INCIDENCE
1. About 100 new cases of acquired aplastic anemia are diagnosed each year in children in the United States.
2. Aplastic anemia may occur at any age.
3. The majority of cases are idiopathic.
4. Long-term survival rate with bone marrow transplant from histocompatible donors is as high as 75% to 95% in children. Without bone marrow transplant, survival is about 50%.
5. Males and females are affected equally with Fanconi’s anemia. Most cases are diagnosed at about 7 years of age, although the disorder may be diagnosed in infancy or as late as 30 to 40 years of age.
CLINICAL MANIFESTATIONS
1. Petechiae, ecchymoses, epistaxis (occur first as a result of low platelet counts)
2. Oral ulcerations, bacterial infections, fever (occur later in course)
3. Anemia, pallor, fatigue, tachycardia (late signs)
4. Café-au-lait spots, melanin-like hyperpigmentation, absent thumbs, renal abnormalities, short stature (Fanconi’s anemia)
5. Pallor and anemia at birth or in early infancy (Diamond-Blackfan anemia)
COMPLICATIONS
LABORATORY AND DIAGNOSTIC TESTS
1. Bone marrow aspiration and biopsy—used to assess the cells in the bone marrow; findings are marrow hypoplasia with less than 25% normal cellularity.
2. Complete blood count with differential—used to evaluate circulating numbers and sizes of red and white blood cells. Findings with aplastic anemia include macrocytic anemia and decreased absolute neutrophil count to less than 500/μL. White blood cell counts are normal in Diamond-Blackfan anemia.
3. Platelet count—used to assess the number of platelets in the blood, which are needed for blood clotting. Findings include a platelet count of less than 20,000/μL. Platelet counts are normal in Diamond-Blackfan anemia.
4. Reticulocyte count—used to indirectly analyze hematopoiesis or the forming and development of blood cell lines. Decreased reticulocyte count in the presence of anemia indicates underlying pathology.
5. Hemoglobin electrophoresis—used to detect presence of fetal hemoglobin, which is increased in Diamond-Blackfan anemia.
6. Chromosome breakage test—used to detect chromatid breaks and other abnormalities. A positive result indicates Fanconi’s anemia.
MEDICAL MANAGEMENT
The first-choice treatment for severe aplastic anemia is bone marrow transplant from a sibling donor who is human lymphocyte antigen (HLA)–matched. In more than 70% of cases, there will be no sibling match. However, there is an increased chance of a match between one parent and the child with aplastic anemia. To avoid sensitization, if bone marrow transplantation is to be done, HLA typing of the family is performed immediately and blood products are used as little as possible. Further, blood should not be donated by the child’s family. Blood products should always be irradiated and filtered to remove white blood cells before being given to a child who is a candidate for bone marrow transplantation. Children with severe aplastic anemia treated with bone marrow transplant recover more rapidly and with fewer complications than adults. More recent advances include using umbilical cord blood that was banked at birth or saved from a newborn sibling at birth and then typed and used. Umbilical cord blood is rich in stem cells, which then grow well in children with aplastic anemia.
Immunotherapy with either antithymocyte globulin or antilymphocyte globulin is the primary treatment for children who are not candidates for bone marrow transplantation. The child will respond within 3 months or not at all to this therapy. Cyclosporine is also an effective immunosuppressant that can be used in the treatment of aplastic anemia. Androgens, used in the past, are rarely used today unless no other treatment is available. Corticosteroids are the initial therapy in Diamond-Blackfan anemia; with a positive response, indicated by an increasing hematocrit, the dose is tapered.
Clinical trials exploring the use of granulocyte-macrophage colony-stimulating factor (GM-CSF) or granulocyte colony-stimulating factor (G-CSF) in pediatric clients continue to show some hematologic improvement with these treatments. Further research continues to determine the role of GM-CSF and G-CSF in treating aplastic anemia and Fanconi’s anemia.
Supportive therapy includes use of antibiotics and administration of blood products. Antibiotics are used to treat fever and neutropenia; prophylactic antibiotics are not indicated for the asymptomatic child. Blood product administration is based on clinical findings. All products should be leukocyte-reduced and irradiated. Blood products used may include the following:
1. Platelets—to maintain platelet count appropriate for the individual child to prevent bleeding—in chronic cases the count may drop to as low as 15,000/mm3 before transfusion is given. Use single-donor platelet pheresis to decrease the number of HLA antigens to which the child is exposed.
2. Packed red blood cells—to maintain hemoglobin level (chronic anemia is often well tolerated). For long-term therapy, deferoxamine is used as a chelating agent to prevent complications of iron overload.
NURSING INTERVENTIONS
1. Identify and report signs and symptoms of hemorrhage.
2. Protect from trauma and prevent/decrease bleeding.
4. Administer blood products and monitor child’s response to their infusion (after bone marrow transplantation, to avoid sensitization to donor transplantation antigen).
5. Provide frequent rest periods. Organize nursing care to increase activity tolerance and prevent fatigue.
6. Monitor child’s therapeutic and untoward response to medications; monitor action and side effects of administered medications.
7. Prepare child and family for bone marrow transplantation.
8. Monitor for signs of bone marrow transplant complications (see the Complications section in this chapter).
9. Provide age-appropriate diversional and recreational activities.
Discharge Planning and Home Care
1. Instruct parents about measures to protect child from infection.
2. Instruct parents to monitor for signs of complications (see the Complications section in this chapter).
3. Instruct parents about administration of medication.
4. Provide child and family with information about community support systems for long-term adaptation.
Brill JR, Baumgardner DJ. Normocytic anemia. Am Fam Physician. 2000;62(10):2255.
D’Andrea AD, et al. Marrow failure. Hematology. 2002:58. (American Society of Hematology education program)
Lemons RS. Bone marrow dysfunction. In: Osborn LM, et al. Pediatrics. St. Louis: Mosby, 2005.
Trigg MN. Hematopoietic stem cells. Pediatrics. 2004;113(4):1051.
