eMedicine Specialties > Pediatrics: General Medicine > Hematology
Anemia, Fanconi: Treatment & Medication
Updated: Sep 9, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
Treatment is recommended for significant cytopenias, such as hemoglobin less than 8 g/dL, platelets fewer than 30,000/µL, or neutrophils fewer than 500/µL. Although the only therapy that can cure the pancytopenia is stem cell transplantation, androgens, to which approximately 50-75% of patients respond, are used for those in whom transplantation is not an option (see Medication).
Supportive care for patients with symptomatic Fanconi anemia includes transfusions of packed RBCs that have been leukodepleted (and are not from family members, to avoid sensitization in case of a future transplantation). Symptomatic thrombocytopenia can be treated with similarly treated platelets; single-donor platelets are preferred to reduce the frequency of antibody formation. Symptomatic neutropenia usually responds to granulocyte colony-stimulating factor (G-CSF). See Medication. In the past, some clinicians advocated corticosteroids, to delay growth plate closure in patients treated with androgens and to improve vascular integrity and reduce bleeding.
Hematopoietic stem cell transplantation (bone marrow, cord blood, or peripheral blood stem cells) may cure aplastic anemia and prevent myelodysplastic syndrome or leukemia.6,7 It should be considered for those who have an human leukocyte antigen (HLA)-matched sibling donor (survival rate is >80%). The survival rate after transplantation from alternative donors is improving, depending on the completeness of the HLA-matching. This procedure had been reserved for patients who have leukemia or myelodysplasia and did not have HLA-matched related donors and for patients either unable to tolerate or refractory to standard medical treatment; this practice is changing as new, less toxic conditioning regimens and more precise HLA typing are developed and as the size of the donor pool increases. In any case transplants should take place at institutions with experience in the treatment of patients with Fanconi anemia.
Surgical Care
Hand surgery and splinting may be indicated for thumb and radial anomalies. Hand surgery should be performed early in life to ensure maximal function. Congenital heart defects may require surgery. GI anomalies, such as tracheoesophageal fistulas and imperforate anus, are also treated surgically. Cancer surgery should be performed by experienced surgeons in consultation with hematologists and oncologists with experience in the management of Fanconi anemia.
Consultations
Patients with specific birth defects or medical problems should be referred to the appropriate consultants (eg, hand surgeon, cardiologist, dermatologist, endocrinologist, gastroenterologist, geneticist).
Activity
Patients with thrombocytopenia should avoid trauma, such as that resulting from contact sports, and should use helmets and padding. Those with anemia should participate in strenuous activities only under supervision and only as tolerated. Those with severe neutropenia need to avoid exposure to people with active infections.
Medication
Androgenic agents
These enhance the production and urinary excretion of erythropoietin in anemias caused by bone marrow failure and often stimulate erythropoiesis in anemias caused by deficient red cell production. They appear to make hematopoietic stem cells more responsive to differentiation, but the exact mechanism is not clear. The usual agent in the United States is oral oxymetholone, a 17-beta-hydroxylated androgen. Although oral androgens have a risk of liver toxicity, they are easier to use in children than parenteral androgens. The lowest effective dose should be used.
Oxymetholone (Anadrol-50)
Anabolic and androgenic derivative of testosterone in an PO formulation.
Adult
2-5 mg/kg/d PO
Pediatric
Administer as in adults
May increase sensitivity to anticoagulants (dosage of an anticoagulant may have to be decreased to maintain PT at desired therapeutic level); may increase insulin effects
Documented hypersensitivity; male breast or prostate cancer; metastatic female breast cancer with hypercalcemia; nephrosis or nephrotic phase of nephritis; known or suspected pregnancy; severe liver disease
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Virilization (deepening of the voice, hirsutism, acne, enlargement of genitalia) common and may be irreversible, even after prompt discontinuance of therapy; menstrual irregularities, including amenorrhea, possible; insulin or PO hypoglycemic dosage may need adjustment; may cause suppression of clotting factors II, V, VII, and X; may cause increase in PT
Cholestatic hepatitis, peliosis hepatitis, liver tumors, and blood lipid changes that increase risk of atherosclerosis possible; monitoring includes liver function tests and liver ultrasound examinations
Nandrolone decanoate (Deca-Durabolin)
A parenteral androgen is sometimes selected because of the lower risk of hepatic tumors. As with oxymetholone, the lowest effective dose should be used. This drug is no longer manufactured in the United States.
Adult
1-2 mg/kg/wk IM
Pediatric
Administer as in adults
May increase sensitivity to anticoagulants (dosage of an anticoagulant may have to be decreased to maintain PT at desired therapeutic level); may increase insulin effects
Documented hypersensitivity; male breast or prostate cancer; metastatic female breast cancer with hypercalcemia; nephrosis or nephrotic phase of nephritis; known or suspected pregnancy; severe liver disease
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Virilization (deepening of the voice, hirsutism, acne, enlargement of genitalia) common and may be irreversible, even after prompt discontinuance of therapy; menstrual irregularities, including amenorrhea, also possible; insulin or PO hypoglycemic dosage may need adjustment; may cause suppression of clotting factors II, V, VII and X and increase in PT
Antifibrinolytic agents
These agents may decrease bleeding, particularly oral mucosal bleeding, in patients with thrombocytopenia by stabilization of thrombi.
Aminocaproic acid (Amicar)
Competitively inhibits activation of plasminogen to plasmin.
Adult
30 g/d PO/IV in divided doses q3-6h; not to exceed 30 g/d
Pediatric
100-200 mg/kg PO/IV loading dose; followed by 200-400 mg/kg/d PO divided q6h for 7-10 d.
Renal impairment: 50 mg/kg/d PO qd
Coadministration with estrogens may cause increase in clotting factors, leading to hypercoagulable state
Documented hypersensitivity; hematuria; evidence of active intravascular clotting process; because aminocaproic acid can be fatal in patients with DIC, differentiate between hyperfibrinolysis and disseminated intravascular coagulation
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Decrease dose to 50 mg/kg/d PO qd in severe renal impairment; caution in cardiac or hepatic disease
Hematopoietic growth factors
These factors are glycoproteins that act on hematopoietic cells by binding to specific cell surface receptors and stimulating proliferation, differentiation, commitment, and some end cell functional activation.
Filgrastim (G-CSF, Neupogen)
G-CSF that activates and stimulates production, maturation, migration, and cytotoxicity of neutrophils.
Adult
2-10 mcg/kg SC qd/qod
Pediatric
Administer as in adults
Caution in coadministration with drugs that may potentiate release of neutrophils (eg, lithium)
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May cause bone pain, flulike symptoms, nausea, or vomiting; do not dilute to concentrations <5 mcg/mL; do not dilute with saline; potential risk of evolution to leukemia
Epoetin alfa (Epogen, Procrit)
Stimulates division and differentiation of committed erythroid progenitor cells; induces release of reticulocytes from bone marrow into blood stream.
Adult
100-250 U/kg SC 3 times/wk
Pediatric
Administer as in adults
None reported
Documented hypersensitivity (including hypersensitivity to human albumin, hypersensitivity to mammalian cell-derived products); uncontrolled hypertension
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in hypertension, history of seizures, thrombocytosis, chronic hepatic impairment, ischemic vascular disease, or malignant tumors; blood pressure must be monitored; use lowest dose possible to achieve Hgb no greater than 10-12 g/dL; decrease dose/discontinue if Hgb rises too rapidly (ie, >1 g/dL within 2 wk) or if achieve target Hgb
Glucocorticoids
Corticosteroids are used on alternate days and may delay the growth acceleration caused by androgens. They may also stabilize endothelial cells, leading to reduced bleeding at a given degree of thrombocytopenia. Some clinicians accept the use of corticosteroids.
Prednisone (Deltasone, Liquid Pred)
Elicits anti-inflammatory properties and causes profound and varied metabolic effects. Modifies the body's immune response to diverse stimuli.
Adult
5-10 mg PO qod
Pediatric
5 mg PO qod
Coadministration with digoxin may increase digitalis toxicity secondary to hypokalemia; estrogens may increase methylprednisolone levels; phenobarbital, phenytoin, and rifampin may decrease methylprednisolone levels (adjust dose); monitor patients for hypokalemia when taking medication concurrently with diuretics
Documented hypersensitivity; viral, fungal, or tubercular skin infections
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
May increase risk of serious or fatal infection in individuals exposed to viral illnesses such as chickenpox or measles; hyperglycemia, edema, osteonecrosis, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, myopathy, and infections are possible complications
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| Differential Diagnoses & Workup: Anemia, Fanconi |
 Treatment & Medication: Anemia, Fanconi |
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References
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Further Reading
Keywords
Fanconi anemia, FA, constitutional aplastic anemia, bone marrow failure, inherited bone marrow failure syndrome, aplastic anemia, leukemia, myelodysplastic syndrome, liver adenoma, hepatoma, radial ray anomalies, poor growth, genitourinary problems, short stature, skin pigmentation, café au lait spots, petechiae, bruises, bruising, pallor, fatigue, infections, thumb anomalies, thumb and radial anomalies, abnormal male gonads, microcephaly, eye anomalies, structural renal defects, low birth weight, developmental delay, abnormal ears, abnormal hearing, Estren Dameshek Fanconi anemia, pancytopenia, treatment, diagnosis
