Immune-mediated PRCA occurs in many idiopathic cases as well as those with thymoma, systemic lupus erythematosus, and chronic lymphocytic leukemia.
Pathology: In vitro erythroid colony assays may reveal the presence of serum lymphocyte inhibitors of erythropoiesis, and about two-thirds will respond to immunosuppression or cytotoxic agents. RBC transfusions are the primary treatment.
B19 parvovirus infects erythroid progenitors and causes transient or chronic RBC aplasia. The chronic type occurs because of persistence of parvovirus in immunodeficient patients who cannot produce neutralizing antibody. The patients have severe transfusion-dependent anemia, and bone marrows show reduced erythroid precursors. The few RBC precursors are giant pronormoblasts. Diagnosis requires demonstration of parvovirus genome (DNA) in serum, blood, or bone marrow cells. Treatment with intravenous γ-globulin (IVIgG) is usually effective.
Transient aplastic crisis (TAC) caused by parvovirus occurs only once in patients with underlying hemolytic anemias . Occasionally, neutrophils and platelets will also be decreased. Diagnostic levels of IgM antibody appear in the first week after infection. In utero infection with parvovirus results in up to 10% fetal death during the first and second trimesters, and neonatal hydrops fetalis occurs occasionally.
Transient erythroblastopenia of childhood (TEC) is an acquired condition in previously hematologically normal children and usually involves only anemia, reticulocytopenia, and marrow erythroblastopenia. The mean age of diagnosis is 26 months, with the majority between 1 and 3 years of age. Although many patients have had an antecedent viral illness, no specific virus has been implicated, and parvovirus has usually been excluded. Pallor and tachycardia are the only relevant findings. The anemia may require one or two transfusions, but patients usually recover spontaneously within 1 to 2 months. Bone marrow shows erythroid hypoplasia, and cultures show decreased colony-forming units-erythroid (CFU-E). Serum or cellular inhibitors of erythropoiesis are often identified. TEC has an excellent prognosis, and later hematologic complications have not been reported.
TEC can be distinguished from Diamond-Blackfan anemia because TEC patients are usually older than 1 year and have normocytic red cells, levels of HbF normal for age, no excess membrane i antigen, and no congenital anomalies.
Diamond-Blackfan anemia (DBA; congenital hypoplastic anemia) is characterized by macrocytic anemia and reticulocytopenia (pure red cell anemia). The bone marrow is normocellular, but erythroid precursors are markedly reduced or absent. Ninety percent of patients are diagnosed under 1 year of age, although a few cases with later onset have been described. Most of the more than 500 reported cases are white, but blacks and Asians have been affected. Three-quarters of cases are sporadic, but both dominant and recessive pedigrees have been described. One DBA gene has been cloned and mapped on chromosome 19, and at least two additional DBA genes may exist.
Approximately one-third of patients have abnormal physical findings . An increase in RBC adenosine deaminase (ADA) activity is present in 90% of cases, and chromosome breakage is not increased.
Management
Approximately 80% of patients improve on corticosteroid therapy, maintain normal hemoglobin levels without transfusions, and can be managed on small alternate-day doses, but some require prohibitively toxic levels, and some respond initially and then become refractory, resulting in an overall response rate of only about 50%. Spontaneous remissions occur in about 25% of cases independent of steroid responsiveness (steroid responders and nonresponders). Bone marrow transplantation was curative in 25 of 35 reported cases. Non–steroid responsive patients require chronic transfusion therapy and inevitably develop iron overload that requires chelation
Prognosis
The current median survival is about 40 to 45 years because of improved transfusion and chelation therapy. A few patients have developed aplastic anemia (see Table 19-15), and about 5% have developed leukemia or myelodysplasias. Thus, DBA may be a myeloid premalignant condition.
Pearson syndrome is characterized by refractory macrocytic sideroblastic anemia with vacuolization of bone marrow myeloid and erythroid precursors, exocrine pancreatic deficiency with malabsorption, and metabolic acidosis. Ringed sideroblasts, which are iron-laden mitochondria, are present, and there are decreased numbers of progenitors. Patients have evidence of mitochondrial cytopathies, including metabolic acidosis and abnormalities of oxidative phosphorylation. Large deletions of mitochondrial DNA can be demonstrated. The inheritance of mitochondrial diseases is maternal because only ova and not sperm have mitochondria, and all of the approximately 50 reported cases have been sporadic. Most patients die in infancy. In children who survive, there is hematologic improvement, but they may develop the neurologic abnormalities of Kayne-Sayres disease
B19 parvovirus infects erythroid progenitors and causes transient or chronic RBC aplasia. The chronic type occurs because of persistence of parvovirus in immunodeficient patients who cannot produce neutralizing antibody. The patients have severe transfusion-dependent anemia, and bone marrows show reduced erythroid precursors. The few RBC precursors are giant pronormoblasts. Diagnosis requires demonstration of parvovirus genome (DNA) in serum, blood, or bone marrow cells. Treatment with intravenous γ-globulin (IVIgG) is usually effective.
Transient aplastic crisis (TAC) caused by parvovirus occurs only once in patients with underlying hemolytic anemias . Occasionally, neutrophils and platelets will also be decreased. Diagnostic levels of IgM antibody appear in the first week after infection. In utero infection with parvovirus results in up to 10% fetal death during the first and second trimesters, and neonatal hydrops fetalis occurs occasionally.
Transient erythroblastopenia of childhood (TEC) is an acquired condition in previously hematologically normal children and usually involves only anemia, reticulocytopenia, and marrow erythroblastopenia. The mean age of diagnosis is 26 months, with the majority between 1 and 3 years of age. Although many patients have had an antecedent viral illness, no specific virus has been implicated, and parvovirus has usually been excluded. Pallor and tachycardia are the only relevant findings. The anemia may require one or two transfusions, but patients usually recover spontaneously within 1 to 2 months. Bone marrow shows erythroid hypoplasia, and cultures show decreased colony-forming units-erythroid (CFU-E). Serum or cellular inhibitors of erythropoiesis are often identified. TEC has an excellent prognosis, and later hematologic complications have not been reported.
TEC can be distinguished from Diamond-Blackfan anemia because TEC patients are usually older than 1 year and have normocytic red cells, levels of HbF normal for age, no excess membrane i antigen, and no congenital anomalies.
Diamond-Blackfan anemia (DBA; congenital hypoplastic anemia) is characterized by macrocytic anemia and reticulocytopenia (pure red cell anemia). The bone marrow is normocellular, but erythroid precursors are markedly reduced or absent. Ninety percent of patients are diagnosed under 1 year of age, although a few cases with later onset have been described. Most of the more than 500 reported cases are white, but blacks and Asians have been affected. Three-quarters of cases are sporadic, but both dominant and recessive pedigrees have been described. One DBA gene has been cloned and mapped on chromosome 19, and at least two additional DBA genes may exist.
Approximately one-third of patients have abnormal physical findings . An increase in RBC adenosine deaminase (ADA) activity is present in 90% of cases, and chromosome breakage is not increased.
Management
Approximately 80% of patients improve on corticosteroid therapy, maintain normal hemoglobin levels without transfusions, and can be managed on small alternate-day doses, but some require prohibitively toxic levels, and some respond initially and then become refractory, resulting in an overall response rate of only about 50%. Spontaneous remissions occur in about 25% of cases independent of steroid responsiveness (steroid responders and nonresponders). Bone marrow transplantation was curative in 25 of 35 reported cases. Non–steroid responsive patients require chronic transfusion therapy and inevitably develop iron overload that requires chelation
Prognosis
The current median survival is about 40 to 45 years because of improved transfusion and chelation therapy. A few patients have developed aplastic anemia (see Table 19-15), and about 5% have developed leukemia or myelodysplasias. Thus, DBA may be a myeloid premalignant condition.
Pearson syndrome is characterized by refractory macrocytic sideroblastic anemia with vacuolization of bone marrow myeloid and erythroid precursors, exocrine pancreatic deficiency with malabsorption, and metabolic acidosis. Ringed sideroblasts, which are iron-laden mitochondria, are present, and there are decreased numbers of progenitors. Patients have evidence of mitochondrial cytopathies, including metabolic acidosis and abnormalities of oxidative phosphorylation. Large deletions of mitochondrial DNA can be demonstrated. The inheritance of mitochondrial diseases is maternal because only ova and not sperm have mitochondria, and all of the approximately 50 reported cases have been sporadic. Most patients die in infancy. In children who survive, there is hematologic improvement, but they may develop the neurologic abnormalities of Kayne-Sayres disease
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