Hypoplastic and aplastic anemias of infancy and childhood: With a consideration of the syndrome of nonhemolytic anemia of the newborn*

Summary From the heterogeneous group ofhypoplastic-aplastic anemias, several well-defined clinical and hematological entities and distinctive blood responses have been chosen for review. These are normochromic and normocytic syndromes differentiated from other blood dyscrasias by the absence of active blood formation and their resistance to all forms of antianemia treatment except transfusion. These anemias have been placed intothe three general categories of pure red-cell, hypoplastic, and aplastic anemias, in accordance with specific criteria. In pure red-cell anemia the failureof the bone marrow is confined to erythropoiesis, without simultaneous depression of granulocytes or platelets or their precursors. These patients survive long periods, provided repeated transfusions are administered to maintain normal blood levels. An adequate appraisal of therapy is not yet available because of lack of experience with large numbers of cases. However, spontaneous remissions have been observed, as well as recovery with steroids and following splenectomy. It was postulated that pure red-cell anemia and related hypoplastic anemias represent examples of congenital hematopoietic anomalies comparable to other somatic malformations originating from disturbances in embryonic and fetal life. The syndrome of “nonhemolyticanemia of the newborn” was described to include those infants who show a rapid fall of red cells and hemoglobin within the first days of life, without jaundice and erythroblastemia. The factors of incompatibility of blood groups, hemorrhage, hemolysis, and infection are not operative and the outlook based on a limited experience has been favorable. The syndrome probably represents an exaggeration of the aregenerative phase of erythropoiesis which characterizes the newborn period. The designation as “nonhemolytic anemia of the newborn” emphasizes its differentiation from erythroblastosis and probably coincides with some of the cases of anemia of the newborn reported before the discovery of the Rh factor. The mechanism of acute erythroblastopeniaand the aplastic crisis was reviewed in connection with their occurrence in hemolytic states such as sickle cell and spherocytic anemias. Under these circumstances the initial examination without knowledge of a pre-existing hemolytic anemia suggests a diagnosis of aplastic anemia. The bone marrow soon becomes reactive and the underlying condition is manifest. The temporary failure of erythropoiesisaccounts for the observation of protracted anemia in occasional cases of erythroblastosis. This inability to maintain normal blood levels may depend upon an inactive bone marrow as evidenced by a decreased erythroid cellular content. Two cases of chronic hypoplastic anemia were described which were suspected to be intermediate stages of aplastic anemia. In each instance the child was known to be allergic and susceptible to severe upper respiratory infections. The anemias resisted all hematinics except transfusion. Both children eventually recovered probably spontaneously although the effect of tonsillectomy in one and cortisone in the other could not be discounted. True aplastic anemia with an acellular bone marrow and pancytopenia is a rare occurrence in infancy and childhood. While search for a myelotoxic agent is usually unsuccessful, chloramphenicol has occasionally been associated with toxic hematopoietic effects. Since this drug has proved the agent of choice in specific clinical conditions, it is important to control its administration by frequent hematologic studies. Precautionary measures including blood and bone marrow examination have been outlined to detect reversible anemia and granulocytopenia. The possible suppressive effect of long-continued transfusions on erythropoiesis in any type of chronic anemia, nonhemolytic as well as hemolytic, may obscure the capacity for inherent blood formation and interfere with the appraisal of a specific blood picture. The optimum amount of blood to be administered and the interval between transfusions require serious consideration. Of major importance is to determine the actual need for transfusion, not in terms of a fixed hemoglobin value, but in relation to the clinical signs and symptoms manifested by the patient, with promise of their relief by this form of treatment.