David K. Melhorn

Vitamin E-dependent anemia in the premature infant. I. Effects of large doses of medicinal iron

Description of a hemolytic anemia associated with vitamin E deficiency in premature infants prompted study of the relationships of medicinal iron, vitamin E, and hematologic parameters during the early life of such infants. A total of 186 patients categorized according to birth weight and gestational age were placed in study groups: (1) no iron or vitamin E supplement, (2) oral vitamin E supplement, (3) oral iron supplement, and (4) iron and vitamin E supplements. Significantly lower mean hemoglobin and serum vitamin E concentrations, with higher reticulocyte count and hydrogen peroxide fragility, were found during the second month of life in infants with a gestational age less than 36 weeks who were not receiving vitamin E. Hemoglobin values were lowest and reticulocyte counts highest in vitamin E-deficient infants of low gestational age who received supplemental iron. These observations suggest that therapeutic doses of iron increase red cell hemolysis during a period of vitamin E deficiency.

Vitamin E-dependent anemia in the premature infant. II. Relationships between gestational age and absorption of vitamin E**

The association of vitamin E deficiency and hemolytic anemia in small premature infants prompted study of intestinal absorption of vitamin E in infants of various gestational and chronologic ages. A direct relationship was found between the gestational age of the premature infant and his ability to maintain vitamin E sufficiency during the first 3 months of life; infants of lowest gestational age were least able to achieve vitamin E sufficiency, even when receiving a vitamin E supplement. In infants whose gestational age was less than 32 weeks, progressive improvement in the intestinal absorption of the vitamin was seen as the chronologic equivalent of a full-term gestational age was approached. Oral administration of iron is implicated as interfering with the intestinal absorption of vitamin E. Since maintenance of vitamin E sufficiency appears to be nutritionally important in the premature infant, the efficacy of other routes of administration of the vitamin should be explored.

Vitamin E-dependent anemia in the premature infant

Studies on serum tocopherol levels, hematopoietic responses, and erythrocyte phospholipid fractions were carried out in agroup of low-birth-weight (mean, 1,530 gm) premature infants whose diets were supplemented with either water-soluble (TPGS) or fat-soluble (TA) forms of d-alpha tocopheryl (25 IU/day). Significantly higher serum tocopherol levels and early maintenance of higher hemoglobin values were observed in the infants who received the water-soluble tocopheryl preparation. Comparable but less marked differences in these values were identified in similarly paired groups fed lower concentrations of the tocopheryls in combination with iron. The lowest hemoglobin levels were recorded in the infants fed formulas containing TA and iron. Among a selected group of vitamin E-deficient infants, evidence of lipid instability in the erythrocyte membrane was manifested by decreased values of phosphatidyl ethanolamine.

Exchange transfusion with citrated whole blood for disseminated intravascular coagulation

Disseminated intravascular coagulation in 4 full-term infants and one 4-year-old child was successfully treated with exchange transfusions of stored, 12- to 72 hour old, citrated whole blood. Heparin was not used. The causative, or related, disorders included the respiratory distress syndrome, ABO incompatibility, and streptococcal sepsis. In all patients, except one, an infant with galactosemia and streptococcemia, the clotting factors promptly returned to normal. In the galactosemic infant with streptococcal sepsis, a rebound delay occurred with return to normal of the secondary clotting disorder following correction of the metabolic defect. The mechanism of action is, in part, related to a “clearing” process by the exchange transfusion, which, because of ready availability, should receive priority as the treatment of choice for disseminated intravascular coagulation in the newborn infant and probably in older patients as well.

The red cell hydrogen peroxide hemolysis test and vitamin E absorption in the differential diagnosis of jaundice in infancy

Studies of red cell hydrogen peroxide hemolysis and intestinal absorption of vitamin E were conducted in 21 infants whose major presenting symptom was jaundice, in order to evaluate the efficacy of these simple laboratory techniques in differentiation of their disease conditions. The peroxide hemolysis test is based upon the assumptions that the intestinal absorption of fat-soluble vitamin E requires adequate amounts of bile salts and that vitamin E deficiency is reflected by abnormal sensitivity of the red cell membrane to hydrogen peroxide. Ultimate diagnoses in the infants studied, 14 of whom underwent open liver biopsy and operative cholangiogram, included biliary atresia, neonatal hepatitis, and primary congenital hemolytic processes. Although a single red cell hydrogen peroxide hemolysis test did not clearly differentiate between the various conditions studied, peroxide hemolysis used in combination with vitamin E absorption curves showed distinctly different patterns for each group of diseases. The information gained thus enabled prediction of the jaundice with accuracy and indicates that these laboratory techniques can be of great value in guiding the decisions regarding the necessity and timing of surgical exploration in jaundiced infants.

Erythrocyte lipids and vitamin E in Type II congenital dyserythropoietic anemia

An 8-year-old girl with Type II congenital dyserythropoietic anemia, characterized by morphologic abnormalities of erythroid precursors, immunologic alterations, hyperbilirubinemia, and chronic anemia, was found to be vitamin E deficient. Nutritional history and vitamin E absorption studies indicated that neither dietary lack nor intenstinal malabsorption was the cause of the deficiency. Striking changes in the patients hematologic status following administration of vitamin E included rise in hemoglobin, decrease in bilirubin and reticulocyte count, and a marked increase in red blood cell survival. Erythrocyte phospholipids, altered while the patient was vitamin E deficient, returned to normal levesl during therapy. However, hematologic improvement was not complete, immunolotic abnormalities persisted, and morphologic aberrations in erythrocyte precursors actually increased during vitamin E therapy. It is therefore concluded that vitamin E deficiency played a secondary role in the production of the childs hematologic disorder and may have been a result of the increased utilization of the vitamin in stabilization of defective cellular membranes.