Holger Dyggve

Prothrombin and Proconvertin in the Newborn and During the First Year of Life

The concentration of both prothrombin and proconvertin in the plasma of newborn infants less than two hours old was somewhat higher in the cases where the mothers received a single oral dose of 20 mg of vitamin K 48 to 4 hours before delivery than in untreated infants. The values could however by no means be corrected to adult levels. The average prothrombin concentration rose from 13% to 22% and the proconvertin from 25% to 39%.

Bilirubin Studies in Premature Infants who Received Menadione Derivatives or Vitamin K1 at Birth

The toxicity of menadione (2-methyl-1,4naphthoquinone), menadiol (2-methyl-1,4naphthohydroquinone) and different esters of these substances has been found to be unequal in different animals. While 25 g/kg orally of vitamin K, was non toxic in mice, DL 50 was about 400 mg orally to mice of menadione and esters (Ansbacher et aZ.(3), Molitor & Robinson (22)). Pronounced haemolytic anaemia and necrotic wounds were observed in dogs recieving 7 doses of 20 mg/ kg menadione subcutaneously and in rabbits when several injections of 20 mg/kg had been given (3). The disuccinate compound had a DL 50 of 100 mg/kg in rabbits and dogs (Fromherz (12)), while 5-7 subcutaneous injections of 20 mg/kg of menadione was a lethal dose for cats (3). In two of three rabbits recieving 3 intravenous injections of 5 mg menadiol per kg anaemia occurred (3). Injections of 15 mg of Synkavit per kg into dogs caused haemoglobinuria (12). The diphosphate and the disuccinate preparations produced convulsions in rabbits in which the deadly dose after intravenous injection was 100-150 mg/kg (12). Molitor & Robinson found no anaemia in rats who had received 350 mg/kg orally of vitamin K, for 30 days. Zbinden et al. (42) gave large doses of Konakion (vitamin K, as an aqueous colloidal suspension fabricated by Hoffmann-La Roche) to animals. While. no signs of haemolysis were observed after subcutaneous injection of 100 mglkg or intravenous injection of 20 mg/kg into dogs, 100-150 mg/kg intravenously produced slight transient haemoglobinuria but no Heinz inclusion bodies. No haemolysis occurred in mice after 4 x 100 mg/kg i.v. of vitamin K, or in rats recieving 100 or 200 mg/kg intravenously. In mice 4 A 100 mg subcutaneously or intravenously of Konakion produced no inclusion bodies, while after subcutaneous injections of Synkavit (menadiol-sodium-diphosphate) 4 x 10 mg/kg into mice more than three quarters of the erythrocytes contained Heinz-bodies. Such bodies were seen in the blood of dogs after a subcutaneous injection of 20 mg of Synkavit per kg whether the dogs were newborn or fully developed. Zbinden et al. found no increased osmotic or mechanical fragility of the erythrocytes when a very high proportion of these contained Heinzbodies (experiments with mice). Allison, Moore & Sharmann (2) found that Synkavit and other vitamin-K substitutes were much more toxic to vitamin-E deficient rats than to rats receiving a normal food. A few hours after the injection of 100 mg/kg of Synkavit haemoglobinuria and severe anaemia occurred when the rats had been on a vitamin-E deficient diet for several weeks, while only slight haemolysis without haemoglobinuria was observed in ordinarily fed rats. Two other vitamin-K substitutes were

Vitamin E to Premature Infants

Lower average bilirubin levels, higher hemoglobin and more normal serum alkaline phosphatase values were found in 67 premature infants who received 100 mg a‐tocopherol intramuscularly at birth, than in a control group. The results are discussed, and the routine administration of ‐vitamin E to premature infants is suggested.

Influence of Vitamin K1 and Synkavit Given Ante Partum on the Prothrombin Time of the Newborn

I t has been thought that the lack of a vitamin K depot in the newllorn, which is reflected in the decrease of prothrombin activity in the first few days after birth, may be the result of a resistance in the placenta to transfer of the natural forms of vitamin K (Kl, K2) from the maternal to the foetal circulation (D y g g v e, 1952). The simple water-soluble menadione derivatives appear to pass the placenta more freely. We have, therefore, found it of interest to study the influence of maternal administration of vitamin K, and Synkavit (;?-methylI,4-naphthohydroquinone diphosphate dicalcium salt) upon the prothrombin time of the newborn during the first six days of life.

Hydrops Foetalis without Blood Group Incompatibility but Associated with Hydramnios

Survival from the condition known as hydrops foetalis (generalized edema, ascites and sometimes hydrothorax of the newborn) is extremely rare. The condition generally occurs in cases of Rhesus immunization and other causes of the disease are not mentioned in the ordinary pediatric text books. One infant who survived will be described in detail and four others who were also associated with hydramnios, but where no immune antibodies were found in the serum of the mothers, are presented in tabular form. A sixth case, with hepatosplenomegaly and erythroblastosis where the mother had diabetes, is also included in this article.

A peculiar case of renal insufficiency simulating diabetes insipidus.

The following findings were made in a boy, aged 12 years, who since the age of 2 to 3 years has suffered from excessive thirst and polyuria (at present 4 to 5 liters daily) and who was considered to be suffering from diabetes insipidus:

Comparison of the action of vitamin K1 with that of synkavit in the newborn.

Summary

Effect of Synkavit1Vikastab2on Bilirubin and Plasma Prothrombin

Alkali salts of menadiol bisulfate are less efficient than the tetrasodium salt of menadiol biphosphate in lowering elevated prothrombin times in experimental animals and newborn infants when given parenterally.

Effect of SynkavitVikastabon Bilirubin and Plasma Prothrombin12

Alkali salts of menadiol bisulfate are less efficient than the tetrasodium salt of menadiol biphosphate in lowering elevated prothrombin times in experimental animals and newborn infants when given parenterally.

Effect of synkavit and vikastab on bilirubin and plasma prothrombin.

Alkali salts of menadiol bisulfate are less efficient than the tetrasodium salt of menadiol biphosphate in lowering elevated prothrombin times in experimental animals and newborn infants when given parenterally.