Vitamin K Deficiency Research Articles

Protein C Level at Birth

The protein C level was determined, on cord blood, for 30 healthy newborns by electro-immuno assay using a monospecific antiserum. For the newborns the mean level of protein C related antigen is about one third of normal adults' mean level. There is a good correlation between Protein C related antigen and prothrombin related antigen. The low level of these vitamin-K-dependent proteins is probably a consequence of partial liver immaturity at birth. Using two-dimensional immuno-electrophoresis we were unable to detect subcarboxylated forms of protein C. However these abnormal forms could be seen in vitamin-K deficiencies of neonates.

Vitamin K Deficiency in Infants

Vitamin K Deficiency in Infants

Vitamin K-dependent γ-carboxyglutamic acid formation by kidney microsomes in vitro

γ-Carboxyglutamic acid has been identified as a constituent of renal tissue in chicken, rat, and rabbit and is depressed by vitamin K-deficiency or dicoumarol diets. Thorough perfusion of rat and rabbit kidneys to remove blood contamination does not remove the γ-carboxyglutamate containing protein(s), which appear to be localized in the cortex. Incubation of kidney microsomes with [ 14C]NaHCO 3 in vitro results in the post-translational formation of protein bound [ 14C]-γ-carboxyglutamic acid. Incorporation is stimulated 1.6- to 34-fold by addition of the active vitamin K 2-methyl, 3-farnesyl, 1,4-naphthoquinone. About 80% of incorporated, non-dialyzable 14C is situated in the γ-carboxyl group of γ-carboxyglutamic acid.

Hematology-oncology: an annotated bibliography of recent literature. References to journal articles and other papers.

Hematology-oncology: an annotated bibliography of recent literature. References to journal articles and other papers.

The Influence of the Thyroid Function on the Metabolic Rate of Prothrombin, Factor VII, and Factor X in the Rat

The influence of the thyroid function on the metabolic rate of prothrombin, factor VII, and X was studied in the rat. Disappearance rates of the three coagulation factors were measured after synthesis had been blocked with appropriate doses of warfarin, and reappearance rates were assessed upon induction of synthesis by high doses of vitamin K1 injected into rats displaying coumarin induced hypocoagulability. No statistically significant difference in the disappearance and production rates of any of the factors could be found between normal euthyroid rats and thyroxin-treated hypothyroid rats proven to be euthyroid. The differences between the two euthyroid groups and the hypothyroid group were highly significant, however: hypothyroidism results in an approximately 50% decrease of the metabolic rates of the three coagulation factors under study. The reappearance of the three factors, under euthyroid as well as hypothyroid conditions, showed a biphasic pattern: in the first two hours after vitamin K1 administration to warfarin treated rats, a rapid reappearance was observed, to the same extent for all three factors, in hypo- as well as euthyroid rats. This finding suggests that in vitamin K1 deficiency an intracellular accumulation of precursor proteins (PIVKAs) occurs, which after rapid conversion into biologically active coagulation factors by vitamin K1 are shed into circulation. The subsequent phase of reappearance is much slower and reflects the synthesis rate of coagulation enzymes. It is characteristic for each factor and clearly slower in hypothyroid rats than in euthyroid rats. From this an influence of thyroid function on the synthesis rate of the protein moiety of coagulation factors can be inferred. An apparent difference between disappearance and reappearance rate of the coagulation factors in the plasma, particularly pronounced for factors VII and X in euthyroid rats, could theoretically be explained as the consequence of the model used for derivation of these rates.

Medium-Chain Triglycerides as Stress Agents in Vitamin K Deficiency

THE feeding of triglycerides containing fatty acids of medium chain length (MCT) creates a stress on vitamin E (Fisher and Kaunitz, 1965; Budowski et al., 1969). Continuing studies in this laboratory have indicated that the replacement of dietary long-chain triglycerides by MCT reduces the hypercholesterolemia of cholesterol-fed chickens (Fisher and Griminger, 1970). It was of interest to see whether one might use dietary MCT to obtain a more severe deficiency of another fat-soluble nutrient, vitamin K. To this end, the degree of vitamin K-deficiency in chickens receiving vitamin K-deficient diets containing MCT, corn oil, or no supplementary fats was compared, and the effect of supplementation of such diets with graded levels of different vitamin K sources investigated.PROCEDUREThe nitrogenous moiety in the vitamin K-deficient diet used in these tests was supplied (in percent) by isolated soy protein, 30, dl-methionine, 0.4, and glycine, 0.5. In addition, the diet contained reagent-grade…

Neonatal coagulation defect due to anticonvulsant drug treatment in pregnancy.

Coagulation-factor assays were performed on 16 neonates born to 16 unselected epileptic mothers who were being treated with anticonvulsant drugs. 2 of the neonates had clinical evidence of a bleeding tendency. A coagulation defect similar to that in vitamin-K deficiency was found in 8 neonates and was severe in 7. The mothers of the 8 affected neonates had been treated with a barbiturate or with a drug metabolised to a barbiturate and with phenytoin. It is suggested that anticonvulsant drug therapy during pregnancy, especially treatment with barbiturates, frequently causes a coagulation defect which may result in bleeding during the early neonatal period. The prophylactic use of vitamin K1 is especially important in this situation.

Vitamin K deficiency in the elderly.

Vitamin K deficiency in the elderly.

Mechanism of the Effect of Retinoic Acid and Squalene on Vitamin K Deficiency in the Rat

The anticoagulant effect of squalene and retinoic acid was studied in adult male rats fed purified diets deficient in vitamin K. Both appear to inhibit absorption of vitamin K although possibly by different mechanisms. The requirement for vitamin K increased with a dietary increase of squalene but maximal action of retinoic acid was easily obtained and further ingestion of vitamin A did not affect prothrombin levels. The requirement for vitamin K in rats fed 0.5% squalene or 50 IU of retinoic acid/g of diet was about 9 µg/day which resembles the requirement in germfree rats. On this basis indigestible oils and retinoic acid may be useful agents for the production of “simple” vitamin K-deficiency in mammalian species.

VITAMIN-K DEFICIENCY IN EARLY PREGNANCY.

VITAMIN-K DEFICIENCY IN EARLY PREGNANCY.

Interrelationships Between Vitamin K and Estrogenic Hormones

Evidence is presented which indicates a protective effect of estroge nic hormones in vitamin-K deficiency. Impetus for the study was provide d when hemorrhagic deaths began occurring in large numbers in a group of rats being fed a diet which did not contain vitamin-K. Only the male rats seemed to be susceptible. In the present experiment it was demonstrated that female rats are more resistant to the development of dietary K deficiency than are male animals. This difference is most pronounced during early adulthood. Castration increases the susceptibility of the female rat and decreases that of the male rat to hypoprothrombinemia and hemorrhagic death during the feeding of vitamin-K-deficient diets. In male animals fed similar diets the injection of estrogens results in improved prothrombin levels and a lower mortality. Administration of testosterone has an opposite effects . A single large dose of the anticoagulant warfarin sodium is followe d by a greater mortality due to hemorrhage in male rats than in female rats of the same age. In male animals some protection against the effects of the anticoagulant is afforded by pretreatment or by simultane ous administration of estrogenic substances. Effects considered to be characteristic of estrogenic hormones such as increases in the uterine weight and cornification of the vaginal epithelium in castrates have been shown to follow the administration of both K-1 and menadione. With K-1 at least paradoxical effects occur with increasing dose level or continued administration. When K-1 is administered concomitantly with estradiol uterine weights are considerably decreased in comparison with those resulting from the same dose of estradiol given alone.(AUTHORS MODIFIED)

Some observations on the coagulation defect in vitamin K deficiency.

Thecoagulation defect produced bythecoumarindrugshasbeenstudied inrecentyearsin greatdetail, butdisturbance in theclotting mechanism produced byvitamin-K deficiency has beeninvestigated toamuchless extent.Ineverydayclinical practice a clotting disorder dueto vitamin-K deficiency isnow lesscommon than thattherapeutically induced bytheuseofcoumarinorallied drugs. Itisgenerally accepted thatthehypoprothrombinaemia produced bythecoumarin drugs hasa duelfacet-adeficiency ofprothrombin, theprecursor ofthrombin, anda deficiency of factor VII,a component required toreactwith tissue intheformation ofextrinsic thromboplastin. Itisalsousually agreed thattheserum ofpatients onthecoumarin drugs hasadefective reaction inthethromboplastin generating system, wheninteracted withnormaladsorbed plasma andplatelets. Itistheobject ofthis papertopresent evidence confirming thatthevitamin K defect hasthesame features asthose produced bythecoumarin drugs andtoshowthatatleast onecomponent ofthe bloodthromboplastin defect isa deficiency of Christmas factor. Thispresent studyiscomplementary to recently reported observations (Douglas andMair,1957) oftheChristmas factor defect incoumarin drugtherapy.

Dicumarol Poisoning and Vitamin K Deficiency in Relation to Quick‘s Concept of the Composition of Prothrombin

IN 1943, Quick1 published some experiments which were taken as evidence for the multiple nature of prothrombin. In the same paper Quick expressed the opinion that the hypoprothrombinaemia in vitamin K deficiency might be due to the disappearance of the same constituent of prothrombin as that which is lacking in dicumarol poisoning, namely, the component which is relatively stable during storage.

Observations on the coagulation anomaly in vitamin K-deficiency and dicumarol poisoning

Clotting times of mixtures in varying proportions of plasmas of vitamin K-deficient chicks and chicks poisoned by dicumarol have been determined by the technique of Larsen and Plum. Provided the difference between the clotting times of the 2 separate plasmas is not too great, mixtures in certain proportions will clot somewhat faster than does the most rapidly clotting of the 2 plasmas, but never as rapidly as normal plasma. This is explained by assuming that the two plasmas are primarily lacking in one and the same component, whereas in addition to this vitamin K-deficient plasma is lacking in another component and dicumarol-plasma in a third.

Vitamin K Deficiency and Prothrombin Levels. Effect of Vitamin K Administration.

Vitamin K Deficiency and Prothrombin Levels. Effect of Vitamin K Administration.