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J Matern Fetal Neonatal Med. 2012 Sep;25(9):1660-3. doi: 10.3109/14767058.2012.657273. Epub 2012 Feb 24.

PIVKA-II plasma levels as markers of subclinical vitamin K deficiency in term infants.

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Department of Maternal and Child Health, S. Giovanni Calibita Hospital, Fatebenefratelli, Rome.



As the vitamin K content of human milk is low and the newborn infant's stores of vitamin K are small, vitamin K deficiency with hemorrhage in the newborn is a worldwide problem. Proteins Induced by Vitamin K Absence (PIVKA-II) are the inactive under-γ-carboxylated forms of vitamin K-dependent clotting factors and they could be useful in predicting subclinical vitamin K deficiency (VKD).


To demonstrate that PIVKA-II are earlier markers of subclinical VKD than Prothrombin time (PT) in exclusively breast-fed newborns.


A prospective, controlled, randomized study, including 53 term newborns receiving vitamin K prophylaxis (0.5 mg i.m.) at birth, was performed. At 30 days newborns were divided into three groups (G) receiving respectively: 25 μg/die of vitamin K (G I), 12 μg/die (G II) or placebo (G III). PIVKA-II and PT were measured on 30th and 90th days of life.


G III and GII showed a significant increase in PIVKA-II from 30 to 90 days of life respectively from 2.6 to 4.7 (p = 0.001) and from 2.3 to 3.5 (p < 0.001). No significant changes were found in GI. PT showed no significant changes among groups.


PT is a less sensitive marker than PIVKA II. Oral supplementation with 25 μg/die avoids an increase of PIVKA-II. Despite increased PIVKA-II do not mean an impending occurrence of bleeding, they highlight a subclinical VKD and its relative risk.

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