Des-Gamma-Carboxyprothrombin (PIVKA II) and Plasma Vitamin K1 in Newborns and Their Mothers

Abstract

SummaryAssessments of the vitamin K status in newborns and their mothers by means of des-γ-carboxy-prothrombin (PIVKA II) measurement have given equivocal results. Part of the variability could be attributed to differences in sensitivity (i.e. the ability to detect small concentrations) and validity (i.e. ability to detect vitamin K deficiency) of the methods applied. None of these methods have yet been validated with respect to plasma vitamin K1. In 22 healthy mother/infant pairs PIVKA II was determined using three different assays including ratio Xa/ecarin (Xa/ec), crossed immunoelectrophoresis (CIE), and an ELISA with a monoclonal antibody (MAB). The results were compared with conventional clotting tests and plasma vitamin K1. The following results were obtained:Cord blood: Clotting tests within age-related normal ranges; PIVKA II detection rates: 0/22 (Xa/ec), 1/22 (CIE), 4/22 (MAB); plasma vitamin K1: undetectable in 20/22.Mothers: Clotting tests all within normal range; PIVKA II detection rates: 1/22 (Xa/ec), 0/22 (CIE), 5/22 (MAB); plasma vitamin K1 (pg/ml) for all mothers (median; range): 186; 55–833; for PIVKA II positive mothers: 213; 59–699.PIVKA II detectability in newborns and mothers was not correlated. The results show an increase in sensitivity for PIVKA II detection in the order of MAB ≫CIE >Xa/ec. Due to the very low plasma vitamin K1 at birth, no correlation was possible between cord PIVKA II detectability and plasma vitamin K1. However, in mothers at term PIVKA II MAB appears to be unrelated to the vitamin K status.

Prevalence of subclinical vitamin K deficiency in Thai newborns: relationship to maternal phylloquinone intakes and delivery risk

“…A lack of correlation between PIVKA-II detectability in mothers and newborns was previously reported for a small European cohort of 22 maternal/cord samples and may be due to several unknowns which include individual differences in maternal placental transport and the lipoprotein transport system that delivers vitamin K to the placenta 27. The factors that govern the placental transport of vitamin K are poorly understood but K 1 does not easily cross the placenta and the maternal/cord concentration gradient is within the range of 20:1 to 40:1 28.…”

Dietary reference values for vitamin K

“…Phylloquinone concentrations were undetectable in cord blood of infants of unsupplemented mothers unless the pregnant women received phylloquinone intravenously before delivery . Liver tissue contents of phylloquinone and of menaquinones in neonates are low (MK-n were undetectable until 14 days post-partum), although these low vitamin K stores seem to be sufficient to maintain normal haemostasis during fetal life (von Kries et al, 1988) (Section 2.3.4.3). Incidence rates of vitamin K deficiency bleeding (VKDB) in infants not given vitamin K prophylaxis have been reviewed (Sutor et al, 1999;Zipursky, 1999;Shearer, 2009).…”

Des-Gamma-Carboxyprothrombin (PIVKA-II) Levels in Maternal Serum throughout Gestation

“…It is well known that PIVKA-II is a sensitive and specific marker of the vitamin K status. 2,5 This precursor molecule of prothrombin can be detected by several methods.…”

“…1 Likewise, protein induced by vitamin K absence (PIVKA-II; des-gamma-carboxyprothrombin) had been detected in some healthy pregnant women at term. 2 These observations would suggest the possibilities of a subclinical deficient status of vitamin K in pregnant women.…”