Variation of Des-Gamma-Carboxyprothrombin (PIVKA-II) Levels in Cord Blood Throughout Gestation

ABSTRACT

The variation of des-gamma-carboxyprothrombin (PIVKA-II, protein induced by vitamin K absence) levels in umbilical cord blood throughout gestation was examined using a highly sensitive method, electrochemiluminescence immunoassay (ECLIA). PIVKA-II levels in infants without any complications were low, but modestly high, exceeding the normal range of healthy adults during the preterm period, followed by a remarkable increase after the 37th week of gestation. Among infants complicated with severe preeclampsia a marked increase of PIVKA-II levels was observed in preterm infants, showing a good correlation with the existence of infarctions on the placenta. On the other hand, among infants complicated with preterm premature rupture of the membranes (PROM) in which antibiotics were administered during the prenatal period, a moderate elevation of PIVKA-II levels was observed. These data suggest that the normal range of PIVKA-II in fetuses is modestly high compared with adults and any deficient status of vitamin K would not exist throughout the preterm period. Nevertheless, the vitamin K status might readily fall into a deficient condition in term infants. Furthermore, it is notable that vitamin K deficiency would be induced in complicated gestation with severe preeclampsia and medication with antibiotics.

KEYWORD

PIVKA-II - newborn infants - vitamin K - preeclampsia - electrochemiluminescence immunoassay (ECLIA)

REFERENCES

• 1 Andrew M, Paes B, Milner R. Development of human coagulation system in the full-term infant.  Blood . 1987;  70 165-172
• 2 Reverdiau-Moalic P, Delahousse B, Body G. Evolution of blood coagulation activators and inhibitors in the healthy human fetus.  Blood . 1996;  88 900-906
• 3 Dube B, Dube R K, Bhargava V. Hemostatic parameters in newborn-1. Effect of gestation and rate of intrauterine growth.  Thromb Haemost . 1986;  55 47-50
• 4 Forestier F, Daffos F, Galacteros F. Hematological values of 163 normal fetuses between 18 and 30 weeks of gestation.  Pediatr Res . 1986;  20 342-346
• 5 Blackburn G F, Shah H P, Kenton J H. Electrochemiluminescence detection for development of immunoassays and DNA probe assays for clinical diagnostics.  Clin Chem . 1991;  37 1534-1539
• 6 Takatsu K, Nakanishi T, Watanabe K. An improved method for determination of des-gamma-carboxyprothrombin (PIVKA II) using electrochemiluminescence technique; development of reagent and evaluation of its property (in Japanese).  Jpn J Clin Exp Med. 1996;  73 2656-2664
• 7 von Kries R, Greer F R, Suttie J W. Assessment of vitamin K status of the newborn infants.  J Pediatr Gastroenterol Nutr . 1993;  16 231-238
• 8 von Kries R, Shearer M J, Widdershoven J. Des-gamma-carboxyprothrombin (PIVKA II) and plasma vitamin K₁ in newborns and their mothers.  Thromb Haemost . 1992;  68 383-387
• 9 Muntean W, Petek W, Rosanelli K. Immunologic studies on prothrombin in newborns.  Pediatr Res . 1979;  13 1262-1265
• 10 Malia R G, Preston F E, Mitchell V E. Evidence against vitamin K deficiency in normal neonates.  Thromb Haemost . 1980;  44 159-160
• 11 Atkinson P M, Bradlow B A, Moulineaux J D. Acarboxy-prothrombin in cord plasma from normal neonates.  J Pediatr Gastroenterol Nutr . 1984;  3 450-453
• 12 Motohara K, Endo F, Matsuda I. Effect of vitamin K administration on acarboxyprothrombin (PIVKA-II) levels in newborns.  Lancet . 1985;  2 242-244
• 13 The Japan Society of Obstetrics and Gynecology. The definition of preeclampsia in Japan (in Japanese).  Acta Obstet Gynecol Jpn . 1992;  44 5-6
• 14 Hiraike H, Kimura M, Itokawa Y. Distribution of K vitamins (phylloquinone and menaquinones) in human placenta and maternal and umbilical cord plasma.  Am J Obstet Gynecol . 1988;  158 564-569
• 15 Mandelbrot L, Guillaumount M, Leclercq M. Placental transfer of vitamin K1 and its implications in fetal hemostasis.  Thromb Haemost . 1988;  60 39-43
• 16 Kisker C T, Robillard J E, Bohlken D P. Glucocorticoid stimulation of blood coagulation factor activities in the fetal lamb.  J Lab Clin Med . 1983;  101 569-575
• 17 The Japan Society of Obstetrics and Gynecology: The Committee Announcement. The revised definition of preeclampsia in Japan (in Japanese).  Acta Obstet Gynecol. 1997;  49 21-22
• 18 Creedon K A, Suttie J W. Effect of N-methyl-thiotetrazole on vitamin K epoxide reductase.  Thromb Res . 1986;  44 147-153