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

R von Kries; M J Shearer; J Widdershoven; K Motohara; G Umbach; U Göbel

doi:10.1055/s-0038-1646281

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1992; 68(04): 383-387
DOI: 10.1055/s-0038-1646281

Original Article

Schattauer GmbH Stuttgart

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

Authors

R von Kries

¹The Department of Pediatric Haematology and Oncology, Heinrich Heine University, Düsseldorf, FRG
M J Shearer

²The Department of Haematology, United Medical and Dental Schools of Guy’s and St. Thomas’s Hospitals, London, UK
J Widdershoven

³The Pediatric Hospital, University of Nijmegen, Nijmegen, The Netherlands
K Motohara

⁴The Department of Pediatrics, Kumamoto University Medical School, Kumamoto, Japan
G Umbach

⁵The Department of Gynecology and Obstetrics, Heinrich Heine University, Düsseldorf, FRG
U Göbel

¹The Department of Pediatric Haematology and Oncology, Heinrich Heine University, Düsseldorf, FRG

Abstract

PDF Download

Summary

Assessments 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.

PDF (871 kb)

References

REFERENCES
1 Andrew M, Paes B, Milner R, Johnston M, Mitchell L, Tollefsen DM, Powers P. Development of the human coagulation in the full-term infant. Blood 1987; 70: 165-172
2 von Kries R, Shearer MJ, Göbel U. Vitamin K in infancy. Eur J Pediatr 1988; 147: 106-112
3 Ganrot PO, Nilehn JE. Plasma prothrombin during treatment with Dicoumarol II. Demonstration of an abnormal prothrombin fraction. Scand J Clin Lab Invest 1968; 22: 23-28
4 Bertina RM, van der Marel-van Nieuwkoop W, Dubbeldam J, Boekhout-Mussert MJ, Veltkamp JJ. New method for rapid detection of vitamin K deficiency. Clin Chem Acta 1980; 105: 93-98
5 Corrigan JJ, Krye JJ. Factor II (prothrombin) level in cord blood: Correlation of coagulation activity with immunoreactive protein. J Pediatr 1980; 97: 979-983
6 Blanchard RA, Furie BC, Furie B. Antibodies specific for bovine abnormal (Des-Gamma-Carboxy-) prothrombin. J Biol Chem 1979; 254: 12513-12520
7 Motohara K, Kuroki Y, Kan H, Endo F, Matsuda I. Detection of vitamin K deficiency by use of an enzyme-linked immunosorbent assay for circulating abnormal prothrombin. Pediatr Res 1985; 19: 354-357
8 Shapiro AD, Jacobsen LL, Armon ME, Manco-Johnson MJ, Hulac P, Lane PA, Hathaway WME. Vitamin K deficiency in the newborn infant: prevalence and perinatal risk factors. J Pediatr 1985; 109: 675-680
9 Bloch CA, Rothberg AD, Bradlow BA. Mother-infant prothrombin precursor status at birth. J Pediatr Gastroent Nutr 1984; 3: 101-103
10 Blanchard RA, Furie BC, Barnet J, Faye K, Jacobs M, DeFurio L, Furie B. Vitamin K deficiency in newborns and their mothers. Thromb Haemostas 1985; 54: 226 (Abstr)
11 Shearer MJ, McCarthy PT, Crampton OE, Mattock MB. The assessment of human vitamin K status from tissue measurements. In: Current Advances in vitamin. Research K, Suttie JW. (ed) Elsevier, New York: 1988. pp 437-452
12 Shearer MJ, Bechthold H, Andrassy K, Koderisch J, McCarthy PT, Trenk D, Jähnchen E, Ritz E. Mechanism of cephalosporin induced hypoprothrombinemia: relation to cephalosporin side chain, vitamin K metabolism, and vitamin K status. J Clin Pharmacol 1988; 28: 88-95
13 Cohen H, Scott SD, Mackie IJ, Shearer MJ, Bax R, Karran SJ, Machin SJ. The development of hypoprothrombinaemia following antibiotic therapy in malnourished patients with low serum vitamin K₁ levels. Br J Haematol 1988; 68: 63-66
14 Pietersma-de Bruyn ALJM, Van Haard PMM. Vitamin K₁ in the newborn. Clin Chim Acta 1985; 150: 095-101
15 Sann L, Leclercq M, Guillemont M, Trouyez R, Bethenod M, Bourgeeay-Causse M. Serum vitamin K₁ concentrations after oral administration of vitamin K₁ in low birthweight infants. J Pediatr 1985; 107: 608-611
16 Greer FR, Mummah-Schendel LL, Marshall S, Suttie JW. Vitamin K₁ (phylloquinone) and vitamin K2 (menaquinone) status in newborns during the first week of life. Pediatrics 1988; 81: 137-140
17 Mandelbrot L, Guillemont M, Leclercq M, Lefrere JJ, Gozin D, Daffos F, Forrestier F. Placental transfer of vitamin K₁ and its implications in fetal hemostasis. Thromb Haemostas 1988; 60: 39-42
18 Widdershoven J, Lambert W, Motohara K, Monnens L, De Leenheer A, Matsuda I, Endo F. Plasma concentrations of vitamin K₁ and PIVKA-II in bottle-fed and breastfed infants with and without vitamin K prophylaxis at birth. Eur J Pediatr 1988; 148: 139-142
19 Pietersma-de Bruyn ALJM, Van Haard PMM, Beunis MH, Haymulyak K, Kuijpers JC. Vitamin K₁ levels and coagulation factors in healthy term newborns till 4 weeks after birth. Haemostasis 1990; 20: 08-14
20 Shearer MJ, Barkhan P, Rahim S, Stimmler L. Plasma vitamin K₁ in mothers and their newborn babies. Lancet 1982; II: 460-463
21 Witt I, Hönninger R. Photometrische Methode zum Nachweis von Prothrombin-Vorstufen (PIVKA II) im Plasma bei Vitamin K-Mangel. J Clin Chem Biochem 1982; 20: 672-673
22 von Kries R, Zensis Ch, Göbel U. Immunoelectrophoretic determination of PIVKA II in capillary plasma. Haemostasis 1985; 15: 42-43
23 Shearer MJ. Vitamins. In: HPLC of Small Molecules: A Practical Approach.. Lim CK. (ed) IRL Press, Oxford: 1986. pp 157-219
24 Van Doorm JM, Muller AD, Hemker HC. Heparin like inhibitor, not vitamin K deficiency in the newborn. Lancet 1977; I: 852-853
25 Muntean W, Petek W, Rosanelli K, Mutz ID. Immunologic studies of prothrombin in newborns. Pediatr Res 1979; 13: 1262-1265
26 Malia RG, Preston FE, Mitchell VE. Evidence against vitamin K deficiency in normal neonates. Thromb Haemostas 1980; 44: 159-160
27 Ekelund H, Hedner U. Prothrombin and vitamin K deficiency in the newborn. Eur J Paediatr Haematol Oncol 1984; 1: 59-65
28 von Kries R, Göbel U, Maase B. Vitamin K deficiency in the newborn. Lancet 1985; II: 728-729
29 von Kries R, Greer FR, Suttie JW. PIVKA: Status as a diagnostic tool for vitamin K deficiency in the newborn. (submitted for publication)
30 Motohara K, Endo F, Matsuda I. Effect of vitamin K administration on acarboxyprothrombin (PIVKA II) levels in newborns. Lancet 1985; II: 242-244
31 Motohara K, Takayi S, Endo F, Kiyoto Y, Matsuda I. Oral supplementation of vitamin K for pregnant women and effects on levels of plasma vitamin K and PIVKA II in the neonate. J Pediatr Gastroenterol Nutr 1990; 11: 32-36
32 Widdershoven J, van Munster P, de Abreu R, Bosman H, van Lith Th, van der Ptteen-van Meyel M, Motohara K, Matsuda I. Four methods compared for measuring des-carboxy-prothrombin (PIVKA II). Clin Chem 1987; 33: 2074-2078
33 Yang YM, Simon N, Maertens P, Brigham S, Liu P. Maternal-fetal transport of vitamin K₁ and its effect on coagulation in premature infants. J Pediatr 1989; 115: 1009-1013
34 Saupe J, Shearer MJ, Kohlmeier M. Influence of lipoproteins on vitamin K transport in blood – preliminary data. Ann Hematol 1992; 64 (suppl.): A57
35 Sadowski JA, Hood SJ, Dallal GE, Garry PJ. Phylloquinone in plasma from elderly and young adults: factors influencing its concentration. Am J Clin Nutr 1989; 50: 100-108
36 Jimenez DM, Pacovi M, Rammon-Cajal J, Romero A, Martinez H, Grande F. Lipoprotein study of plasma lipids and lipoprotein in cholesterol in normal pregnancy and puerperium. Gynecol Obstet Invest 1988; 25: 158-162
37 Knopp RH, Bergelin RO, Wahl PW. Population-based lipoprotein reference values for pregnant women compared to nonpregnant women classified by sex hormone usage. Am J Obstet Gynecol 1982; 143: 626-633
38 Suttie JW, Kindberg CG, Greger JL, Bang NU. Effects of vitamin K (phylloquinone) restriction in the human. In: Current Advances in Vitamin K Research.. Suttie JW. (ed) Elsevier, New York: 1988: 465-467
39 Usui Y, Tanimura H, Nishimura N, Kobayashi N, Okanoue T, Ozawa K. Vitamin K concentrations in the plasma and liver of surgical patients. Am J Clin Nutr 1990; 5: 846-852
40 Kayata S, Kindberg C, Greer FR, Suttie JW. Vitamin K₁ and K₂ in infant human liver. J Pediatr Gastroenterol Nutr 1989; 8: 304-307
41 Shirahata A, Nakamura T, Ariyoshi N. Vitamin K₁ and K₂ contents in blood, stool and liver tissues of neonates and young infants. In: Perinatal Thrombosis and Hemostasis. Suzuki S, Hathaway WE, Bonnar J, Sutor AH. (eds) Springer, Tokyo: 1991. pp 213-223