Production of a New Monoclonal Antibody Specific to Human Des-Gamma-Carboxyprothrombin in the Presence of Calcium Ions. Application to the Development of a Sensitive ELISA-Test

Belle, M; Brebant, R.; Guinet, R; Leclercq, M.

doi:10.1080/15321819508013559

Cited by 43 publications

(50 citation statements)

References 6 publications

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“…When g-carboxylation is impaired because of deficiency or antagonism of vitamin K, inert precursors of vitamin K-dependent proteins-known as Proteins Induced by Vitamin K Absence or Antagonism (PIVKA)-are synthesised in the liver and released into the blood [2,3]. In the case of prothrombin, specific and sensitive immunoassays have been developed which can detect small decreases in the Gla content of prothrombin before any changes occur in conventional coagulation tests such as the International Normalised Ratio (INR) [3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics and efficacy of oral versus intravenous mixed-micellar phylloquinone (vitamin K1) in severe acute liver disease

Pereira

Rowbotham

Fitt

et al. 2005

Journal of Hepatology

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Section: Introductionmentioning

confidence: 99%

Pharmacokinetics and efficacy of oral versus intravenous mixed-micellar phylloquinone (vitamin K1) in severe acute liver disease

Pereira

Rowbotham

Fitt

et al. 2005

Journal of Hepatology

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“…Using electrophoretic techniques, 1 AU is equivalent to 1 g purified ucFII. 28 The lower detection limit was 150 AU/L plasma. ucOC and cOC were determined by separate assay using the Glu-OC and Gla-OC kits from Takara Shuzo (Tokyo, Japan), respectively.…”

Section: Coagulation and Biochemical Assaysmentioning

confidence: 99%

“…Species of ucFII were measured using a conformation-specific monoclonal antibody in an enzymelinked immunosorbent assay (ELISA) format. 28 Results are expressed as arbitrary units per liter (AU/L) because in states of vitamin K deficiency, circulating ucFII may comprise multiple forms of partially carboxylated FII and neither their relative abundance in plasma nor their relative affinity for the antibody is known. Using electrophoretic techniques, 1 AU is equivalent to 1 g purified ucFII.…”

Section: Coagulation and Biochemical Assaysmentioning

confidence: 99%

Effect of vitamin K intake on the stability of oral anticoagulant treatment: dose-response relationships in healthy subjects

Schurgers

Shearer

Hamulyák

et al. 2004

Blood

122

103

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Oral anticoagulants exert their effect by blocking the utilization of vitamin K, yet little is known about competitive aspects of their interaction with dietary vitamin K. We carried out systematic dose-response studies in healthy volunteers who had been stably anticoagulated and maintained on their individualized doses for 13 weeks. First, we studied the response to weekly incremental doses (50 g-500 g) of vitamin K 1 supplements (K 1 ) taken daily for 7 days. The threshold K 1 dose causing a statistically significant lowering of the INR was 150 g/day. In 25% of the participants the INR change was regarded as clinically relevant at a vitamin K intake of 150 g/day. Circulating undercarboxylated osteocalcin did not decrease until 300 g K 1 /day compared with 100 g K 1 /day for undercarboxylated FII, suggesting differential antidotal effects on bone and hepatic ␥-carboxylation. Next, we tested the response to vitamin K-rich food items. The short-lived response after meals of spinach and broccoli suggested an inefficient bioavailability from these 2 sources. We conclude that shortterm variability in intake of K 1 is less important to fluctuations in the international normalized ratio (INR) than has been commonly assumed and that food supplements providing 100 g/day of vitamin K 1 do not significantly interfere with oral anticoagulant therapy. IntroductionOral anticoagulants (OACs) are antagonists of vitamin K that are widely used for the treatment and prophylaxis of thromboembolic disease. 1 Vitamin K is an essential micronutrient that, as the reduced hydroquinone (vitamin KH 2 ), serves as a cofactor for the transformation of selective glutamic acid (Glu) residues into ␥-carboxyglutamic acid (Gla) during the biosynthesis of vitamin K-dependent proteins, also called Gla proteins. The Gla residues confer metal binding properties and, in the case of the coagulation factors, facilitate a calcium-ion-dependent structural transition essential for the interaction of these proteins with phospholipid membranes. 2 The clinical effectiveness of OACs derives from their ability to block posttranslational ␥-carboxylation of the 4 vitamin K-dependent procoagulants (II, VII, IX, and X). Hence treatment with OACs results in the production of dysfunctional, undercarboxylated species of coagulation factors (also known as PIVKAs). OAC treatment also affects the synthesis and functional activity of a number of other Gla proteins including the anticoagulant protein C 3 and noncoagulation proteins such as osteocalcin in bone 4 and matrix Gla protein (MGP) in cartilage and the vasculature. 5 The cellular target receptor for OAC that best explains their mode of action is the enzyme vitamin K epoxide reductase. [6][7][8] In the absence of OACs, this microsomal, dithiol-dependent enzyme is responsible for the recycling of the vitamin K epoxide metabolite (produced during ␥-glutamyl carboxylation) by successively reducing vitamin K epoxide to vitamin K and then to vitamin KH 2 . In blocking the reutilization of the epoxide metabolite, OACs ...

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“…Serum PIVKA-II concentrations were determined using a MAb (C4B6) to PIVKA-II in an ELISA format that is conformation specific such that it binds only undercarboxylated species of prothrombin and is not cross-reactive with fully carboxylated native prothrombin (23,24). Results are expressed as arbitrary units (AU) per mL, where 1 AU is equivalent to 1 g of multiple PIVKA-II species.…”

Section: Assessment Of Vitamin K Statusmentioning

confidence: 99%

Urinary Excretion of Vitamin K Metabolites in Term and Preterm Infants: Relationship to Vitamin K Status and Prophylaxis

et al. 2010

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ABSTRACT:Little is known about the metabolic turnover and excretion of vitamin K in healthy newborn infants and the metabolic consequences of prophylactic regimens designed to protect against vitamin K deficiency bleeding (VKDB). We measured the excretion of two urinary metabolites (Յ24 h) of vitamin K (5C-and 7C-aglycones) in term infants before (n ϭ 11) and after (n ϭ 5) a 1000 g i.m. dose of vitamin K 1 (K 1 ) and in preterm infants after 200 g i.m. (n ϭ 4), 500 g i.m. (n ϭ 4), or 200 g i.v. (n ϭ 5). In preterm infants, we also measured serum K 1 , vitamin K 1 2,3-epoxide, and PIVKA-II at 5 d postpartum. Before prophylaxis, the rate of 5C-and 7C-aglycone excretion was 25 times lower than adults, reflecting low vitamin K stores at birth. After prophylaxis, the excretion rate correlated to K 1 dose (r ϭ 0.6) but was two orders of magnitude lower than that in adults, probably reflecting the immaturity of neonatal catabolism. All term and 10 of 13 preterm infants mainly excreted 5C-aglycone. We present evidence that increased excretion of the 7C-aglycone was associated with metabolic overload because of the exposure to high-tissue K 1 concentrations. Measurement of the 5C-and 7C-aglycones may facilitate longitudinal studies of vitamin K status in neonates and aid the development of improved prophylactic regimens. (Pediatr Res 68: 508-512, 2010)

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Production of a New Monoclonal Antibody Specific to Human Des-Gamma-Carboxyprothrombin in the Presence of Calcium Ions. Application to the Development of a Sensitive ELISA-Test

Cited by 43 publications

References 6 publications

Pharmacokinetics and efficacy of oral versus intravenous mixed-micellar phylloquinone (vitamin K1) in severe acute liver disease

Pharmacokinetics and efficacy of oral versus intravenous mixed-micellar phylloquinone (vitamin K1) in severe acute liver disease

Effect of vitamin K intake on the stability of oral anticoagulant treatment: dose-response relationships in healthy subjects

Urinary Excretion of Vitamin K Metabolites in Term and Preterm Infants: Relationship to Vitamin K Status and Prophylaxis

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