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Plasma Vitamin K1 Levels in Italian Patients Receiving Oral Anticoagulant Therapy for Mechanical Heart Prosthesis: A Case–Control Study

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A Correction to this article was published on 09 February 2019

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Abstract

Background

Oral anticoagulant therapy (OAT) with a vitamin K antagonist (VKA) is the choice of treatment for preventing thromboembolism in patients with mechanical heart valve prosthesis (MHP). The percentage of time in the therapeutic range (TTR%) expresses the OAT quality. We planned a case–control study in order to determine vitamin K1 plasmatic concentrations in MHP patients and to correlate these with TTR%.

Materials and Methods

Of 756 MHP patients receiving OAT, 125 patients (61 younger than 65 years, and 64 older than 65 years) and 120 healthy blood donors, matched for sex and age, were enrolled in the study. All subjects completed a living questionnaire regarding diet, and underwent blood collection. Vegetable and fruit intake was categorized as optimal or suboptimal, and the high-performance liquid chromatography method was used to determine vitamin K1 levels.

Results

Neither the patients nor controls had been taking vitamin supplements prior to the start of the study. The median vitamin K1 level was 290 pg/L in 72 controls with optimal intake, and 274 pg/L in 48 controls with suboptimal intake, while the median vitamin K1 level in MHP patients with optimal intake was 409 pg/L, significantly higher (p < 0.001) than the 133.5 pg/L in patients with suboptimal intake. Vitamin K1 concentration in MHP patients appears to be linked to an age-related threshold: in patients younger than 65 years of age, the median vitamin K1 level was 431 pg/L, significantly higher (p < 0.05) than the 290 pg/L in patients older than 65 years of age. No clear relation was found between vitamin K1 levels and TTR% (Pearson = 0.14). However, patients with vitamin K1 >160 pg/L showed a TTR% >60 %. Among patients younger than 65 years, subjects with vitamin K1 >160 pg/L showed a median TTR of 66 %, this being significantly higher (p < 0.001) than the 46 % level shown by patients with vitamin K1 <160 pg/L.

Conclusions

Vitamin K1 concentrations in MHP patients seem to be related to both diet and age.

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Change history

  • 09 February 2019

    Throughout the manuscript the units of plasma vitamin K1 concentration which previously read

  • 09 February 2019

    Throughout the manuscript the units of plasma vitamin K1 concentration which previously read

  • 09 February 2019

    Throughout the manuscript the units of plasma vitamin K1 concentration which previously read

References

  1. Sun JC, Davidson MJ, Lamy A, Eikelboom JW. Antithrombotic management of patients with prosthetic heart valves: current evidence and future trends. Lancet. 2009;374:565–76.

    Article  PubMed  Google Scholar 

  2. Eikelboom JW, Connoly SJ, Bruekmann M, Granger CB, et al. Dabigatran versus warfarin in patients with mechanical heart valves. N Engl J Med. 2013;369:1206–14.

    Article  CAS  PubMed  Google Scholar 

  3. Franco V, Polanczyk CA, Clausell N, Rohde LE. Role of dietary vitamin K intake in chronic oral anticoagulant: prospective evidence from observational and randomized protocol. Am J Med. 2004;116:651–6.

    Article  CAS  PubMed  Google Scholar 

  4. Herijgers P, Verhamme P. Improving the quality of anticoagulant therapy in patients with mechanical heart valves: what are we waiting for? Eur Heart J. 2007;28:2424–6.

    Article  CAS  PubMed  Google Scholar 

  5. Ansell J, Hirsh J, Poller L, Bussey H, Jacobson A, Hylek E. The pharmacology and management of the vitamin K antagonist: the Seventh ACCP Conference on Antithrombotic and Thrombolitic Therapy. Chest. 2004;126:204S–33S.

    Article  CAS  PubMed  Google Scholar 

  6. Koertke H, Zittermann A, Wagner O, Koerfer R. Self-management of oral anticoagulation therapy improves long-term survival in patients with mechanical heart valve replacement. Ann Thorac Surg. 2007;83(1):24–9.

    Article  PubMed  Google Scholar 

  7. Grzymala-Lubanski B, Labaf A, Englund E, Svensson PJ, Själander A. Mechanical heart valve prosthesis and warfarin: treatment quality and prognosis. Thromb Res. 2014;133:795–8.

    Article  CAS  PubMed  Google Scholar 

  8. Holbrook AM, Pereira JA, Labiris R, McDonald H, Douketis JD, Crowther M, et al. Systematic overview of warfarin and its drug and food interactions. Arch Intern Med. 2005;165:1095–106.

    Article  CAS  PubMed  Google Scholar 

  9. Sconce E, Khan T, Mason J, Noble F, Wynne H, Kamali F. Patients with unstable control have a poorer dietary intake of vitamin K compared to patients with stable control of anticoagulation. Thromb Haemost. 2005;93:872–5.

    CAS  PubMed  Google Scholar 

  10. Sconce E, Avery P, Wynne H, Kamali F. Vitamin K supplementation can improve stability of anticoagulation for patients with unexplained variability in response to warfarin. Blood. 2007;109:2419–23.

    Article  CAS  PubMed  Google Scholar 

  11. Rombouts EK, Rosendaal FR, van der Meer FJM. Influence of dietary vitamin K intake on sub-therapeutic oral anticoagulant therapy. Br J Haematol. 2010;149:598–605.

    Article  CAS  PubMed  Google Scholar 

  12. Gebius EPA, Rosendaal FR, van Meegen E, van der Meer FJM. Vitamin K1 supplementation to improve the stability of anticoagulation therapy with vitamin K antagonists: a dose finding study. Haematologica. 2011;96:583–9.

    Article  Google Scholar 

  13. de Assis MC, Rabelo ER, Avila CW, Polanczyk CA, Rohde LE. Improvedoralanticoagulationafter a dietary vitamin K-guided strategy. A randomized controlled trial. Circulation. 2009;120:1115–22.

    Article  PubMed  Google Scholar 

  14. Società Italiana di Nutrizione Umana (S.I.N.U.). Livelli di assunzione raccomandata di energia e nutrienti per la popolazione Italiana. LARN Revisione; 1996, pp 103–4.

  15. Gentili A, Cafolla A, Gasperi T, Bellante S, Caretti F, Curini R, et al. Rapid, high performance method of vitamin K1, menaquinone-4 and vitamin K1 2,3-epoxide in human serum and plasma using liquid chromatography-hybrid quadropole linear ion trap mass spectrometry. J Chromatogr. 2014;1338:102–10.

    Article  CAS  Google Scholar 

  16. Cafolla A, Melizzi R, Baldacci E, Pignoloni P, Dragoni F, Campanelli M, et al. “Zeus” a new oral anticoagulant therapy dosing algorithm: a cohort study. Thrombosis Res. 2011;128:325–30.

    Article  CAS  Google Scholar 

  17. Rosendaal FR, Cannegieter SC, van der Meer FJM, Briët E. A method to determine the optimal intensity of an oral anticoagulant therapy. Thromb Haemost. 1993;69:236–9.

    CAS  PubMed  Google Scholar 

  18. Booth SL, Centurelli MA. Vitamin K: a pratical guide to the dietary management of patients on warfarin. Nutr Rev. 1999;57:288–96.

    Article  CAS  PubMed  Google Scholar 

  19. Thane CW, Wang LY, Coward WA. Plasma phylloquinone (vitamin K1) concentration and its relationship to intake in British adults aged 19–64 years. Br J Nutr. 2006;96:1116–24.

    Article  CAS  PubMed  Google Scholar 

  20. Vermeer C, Shearer MJ, Zittermann A, Bolton-Smith C, Szulc P, Hodges S, et al. Beyond deficiency: potential benefits of increased intakes of vitamin k for bone and vascular health. Eur J Nutr. 2004;43:325–35.

    Article  CAS  PubMed  Google Scholar 

  21. Chouet J, Ferland G, Fèart C, Rolland Y, Presse N, Boucher K, et al. Dietary vitamin K intake is associated with cognition and behaviour among geriatric patients: the CLIP study. Nutrients. 2015;7:6739–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

The authors are extremely grateful to Mr C.J.L. Hewlett (Durham University, UK) who revised the English form of the manuscript.

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Authors and Affiliations

  1. Hematology, Department of Cellular Biotechnology and Hematology, “Sapienza” Università, Via Benevento 6, 00161, Rome, Italy

    Arturo Cafolla & Erminia Baldacci

  2. Department of Chemistry, “Sapienza” Università, Rome, Italy

    Alessandra Gentili, Virginia Perez & Roberta Curini

  3. Physics Department, Durham University, Durham, UK

    Clodomiro Cafolla

  4. Immunohematology, Policlinico “Umberto I”, Rome, Italy

    Daniela Pasqualetti & Bruna Demasi

Authors
  1. Arturo Cafolla
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  2. Alessandra Gentili
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  3. Clodomiro Cafolla
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  4. Virginia Perez
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  5. Erminia Baldacci
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  6. Daniela Pasqualetti
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  7. Bruna Demasi
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  8. Roberta Curini
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Corresponding author

Correspondence to Arturo Cafolla.

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Conflicts of interest

Arturo Cafolla, Alessandra Gentili, Clodomiro Cafolla, Virginia Perez, Erminia Baldacci, Daniela Pasqualetti, Bruna Demasiand, and Roberta Curini declare that they have no conflicts of interest.

Funding

No external funding was used in the conduct of this study.

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Cafolla, A., Gentili, A., Cafolla, C. et al. Plasma Vitamin K1 Levels in Italian Patients Receiving Oral Anticoagulant Therapy for Mechanical Heart Prosthesis: A Case–Control Study. Am J Cardiovasc Drugs 16, 267–274 (2016). https://doi.org/10.1007/s40256-016-0169-0

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  • DOI: https://doi.org/10.1007/s40256-016-0169-0

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