Back
 PP  Vol.5 No.13 , December 2014
Possible Correlation between INR and Serum Calcium
Tuukka A. Helin1, Niko Wickholm2, Hannu Kautiainen3, Heikki Vapaatalo2
Show more
Abstract: Experimental and clinical studies have shown that long term anticoagulation therapy with warfarin can induce vascular calcification which is preventable by vitamin K. Osteoporosis has been shown to be associated with vascular calcification. In the present study, we wanted to see, whether INR (International Normalized Ratio), a measure of prothrombin time, and serum calcium (corrected by albumin) correlate in laboratory data of 94 anticoagulation patients on warfarin therapy. When adjusted on age and sex, there was an inverse correlation between the two variables. Clinical relevance of this observation and explanation of lowered calcium levels in blood parallel to increase in INR-values remain to be studied further.
Keywords: Warfarin, INR, Serum Calcium, Vascular Calcification
Cite this paper: Helin, T. , Wickholm, N. , Kautiainen, H. and Vapaatalo, H. (2014) Possible Correlation between INR and Serum Calcium. Pharmacology & Pharmacy, 5, 1180-1184. doi: 10.4236/pp.2014.513129.
References

[1]   Geleijnse, J.M., Vermeer, C., Grobee, D.E., Schurgers, L.J., Knapen, M.H.J., van der Meer, I.M., et al. (2004) Dietary Intake of Menaquinone Is Associated with a Reduced Risk of Coronary Heart Disease: The Rotterdam Study. Journal of Nutrition, 134, 3100-3105.

[2]   Beulens, J.W.J., Bots, M.L., Atsma, F., Bartelink, M.-A.E.L., Procop, M., Geleijnse, J.M., et al. (2008) High Dietary Menaquinone Intake Is Associated with Reduced Coronary Calcification. Atherosclerosis, 203, 489-493.
http://dx.doi.org/10.1016/j.atherosclerosis.2008.07.010

[3]   Gast, G.C.M., de Roos, N.M., Bots, M.L., Beulens, J.W.J., Geleijnse, J.M., Witteman, J.C., et al. (2009) High Menaquinone Intake Reduces the Incidence of Coronary Heart Disease. Nutrition, Metabolism and Cardiovascular Diseases, 19, 504-507.
http://dx.doi.org/10.1016/j.numecd.2008.10.004

[4]   Danzinger, J. (2008) Vitamin K-Dependent Proteins, Warfarin, and Vascular Calcification. Clinical Journal of the American Society of Nephrology, 3, 1504-1510.
http://dx.doi.org/10.2215/CJN.00770208

[5]   Chatrou, M.L.L., Winkers, K., Hackeng, T.M., Reutelingsperger, C.P. and Schurgers, L.J. (2012) Vascular Calcification: The Price to Pay for Anticoagulation Therapy with Vitamin K-Antagonists. Blood Reviews, 26, 155-166.
http://dx.doi.org/10.1016/j.blre.2012.03.002

[6]   Zhang, Y.-T. and Tang, Z.-Y. (2014) Research Progress of Warfarin-Associated Vascular Calcification and Its Possible Therapy. Cardiovascular Pharmacology, 63, 76-82.
http://dx.doi.org/10.1097/FJC.0000000000000008

[7]   Price, P.A., Faus, S.A. and Williamson, M.K. (1998) Warfarin Causes Rapid Calcification of the Elastic Lamellae in Rat Arteries and Heart Valves. Arteriosclerosis, Thrombosis, and Vascular Biology, 18, 1400-1407.
http://dx.doi.org/10.1161/01.ATV.18.9.1400

[8]   Howe, A.M. and Webster, W.S. (2000) Warfarin Exposure and Calcification of the Arterial System of the Rat. International Journal of Experimental Pathology, 81, 51-56.
http://dx.doi.org/10.1046/j.1365-2613.2000.00140.x

[9]   Spronk, H.M.H., Soute, B.A.M., Schungers, L.J., Thijssen, H.H.W., De Mey, J.G.R. and Vermeer, C. (2003) Tisssue-Specific Utilization of Menaquinone-4 Results in the Prevention of Arterial Calcification in Warfarin-Treated Rats. Journal of Vascular Research, 40, 531-537.
http://dx.doi.org/10.1159/000075344

[10]   Dao, H.H., Essalihi, R., Graillon, J.-F., Lariviere, R., de Champlain, J. and Moreau, P. (2002) Pharmacological Prevention and Regression of Arterial Remodeling in a Rat Model of Isolated Systolic Hypertension. Journal of Hypertension, 20, 1597-1606.
http://dx.doi.org/10.1097/00004872-200208000-00023

[11]   Schungers, L.J., Spronk, H.M.H., Soute, B.A.M., Schiffers, P.M., De Mey, J.G.R. and Vermeer, C. (2007) Regression of Warfarin-Induced Medial Elastocalcinosis by High Intake of Vitamin K in Rats. Blood, 109, 2823-2831.
http://dx.doi.org/10.1182/blood-2006-07-035345

[12]   Beazley, K.E., Banyard, D., Lima, F., Deasey, S.C., Nurminsky, D.I., Konoplyannikov, M. and Nurminskay, M.V. (2013) Transglutaminase Inhibitors Attenuate Vascular Calcification in a Preclinical Model. Arteriosclerosis, Thrombosis, and Vascular Biology, 33, 43-51.
http://dx.doi.org/10.1161/ATVBAHA.112.300260

[13]   Rubin, M.R. and Silverberg, S.J. (2004) Vascular Calcification and Osteoporosis—The Nature of the Nexus. The Journal of Clinical Endocrinology and Metabolism, 89, 4243-4245.
http://dx.doi.org/10.1210/jc.2004-1324

[14]   Binkley, N., Krueger, D., Engelke, J. and Suttle, J. (2007) Vitamin K Deficiency from Long-Term Warfarin Anticoagulation Does Not Alter Skeletal Status in Male Rhesus Monkeys. Journal of Bone and Mineral Research, 22, 695-700.
http://dx.doi.org/10.1359/jbmr.070208

[15]   Sokol’nikov, A.A., Kodentsova, V.M., Sergeev, I.N. Strunin, S.E. and Sklimov, O.A. (1989) Calcium Metabolism in the Case of Vitamin D and K Deficiencies. Voprosy Pitaniia, 1, 56-60.

[16]   Payne, R.B., Little, A.J., Williams, R.B. and Milner, J.R. (1973) Interpretation of Serum Calcium in Patients with Abnormal Serum Proteins. British Medical Journal, 4, 643-646.
http://dx.doi.org/10.1136/bmj.4.5893.643

[17]   Cheung, C.L., Sahni, S., Cheung, B.M., Sing, C.W. and Wong, I.C. (2014) Vitamin K Intake and Mortality in People with Chronic Disease from NHANES III. Clinical Nutrition, in Press.
http://dx.doi.org/10.1016/j.clnu.2014.03.011

[18]   Ferland, G. (1998) The Vitamin K-Dependent Proteins: An Update. Nutrition Reviews, 56, 223-230.
http://dx.doi.org/10.1111/j.1753-4887.1998.tb01753.x

[19]   Luo, G., Ducy, P., McKee, M.D., Pinero, G.J., Loyer, E., Behringer, R.R. and Karsenty, G. (1997) Spontaneous Calcification of Arteries and Cartilage in Mice Lacking Matrix GLA Protein. Nature, 386, 78-81.
http://dx.doi.org/10.1038/386078a0

[20]   Erkkil?, A.T. and Booth, S.L. (2008) Vitamin K Intake and Atherosclerosis. Current Opinion in Lipidology, 19, 39-42.
http://dx.doi.org/10.1097/MOL.0b013e3282f1c57f

[21]   Demer, L.L. and Tintut, Y. (2014) Inflammatory, Metabolic and Genetic Mechanisms of Vascular Calcification. Arteriosclerosis, Thrombosis, and Vascular Biology, 34, 715-723.
http://dx.doi.org/10.1161/ATVBAHA.113.302070

[22]   Frye, M.A., Melton III, L.J., Bryant, S.C., Fitzpatrick, L.A., Wahner, H.V.V., Schwartz, R.S. and Riggs, B.L. (1992) Osteoporosis and Calcification of the Aorta. Bone and Mineral, 19, 185-194.
http://dx.doi.org/10.1016/0169-6009(92)90925-4

[23]   Szulc, P., Kiel, D.P. and Delmas, P.D. (2008) Calcifi-cations in the Abdominal Aorta Predict Fractures in Men: MINOS Study. Journal of Bone and Mineral Research, 23, 95-102.
http://dx.doi.org/10.1359/jbmr.070903

[24]   Naves, M., Rodriguez-Garcia, M., Diaz-López, J.B. Gómez-Alonso, C. and Cannata-Andia, J.B. (2008) Progression of Vascular Calcifications Is Associated with Greater Bone Loss and Increased Bone-Fractures. Osteoporosis International, 19, 1161-1166.
http://dx.doi.org/10.1007/s00198-007-0539-1

[25]   Siltari, A., Wickholm, N., Kivimäki, A.S., Olli, K., Salli, K., Tiihonen, K., Korpela, R. and Vapaatalo, H. (2014) Effects of Vitamin K-1 and Menaquinone-7 on Vascular Function and Blood Pressure in Warfarin-Induced Calcification-Model in Rats. Pharmacology & Pharmacy, 5, 1095-1105.
http://dx.doi.org/10.4236/pp.2014.512119

 
 
Top