Loading Pathway...
Error: Pathway image not found.
Hide
Pathway Description
Warfarin Action Pathway (New)
Homo sapiens
Category:
Metabolite Pathway
Sub-Category:
Drug Action
Created: 2021-12-22
Last Updated: 2024-01-19
Warfarin is an anticoagulant drug normally used to prevent blood clot formation as well as migration.
Indicated for: prophylaxis and treatment of venous thromboembolism and related pulmonary embolism, prophylaxis and treatment of thromboembolism associated with atrial fibrillation, prophylaxis and treatment of thromboembolism associated with cardiac valve replacement, use as adjunct therapy to reduce mortality, recurrent myocardial infarction, and thromboembolic events post myocardial infarction.
Off-label uses include secondary prevention of stroke and transient ischemic attacks in patients with rheumatic mitral valve disease but without atrial fibrillation.
Warfarin does not actually affect blood viscosity, rather, it inhibits vitamin-k dependent synthesis of biologically active forms of various clotting factors in addition to several regulatory factors.
Warfarin is a [vitamin K] antagonist which acts to inhibit the production of vitamin K by inhibiting vitamin K epoxide reductase. By doing this the carboxylation of vitamin-k dependent factors such as II, VII, IX and X are prevented. As the concentration of reduced form of vitamin K decreases this leads to a depletion of the cofactor for future reactions that are vitamin k dependent. This ultimately leads to interference with coagulation, because of this patient should not give blood during the time they are using Warfarin.
Warfarin has several properties that should be noted when used medicinally, including its ability to cross the placental barrier during pregnancy which can result in fetal bleeding, spontaneous abortion, preterm birth, stillbirth, and neonatal death. Additional adverse effects such as necrosis, purple toe syndrome, osteoporosis, valve and artery calcification, and drug interactions have also been documented with warfarin use.
References
Warfarin Pathway (New) References
Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M: DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037.
Norris LA: Blood coagulation. Best Pract Res Clin Obstet Gynaecol. 2003 Jun;17(3):369-83. doi: 10.1016/s1521-6934(03)00014-2.
van der Meijden PE, Munnix IC, Auger JM, Govers-Riemslag JW, Cosemans JM, Kuijpers MJ, Spronk HM, Watson SP, Renne T, Heemskerk JW: Dual role of collagen in factor XII-dependent thrombus formation. Blood. 2009 Jul 23;114(4):881-90. doi: 10.1182/blood-2008-07-171066. Epub 2009 Apr 16.
Rost S, Fregin A, Ivaskevicius V, Conzelmann E, Hortnagel K, Pelz HJ, Lappegard K, Seifried E, Scharrer I, Tuddenham EG, Muller CR, Strom TM, Oldenburg J: Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature. 2004 Feb 5;427(6974):537-41. doi: 10.1038/nature02214.
Pubmed: 14765194
Watzka M, Geisen C, Bevans CG, Sittinger K, Spohn G, Rost S, Seifried E, Muller CR, Oldenburg J: Thirteen novel VKORC1 mutations associated with oral anticoagulant resistance: insights into improved patient diagnosis and treatment. J Thromb Haemost. 2011 Jan;9(1):109-18. doi: 10.1111/j.1538-7836.2010.04095.x.
Pubmed: 20946155
Li T, Chang CY, Jin DY, Lin PJ, Khvorova A, Stafford DW: Identification of the gene for vitamin K epoxide reductase. Nature. 2004 Feb 5;427(6974):541-4. doi: 10.1038/nature02254.
Pubmed: 14765195
Wu SM, Cheung WF, Frazier D, Stafford DW: Cloning and expression of the cDNA for human gamma-glutamyl carboxylase. Science. 1991 Dec 13;254(5038):1634-6. doi: 10.1126/science.1749935.
Pubmed: 1749935
Wu SM, Stafford DW, Frazier LD, Fu YY, High KA, Chu K, Sanchez-Vega B, Solera J: Genomic sequence and transcription start site for the human gamma-glutamyl carboxylase. Blood. 1997 Jun 1;89(11):4058-62.
Pubmed: 9166845
Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. doi: 10.1038/ng1285. Epub 2003 Dec 21.
Pubmed: 14702039
Chung DW, Chan WY, Davie EW: Characterization of a complementary deoxyribonucleic acid coding for the gamma chain of human fibrinogen. Biochemistry. 1983 Jun 21;22(13):3250-6. doi: 10.1021/bi00282a033.
Pubmed: 6688357
Rixon MW, Chung DW, Davie EW: Nucleotide sequence of the gene for the gamma chain of human fibrinogen. Biochemistry. 1985 Apr 9;24(8):2077-86. doi: 10.1021/bi00329a041.
Pubmed: 2990550
Petersen TE, Martzen MR, Ichinose A, Davie EW: Characterization of the gene for human plasminogen, a key proenzyme in the fibrinolytic system. J Biol Chem. 1990 Apr 15;265(11):6104-11.
Pubmed: 2318848
Forsgren M, Raden B, Israelsson M, Larsson K, Heden LO: Molecular cloning and characterization of a full-length cDNA clone for human plasminogen. FEBS Lett. 1987 Mar 23;213(2):254-60. doi: 10.1016/0014-5793(87)81501-6.
Pubmed: 3030813
Mungall AJ, Palmer SA, Sims SK, Edwards CA, Ashurst JL, Wilming L, Jones MC, Horton R, Hunt SE, Scott CE, Gilbert JG, Clamp ME, Bethel G, Milne S, Ainscough R, Almeida JP, Ambrose KD, Andrews TD, Ashwell RI, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beare DM, Beasley H, Beasley O, Bird CP, Blakey S, Bray-Allen S, Brook J, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Clark SY, Clark G, Clee CM, Clegg S, Cobley V, Collier RE, Collins JE, Colman LK, Corby NR, Coville GJ, Culley KM, Dhami P, Davies J, Dunn M, Earthrowl ME, Ellington AE, Evans KA, Faulkner L, Francis MD, Frankish A, Frankland J, French L, Garner P, Garnett J, Ghori MJ, Gilby LM, Gillson CJ, Glithero RJ, Grafham DV, Grant M, Gribble S, Griffiths C, Griffiths M, Hall R, Halls KS, Hammond S, Harley JL, Hart EA, Heath PD, Heathcott R, Holmes SJ, Howden PJ, Howe KL, Howell GR, Huckle E, Humphray SJ, Humphries MD, Hunt AR, Johnson CM, Joy AA, Kay M, Keenan SJ, Kimberley AM, King A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd CR, Lloyd DM, Loveland JE, Lovell J, Martin S, Mashreghi-Mohammadi M, Maslen GL, Matthews L, McCann OT, McLaren SJ, McLay K, McMurray A, Moore MJ, Mullikin JC, Niblett D, Nickerson T, Novik KL, Oliver K, Overton-Larty EK, Parker A, Patel R, Pearce AV, Peck AI, Phillimore B, Phillips S, Plumb RW, Porter KM, Ramsey Y, Ranby SA, Rice CM, Ross MT, Searle SM, Sehra HK, Sheridan E, Skuce CD, Smith S, Smith M, Spraggon L, Squares SL, Steward CA, Sycamore N, Tamlyn-Hall G, Tester J, Theaker AJ, Thomas DW, Thorpe A, Tracey A, Tromans A, Tubby B, Wall M, Wallis JM, West AP, White SS, Whitehead SL, Whittaker H, Wild A, Willey DJ, Wilmer TE, Wood JM, Wray PW, Wyatt JC, Young L, Younger RM, Bentley DR, Coulson A, Durbin R, Hubbard T, Sulston JE, Dunham I, Rogers J, Beck S: The DNA sequence and analysis of human chromosome 6. Nature. 2003 Oct 23;425(6960):805-11. doi: 10.1038/nature02055.
Pubmed: 14574404
Kurachi K, Davie EW: Isolation and characterization of a cDNA coding for human factor IX. Proc Natl Acad Sci U S A. 1982 Nov;79(21):6461-4. doi: 10.1073/pnas.79.21.6461.
Pubmed: 6959130
Jaye M, de la Salle H, Schamber F, Balland A, Kohli V, Findeli A, Tolstoshev P, Lecocq JP: Isolation of a human anti-haemophilic factor IX cDNA clone using a unique 52-base synthetic oligonucleotide probe deduced from the amino acid sequence of bovine factor IX. Nucleic Acids Res. 1983 Apr 25;11(8):2325-35. doi: 10.1093/nar/11.8.2325.
Pubmed: 6687940
Anson DS, Choo KH, Rees DJ, Giannelli F, Gould K, Huddleston JA, Brownlee GG: The gene structure of human anti-haemophilic factor IX. EMBO J. 1984 May;3(5):1053-60.
Pubmed: 6329734
Truett MA, Blacher R, Burke RL, Caput D, Chu C, Dina D, Hartog K, Kuo CH, Masiarz FR, Merryweather JP, et al.: Characterization of the polypeptide composition of human factor VIII:C and the nucleotide sequence and expression of the human kidney cDNA. DNA. 1985 Oct;4(5):333-49. doi: 10.1089/dna.1985.4.333.
Pubmed: 3935400
Wood WI, Capon DJ, Simonsen CC, Eaton DL, Gitschier J, Keyt B, Seeburg PH, Smith DH, Hollingshead P, Wion KL, Delwart E, Tuddenham EG, Vehar GA, Lawn RM: Expression of active human factor VIII from recombinant DNA clones. Nature. 1984 Nov 22-28;312(5992):330-7. doi: 10.1038/312330a0.
Pubmed: 6438526
Levinson B, Kenwrick S, Gamel P, Fisher K, Gitschier J: Evidence for a third transcript from the human factor VIII gene. Genomics. 1992 Nov;14(3):585-9.
Pubmed: 1427887
Highlighted elements will appear in red.
Highlight Compounds
Highlight Proteins
Enter relative concentration values (without units). Elements will be highlighted in a color gradient where red = lowest concentration and green = highest concentration. For the best results, view the pathway in Black and White.
Visualize Compound Data
Visualize Protein Data
Downloads
Settings