{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T09:02:29Z","timestamp":1790240549432,"version":"4.1.0"},"reference-count":49,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"published-print":{"date-parts":[[2010,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Hereditary combined vitamin K-dependent clotting factors deficiency (VKCFD) is a rare congenital bleeding disorder resulting from variably decreased levels of coagulation factors II, VII, IX and X as well as natural anticoagulants protein C, protein S and protein Z. The spectrum of bleeding symptoms ranges from mild to severe with onset in the neonatal period in severe cases. The bleeding symptoms are often life-threatening, occur both spontaneously and in a surgical setting, and usually involve the skin and mucosae. A range of non-haemostatic symptoms are often present, including developmental and skeletal anomalies. VKCFD is an autosomal recessive disorder caused by mutations in the genes of either <jats:italic>gamma-glutamyl carboxylase<\/jats:italic> or <jats:italic>vitamin K2,3-epoxide reductase complex<\/jats:italic>. These two proteins are necessary for gamma-carboxylation, a post-synthetic modification that allows coagulation proteins to display their proper function. The developmental and skeletal anomalies seen in VKCFD are the result of defective gamma-carboxylation of a number of non-haemostatic proteins. Diagnostic differentiation from other conditions, both congenital and acquired, is mandatory and genotype analysis is needed to confirm the defect. Vitamin K administration is the mainstay of therapy in VKCFD, with plasma supplementation during surgery or severe bleeding episodes. In addition, prothrombin complex concentrates and combination therapy with recombinant activated FVII and vitamin K supplementation may constitute alternative treatment options. The overall prognosis is good and with the availability of several effective therapeutic options, VKCFD has only a small impact on the quality of life of affected patients.<\/jats:p>","DOI":"10.1186\/1750-1172-5-21","type":"journal-article","created":{"date-parts":[[2010,7,14]],"date-time":"2010-07-14T18:14:19Z","timestamp":1279131259000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Hereditary combined deficiency of the vitamin K-dependent clotting factors"],"prefix":"10.1186","volume":"5","author":[{"given":"Mariasanta","family":"Napolitano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guglielmo","family":"Mariani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Lapecorella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2010,7,14]]},"reference":[{"key":"184_CR1","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1055\/s-2007-1005073","volume":"7","author":"GA Soff","year":"1981","unstructured":"Soff GA, Levin J: Familial multiple coagulation factor deficiencies. I. Review of the literature: differentiation of single hereditary disorders associated with multiple factor deficiencies from coincidental concurrence of single factor deficiency states. Semin Thromb Hemost. 1981, 7: 112-148. 10.1055\/s-2007-1005073.","journal-title":"Semin Thromb Hemost"},{"key":"184_CR2","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1055\/s-2007-1005074","volume":"7","author":"GA Soff","year":"1981","unstructured":"Soff GA, Levin J, Bell WR: Familial multiple coagulation factor deficiencies. II. Combined factor VIII, IX, and XI deficiency and combined factor IX and XI deficiency: two previously uncharacterized familial multiple factor deficiency syndromes. Semin Thromb Hemost. 1981, 7: 149-169. 10.1055\/s-2007-1005074.","journal-title":"Semin Thromb Hemost"},{"key":"184_CR3","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1111\/j.1365-2516.2008.01897.x","volume":"15","author":"PJ Robson","year":"2009","unstructured":"Robson PJ, Mumford AD: Familial multiple coagulation factor deficiencies-chance associations and distinct clinical disorders. Haemophilia. 2009, 15: 11-19. 10.1111\/j.1365-2516.2008.01897.x.","journal-title":"Haemophilia"},{"key":"184_CR4","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1055\/s-0038-1646311","volume":"68","author":"BAM Soute","year":"1992","unstructured":"Soute BAM, Ulrich MMW, Watson ADJ, Maddison JE, Ebberink RHM, Vermeer C: Congenital deficiency of all vitamin K-dependent blood coagulation factors due to a defective vitamin K-dependent carboxylase in Devon Rex cats. Thromb Haemost. 1992, 68: 521-525.","journal-title":"Thromb Haemost"},{"key":"184_CR5","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1055\/s-0037-1614152","volume":"84","author":"J Oldenburg","year":"2000","unstructured":"Oldenburg J, von Brederlow B, Fregin A, Rost S, Wolz W, Eberl W, Eber S, Lenz E, Schwaab R, Brackmann HH, Effenberger W, Harbrecht U, Schurgers LJ, Vermeer C, Muller CR: Congenital deficiency of vitamin K dependent coagulation factors in two families presents as a genetic defect of the vitamin K-epoxide-reductase-complex. Thromb Haemost. 2000, 84: 937-941.","journal-title":"Thromb Haemost"},{"key":"184_CR6","doi-asserted-by":"publisher","first-page":"1313","DOI":"10.1056\/NEJM196606092742309","volume":"274","author":"CW McMillan","year":"1966","unstructured":"McMillan CW, Roberts HR: Congenital combined deficiency of coagulation factors II VII, IX, and X. Report of a case. N Engl J Med. 1966, 274: 1313-1315. 10.1056\/NEJM196606092742309.","journal-title":"N Engl J Med"},{"key":"184_CR7","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1002\/(SICI)1096-8628(19961028)65:3<241::AID-AJMG13>3.0.CO;2-O","volume":"65","author":"A Boneh","year":"1996","unstructured":"Boneh A, Bar-Ziv J: Hereditary deficiency of vitamin K-dependent coagulation factors with skeletal abnormalities. Am J Med Genet. 1996, 65: 241-243. 10.1002\/(SICI)1096-8628(19961028)65:3<241::AID-AJMG13>3.0.CO;2-O.","journal-title":"Am J Med Genet"},{"key":"184_CR8","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1111\/j.1365-2141.1990.tb07795.x","volume":"75","author":"B Brenner","year":"1990","unstructured":"Brenner B, Tavori S, Zivelin A, Keller CB, Suttie JW, Tatarsky I, Seligsohn U: Hereditary deficiency of all vitamin K-dependent procoagulants and anticoagulants. Br J Haematol. 1990, 75: 537-542. 10.1111\/j.1365-2141.1990.tb07795.x.","journal-title":"Br J Haematol"},{"key":"184_CR9","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.1172\/JCI110564","volume":"69","author":"GH Goldsmith Jr","year":"1982","unstructured":"Goldsmith GH, Pence RE, Ratnoff OD, Adelsteinn DJ, Furie B: Studies on a family with combined functional deficiencies of vitamin K-dependent coagulation factors. J Clin Invest. 1982, 69: 1253-1260. 10.1172\/JCI110564.","journal-title":"J Clin Invest"},{"key":"184_CR10","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1055\/s-0037-1616072","volume":"86","author":"M Mousallem","year":"2001","unstructured":"Mousallem M, Spronk HM, Sacy R, Hakime N, Soute BA: Congenital combined deficiencies of all vitamin K-dependent coagulation factors. Thromb Haemost. 2001, 86: 1334-1336.","journal-title":"Thromb Haemost"},{"key":"184_CR11","first-page":"566","volume":"41","author":"RM Pauli","year":"1987","unstructured":"Pauli RM, Lian JB, Mosher DF, Suttie JW: Association of congenital deficiency of multiple vitamin K-dependent coagulation factors and the phenotype of the warfarin embryopathy: clues to the mechanism of teratogenicity of coumarin derivatives. Am J Hum Genet. 1987, 41: 566-583.","journal-title":"Am J Hum Genet"},{"key":"184_CR12","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1055\/s-0038-1646327","volume":"68","author":"C Pechlaner","year":"1992","unstructured":"Pechlaner C, Vogel W, Erhart R, P\u00fcmpel E, Kunz F: A new case of combined deficiency of vitamin K-dependent coagulation factors. Thromb Haemost. 1992, 68: 617-","journal-title":"Thromb Haemost"},{"issue":"Suppl 1","key":"184_CR13","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1097\/00001721-200306001-00013","volume":"14","author":"A Thomas","year":"2003","unstructured":"Thomas A, Stirling D: Four factor deficiency. Blood Coagul Fibrinol. 2003, 14 (Suppl 1): 55-57. 10.1097\/00001721-200306001-00013.","journal-title":"Blood Coagul Fibrinol"},{"key":"184_CR14","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1055\/s-0038-1661097","volume":"51","author":"V Vicente","year":"1984","unstructured":"Vicente V, Maia R, Alberca I, Tamagnini GP, Lopez BA: Congenital deficiency of vitamin K-dependent coagulation factors and protein C. Thromb Haemost. 1984, 51: 343-346.","journal-title":"Thromb Haemost"},{"key":"184_CR15","doi-asserted-by":"publisher","first-page":"187","DOI":"10.3109\/08880018609031217","volume":"3","author":"H Ekelund","year":"1986","unstructured":"Ekelund H, Lindeberg L, Wranne L: Combined deficiency of coagulation factors II, VII, IX, and X a case of probable congenital origin. Pediatric Haematol Oncol. 1986, 3: 187-193. 10.3109\/08880018609031217.","journal-title":"Pediatric Haematol Oncol"},{"key":"184_CR16","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1097\/01.mbc.0000183634.68071.3b","volume":"16","author":"J Bhattacharyya","year":"2005","unstructured":"Bhattacharyya J, Dutta P, Mishra P, Dixit A, Srinivas U, Kannan M, Kumar R, Choudhry VP, Saxena R: Congenital vitamin K-dependent coagulation factor deficiency: a case report. Blood Coagul Fibrinolysis. 2005, 16: 525-527. 10.1097\/01.mbc.0000183634.68071.3b.","journal-title":"Blood Coagul Fibrinolysis"},{"key":"184_CR17","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1177\/1076029608330473","volume":"16","author":"M Lapecorella","year":"2010","unstructured":"Lapecorella M, Napolitano M, Bernardi F, Pinotti M, Sbrighi P, Marchetti G, Canella A, Caruso P, Orecchioni A, Mariani G: Effective hemostasis during minor surgery in a case of hereditary combined deficiency of vitamin K-dependent clotting factors. Clin Appl Thromb Hemost. 2010, 16: 221-223. 10.1177\/1076029608330473.","journal-title":"Clin Appl Thromb Hemost"},{"key":"184_CR18","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1038\/sj.jid.5700610","volume":"127","author":"OM Vanakker","year":"2007","unstructured":"Vanakker OM, Martin l, Gheduzzi D, Leroy BP, Loeys BL, Guerci VI, Matthys D, Terry SF, Coucke PJ, Pasquali-Ronchetti I, De Paepe A: Pseudoxanthoma elasticum-like phenotype with cutis laxa and multiple coagulation factor deficiency represents a separate genetic entity. J Invest Dermatol. 2007, 127: 581-587. 10.1038\/sj.jid.5700610.","journal-title":"J Invest Dermatol"},{"key":"184_CR19","doi-asserted-by":"publisher","first-page":"1925","DOI":"10.1182\/blood-2005-12-010660","volume":"108","author":"D Darghouth","year":"2006","unstructured":"Darghouth D, Hallgren KW, Shtofman RL, Mrad A, Gharbi Y, Maherzi A, Kastally R, LeRicousse S, Berkner KL, Rosa JP: Compound heterozygosity of novel missense mutations in the gamma-glutamyl-carboxylase gene causes hereditary combined vitamin K-dependent coagulation factor deficiency. Blood. 2006, 108: 1925-1931. 10.1182\/blood-2005-12-010660.","journal-title":"Blood"},{"key":"184_CR20","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1182\/blood.V75.9.1753.1753","volume":"75","author":"B Furie","year":"1990","unstructured":"Furie B, Furie BC: Molecular basis of vitamin K-dependent gamma-carboxylation. Blood. 1990, 75: 1753-1762.","journal-title":"Blood"},{"key":"184_CR21","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1055\/s-0037-1613115","volume":"87","author":"SR Presnell","year":"2002","unstructured":"Presnell SR, Stafford DW: The vitamin K-dependent carboxylase. Thromb Haemost. 2002, 87: 937-946.","journal-title":"Thromb Haemost"},{"key":"184_CR22","doi-asserted-by":"crossref","first-page":"12467","DOI":"10.1016\/S0021-9258(19)38369-3","volume":"265","author":"P Huber","year":"1990","unstructured":"Huber P, Schmitz T, Griffin J, Jacobs M, Walsh C, Furie B, Furie BC: Identification of amino-acids in the gamma-carboxylation recognition site on the propeptide of prothrombin. J Biol Chem. 1990, 265: 12467-12473.","journal-title":"J Biol Chem"},{"key":"184_CR23","doi-asserted-by":"publisher","first-page":"2236","DOI":"10.1073\/pnas.88.6.2236","volume":"88","author":"SM Wu","year":"1991","unstructured":"Wu SM, Morris DP, Stafford DW: Identification and purification to near homogeneity of the vitamin K-dependent carboxylase. Proc Natl Acad Sci USA. 1991, 88: 2236-2240. 10.1073\/pnas.88.6.2236.","journal-title":"Proc Natl Acad Sci USA"},{"key":"184_CR24","doi-asserted-by":"publisher","first-page":"1634","DOI":"10.1126\/science.1749935","volume":"254","author":"SM Wu","year":"1991","unstructured":"Wu SM, Cheung WF, Frazier D, Stafford DW: Cloning and expression of cDNA for human gamma-glutamyl carboxylase. Science. 1991, 254: 1634-1636. 10.1126\/science.1749935.","journal-title":"Science"},{"key":"184_CR25","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1111\/j.1365-2141.2004.05071.x","volume":"126","author":"S Rost","year":"2004","unstructured":"Rost S, Fregin A, Koch D, Compes M, M\u00fcller CR, Oldenburg J: Compound heterozygous mutations in the gamma-glutamyl carboxylase gene cause combined deficiency of all vitamin K-dependent blood coagulation factors. Br J Haematol. 2004, 126: 546-549. 10.1111\/j.1365-2141.2004.05071.x.","journal-title":"Br J Haematol"},{"key":"184_CR26","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1097\/01.mbc.0000240927.88177.d1","volume":"17","author":"S Rost","year":"2006","unstructured":"Rost S, Geisen C, Fregin A, Seifried E, M\u00fcller CR, Oldenburg J: Founder mutation Arg485Pro led to recurrent compound heterozygous GGCX genotypes in two German patients with VKCFD type 1. Blood Coagul Fibrinolysis. 2006, 17: 503-507. 10.1097\/01.mbc.0000240927.88177.d1.","journal-title":"Blood Coagul Fibrinolysis"},{"key":"184_CR27","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1002\/pbc.22011","volume":"53","author":"R Titapiwatanakun","year":"2009","unstructured":"Titapiwatanakun R, Rodriguez V, Middha S, Dukek BA, Pruthi RK: Novel splice site mutations in the gamma glutamyl carboxylase gene in a child with congenital combined deficiency of the vitamin K-dependent coagulation factors (VKCFD). Pediatr Blood Cancer. 2009, 53: 92-95. 10.1002\/pbc.22011.","journal-title":"Pediatr Blood Cancer"},{"key":"184_CR28","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1016\/0006-2952(74)90002-1","volume":"23","author":"A Zimmermann","year":"1974","unstructured":"Zimmermann A, Matschiner JT: Biochemical basis of hereditary resistance to warfarin in rat. Biochem Pharmacol. 1974, 23: 1033-1040. 10.1016\/0006-2952(74)90002-1.","journal-title":"Biochem Pharmacol"},{"key":"184_CR29","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1038\/nature02254","volume":"427","author":"T Li","year":"2004","unstructured":"Li T, Chang CY, Jin DY, Lin PJ, Khvorova A, Stafford DW: Identification of the gene for vitamin K epoxide reducatse. Nature. 2004, 427: 541-544. 10.1038\/nature02254.","journal-title":"Nature"},{"key":"184_CR30","doi-asserted-by":"publisher","first-page":"3229","DOI":"10.1182\/blood-2002-03-0698","volume":"100","author":"A Fregin","year":"2002","unstructured":"Fregin A, Rost S, Wolz W, Krebsova A, Muller CR, Oldenburg J: Homozygosity mapping of a second gene locus for hereditary combined deficiency of vitamin K-dependent clotting factors to the centromeric region of chromosome 16. Blood. 2002, 100: 3229-3232. 10.1182\/blood-2002-03-0698.","journal-title":"Blood"},{"key":"184_CR31","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1111\/j.1538-7836.2008.02934.x","volume":"6","author":"G Marchetti","year":"2008","unstructured":"Marchetti G, Caruso P, Lunghi B, Pinotti M, Lapecorella M, Napolitano M, Canella A, Mariani G, Bernardi F: Vitamin K-induced modification of coagulation phenotype in VKORC1 homozygous deficiency. J Thromb Haemost. 2008, 6: 797-803. 10.1111\/j.1538-7836.2008.02934.x.","journal-title":"J Thromb Haemost"},{"key":"184_CR32","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1038\/nature02214","volume":"427","author":"S Rost","year":"2004","unstructured":"Rost S, Fregin A, Ivaskevicius V, Conzelmann E, H\u00f6rtnagel K, Pelz HJ, Lappegard K, Seifried E, Scharrer I, Tuddenham EG, M\u00fcller CR, Strom TM, Oldenburg J: Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature. 2004, 427: 537-541. 10.1038\/nature02214.","journal-title":"Nature"},{"key":"184_CR33","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1152\/physrev.1989.69.3.990","volume":"69","author":"PV Hauschka","year":"1989","unstructured":"Hauschka PV, Lian JB, Cole DE, Gundberg CM: Osteocalcin and matrix Gla protein: vitamin K-dependent proteins in bone. Physiol Rev. 1989, 69: 990-1047.","journal-title":"Physiol Rev"},{"key":"184_CR34","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1016\/0092-8674(95)90520-0","volume":"80","author":"TN Stitt","year":"1995","unstructured":"Stitt TN, Conn G, Gore M, Lai C, Bruno J, Radzeijewski C, Mattsson K, Fisher J, Gies DR, Jones PF, Masiakowski P, Ryan TE, Tobkes NJ, Chen DH, Di Stefano PS, Long GL, Basilico C, Goldfarb MP, Lemke G, Glass DJ, Yancopoulos GD: The anticoagulation factor protein S and its relative, Gas6, are ligands for the Tyro3\/Axl family of receptor tyrosine kinases. Cell. 1995, 80: 661-670. 10.1016\/0092-8674(95)90520-0.","journal-title":"Cell"},{"key":"184_CR35","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1007\/s11481-007-9090-2","volume":"3","author":"C Grommes","year":"2008","unstructured":"Grommes C, Lee CY, Wilkinson BL, Jiang Q, Koenigsknecht-Talboo JL, Varnum B, Landreth GE: Regulation of microglial phagocytosis and inflammatory gene expression by Gas6 acting on the Axl\/Mer family of tyrosine kinases. J Neuroimmune Pharmacol. 2008, 3: 130-140. 10.1007\/s11481-007-9090-2.","journal-title":"J Neuroimmune Pharmacol"},{"key":"184_CR36","doi-asserted-by":"publisher","first-page":"11323","DOI":"10.1073\/pnas.91.24.11323","volume":"91","author":"D Mustafi","year":"1994","unstructured":"Mustafi D, Nakagawa Y: Characterization of calcium-binding sites in the kidney stone inhibitor glycoprotein nephrocalcin with vanadyl ions: electron paramagnetic resonance and electron nuclear double resonance spectroscopy. Proc Natal Acad Sci USA. 1994, 91: 11323-11327. 10.1073\/pnas.91.24.11323.","journal-title":"Proc Natal Acad Sci USA"},{"key":"184_CR37","doi-asserted-by":"publisher","first-page":"1370","DOI":"10.1073\/pnas.98.4.1370","volume":"98","author":"JD Kulman","year":"2001","unstructured":"Kulman JD, Harris JE, Xie L, Davie EW: Identification of two novel transemembrane gamma-carboxyglutamic acid proteins expressed broadly in fetal and adult tissues. Proc Natal Acad Sci USA. 2001, 98: 1370-1375. 10.1073\/pnas.98.4.1370.","journal-title":"Proc Natal Acad Sci USA"},{"key":"184_CR38","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1111\/j.1365-2141.1980.tb05916.x","volume":"44","author":"CA Johnson","year":"1980","unstructured":"Johnson CA, Chung KS, McGrath KM, Bean PE, Roberts HR: Characterization of a variant prothrombin in a patient congenitally deficient in factors II, VII, IX and X. Br J Haematol. 1980, 44: 461-469. 10.1111\/j.1365-2141.1980.tb05916.x.","journal-title":"Br J Haematol"},{"key":"184_CR39","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/S1386-6346(01)00150-4","volume":"22","author":"M Tamano","year":"2002","unstructured":"Tamano M, Sugaya H, Oguma M, Iijima M, Yoneda M, Murohisa T, Kojima K, Kuniyoshi T, Majima Y, Hashimoto T, Terano A: Serum and tissue PIVKA-II expression reflect the biological malignant potential of small hepatocellular carcinoma. Hepatol Res. 2002, 22: 261-269. 10.1016\/S1386-6346(01)00150-4.","journal-title":"Hepatol Res"},{"key":"184_CR40","doi-asserted-by":"publisher","first-page":"6409","DOI":"10.1074\/jbc.M406714200","volume":"280","author":"M Suzuki","year":"2005","unstructured":"Suzuki M, Shiraha H, Fujikawa T, Takaoka N, Ueda N, Nakanishi Y, Koike K, Takaki A, Shiratori Y: Des-gamma-carboxy prothrombin is a potential autologous growth factor for hepatocellular carcinoma. J Biol Chem. 2005, 280: 6409-6415. 10.1074\/jbc.M406714200.","journal-title":"J Biol Chem"},{"key":"184_CR41","doi-asserted-by":"crossref","first-page":"4058","DOI":"10.1182\/blood.V89.11.4058","volume":"89","author":"SM Wu","year":"1997","unstructured":"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, 89: 4058-4062.","journal-title":"Blood"},{"key":"184_CR42","doi-asserted-by":"publisher","first-page":"1209","DOI":"10.1111\/j.1365-2516.2008.01853.x","volume":"14","author":"BW Weston","year":"2008","unstructured":"Weston BW, Monahan PE: Familial deficiency of vitamin K-dependent clotting factors. Haemophilia. 2008, 14: 1209-1213. 10.1111\/j.1365-2516.2008.01853.x.","journal-title":"Haemophilia"},{"key":"184_CR43","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1042\/bj1690095","volume":"169","author":"R Wallin","year":"1978","unstructured":"Wallin R, Gebhardt O, Prydz H: NAD(P)H dehydrogenase and its role in the vitamin K (2-methyl-3-phytyl-1,4-naphthaquinone)-dependent carboxylation reaction. Biochem J. 1978, 169: 95-101.","journal-title":"Biochem J"},{"key":"184_CR44","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1016\/S0021-9258(19)68073-7","volume":"257","author":"R Wallin","year":"1982","unstructured":"Wallin R, Hutson S: Vitamin K-dependent carboxylation. Evidence that at least two microsomal dehydrogenases reduce vitamin K1 to support carboxylation. J Biol Chem. 1982, 257: 1583-1586.","journal-title":"J Biol Chem"},{"key":"184_CR45","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1046\/j.1365-2141.1998.00715.x","volume":"101","author":"TP Baglin","year":"1998","unstructured":"Baglin TP, Rose PE: Guidelines on oral anticoagulation: third edition. Br J Haematol. 1998, 101: 374-387. 10.1046\/j.1365-2141.1998.00715.x.","journal-title":"Br J Haematol"},{"key":"184_CR46","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1002\/ajh.21046","volume":"83","author":"CA Leissinger","year":"2008","unstructured":"Leissinger CA, Blatt PM, Hoors WK, Ewenstein B: Role of prothrombin complex concentrates in reversing warfarin anticoagulation: a review of the literature. Am J Hematol. 2008, 83: 137-143. 10.1002\/ajh.21046.","journal-title":"Am J Hematol"},{"key":"184_CR47","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1016\/j.thromres.2004.04.004","volume":"113","author":"A Lubetsky","year":"2004","unstructured":"Lubetsky A, Hoffman R, Zimlichman R, Eldor A, Zvi J, Kostenko V, Brenner B: Efficacy and safety of a prothrombin complex concentrate (Octaplex) for rapid reversal of oral anticoagulation. Thromb Res. 2004, 113: 371-378. 10.1016\/j.thromres.2004.04.004.","journal-title":"Thromb Res"},{"key":"184_CR48","doi-asserted-by":"publisher","first-page":"1132","DOI":"10.1136\/jcp.2003.008904","volume":"57","author":"JP Hanley","year":"2004","unstructured":"Hanley JP: Warfarin reversal. J Clin Pathol. 2004, 57: 1132-1139. 10.1136\/jcp.2003.008904.","journal-title":"J Clin Pathol"},{"key":"184_CR49","doi-asserted-by":"publisher","first-page":"15","DOI":"10.3177\/jnsv.55.15","volume":"55","author":"N Koitaya","year":"2009","unstructured":"Koitaya N, Ezaki J, Nishimuta M, Yamauchi J, Hashizume E, Morishita K, Miyachi M, Sasaki S, Ishimi Y: Effect of low dose vitamin K2 (MK-4) supplementation on bio-indices in postmenopausal Japanese women. J Nutr Sci Vitaminol (Tokyo). 2009, 55: 15-21. 10.3177\/jnsv.55.15.","journal-title":"J Nutr Sci Vitaminol (Tokyo)"}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1750-1172-5-21.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T04:20:50Z","timestamp":1630470050000},"score":1,"resource":{"primary":{"URL":"https:\/\/ojrd.biomedcentral.com\/articles\/10.1186\/1750-1172-5-21"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,7,14]]},"references-count":49,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2010,12]]}},"alternative-id":["184"],"URL":"https:\/\/doi.org\/10.1186\/1750-1172-5-21","relation":{},"ISSN":["1750-1172"],"issn-type":[{"value":"1750-1172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,7,14]]},"assertion":[{"value":"16 February 2009","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 July 2010","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 July 2010","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"21"}}