Abstract
A prolonged prothrombin time usually involves a problem with factor VII, either under synthesis or with the gamma-carboxylation of an inactive form of factor VII. This latter problem is mostly due to a problem with vitamin K, either antagonism to it, such as warfarin use, or low levels of it, such as interference with normal gut flora. This chapter will discuss congenital deficiency states of factor VII, as well as the rare inhibitor to factor VII activity. Much of the chapter will discuss how vitamin K works and the various ways vitamin K deficiency can lead to a bleeding diathesis.
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Ageno W, Gallus AS, Wittkowsky A, Crowther M, Hylek EM, Palareti G. Antithrombotic therapy and prevention of thrombosis, 9th edition: American College of Chest Physicians evidence based clinical practice guidelines. Chest. 2012;141(2):e44S–88S.
Au N, Rettie AE. Pharmacogenomics of 4-hydroxycoumarin anticoagulants. Drug Metab Rev. 2008;40(355–375):2008.
Coyer DN, Millar DS, Wacey A, et al. Inherited factor VII deficiency, molecular genetics and pathophysiology. Thromb Haemost. 1997;78(1):151–60.
Dam H, Glavind J. Vitamin K in human pathology. Lancet. 1938;231:720–1.
D’Andrea G, D’Ambrosio RL, DiPerna P, et al. A polymorphism in the VKORC1 gene is associated with an interindividual variability in the dose-anticoagulant effect of warfarin. Blood. 2005;105:645.
Dantzenberg MD, Sandubray JM, Girot R. Factor VII deficiency in homocystinuria. Thromb Haemost. 1983;50:409 (abstract).
Delmer A, Horellou MH, Andreu G, LeCompte T, Rossi F, Kazatchkine MD, et al. Life threatening intracranial bleeding associated with the presence of an anti-factor VII autoantibody. Blood. 1989;74:229–32.
Fiore LD, Scola MA, Cantillon CE, et al. Anaphylactoid reactions to Vitamin K. J Thromb Thrombolysis. 2001;11(2):175–83.
Furie B, Bouchard BA, Furie BC. Vitamin K dependent biosynthesis of gamma-carboxyglutamic acid. Blood. 1999;93:1798–808.
Gailani D, Neff AT. Rare coagulation factor deficiencies. In: Hoffman R, Benz Jr EJ, Shattil SJ, et al., editors. Hoffman hematology: basic principles and practice. 5th ed. Philadelphia: Churchill Livingston Elsevier; 2008.
Garcia-Martin E, Martinez C, Ladero JM, Agundez JA. Interethnic and intraethnic variability of CYPC28 and CYPC29 polymorphisms in healthy individuals. Mol Diagn Ther. 2006;10:29–40.
Girolani A, Ruzzon E, Tezza F, et al. Congenital combined defects of factor VII: a critical review. Acta Haematol. 2007;117:51–6.
Hill MJ. Intestinal flora and endogenous vitamin synthesis. Eur J Cancer Prev. 1997;6 suppl 1:S43–5.
Kitchen S, Preston FE. Standardization of prothrombin time for laboratory control of oral anticoagulant therapy. Semin Thromb Hemost. 1999;25:17–25.
Kitzmiller JP, Groen DK, Pehlps MA, Sadee W. Pharmacogenetic testing: relevance in medical practice. Cleve Clin J Med. 2011;78(4):243–57.
Lusher J, Ingerslev J, Roberts H, Hedner U. Clinical experience with recombinant VIIa. Blood Coagul Fibrinolysis. 1998;9(2):119–28.
Mariani G, Herrmann FH, Dolce A, et al. Clinical phenotypes and factor VII genotype in congenital FVII deficiency. Thromb Haemost. 2005;93:481–7.
Mullighan LG, Rischbieth A, Duncan EM, Lloyd JV. Acquired isolated factor VII deficiency associated with severe bleeding and successful treatment with recombinant FVIIa. Blood Coagul Fibrinolysis. 2004; 15(4):347–51.
Patriquin C, Crowther M. Treatment of warfarin associated coagulopathy with Vitamin K. Expert Rev Hematol. 2011;4(6):657–67.
Rieder MJ, Reiner AP, Gage BF, et al. Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose. N Engl J Med. 2005;352:2285–93.
Roberts HR, Escobar MA. Less common congenital disorders of hemostasis. In: Kitchens CS, Alving BM, Kessler CM, editors. Consultative hemostasis and thrombosis. 1st ed. Philadelphia: WB Sanders; 2002.
Sabater-Lleal M, Martinez-Marchan E, Martinez-Sanchez E, Coll M, Vallve L, Seuto MJ, et al. Complexity of the genetic contribution to factor VII deficiency in two Spanish families: clinical & biological implications. Haematologica. 2003;88(8):906–13.
Seligsohn U, Shani M, Ramot B. Gilbert syndrome and factor VII deficiency. Lancet. 1970;7661:1398.
Seligsohn U, Shani M, Ramot B, et al. Hereditary deficiency of clotting factor VII and Dubin-Johnson syndrome in an Israeli family. Isr J Med Sci. 1969;5(5):1060–5.
Shikata E, Ieiri I, Ishiguro S, et al. Association of pharmacokinetic (CYP2C9) and pharmacodynamic (factors II, VII, IX and X; proteins S and C; and gamma-glutamyl carboxylase) gene variants with warfarin sensitivity. Blood. 2004;103:2630–5.
Taube J, Halsall D, Baglin T. Influence of cytochrome P-450 CYP2C9 polymorphisms on warfarin sensitivity and risk of over-anticoagulation in patients on long-term treatment. Blood. 2000;96(5):1816–9.
Weisdorf D, Hasegawa D, Fair DS. Acquired Factor VII deficiency associated with aplastic anemia: correction with bone marrow transplantation. Br J Haematol. 1989;71(3):409–13.
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Lichtin, A. (2014). Prolonged PT. In: Lichtin, A., Bartholomew, J. (eds) The Coagulation Consult. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-9560-4_3
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