Congenital Prothrombin Deficiency
Journal of Cellular & Molecular Anesthesia,
Vol. 3 No. 4 (2018),
22 February 2019
,
Page 146-154
https://doi.org/10.22037/jcma.v3i4.23494
Abstract
Congenital prothrombin deficiency is an extremely rare hemorrhagic disorder with estimated prevalence of 1 per 2,000,000 in the general population. Since the disorder is an autosomal recessive disorder, the disorder is more frequent in areas with high rate of consanguinity. Clinical manifestations of disorder are highly variable ranging from mild bleeding episodes to severe life-threatening hemorrhages. The disorder can be diagnosed based on routine and specific tests. No specific factor II concentrate is available, but patients can receive fresh frozen plasma and prothrombin complex concentrate (PCC). Traditionally patients with prothrombin deficiency receive on-demand therapy, but secondary prophylaxis can be used for those patients with high risk of severe life-threatening bleeding. With timely diagnosis and appropriate management of disorder, the quality of life in these patients can significantly improve.
Keywords: Prothrombin deficiency, Clinical manifestations, Diagnosis, Treatment
- Prothrombin deficiency
- Clinical manifestations
- Diagnosis
- Treatment
How to Cite
References
References
Downing, M.R., et al., Human prothrombin activation. Journal of Biological Chemistry, 1975. 250(23): p. 8897-8906.
Pozzi, N. and E. Di Cera, Prothrombin structure: unanticipated features and opportunities. 2014, Taylor & Francis.
Sun, W.Y., et al., Prothrombin deficiency results in embryonic and neonatal lethality in mice. Proceedings of the National Academy of Sciences, 1998. 95(13): p. 7597-7602.
Davie, E.W. and J.D. Kulman. An overview of the structure and function of thrombin. in Seminars in thrombosis and hemostasis. 2006. Copyright© 2006 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.
Krishnaswamy, S., The transition of prothrombin to thrombin. Journal of Thrombosis and Haemostasis, 2013. 11(s1): p. 265-276.
Weinreb, G.E., et al., Cooperative roles of factor Va and phosphatidylserine-containing membranes as cofactors in prothrombin activation. Journal of Biological Chemistry, 2003. 278(8): p. 5679-5684.
Wu, J.R., et al., Role of procoagulant lipids in human prothrombin activation. 1. Prothrombin activation by factor Xa in the absence of factor Va and in the absence and presence of membranes. Biochemistry, 2002. 41(3): p. 935-949.
Di Cera, E., Thrombin interactions. Chest, 2003. 124(3): p. 11S-17S.
Bode, W. The structure of thrombin: a janus-headed proteinase. in Seminars in thrombosis and hemostasis. 2006. Copyright© 2006 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.
Di Cera, E., Thrombin. Molecular aspects of medicine, 2008. 29(4): p. 203-254.
Bush-Pelc, L.A., et al., Important Role of the Cys-191–Cys-220 Disulfide Bond in Thrombin Function and Allostery. Journal of Biological Chemistry, 2007. 282(37): p. 27165-27170.
Koh, C.Y., et al., Crystal structure of thrombin in complex with S-variegin: insights of a novel mechanism of inhibition and design of tunable thrombin inhibitors. PloS one, 2011. 6(10): p. e26367.
Lane, D.A., H. Philippou, and J.A. Huntington, Directing thrombin. Blood, 2005. 106(8): p. 2605-2612.
Huntington, J., Molecular recognition mechanisms of thrombin. Journal of thrombosis and haemostasis, 2005. 3(8): p. 1861-1872.
Huntington, J.A., Natural inhibitors of thrombin. Thrombosis and haemostasis, 2014. 112(04): p. 583-589.
Bode, W., Structure and interaction modes of thrombin. Blood Cells, Molecules, and Diseases, 2006. 36(2): p. 122-130.
Rungroj, N., et al., Association between human prothrombin variant (T165M) and kidney stone disease. PloS one, 2012. 7(9): p. e45533.
Poort, S.R., et al., A common genetic variation in the 3'-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood, 1996. 88(10): p. 3698-3703.
Lancellotti, S. and R. De Cristofaro. Congenital prothrombin deficiency. in Seminars in thrombosis and hemostasis. 2009. © Thieme Medical Publishers.
Warshawsky, I., et al., Prothrombin 20209C> T: 16 new cases, association with the 19911A> G polymorphism, and literature review. Journal of Thrombosis and Haemostasis, 2009. 7(9): p. 1585-1587.
Pérez‐Ceballos, E., et al., Prothrombin A19911G and G20210A polymorphisms' role in thrombosis. British journal of haematology, 2002. 118(2): p. 610-614.
Kallel, A., et al., Association Between the G20210A Polymorphism of Prothrombin Gene and Myocardial Infarction in Tunisian Population. Biochemical genetics, 2016. 54(5): p. 653-664.
Demirci, F.Y.K., et al., Functional polymorphisms of the coagulation factor II gene (F2) and susceptibility to systemic lupus erythematosus. The Journal of rheumatology, 2011. 38(4): p. 652-657.
Bourouba, R., et al., The prevalence of methylenetetrahydrofolate reductase 677 CT, factor V 1691 GA, and prothrombin 20210 GA mutations in healthy populations in Setif, Algeria. Clinical and Applied Thrombosis/Hemostasis, 2009. 15(5): p. 529-534.
Nusier, M.K., et al., Prevalence of factor V G1691A (Leiden) and prothrombin G20210A polymorphisms among apparently healthy Jordanians. Neuro endocrinology letters, 2007. 28(5): p. 699-703.
Eid, S.S. and T. Shubeilat, Prevalence of Factor V Leiden, prothrombin G20210A, and MTHFR G677A among 594 thrombotic Jordanian patients. Blood coagulation & fibrinolysis, 2005. 16(6): p. 417-421.
Jadaon, M.M., Epidemiology of prothrombin G20210A mutation in the Mediterranean region. Mediterranean journal of hematology and infectious diseases, 2011. 3(1).
Xenophontos, S., et al., Spectrum and prevalence of prothrombotic single nucleotide polymorphism profiles in the Greek Cypriot population. International angiology, 2002. 21(4): p. 322.
Sottilotta, G., et al., High incidence of factor V Leiden and prothrombin G20210A in healthy southern Italians. Clinical and Applied Thrombosis/Hemostasis, 2009. 15(3): p. 356-359.
Frances, F., et al., Factor V Leiden (G1691A) and prothrombin-G20210A alleles among patients with deep venous thrombosis and in the general population from Spain. Revista medica de Chile, 2006. 134(1): p. 13-20.
Said, J.M., et al., The prevalence of inherited thrombophilic polymorphisms in an asymptomatic Australian antenatal population. Australian and New Zealand Journal of Obstetrics and Gynaecology, 2008. 48(6): p. 536-541.
Conroy, J.M., et al., The allele frequency of mutations in four genes that confer enhanced susceptibility to venous thromboembolism in an unselected group of New York State newborns. Thrombosis research, 2000. 99(4): p. 317-324.
Dowling, N., et al., The epidemiology of venous thromboembolism in Caucasians and African‐Americans: the GATE Study. Journal of Thrombosis and Haemostasis, 2003. 1(1): p. 80-87.
de Haan, H.G., et al., Multiple SNP testing improves risk prediction of first venous thrombosis. Blood, 2012. 120(3): p. 656-663.
Ridker, P.M., C.H. Hennekens, and J.P. Miletich, G20210A mutation in prothrombin gene and risk of myocardial infarction, stroke, and venous thrombosis in a large cohort of US men. Circulation, 1999. 99(8): p. 999-1004.
Prat, M., et al., “20209C-T” a Variant Mutation of Prothrombin Gene Mutation in a Patient with Recurrent Pregnancy Loss. Annals of Clinical & Laboratory Science, 2014. 44(3): p. 334-336.
Kuhli-Hattenbach, C., et al., Prothrombin polymorphism A19911G, factor V HR2 haplotype A4070G, and plasminogen activator-inhibitor-1 polymorphism 4G/5G and the risk of retinal vein occlusion. Ophthalmic genetics, 2017. 38(5): p. 413-417.
Girolami, A., et al., Congenital prothrombin defects: they are not only associated with bleeding but also with thrombosis: a new classification is needed. Hematology, 2018. 23(2): p. 105-110.
Lancellotti, S., M. Basso, and R. De Cristofaro. Congenital prothrombin deficiency: an update. in Seminars in thrombosis and hemostasis. 2013. Thieme Medical Publishers.
Sun WY, Witte DP, Degen JL, Colbert MC, Burkart MC, Holmbäck K, et al. Prothrombin deficiency results in embryonic and neonatal lethality in mice. Proceedings of the National Academy of Sciences. 1998;95(13):7597-602.
Peyvandi F, Palla R, Menegatti M, Mannucci PM, editors. Introduction: rare bleeding disorders: general aspects of clinical features, diagnosis, and management. Seminars in thrombosis and hemostasis; 2009: © Thieme Medical Publishers.
Peyvandi F, Menegatti M, Palla R, editors. Rare bleeding disorders: worldwide efforts for classification, diagnosis, and management. Seminars in thrombosis and hemostasis; 2013: Thieme Medical Publishers.
Peyvandi F, Di Michele D, Bolton-Maggs P, Lee C, Tripodi A, Srivastava A. Project on Consensus Definitions in Rare Bleeeding Disorders of the Factor VIII/Factor IX Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. Classification of rare bleeding disorders (RBDs) based on the association between coagulant factor activity and clinical bleeding severity. J Thromb Haemost. 2012;10(9):1938-43.
Strijks E, Poort S, Renier W, Gabreëls F, Bertina R. Hereditary prothrombin deficiency presenting as intracranial haematoma in infancy. Neuropediatrics. 1999;30(06):320-4.
Pasmant E, Dumont B, Lacapere JJ, Dautzenberg MD, Bezeaud A. A severe neonatal presentation of factor II deficiency. European journal of haematology. 2011;87(5):464-6.
Lancellotti S, Basso M, De Cristofaro R, editors. Congenital prothrombin deficiency: an update. Seminars in thrombosis and hemostasis; 2013: Thieme Medical Publishers.
Imane S, Laalej Z, Faez S, Oukkache B. Congenital factor II deficiency: Moroccan cases. International journal of laboratory hematology. 2013;35(4):416-20.
Peyvandi F, Mannucci P. Rare coagulation disorders. Thrombosis and haemostasis. 1999;81(04):1207-14.
Girolami A, Scarano L, Saggiorato G, Girolami B, Bertomoro A, Marchiori A. Congenital deficiencies and abnormalities of prothrombin. Blood coagulation & fibrinolysis: an international journal in haemostasis and thrombosis. 1998;9(7):557-69.
Girolami A, Scarparo P, Allemand E. Mutations are no substitutes for clotting, chromogenic and immunological assays in patients with congenital prothrombin deficiency. American journal of hematology. 2008;83(6):518-.
Akhavan S, Mannucci PM, Lak M, Mancuso G, Mazzucconi MG, Rocino A, et al. Identification and three-dimensional structural analysis of nine novel mutations in patients with prothrombin deficiency. Thrombosis and haemostasis. 2000;83(06):989-97.
François D, Chevreaud C, Vignon D, de Mazancourt P. Prothrombin Suresnes: a case of homozygous F299V mutation responsible for hypodysprothrombinemia. haematologica. 2006;91(3):431-2.
Peyvandi F, Duga S, Akhavan S, Mannucci P. Rare coagulation deficiencies. Haemophilia. 2002;8(3):308-21.
Bolton‐Maggs P, Perry D, Chalmers E, Parapia L, Wilde J, Williams M, et al. The rare coagulation disorders–review with guidelines for management from the United Kingdom Haemophilia Centre Doctors' Organisation. Haemophilia. 2004;10(5):593-628.
Akhavan S, De Cristofaro R, Peyvandi F, Lavoretano S, Landolfi R, Mannucci PM. Molecular and functional characterization of a natural homozygous Arg67His mutation in the prothrombin gene of a patient with a severe procoagulant defect contrasting with a mild hemorrhagic phenotype. Blood. 2002;100(4):1347-53.
Miyata T, Aruga R, Umeyama H, Bezeaud A, Guillin MC, Iwanaga S. Prothrombin Salakta: substitution of glutamic acid-466 by alanine reduces the fibrinogen clotting activity and the esterase activity. Biochemistry. 1992;31(33):7457-62.
Morishita E, Saito M, Kumabashiri I, Asakura H, Matsuda T, Yamaguchi K. Prothrombin Himi: a compound heterozygote for two dysfunctional prothrombin molecules (Met-337--> Thr and Arg-388--> His). Blood. 1992;80(9):2275-80.
Miyawaki Y, Suzuki A, Fujita J, Maki A, Okuyama E, Murata M, et al. Thrombosis from a prothrombin mutation conveying antithrombin resistance. New England Journal of Medicine. 2012;366(25):2390-6.
Lancellotti S, De Cristofaro R, editors. Congenital prothrombin deficiency. Seminars in thrombosis and hemostasis; 2009: © Thieme Medical Publishers.
Mannucci PM, Duga S, Peyvandi F. Recessively inherited coagulation disorders. Blood. 2004;104(5):1243-52.
Peyvandi F, Kaufman R, Seligsohn U, Salomon O, BOLTON‐MAGGS P, Spreafico M, et al. Rare bleeding disorders. Haemophilia. 2006;12(s3):137-42.
BOLTON‐MAGGS P, Favaloro E, Hillarp A, Jennings I, Kohler H. Difficulties and pitfalls in the laboratory diagnosis of bleeding disorders. Haemophilia. 2012;18(s4):66-72.
Chitlur M. Challenges in the laboratory analyses of bleeding disorders. Thrombosis research. 2012;130(1):1-6.
Hemker HC, Giesen P, Al Dieri R, Regnault V, De Smedt E, Wagenvoord R, et al. Calibrated automated thrombin generation measurement in clotting plasma. Pathophysiology of haemostasis and thrombosis. 2003;33(1):4-15.
Chitlur M, Sorensen B, Rivard G, Young G, Ingerslev J, Othman M, et al. Standardization of thromboelastography: a report from the TEG‐ROTEM working group. Haemophilia. 2011;17(3):532-7.
Geffen Mv, Loof A, Lap P, Boezeman J, Laros-van Gorkom BA, Brons P, et al. A novel hemostasis assay for the simultaneous measurement of coagulation and fibrinolysis. Hematology. 2011;16(6):327-36.
Al Dieri R, Peyvandi F, Santagostino E, Giansily M, Mannucci PM, Schved JF, et al. The thrombogram in rare inherited coagulation disorders: its relation to clinical bleeding. Thrombosis and haemostasis. 2002;88:576-82.
Van Geffen M, Menegatti M, Loof A, Lap P, Karimi M, GORKOM Lv, et al. Retrospective evaluation of bleeding tendency and simultaneous thrombin and plasmin generation in patients with rare bleeding disorders. Haemophilia. 2012;18(4):630-8.
Strey RF, Siegemund A, Siegemund T, Schubert C, Schuster G, Wulff K, et al. Influence of factor V HR2 on thrombin generation and clinical manifestation in rare bleeding disorders. Pathophysiology of haemostasis and thrombosis. 2005;34(6):279-83.
Johnson WT, Leary JM. Management of dental patients with bleeding disorders: review and update. Oral Surgery, Oral Medicine, Oral Pathology. 1988;66(3):297-303.
Organisation UKHCD. Guidelines on the selection and use of therapeutic products to treat haemophilia and other hereditary bleeding disorders. Haemophilia: the official journal of the World Federation of Hemophilia. 2003;9(1):1.
Kushimoto S, Fukuoka T, Kimura A, Toyoda K, Brainsky A, Harman A, et al. Efficacy and safety of a 4-factor prothrombin complex concentrate for rapid vitamin K antagonist reversal in Japanese patients presenting with major bleeding or requiring urgent surgical or invasive procedures: a prospective, open-label, single-arm phase 3b study. International journal of hematology. 2017;106(6):777-86.
Mumford AD, Ackroyd S, Alikhan R, Bowles L, Chowdary P, Grainger J, et al. Guideline for the diagnosis and management of the rare coagulation disorders. British journal of haematology. 2014;167(3):304-26.
Rahimi A, Philbert R, Willoughby JH, Jackman DS. Hypoprothrombinemia (Factor II deficiency): report of a case and review of literature. Journal of oral and maxillofacial surgery. 1991;49(1):84-7.
- Abstract Viewed: 366 times
- PDF Downloaded: 183 times