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Review

Thrombophilia, risk factors and prevention

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Pages 147-158 | Received 31 Dec 2018, Accepted 13 Feb 2019, Published online: 26 Feb 2019

References

  • Bagot CN, Arya R. Virchow and his triad: a question of attribution. Br J Haematol. 2008;143(2):180–190.
  • Middeldorp S, van Hylckama Vlieg A. Does thrombophilia testing help in the clinical management of patients? Br J Haematol. 2008;143(3):321–335.
  • Mannucci PM, Franchini M. The real value of thrombophilia markers in identifying patients at high risk of venous thromboembolism. Expert Rev Hematol. 2014;7(6):757–765.
  • Martinelli I, De Stefano V, Mannucci PM. Inherited risk factors for venous thromboembolism. Nat Rev Cardiol. 2014;11(3):140–156.
  • Crowther MA, Kelton JG. Congenital thrombophilic states associated with venous thrombosis: a qualitative overview and proposed classification system. Ann Intern Med. 2003;138(2):128–134.
  • Dahlback B. Advances in understanding pathogenic mechanisms of thrombophilic disorders. Blood. 2008;112(1):19–27.
  • Margaglione M, Brancaccio V, Giuliani N, et al. Increased risk for venous thrombosis in carriers of the prothrombin G–>A20210 gene variant. Ann Intern Med. 1998;129(2):89–93.
  • Mateo J, Oliver A, Borrell M, et al. Laboratory evaluation and clinical characteristics of 2,132 consecutive unselected patients with venous thromboembolism–results of the Spanish multicentric study on thrombophilia (EMET-study). Thromb Haemost. 1997;77(3):444–451.
  • Castoldi E, Kalafatis M, Lunghi B, et al. Molecular bases of pseudo-homozygous APC resistance: the compound heterozygosity for FV R506Q and a FV null mutation results in the exclusive presence of FV Leiden molecules in plasma. Thromb Haemost. 1998;80(3):403–406.
  • Simioni P, Tormene D, Tognin G, et al. X-linked thrombophilia with a mutant factor IX (factor IX Padua). N Engl J Med. 2009;361(17):1671–1675.
  • Takagi Y, Murata M, Kozuka T, et al. Missense mutations in the gene encoding prothrombin corresponding to Arg596 cause antithrombin resistance and thrombomodulin resistance. Thromb Haemost. 2016;116(6):1022–1031.
  • Wu O, Bayoumi N, Vickers MA, et al. ABO(H) blood groups and vascular disease: a systematic review and meta-analysis. J Thromb Haemost. 2008;6(1):62–69.
  • Dahlback B, Carlsson M, Svensson PJ. Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C. Proc Natl Acad Sci U S A. 1993;90(3):1004–1008.
  • Svensson PJ, Dahlback B. Resistance to activated protein C as a basis for venous thrombosis. N Engl J Med. 1994;330(8):517–522.
  • Norstrom E, Thorelli E, Dahlback B. Functional characterization of recombinant FV Hong Kong and FV Cambridge. Blood. 2002;100(2):524–530.
  • Castoldi E, Rosing J. APC resistance: biological basis and acquired influences. J Thromb Haemost. 2010;8(3):445–453.
  • Chan WP, Lee CK, Kwong YL, et al. A novel mutation of Arg306 of factor V gene in Hong Kong Chinese. Blood. 1998;91(4):1135–1139.
  • Bernardi F, Faioni EM, Castoldi E, et al. A factor V genetic component differing from factor V R506Q contributes to the activated protein C resistance phenotype. Blood. 1997;90(4):1552–1557.
  • Poort SR, Rosendaal FR, Reitsma PH, et al. A common genetic variation in the 3ʹ-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood. 1996;88(10):3698–3703.
  • Kyrle PA, Mannhalter C, Beguin S, et al. Clinical studies and thrombin generation in patients homozygous or heterozygous for the G20210A mutation in the prothrombin gene. Arterioscler Thromb Vasc Biol. 1998;18(8):1287–1291.
  • Smirnov MD, Safa O, Esmon NL, et al. Inhibition of activated protein C anticoagulant activity by prothrombin. Blood. 1999;94(11):3839–3846.
  • Campello E, Spiezia L, Simioni P. Diagnosis and management of factor V Leiden. Expert Rev Hematol. 2016;9(12):1139–1149.
  • Van Cott EM, Khor B, Zehnder JL. Factor V Leiden. Am J Hematol. 2016;91(1):46–49.
  • Salomon O, Steinberg DM, Zivelin A, et al. Single and combined prothrombotic factors in patients with idiopathic venous thromboembolism: prevalence and risk assessment. Arterioscler Thromb Vasc Biol. 1999;19(3):511–518.
  • Shemesh A, Hoffman R, Nadir Y, et al. Clinical significance of prothrombin G20210A mutation in homozygous patients. Am J Hematol. 2017;92(10):E618–E620.
  • MacCallum P, Bowles L, Keeling D. Diagnosis and management of heritable thrombophilias. BMJ. 2014;349:g4387.
  • Martinelli I, Bucciarelli P, Margaglione M, et al. The risk of venous thromboembolism in family members with mutations in the genes of factor V or prothrombin or both. Br J Haematol. 2000;111(4):1223–1229.
  • Emmerich J, Rosendaal FR, Cattaneo M, et al. Combined effect of factor V Leiden and prothrombin 20210A on the risk of venous thromboembolism–pooled analysis of 8 case-control studies including 2310 cases and 3204 controls. Study group for pooled-analysis in venous thromboembolism. Thromb Haemost. 2001;86(3):809–816.
  • Lane DA, Kunz G, Olds RJ, et al. Molecular genetics of antithrombin deficiency. Blood Rev. 1996;10(2):59–74.
  • Bauer KA, Nguyen-Cao TM, Spears JB. Issues in the diagnosis and management of hereditary antithrombin deficiency. Ann Pharmacother. 2016;50(9):758–767.
  • Finazzi G, Caccia R, Barbui T. Different prevalence of thromboembolism in the subtypes of congenital antithrombin III deficiency: review of 404 cases. Thromb Haemost. 1987;58(4):1094.
  • Rossi E, Chiusolo P, Za T, et al. Report of a novel kindred with antithrombin heparin-binding site variant (47 Arg to His): demand for an automated progressive antithrombin assay to detect molecular variants with low thrombotic risk. Thromb Haemost. 2007;98(3):695–697.
  • Middeldorp S. Evidence-based approach to thrombophilia testing. J Thromb Thrombolysis. 2011;31(3):275–281.
  • Esmon CT. Regulation of blood coagulation. Biochim Biophys Acta. 2000;1477(1–2):349–360.
  • De Stefano V, Finazzi G, Mannucci PM. Inherited thrombophilia: pathogenesis, clinical syndromes, and management. Blood. 1996;87(9):3531–3544.
  • Price VE, Ledingham DL, Krumpel A, et al. Diagnosis and management of neonatal purpura fulminans. Semin Fetal Neonatal Med. 2011;16(6):318–322.
  • Reitsma PH, Bernardi F, Doig RG, et al. Protein C deficiency: a database of mutations, 1995 update. On behalf of the subcommittee on plasma coagulation inhibitors of the scientific and standardization committee of the ISTH. Thromb Haemost. 1995;73(5):876–889.
  • Dahlback B. Inhibition of protein Ca cofactor function of human and bovine protein S by C4b-binding protein. J Biol Chem. 1986;261(26):12022–12027.
  • Gill JC, Endres-Brooks J, Bauer PJ, et al. The effect of ABO blood group on the diagnosis of von Willebrand disease. Blood. 1987;69(6):1691–1695.
  • Sodetz JM, Pizzo SV, McKee PA. Relationship of sialic acid to function and in vivo survival of human factor VIII/von Willebrand factor protein. J Biol Chem. 1977;252(15):5538–5546.
  • Dentali F, Sironi AP, Ageno W, et al. Non-O blood type is the commonest genetic risk factor for VTE: results from a meta-analysis of the literature. Semin Thromb Hemost. 2012;38(5):535–548.
  • Spiezia L, Campello E, Bon M, et al. ABO blood groups and the risk of venous thrombosis in patients with inherited thrombophilia. Blood Transfus. 2013;11(2):250–253.
  • Simioni P, Castoldi E, Lunghi B, et al. An underestimated combination of opposites resulting in enhanced thrombotic tendency. Blood. 2005;106(7):2363–2365.
  • Lijfering WM, Brouwer JL, Veeger NJ, et al. Selective testing for thrombophilia in patients with first venous thrombosis: results from a retrospective family cohort study on absolute thrombotic risk for currently known thrombophilic defects in 2479 relatives. Blood. 2009;113(21):5314–5322.
  • VormittagR, BencurP, AyC, et al. Low-density lipoprotein receptor-related protein 1 polymorphism 663 C > T affects clotting factor VIII activity and increases the risk of venous thromboembolism. J Thromb Haemost. 2007;5(3):497–502.
  • Viel KR, Machiah DK, Warren DM, et al. A sequence variation scan of the coagulation factor VIII (FVIII) structural gene and associations with plasma FVIII activity levels. Blood. 2007;109(9):3713–3724.
  • van Hylckama Vlieg A, van der Linden IK, Bertina RM, et al. High levels of factor IX increase the risk of venous thrombosis. Blood. 2000;95(12):3678–3682.
  • Bezemer ID, Arellano AR, Tong CH, et al. F9 Malmo, factor IX and deep vein thrombosis. Haematologica. 2009;94(5):693–699.
  • Koenderman JS, Bertina RM, Reitsma PH, et al. Factor IX-R338L (Factor IX Padua) screening in a Dutch population of sibpairs with early onset venous thromboembolism. Thromb Res. 2011;128(6):603.
  • Meijers JC, Tekelenburg WL, Bouma BN, et al. High levels of coagulation factor XI as a risk factor for venous thrombosis. N Engl J Med. 2000;342(10):696–701.
  • Miyawaki Y, Suzuki A, Fujita J, et al. Thrombosis from a prothrombin mutation conveying antithrombin resistance. N Engl J Med. 2012;366(25):2390–2396.
  • Djordjevic V, Kovac M, Miljic P, et al. A novel prothrombin mutation in two families with prominent thrombophilia–the first cases of antithrombin resistance in a Caucasian population. J Thromb Haemost. 2013;11(10):1936–1939.
  • Bulato C, Radu CM, Campello E, et al. New prothrombin mutation (Arg596Trp, Prothrombin Padua 2) associated with venous thromboembolism. Arterioscler Thromb Vasc Biol. 2016;36(5):1022–1029.
  • Sivasundar S, Oommen AT, Prakash O, et al. Molecular defect of ‘Prothrombin Amrita’: substitution of arginine by glutamine (Arg553 to Gln) near the Na(+) binding loop of prothrombin. Blood Cells Mol Dis. 2013;50(3):182–183.
  • Garcia D, Erkan D. Diagnosis and management of the antiphospholipid syndrome. N Engl J Med. 2018;378(21):2010–2021.
  • Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4(2):295–306.
  • Giannakopoulos B, Krilis SA. The pathogenesis of the antiphospholipid syndrome. N Engl J Med. 2013;368(11):1033–1044.
  • Pengo V, Ruffatti A, Legnani C, et al. Clinical course of high-risk patients diagnosed with antiphospholipid syndrome. J Thromb Haemost. 2010;8(2):237–242.
  • Eldibany MM, Caprini JA. Hyperhomocysteinemia and thrombosis: an overview. Arch Pathol Lab Med. 2007;131(6):872–884.
  • Ray JG. Meta-analysis of hyperhomocysteinemia as a risk factor for venous thromboembolic disease. Arch Intern Med. 1998;158(19):2101–2106.
  • Martinelli I, Bucciarelli P, Zighetti ML, et al. Low risk of thrombosis in family members of patients with hyperhomocysteinaemia. Br J Haematol. 2002;117(3):709–711.
  • Rybstein MD, DeSancho MT. Hypercoagulable states and thrombophilias: risks relating to recurrent venous thromboembolism. Semin Intervent Radiol. 2018;35(2):99–104.
  • Montagnana M, Lippi G, Danese E. An overview of thrombophilia and associated laboratory testing. Methods Mol Biol. 2017;1646:113–135.
  • Campello E, Henderson MW, Noubouossie DF, et al. Contact system activation and cancer: new insights in the pathophysiology of cancer-associated thrombosis. Thromb Haemost. 2018;118(2):251–265.
  • Mihaila RG. Thrombin generation - a potentially useful biomarker of thrombotic risk in Philadelphia-negative myeloproliferative neoplasms. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2017;161(1):50–53.
  • Bucciarelli P, Passamonti SM, Biguzzi E, et al. Low borderline plasma levels of antithrombin, protein C and protein S are risk factors for venous thromboembolism. J Thromb Haemost. 2012;10(9):1783–1791.
  • Favaloro EJ, McDonald D, Lippi G. Laboratory investigation of thrombophilia: the good, the bad, and the ugly. Semin Thromb Hemost. 2009;35(7):695–710.
  • Brouwer JL, Veeger NJ, Kluin-Nelemans HC, et al. The pathogenesis of venous thromboembolism: evidence for multiple interrelated causes. Ann Intern Med. 2006;145(11):807–815.
  • Campello E, Radu CM, Spiezia L, et al. Modulating thrombotic diathesis in hereditary thrombophilia and antiphospholipid antibody syndrome: a role for circulating microparticles? Clin Chem Lab Med. 2017;55(7):934–943.
  • Campello E, Spiezia L, Radu CM, et al. Circulating microparticles in carriers of factor V Leiden with and without a history of venous thrombosis. Thromb Haemost. 2012;108(4):633–639.
  • Campello E, Spiezia L, Radu CM, et al. Circulating microparticles and the risk of thrombosis in inherited deficiencies of antithrombin, protein C and protein S. Thromb Haemost. 2016;115(1):81–88.
  • Gould MK, Garcia DA, Wren SM, et al. Prevention of VTE in nonorthopedic surgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2 Suppl):e227S–e277S.
  • Caprini JA. Thrombosis risk assessment as a guide to quality patient care. Dis Mon. 2005;51(2–3):70–78.
  • Coppola A, Tufano A, Cerbone AM, et al. Inherited thrombophilia: implications for prevention and treatment of venous thromboembolism. Semin Thromb Hemost. 2009;35(7):683–694.
  • Patnaik MM, Moll S. Inherited antithrombin deficiency: a review. Haemophilia. 2008;14(6):1229–1239.
  • Clark P, Walker ID, Neilson RF. Coronary artery bypass surgery in patients with inherited antithrombin deficiency. Br J Haematol. 1995;90(2):479–482.
  • Rodgers GM. Role of antithrombin concentrate in treatment of hereditary antithrombin deficiency. An update. Thromb Haemost. 2009;101(5):806–812.
  • Tufano A, Coppola A, Cerbone AM, et al. Preventing postsurgical venous thromboembolism: pharmacological approaches. Semin Thromb Hemost. 2011;37(3):252–266.
  • Greer IA, Nelson-Piercy C. Low-molecular-weight heparins for thromboprophylaxis and treatment of venous thromboembolism in pregnancy: a systematic review of safety and efficacy. Blood. 2005;106(2):401–407.
  • Robertson L, Wu O, Langhorne P, et al. Thrombophilia in pregnancy: a systematic review. Br J Haematol. 2006;132(2):171–196.
  • Bates SM, Middeldorp S, Rodger M, et al. Guidance for the treatment and prevention of obstetric-associated venous thromboembolism. J Thromb Thrombolysis. 2016;41(1):92–128.
  • Galli M, Barbui T. Antiphospholipid syndrome: clinical and diagnostic utility of laboratory tests. Semin Thromb Hemost. 2005;31(1):17–24.
  • James A. Committee on practice B-O. Practice bulletin no. 123: thromboembolism in pregnancy. Obstet Gynecol. 2011;118(3):718–729.
  • Chan WS, Rey E, Kent NE, et al. Venous thromboembolism and antithrombotic therapy in pregnancy. J Obstet Gynaecol Can. 2014;36(6):527–553.
  • Royal College of Obstetricians and Gynaecologists. Green-top Guideline No. 37a. Reducing the risk of thrombosis and embolism during pregnancy and the puerperium; 2015. Available from: https://www.rcog.org.uk/en/guidelines-research-services/guidelines/gtg37a
  • Bates SM, Greer IA, Middeldorp S, et al. VTE, thrombophilia, antithrombotic therapy, and pregnancy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2Suppl):e691S–e736S.
  • Lidegaard O, Lokkegaard E, Svendsen AL, et al. Hormonal contraception and risk of venous thromboembolism: national follow-up study. BMJ. 2009;339:b2890.
  • Larivée N, Suissa S, Coulombe J, et al. Drospirenone-containing oral contraceptive pills and the risk of venous thromboembolism: an assessment of risk in first-time users and restarters. Drug Saf. 2017;40(7):583–596.
  • van Vlijmen EF, Wiewel-Verschueren S, Monster TB, et al. Combined oral contraceptives, thrombophilia and the risk of venous thromboembolism: a systematic review and meta-analysis. J Thromb Haemost. 2016;14(7):1393–1403.
  • Hugon-Rodin J, Horellou MH, Conard J, et al. Type of combined contraceptives, factor V Leiden mutation and risk of venous thromboembolism. Thromb Haemost. 2018;118(5):922–928.
  • WHO. Medical eligibility criteria for contraceptive use. reproductive health and research. 5th ed. Geneva, Switzerlanda: World Health Organization; 2015.
  • Middeldorp S. Is thrombophilia testing useful? Hematology Am Soc Hematol Educ Program. 2011;2011:150–155.
  • Horowitz N, Brenner B. Thrombophilia and cancer. Pathophysiol Haemost Thromb. 2008;36(3–4):131–136.
  • Blom JW, Doggen CJ, Osanto S, et al. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA. 2005;293(6):715–722.
  • Eroglu A, Ulu A, Cam R, et al. Prevalence of Factor V 1691 G-A (Leiden) and prothrombin G20210A polymorphisms and the risk of venous thrombosis among cancer patients. J Thromb Thrombolysis. 2007;23(1):31–34.
  • Dentali F, Gianni M, Agnelli G, et al. Association between inherited thrombophilic abnormalities and central venous catheter thrombosis in patients with cancer: a meta-analysis. J Thromb Haemost. 2008;6(1):70–75.
  • Decousus H, Moulin N, Quenet S, et al. Thrombophilia and risk of venous thrombosis in patients with cancer. Thromb Res. 2007;120(Suppl 2):S51–61.
  • Falvella FS, Cremolini C, Miceli R, et al. Variant alleles in factor V, prothrombin, plasminogen activator inhibitor-1, methylenetetrahydrofolate reductase and risk of thromboembolism in metastatic colorectal cancer patients treated with first-line chemotherapy plus bevacizumab. Pharmacogenomics J. 2017;17(4):331–336.
  • Caruso V, Iacoviello L, Di Castelnuovo A, et al. Thrombotic complications in childhood acute lymphoblastic leukemia: a meta-analysis of 17 prospective studies comprising 1752 pediatric patients. Blood. 2006;108(7):2216–2222.
  • Dusse LMS, Silva MVF, Freitas LG, et al. Economy class syndrome: what is it and who are the individuals at risk? Rev Bras Hematol Hemoter. 2017;39(4):349–353.
  • Chandra D, Parisini E, Mozaffarian D. Meta-analysis: travel and risk for venous thromboembolism. Ann Intern Med. 2009;151(3):180–190.
  • Martinelli I, Taioli E, Battaglioli T, et al. Risk of venous thromboembolism after air travel: interaction with thrombophilia and oral contraceptives. Arch Intern Med. 2003;163(22):2771–2774.
  • Thibeault C, Evans AD. AsMA medical guidelines for air travel: airline special services. Aerosp Med Hum Perform. 2015;86(7):657–658.
  • Nishimoto Y, Yamashita Y, Morimoto T, et al. Risk factors for post-thrombotic syndrome in patients with deep vein thrombosis: from the COMMAND VTE registry. Heart Vessels. 2018.
  • Rabinovich A, Cohen JM, Prandoni P, et al. Association between thrombophilia and the post-thrombotic syndrome: a systematic review and meta-analysis. J Thromb Haemost. 2014;12(1):14–23.
  • Spiezia L, Campello E, Valle FD, et al. ABO blood group and the risk of post-thrombotic syndrome. Ann Hematol. 2018;97(6):1057–1060.

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