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Thrombosis

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Concise Guide to Hematology

Abstract

Thromboembolism is a leading cause of morbidity and mortality globally. Survival after VTE (venous thromboembolism including deep venous thrombosis and pulmonary embolism) is worse than the expected survival in age- and sex-matched controls [1, 2]. Moreover, the risk of death after a pulmonary embolism (PE) is 18-fold higher than after a deep vein thrombosis (DVT) [3]. VTE also poses a significant burden globally in terms of disability-adjusted life years (DALYs) lost in low-, middle-, and high-income countries [4]. In the year 2010, one in four deaths worldwide was attributed to arterial thromboembolic conditions (12.9 million deaths from arterial thromboembolic conditions compared to eight million deaths from cancer) [5]. These arterial thromboses primarily include myocardial infarction, ischemic strokes, and limb ischemia, whereas deep vein thrombosis and pulmonary embolism comprise the bulk of venous thrombosis.

In 1856, Virchow described the three causes of thrombosis: blood hypercoagulability, stasis, and vessel wall abnormalities (Virchow’s triad). Blood components (including blood cells and plasma proteins) are the best studied of this triad, and the importance of alterations in pro- and anticoagulant proteins in the genesis of thrombosis is well established. In addition, the vessel wall is a major contributor to thrombosis risk and prevention. Its basic nature is antithrombotic, but with injury and inflammation, it turns into a prothrombotic organ. The vessel wall provides adhesion receptors that enable recruitment of leukocytes and platelets to sites of vascular injury and dysfunction. Upon injury, endothelium expresses tissue factor and exposes vascular smooth muscle tissue factor that is constitutively present. Additionally, vascular endothelial cells are constantly subjected to mechanical shear stress imposed by blood flow. Fluid shear stress itself through oscillatory and turbulent flow regulates vascular biology and pathology by ordering changes in protein expression via induction of vascular transcription factors. In this chapter we provide an overview of arterial and venous thrombosis. It will then focus on the pathogenesis of the complex and dynamic processes underlying venous and arterial thrombosis and the conditions that predispose to them. It will highlight disorders and pathogenetic markers to both. It aims to convey the concept that venous and arterial thrombosis forms a continuum with some features unique to each and others common to both.

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References

  1. Andresen MS, Sandven I, Brunborg C, et al. Mortality and recurrence after treatment of VTE: long term follow-up of patients with good life-expectancy. Thromb Res. 2011;127(6):540–6.

    Article  CAS  PubMed  Google Scholar 

  2. Sogaard KK, Schmidt M, Pedersen L, Horvath-Puho E, Sorensen HT. 30-year mortality after venous thromboembolism: a population-based cohort study. Circulation. 2014;130(10):829–36.

    Article  PubMed  Google Scholar 

  3. Heit JA, Silverstein MD, Mohr DN, Petterson TM, O’Fallon WM, Melton LJ 3rd. Predictors of survival after deep vein thrombosis and pulmonary embolism: a population-based, cohort study. Arch Intern Med. 1999;159(5):445–53.

    Article  CAS  PubMed  Google Scholar 

  4. Raskob GE, Angchaisuksiri P, Blanco AN, et al. Thrombosis: a major contributor to global disease burden. Arterioscler Thromb Vasc Biol. 2014;34(11):2363–71.

    Article  CAS  PubMed  Google Scholar 

  5. Lozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2095–128.

    Article  Google Scholar 

  6. Turpie AG, Esmon C. Venous and arterial thrombosis – pathogenesis and the rationale for anticoagulation. Thromb Haemost. 2011;105(4):586–96.

    Article  CAS  PubMed  Google Scholar 

  7. Prandoni P, Bilora F, Marchiori A, et al. An association between atherosclerosis and venous thrombosis. N Engl J Med. 2003;348(15):1435–41.

    Article  PubMed  Google Scholar 

  8. Prandoni P. Venous and arterial thrombosis: two aspects of the same disease? Eur J Intern Med. 2009;20(6):660–1.

    Article  PubMed  Google Scholar 

  9. Spencer FA, Emery C, Lessard D, et al. The Worcester Venous Thromboembolism study: a population-based study of the clinical epidemiology of venous thromboembolism. J Gen Intern Med. 2006;21(7):722–7.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Heijboer H, Brandjes DP, Buller HR, Sturk A, ten Cate JW. Deficiencies of coagulation-inhibiting and fibrinolytic proteins in outpatients with deep-vein thrombosis. N Engl J Med. 1990;323(22):1512–6.

    Article  CAS  PubMed  Google Scholar 

  11. Ridker PM, Hennekens CH, Lindpaintner K, Stampfer MJ, Eisenberg PR, Miletich JP. Mutation in the gene coding for coagulation factor V and the risk of myocardial infarction, stroke, and venous thrombosis in apparently healthy men. N Engl J Med. 1995;332(14):912–7.

    Article  CAS  PubMed  Google Scholar 

  12. 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.

    Article  CAS  PubMed  Google Scholar 

  13. Ivanciu L, Stalker TJ. Spatiotemporal regulation of coagulation and platelet activation during the hemostatic response in vivo. J Thromb Haemost. 2015;13(11):1949–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Swieringa F, Baaten CC, Verdoold R, et al. Platelet control of fibrin distribution and microelasticity in thrombus formation under flow. Arterioscler Thromb Vasc Biol. 2016;36(4):692–9.

    Article  CAS  PubMed  Google Scholar 

  15. Rosendaal FR, Koster T, Vandenbroucke JP, Reitsma PH. High risk of thrombosis in patients homozygous for factor V Leiden (activated protein C resistance). Blood. 1995;85(6):1504–8.

    CAS  PubMed  Google Scholar 

  16. Heijmans BT, Westendorp RG, Knook DL, Kluft C, Slagboom PE. The risk of mortality and the factor V Leiden mutation in a population-based cohort. Thromb Haemost. 1998;80(4):607–9.

    CAS  PubMed  Google Scholar 

  17. Hille ET, Westendorp RG, Vandenbroucke JP, Rosendaal FR. Mortality and causes of death in families with the factor V Leiden mutation (resistance to activated protein C). Blood. 1997;89(6):1963–7.

    CAS  PubMed  Google Scholar 

  18. Goldenberg NA, Manco-Johnson MJ. Protein C deficiency. Haemophilia. 2008;14(6):1214–21.

    Article  CAS  PubMed  Google Scholar 

  19. ten Kate MK, van der Meer J. Protein S deficiency: a clinical perspective. Haemophilia. 2008;14(6):1222–8.

    PubMed  Google Scholar 

  20. Brouwer JL, Lijfering WM, Ten Kate MK, Kluin-Nelemans HC, Veeger NJ, van der Meer J. High long-term absolute risk of recurrent venous thromboembolism in patients with hereditary deficiencies of protein S, protein C or antithrombin. Thromb Haemost. 2009;101(1):93–9.

    Article  CAS  PubMed  Google Scholar 

  21. D’Angelo A, Vigano-D’Angelo S, Esmon CT, Comp PC. Acquired deficiencies of protein S. Protein S activity during oral anticoagulation, in liver disease, and in disseminated intravascular coagulation. J Clin Invest. 1988;81(5):1445–54.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Casini A, Blondon M, Lebreton A, et al. Natural history of patients with congenital dysfibrinogenemia. Blood. 2015;125(3):553–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Nagler M, Kremer Hovinga JA, Alberio L, et al. Thromboembolism in patients with congenital afibrinogenaemia. Long-term observational data and systematic review. Thromb Haemost. 2016;116(4):722–32.

    Article  PubMed  Google Scholar 

  24. von Depka M, Nowak-Gottl U, Eisert R, et al. Increased lipoprotein (a) levels as an independent risk factor for venous thromboembolism. Blood. 2000;96(10):3364–8.

    Google Scholar 

  25. Heit JA, Spencer FA, White RH. The epidemiology of venous thromboembolism. J Thromb Thrombolysis. 2016;41(1):3–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Naess IA, Christiansen SC, Romundstad P, Cannegieter SC, Rosendaal FR, Hammerstrom J. Incidence and mortality of venous thrombosis: a population-based study. J Thromb Haemost. 2007;5(4):692–9.

    Article  CAS  PubMed  Google Scholar 

  27. White RH, Romano PS, Zhou H, Rodrigo J, Bargar W. Incidence and time course of thromboembolic outcomes following total hip or knee arthroplasty. Arch Intern Med. 1998;158(14):1525–31.

    Article  CAS  PubMed  Google Scholar 

  28. Planes A, Vochelle N, Darmon JY, Fagola M, Bellaud M, Huet Y. Risk of deep-venous thrombosis after hospital discharge in patients having undergone total hip replacement: double-blind randomised comparison of enoxaparin versus placebo. Lancet. 1996;348(9022):224–8.

    Article  CAS  PubMed  Google Scholar 

  29. Lip GY, Gibbs CR. Does heart failure confer a hypercoagulable state? Virchow’s triad revisited. J Am Coll Cardiol. 1999;33(5):1424–6.

    Article  CAS  PubMed  Google Scholar 

  30. Abdollahi M, Cushman M, Rosendaal FR. Obesity: risk of venous thrombosis and the interaction with coagulation factor levels and oral contraceptive use. Thromb Haemost. 2003;89(3):493–8.

    Article  CAS  PubMed  Google Scholar 

  31. Grainge MJ, West J, Card TR. Venous thromboembolism during active disease and remission in inflammatory bowel disease: a cohort study. Lancet. 2010;375(9715):657–63.

    Article  PubMed  Google Scholar 

  32. Lee AY. Management of thrombosis in cancer: primary prevention and secondary prophylaxis. Br J Haematol. 2005;128(3):291–302.

    Article  PubMed  Google Scholar 

  33. Khorana AA, Francis CW, Culakova E, Kuderer NM, Lyman GH. Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J Thromb Haemost. 2007;5(3):632–4.

    Article  CAS  PubMed  Google Scholar 

  34. Geddings JE, Mackman N. Tumor-derived tissue factor-positive microparticles and venous thrombosis in cancer patients. Blood. 2013;122(11):1873–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Falanga A, Russo L, Milesi V, Vignoli A. Mechanisms and risk factors of thrombosis in cancer. Crit Rev Oncol Hematol. 2017;118:79–83.

    Article  PubMed  Google Scholar 

  36. Lippi G, Franchini M, Targher G. Arterial thrombus formation in cardiovascular disease. Nat Rev Cardiol. 2011;8(9):502–12.

    Article  PubMed  Google Scholar 

  37. Robinson K, Arheart K, Refsum H, et al. Low circulating folate and vitamin B6 concentrations: risk factors for stroke, peripheral vascular disease, and coronary artery disease. European COMAC Group. Circulation. 1998;97(5):437–43.

    Article  CAS  PubMed  Google Scholar 

  38. Hung J, Beilby JP, Knuiman MW, Divitini M. Folate and vitamin B-12 and risk of fatal cardiovascular disease: cohort study from Busselton, Western Australia. BMJ. 2003;326(7381):131.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. 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.

    Article  CAS  PubMed  Google Scholar 

  40. Engelmann B, Massberg S. Thrombosis as an intravascular effector of innate immunity. Nat Rev Immunol. 2013;13(1):34–45.

    Article  CAS  PubMed  Google Scholar 

  41. Boon RA, Horrevoets AJ. Key transcriptional regulators of the vasoprotective effects of shear stress. Hamostaseologie. 2009;29(1):39–40. 41-33

    Article  CAS  PubMed  Google Scholar 

  42. Sangwung P, Zhou G, Nayak L, et al. KLF2 and KLF4 control endothelial identity and vascular integrity. JCI Insight. 2017;2(4):e91700.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Satta S, Mahmoud AM, Wilkinson FL, et al. The role of Nrf2 in cardiovascular function and disease. Oxidative Med Cell Longev. 2017;2017:9237263.

    Article  Google Scholar 

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Correspondence to Lalitha Nayak .

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Kapoor, S., Jain, M.K., Nayak, L. (2019). Thrombosis. In: Lazarus, H., Schmaier, A. (eds) Concise Guide to Hematology. Springer, Cham. https://doi.org/10.1007/978-3-319-97873-4_16

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  • DOI: https://doi.org/10.1007/978-3-319-97873-4_16

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