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Semin Thromb Hemost 2023; 49(07): 744-755
DOI: 10.1055/s-0042-1758869
Review Article

The Journey Through the Pathogenesis and Treatment of Venous Thromboembolism in Inflammatory Bowel Diseases: A Narrative Review

Andrea Boccatonda
1   Department of Internal Medicine, Bentivoglio Hospital, AUSL Bologna, Bologna, Italy
,
Marco Balletta
2   Department of Internal Medicine, Bologna University, Bologna, Italy
,
Susanna Vicari
1   Department of Internal Medicine, Bentivoglio Hospital, AUSL Bologna, Bologna, Italy
,
Ariela Hoxha
3   Hemorrhagic and Thrombotic Diseases Unit, Department of Medicine (DIMED), Padova University Hospital, Padova, Italy
,
Paolo Simioni
3   Hemorrhagic and Thrombotic Diseases Unit, Department of Medicine (DIMED), Padova University Hospital, Padova, Italy
,
Elena Campello
3   Hemorrhagic and Thrombotic Diseases Unit, Department of Medicine (DIMED), Padova University Hospital, Padova, Italy
› Author Affiliations
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Abstract

Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders of the gastrointestinal tract including Crohn's disease and ulcerative colitis, which may result in several extraintestinal complications (∼20–30% of cases), such as increased risk of venous thromboembolism (VTE). The main pathophysiological mechanism of VTE is an inflammation-induced hypercoagulable state, and recent data have shown that endothelial dysregulation due to gut and systemic inflammation may also lead to a prothrombotic state. Several prothrombotic alterations have been described, such as the activation of the coagulation system, platelet abnormalities, and dysregulation of fibrinolysis. Furthermore, the dysregulation of the gut microbiome seems to play a vital role in increasing systemic inflammation and thus inducing a procoagulant state. Our review aims to examine the main correlations between IBD and VTE, the underlying pathophysiology, and current therapeutic options.

Keywords

immunothrombosis - hypercoagulability - pulmonary embolism - thromboinflammation - venous thrombosis


Publication History

Article published online:
01 December 2022

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  • References

  • 1 Vegh Z, Kurti Z, Gonczi L. et al. Association of extraintestinal manifestations and anaemia with disease outcomes in patients with inflammatory bowel disease. Scand J Gastroenterol 2016; 51 (07) 848-854
    CrossrefPubMedGoogle Scholar
  • 2 Yarur AJ, Deshpande AR, Pechman DM, Tamariz L, Abreu MT, Sussman DA. Inflammatory bowel disease is associated with an increased incidence of cardiovascular events. Am J Gastroenterol 2011; 106 (04) 741-747
    CrossrefPubMedGoogle Scholar
  • 3 Zezos P, Kouklakis G, Saibil F. Inflammatory bowel disease and thromboembolism. World J Gastroenterol 2014; 20 (38) 13863-13878
    CrossrefPubMedGoogle Scholar
  • 4 Bernstein CN, Blanchard JF, Houston DS, Wajda A. The incidence of deep venous thrombosis and pulmonary embolism among patients with inflammatory bowel disease: a population-based cohort study. Thromb Haemost 2001; 85 (03) 430-434
    Article in Thieme ConnectPubMedGoogle Scholar
  • 5 Bafford AC, Cross RK. Risk of venous thromboembolism in patients with inflammatory bowel disease extends beyond hospitalization. Inflamm Bowel Dis 2020; 26 (11) 1769-1770
    CrossrefPubMedGoogle Scholar
  • 6 Setyawan J, Mu F, Zichlin ML. et al. Risk of thromboembolic events and associated healthcare costs in patients with inflammatory bowel disease. Adv Ther 2022; 39 (01) 738-753
    CrossrefPubMedGoogle Scholar
  • 7 Papay P, Miehsler W, Tilg H. et al. Clinical presentation of venous thromboembolism in inflammatory bowel disease. J Crohn's Colitis 2013; 7 (09) 723-729
    CrossrefPubMedGoogle Scholar
  • 8 Faye AS, Lee KE, Dodson J. et al. Increasing rates of venous thromboembolism among hospitalised patients with inflammatory bowel disease: a nationwide analysis. Aliment Pharmacol Ther 2022; 56 (07) 1157-1167
    CrossrefPubMedGoogle Scholar
  • 9 Solem CA, Loftus EV, Tremaine WJ, Sandborn WJ. Venous thromboembolism in inflammatory bowel disease. Am J Gastroenterol 2004; 99 (01) 97-101
    CrossrefPubMedGoogle Scholar
  • 10 Landman C, Nahon S, Cosnes J. et al; Groupe d'Etude Thérapeutique des Affections Inflammatoires du Tube Digestif. Portomesenteric vein thrombosis in patients with inflammatory bowel disease. Inflamm Bowel Dis 2013; 19 (03) 582-589
    CrossrefPubMedGoogle Scholar
  • 11 DeFilippis EM, Barfield E, Leifer D. et al. Cerebral venous thrombosis in inflammatory bowel disease. J Dig Dis 2015; 16 (02) 104-108
    CrossrefPubMedGoogle Scholar
  • 12 Nylund CM, Goudie A, Garza JM, Crouch G, Denson LA. Venous thrombotic events in hospitalized children and adolescents with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2013; 56 (05) 485-491
    CrossrefPubMedGoogle Scholar
  • 13 Quera R, Shanahan F. Thromboembolism – an important manifestation of inflammatory bowel disease. Am J Gastroenterol 2004; 99 (10) 1971-1973
    CrossrefPubMedGoogle Scholar
  • 14 Novacek G, Weltermann A, Sobala A, Tilg H, Petritsch W, Reinisch W. et al. Inflammatory bowel disease is a risk factor for recurrent venous thromboembolism. Gastroenterology 2010; 139 (03) 779-787 , 87.e1
    CrossrefPubMedGoogle Scholar
  • 15 Bollen L, Vande Casteele N, Peeters M. et al. The occurrence of thrombosis in inflammatory bowel disease is reflected in the clot lysis profile. Inflamm Bowel Dis 2015; 21 (11) 2540-2548
    CrossrefPubMedGoogle Scholar
  • 16 Galanaud JP, Holcroft CA, Rodger MA. et al. Predictors of post-thrombotic syndrome in a population with a first deep vein thrombosis and no primary venous insufficiency. J Thromb Haemost 2013; 11 (03) 474-480
    CrossrefPubMedGoogle Scholar
  • 17 Cromer WE, Mathis JM, Granger DN, Chaitanya GV, Alexander JS. Role of the endothelium in inflammatory bowel diseases. World J Gastroenterol 2011; 17 (05) 578-593
    CrossrefPubMedGoogle Scholar
  • 18 Van de Wouwer M, Collen D, Conway EM. Thrombomodulin-protein C-EPCR system: integrated to regulate coagulation and inflammation. Arterioscler Thromb Vasc Biol 2004; 24 (08) 1374-1383
    CrossrefPubMedGoogle Scholar
  • 19 Palkovits J, Novacek G, Kollars M. et al. Tissue factor exposing microparticles in inflammatory bowel disease. J Crohn's Colitis 2013; 7 (03) 222-229
    CrossrefPubMedGoogle Scholar
  • 20 Klein NJ, Shennan GI, Heyderman RS, Levin M. Alteration in glycosaminoglycan metabolism and surface charge on human umbilical vein endothelial cells induced by cytokines, endotoxin and neutrophils. J Cell Sci 1992; 102 (Pt 4): 821-832
    CrossrefPubMedGoogle Scholar
  • 21 Fukudome K, Esmon CT. Identification, cloning, and regulation of a novel endothelial cell protein C/activated protein C receptor. J Biol Chem 1994; 269 (42) 26486-26491
    CrossrefPubMedGoogle Scholar
  • 22 Stouthard JM, Levi M, Hack CE. et al. Interleukin-6 stimulates coagulation, not fibrinolysis, in humans. Thromb Haemost 1996; 76 (05) 738-742
    Article in Thieme ConnectPubMedGoogle Scholar
  • 23 Jones SC, Banks RE, Haidar A. et al. Adhesion molecules in inflammatory bowel disease. Gut 1995; 36 (05) 724-730
    CrossrefPubMedGoogle Scholar
  • 24 Vetrano S, Ploplis VA, Sala E. et al. Unexpected role of anticoagulant protein C in controlling epithelial barrier integrity and intestinal inflammation. Proc Natl Acad Sci U S A 2011; 108 (49) 19830-19835
    CrossrefPubMedGoogle Scholar
  • 25 Remková A, Kovácová E, Príkazská M, Kratochvíl'ová H. Thrombomodulin as a marker of endothelium damage in some clinical conditions. Eur J Intern Med 2000; 11 (02) 79-84
    CrossrefPubMedGoogle Scholar
  • 26 Scaldaferri F, Sans M, Vetrano S. et al. Crucial role of the protein C pathway in governing microvascular inflammation in inflammatory bowel disease. J Clin Invest 2007; 117 (07) 1951-1960
    CrossrefPubMedGoogle Scholar
  • 27 Souto JC, Martínez E, Roca M. et al. Prothrombotic state and signs of endothelial lesion in plasma of patients with inflammatory bowel disease. Dig Dis Sci 1995; 40 (09) 1883-1889
    CrossrefPubMedGoogle Scholar
  • 28 Reichman-Warmusz E, Kurek J, Gabriel A. et al. Tissue hemostasis and chronic inflammation in colon biopsies of patients with inflammatory bowel disease. Pathol Res Pract 2012; 208 (09) 553-556
    CrossrefPubMedGoogle Scholar
  • 29 Cibor D, Owczarek D, Butenas S, Salapa K, Mach T, Undas A. Levels and activities of von Willebrand factor and metalloproteinase with thrombospondin type-1 motif, number 13 in inflammatory bowel diseases. World J Gastroenterol 2017; 23 (26) 4796-4805
    CrossrefPubMedGoogle Scholar
  • 30 Meucci G, Pareti F, Vecchi M, Saibeni S, Bressi C, de Franchis R. Serum von Willebrand factor levels in patients with inflammatory bowel disease are related to systemic inflammation. Scand J Gastroenterol 1999; 34 (03) 287-290
    CrossrefPubMedGoogle Scholar
  • 31 Stevens TR, James JP, Simmonds NJ. et al. Circulating von Willebrand factor in inflammatory bowel disease. Gut 1992; 33 (04) 502-506
    CrossrefPubMedGoogle Scholar
  • 32 Andrade AR, da Rocha TRF, Ortiz-Agostinho CL. et al. Endoscopic activity, tissue factor and Crohn's disease: findings in clinical remission patients. Therap Adv Gastroenterol 2020; 13: 1756284820939412
    CrossrefPubMedGoogle Scholar
  • 33 Tripodi A, Spina L, Pisani LF. et al. Anti-TNF-α treatment reduces the baseline procoagulant imbalance of patients with inflammatory bowel diseases. Inflamm Bowel Dis 2021; 27 (12) 1901-1908
    CrossrefPubMedGoogle Scholar
  • 34 Boehme MW, Autschbach F, Zuna I. et al. Elevated serum levels and reduced immunohistochemical expression of thrombomodulin in active ulcerative colitis. Gastroenterology 1997; 113 (01) 107-117
    CrossrefPubMedGoogle Scholar
  • 35 Alkim H, Ayaz S, Alkim C, Ulker A, Sahin B. Continuous active state of coagulation system in patients with nonthrombotic inflammatory bowel disease. Clin Appl Thromb Hemost 2011; 17 (06) 600-604
    CrossrefPubMedGoogle Scholar
  • 36 Hayat M, Ariëns RA, Moayyedi P, Grant PJ, O'Mahony S. Coagulation factor XIII and markers of thrombin generation and fibrinolysis in patients with inflammatory bowel disease. Eur J Gastroenterol Hepatol 2002; 14 (03) 249-256
    CrossrefPubMedGoogle Scholar
  • 37 Saibeni S, Saladino V, Chantarangkul V. et al. Increased thrombin generation in inflammatory bowel diseases. Thromb Res 2010; 125 (03) 278-282
    CrossrefPubMedGoogle Scholar
  • 38 de Jong E, Porte RJ, Knot EA, Verheijen JH, Dees J. Disturbed fibrinolysis in patients with inflammatory bowel disease. A study in blood plasma, colon mucosa, and faeces. Gut 1989; 30 (02) 188-194
    CrossrefPubMedGoogle Scholar
  • 39 Yazici A, Senturk O, Aygun C, Celebi A, Caglayan C, Hulagu S. Thrombophilic risk factors in patients with inflammatory bowel disease. Gastroenterol Res 2010; 3 (03) 112-119
    PubMedGoogle Scholar
  • 40 Steinhoff M, Buddenkotte J, Shpacovitch V. et al. Proteinase-activated receptors: transducers of proteinase-mediated signaling in inflammation and immune response. Endocr Rev 2005; 26 (01) 1-43
    CrossrefPubMedGoogle Scholar
  • 41 Dolapcioglu C, Soylu A, Kendir T. et al. Coagulation parameters in inflammatory bowel disease. Int J Clin Exp Med 2014; 7 (05) 1442-1448
    PubMedGoogle Scholar
  • 42 Kjeldsen J, Lassen JF, Brandslund I, Schaffalitzky de Muckadell OB. Markers of coagulation and fibrinolysis as measures of disease activity in inflammatory bowel disease. Scand J Gastroenterol 1998; 33 (06) 637-643
    CrossrefPubMedGoogle Scholar
  • 43 Zezos P, Papaioannou G, Nikolaidis N, Vasiliadis T, Giouleme O, Evgenidis N. Elevated plasma von Willebrand factor levels in patients with active ulcerative colitis reflect endothelial perturbation due to systemic inflammation. World J Gastroenterol 2005; 11 (48) 7639-7645
    CrossrefPubMedGoogle Scholar
  • 44 Chamouard P, Grunebaum L, Wiesel ML. et al. Significance of diminished factor XIII in Crohn's disease. Am J Gastroenterol 1998; 93 (04) 610-614
    CrossrefPubMedGoogle Scholar
  • 45 Saibeni S, Bottasso B, Spina L. et al. Assessment of thrombin-activatable fibrinolysis inhibitor (TAFI) plasma levels in inflammatory bowel diseases. Am J Gastroenterol 2004; 99 (10) 1966-1970
    CrossrefPubMedGoogle Scholar
  • 46 Owczarek D, Undas A, Foley JH, Nesheim ME, Jabłonski K, Mach T. Activated thrombin activatable fibrinolysis inhibitor (TAFIa) is associated with inflammatory markers in inflammatory bowel diseases TAFIa level in patients with IBD. J Crohn's Colitis 2012; 6 (01) 13-20
    CrossrefPubMedGoogle Scholar
  • 47 Schmid W, Vogelsang H, Papay P. et al. Increased responsiveness to thrombin through protease-activated receptors (PAR)-1 and -4 in active Crohn's disease. J Crohn's Colitis 2014; 8 (06) 495-503
    CrossrefPubMedGoogle Scholar
  • 48 Ye L, Zhang YP, Yu N, Jia YX, Wan SJ, Wang FY. Serum platelet factor 4 is a reliable activity parameter in adult patients with inflammatory bowel disease: a pilot study. Medicine (Baltimore) 2017; 96 (11) e6323
    CrossrefPubMedGoogle Scholar
  • 49 Gardiner KR, Halliday MI, Barclay GR. et al. Significance of systemic endotoxaemia in inflammatory bowel disease. Gut 1995; 36 (06) 897-901
    CrossrefPubMedGoogle Scholar
  • 50 Panés J, Granger DN. Leukocyte-endothelial cell interactions: molecular mechanisms and implications in gastrointestinal disease. Gastroenterology 1998; 114 (05) 1066-1090
    CrossrefPubMedGoogle Scholar
  • 51 Hsieh HJ, Liu CA, Huang B, Tseng AH, Wang DL. Shear-induced endothelial mechanotransduction: the interplay between reactive oxygen species (ROS) and nitric oxide (NO) and the pathophysiological implications. J Biomed Sci 2014; 21 (01) 3
    CrossrefPubMedGoogle Scholar
  • 52 Larabi A, Barnich N, Nguyen HTT. New insights into the interplay between autophagy, gut microbiota and inflammatory responses in IBD. Autophagy 2020; 16 (01) 38-51
    CrossrefPubMedGoogle Scholar
  • 53 Kappelman MD, Horvath-Puho E, Sandler RS. et al. Thromboembolic risk among Danish children and adults with inflammatory bowel diseases: a population-based nationwide study. Gut 2011; 60 (07) 937-943
    CrossrefPubMedGoogle Scholar
  • 54 Danese S, Katz JA, Saibeni S. et al. Gut 2003; 52 (10) 1435-1441
    CrossrefPubMed
  • 55 Ando K, Fujiya M, Nomura Y. et al. The incidence and risk factors of venous thromboembolism in Japanese inpatients with inflammatory bowel disease: a retrospective cohort study. Intest Res 2018; 16 (03) 416-425
    CrossrefPubMedGoogle Scholar
  • 56 Collins CE, Cahill MR, Newland AC, Rampton DS. Platelets circulate in an activated state in inflammatory bowel disease. Gastroenterology 1994; 106 (04) 840-845
    CrossrefPubMedGoogle Scholar
  • 57 Cognasse F, Hamzeh H, Chavarin P, Acquart S, Genin C, Garraud O. Evidence of Toll-like receptor molecules on human platelets. Immunol Cell Biol 2005; 83 (02) 196-198
    CrossrefPubMedGoogle Scholar
  • 58 Faure E, Equils O, Sieling PA. et al. Bacterial lipopolysaccharide activates NF-kappaB through toll-like receptor 4 (TLR-4) in cultured human dermal endothelial cells. Differential expression of TLR-4 and TLR-2 in endothelial cells. J Biol Chem 2000; 275 (15) 11058-11063
    CrossrefPubMedGoogle Scholar
  • 59 Hasan RA, Koh AY, Zia A. The gut microbiome and thromboembolism. Thromb Res 2020; 189: 77-87
    CrossrefPubMedGoogle Scholar
  • 60 Pastorelli L, Dozio E, Pisani LF. et al. Procoagulatory state in inflammatory bowel diseases is promoted by impaired intestinal barrier function. Gastroenterol Res Pract 2015; 2015: 189341
    CrossrefPubMedGoogle Scholar
  • 61 Santilli F, Boccatonda A, Davì G. Coagulation at the crossroads of the communicable/non-communicable disease dyad: the case of pneumonia. Respirology 2016; 21 (08) 1344-1346
    CrossrefPubMedGoogle Scholar
  • 62 Levi M, van der Poll T, Schultz M. Infection and inflammation as risk factors for thrombosis and atherosclerosis. Semin Thromb Hemost 2012; 38 (05) 506-514
    Article in Thieme ConnectPubMedGoogle Scholar
  • 63 Faye AS, Wen T, Ananthakrishnan AN. et al. Acute venous thromboembolism risk highest within 60 days after discharge from the hospital in patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol 2020; 18 (05) 1133-1141 .e3
    CrossrefPubMedGoogle Scholar
  • 64 Grainge MJ, West J, Card TR. Venous thromboembolism during active disease and remission in inflammatory bowel disease: a cohort study. Lancet 2010; 375 (9715): 657-663
    CrossrefPubMedGoogle Scholar
  • 65 Weng MT, Park SH, Matsuoka K. et al. Incidence and risk factor analysis of thromboembolic events in East Asian patients with inflammatory bowel disease, a multinational collaborative study. Inflamm Bowel Dis 2018; 24 (08) 1791-1800
    CrossrefPubMedGoogle Scholar
  • 66 Alhassan N, Trepanier M, Sabapathy C. et al. Risk factors for post-discharge venous thromboembolism in patients undergoing colorectal resection: a NSQIP analysis. Tech Coloproctol 2018; 22 (12) 955-964
    CrossrefPubMedGoogle Scholar
  • 67 McKechnie T, Wang J, Springer JE, Gross PL, Forbes S, Eskicioglu C. Extended thromboprophylaxis following colorectal surgery in patients with inflammatory bowel disease: a comprehensive systematic clinical review. Colorectal Dis 2020; 22 (06) 663-678
    CrossrefPubMedGoogle Scholar
  • 68 Kim TJ, Kong SM, Shin JB. et al. P196 risk of venous thromboembolism according to disease activity, hospitalisation, or surgery in inflammatory bowel disease: a nationwide cohort study. Journal of Crohn's and Colitis 2019; 13 (Suppl 1): S189-S190
    CrossrefPubMedGoogle Scholar
  • 69 Benlice C, Holubar SD, Gorgun E. et al. Extended venous thromboembolism prophylaxis after elective surgery for IBD patients: nomogram-based risk assessment and prediction from nationwide cohort. Dis Colon Rectum 2018; 61 (10) 1170-1179
    CrossrefPubMedGoogle Scholar
  • 70 Bhandari S, Mohammed Abdul MK, Dhakal B, Kreuziger LB, Saeian K, Stein D. Increased rate of venous thromboembolism in hospitalized inflammatory bowel disease patients with Clostridium difficile infection. Inflamm Bowel Dis 2017; 23 (10) 1847-1852
    CrossrefPubMedGoogle Scholar
  • 71 Anderson A, Click B, Ramos-Rivers C. et al. Lasting impact of Clostridium difficile infection in inflammatory bowel disease: a propensity score matched analysis. Inflamm Bowel Dis 2017; 23 (12) 2180-2188
    CrossrefPubMedGoogle Scholar
  • 72 Ananthakrishnan AN, Cagan A, Gainer VS. et al. Thromboprophylaxis is associated with reduced post-hospitalization venous thromboembolic events in patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol 2014; 12 (11) 1905-1910
    CrossrefPubMedGoogle Scholar
  • 73 Simion C, Campello E, Bensi E. et al. Use of glucocorticoids and risk of venous thromboembolism: a narrative review. Semin Thromb Hemost 2021; 47 (06) 654-661
    Article in Thieme ConnectPubMedGoogle Scholar
  • 74 Maxwell SR, Moots RJ, Kendall MJ. Corticosteroids: do they damage the cardiovascular system?. Postgrad Med J 1994; 70 (830) 863-870
    CrossrefPubMedGoogle Scholar
  • 75 Sandborn WJ, Lawendy N, Danese S. et al. Safety and efficacy of tofacitinib for treatment of ulcerative colitis: final analysis of OCTAVE Open, an open-label, long-term extension study with up to 7.0 years of treatment. Aliment Pharmacol Ther 2022; 55 (04) 464-478
    CrossrefPubMedGoogle Scholar
  • 76 Mori S, Ogata F, Tsunoda R. Risk of venous thromboembolism associated with Janus kinase inhibitors for rheumatoid arthritis: case presentation and literature review. Clin Rheumatol 2021; 40 (11) 4457-4471
    CrossrefPubMedGoogle Scholar
  • 77 FDA approves Boxed Warning about increased risk of blood clots and death with higher dose of arthritis and ulcerative colitis medicine tofacitinib (Xeljanz, Xeljanz XR): FDA drug safety communication. 2019
    PubMed
  • 78 Deepak P, Alayo QA, Khatiwada A. et al. Safety of tofacitinib in a real-world cohort of patients with ulcerative colitis. Clin Gastroenterol Hepatol 2021; 19 (08) 1592-1601 .e3
    CrossrefPubMedGoogle Scholar
  • 79 Koutroubakis IE, Sfiridaki A, Tsiolakidou G. et al. Genetic risk factors in patients with inflammatory bowel disease and vascular complications: case-control study. Inflamm Bowel Dis 2007; 13 (04) 410-415
    CrossrefPubMedGoogle Scholar
  • 80 Guédon C, Le Cam-Duchez V, Lalaude O, Ménard JF, Lerebours E, Borg JY. Prothrombotic inherited abnormalities other than factor V Leiden mutation do not play a role in venous thrombosis in inflammatory bowel disease. Am J Gastroenterol 2001; 96 (05) 1448-1454
    CrossrefPubMedGoogle Scholar
  • 81 Papa A, De Stefano V, Gasbarrini A. et al. Prevalence of factor V Leiden and the G20210A prothrombin-gene mutation in inflammatory bowel disease. Blood Coagul Fibrinolysis 2000; 11 (05) 499-503
    CrossrefPubMedGoogle Scholar
  • 82 Cattaneo M, Vecchi M, Zighetti ML. et al. High prevalence of hyperchomocysteinemia in patients with inflammatory bowel disease: a pathogenic link with thromboembolic complications?. Thromb Haemost 1998; 80 (04) 542-545
    PubMedGoogle Scholar
  • 83 Danese S, Sgambato A, Papa A. et al. Homocysteine triggers mucosal microvascular activation in inflammatory bowel disease. Am J Gastroenterol 2005; 100 (04) 886-895
    CrossrefPubMedGoogle Scholar
  • 84 Koutroubakis IE, Petinaki E, Anagnostopoulou E. et al. Anti-cardiolipin and anti-beta2-glycoprotein I antibodies in patients with inflammatory bowel disease. Dig Dis Sci 1998; 43 (11) 2507-2512
    CrossrefPubMedGoogle Scholar
  • 85 Sipeki N, Davida L, Palyu E. et al. Prevalence, significance and predictive value of antiphospholipid antibodies in Crohn's disease. World J Gastroenterol 2015; 21 (22) 6952-6964
    CrossrefPubMedGoogle Scholar
  • 86 Koutroubakis IE, Malliaraki N, Vardas E. et al. Increased levels of lipoprotein (a) in Crohn's disease: a relation to thrombosis?. Eur J Gastroenterol Hepatol 2001; 13 (12) 1415-1419
    CrossrefPubMedGoogle Scholar
  • 87 Nguyen GC, Sam J. Rising prevalence of venous thromboembolism and its impact on mortality among hospitalized inflammatory bowel disease patients. Am J Gastroenterol 2008; 103 (09) 2272-2280
    CrossrefPubMedGoogle Scholar
  • 88 Miehsler W, Reinisch W, Valic E. et al. Is inflammatory bowel disease an independent and disease specific risk factor for thromboembolism?. Gut 2004; 53 (04) 542-548
    CrossrefPubMedGoogle Scholar
  • 89 van Bodegraven AA, Schoorl M, Linskens RK, Bartels PC, Tuynman HA. Persistent activation of coagulation and fibrinolysis after treatment of active ulcerative colitis. Eur J Gastroenterol Hepatol 2002; 14 (04) 413-418
    CrossrefPubMedGoogle Scholar
  • 90 Hansen AT, Erichsen R, Horváth-Puhó E, Sørensen HT. Inflammatory bowel disease and venous thromboembolism during pregnancy and the postpartum period. J Thromb Haemost 2017; 15 (04) 702-708
    CrossrefPubMedGoogle Scholar
  • 91 Kim YH, Pfaller B, Marson A, Yim HW, Huang V, Ito S. The risk of venous thromboembolism in women with inflammatory bowel disease during pregnancy and the postpartum period: a systematic review and meta-analysis. Medicine (Baltimore) 2019; 98 (38) e17309
    CrossrefPubMedGoogle Scholar
  • 92 Vrij AA, Rijken J, van Wersch JW, Stockbrügger RW. Coagulation and fibrinolysis in inflammatory bowel disease and in giant cell arteritis. Pathophysiol Haemost Thromb 2003; 33 (02) 75-83
    CrossrefPubMedGoogle Scholar
  • 93 Nguyen GC, Bernstein CN, Bitton A. et al. Consensus statements on the risk, prevention, and treatment of venous thromboembolism in inflammatory bowel disease: Canadian Association of Gastroenterology. Gastroenterology 2014; 146 (03) 835-848 .e6
    CrossrefPubMedGoogle Scholar
  • 94 Mowat C, Cole A, Windsor A. et al; IBD Section of the British Society of Gastroenterology. Guidelines for the management of inflammatory bowel disease in adults. Gut 2011; 60 (05) 571-607
    CrossrefPubMedGoogle Scholar
  • 95 Harbord M, Annese V, Vavricka SR. et al; European Crohn's and Colitis Organisation. The first European evidence-based consensus on extra-intestinal manifestations in inflammatory bowel disease. J Crohn's Colitis 2016; 10 (03) 239-254
    CrossrefPubMedGoogle Scholar
  • 96 Scoville EA, Konijeti GG, Nguyen DD, Sauk J, Yajnik V, Ananthakrishnan AN. Venous thromboembolism in patients with inflammatory bowel diseases: a case-control study of risk factors. Inflamm Bowel Dis 2014; 20 (04) 631-636
    CrossrefPubMedGoogle Scholar
  • 97 Nguyen GC, Murthy SK, Bressler B. et al; CINERGI Group. Quality of care and outcomes among hospitalized inflammatory bowel disease patients: a multicenter retrospective study. Inflamm Bowel Dis 2017; 23 (05) 695-701
    CrossrefPubMedGoogle Scholar
  • 98 Ra G, Thanabalan R, Ratneswaran S, Nguyen GC. Predictors and safety of venous thromboembolism prophylaxis among hospitalized inflammatory bowel disease patients. J Crohn's Colitis 2013; 7 (10) e479-e485
    CrossrefPubMedGoogle Scholar
  • 99 Faye AS, Hung KW, Cheng K. et al. Minor hematochezia decreases use of venous thromboembolism prophylaxis in patients with inflammatory bowel disease. Inflamm Bowel Dis 2020; 26 (09) 1394-1400
    CrossrefPubMedGoogle Scholar
  • 100 Lee KE, Lim F, Colombel JF, Hur C, Faye AS. Cost-effectiveness of venous thromboembolism prophylaxis after hospitalization in patients with inflammatory bowel disease. Inflamm Bowel Dis 2022; 28 (08) 1169-1176
    CrossrefPubMedGoogle Scholar
  • 101 Cotton CC, Baird D, Sandler RS, Long MD. Hormonal contraception use is common among patients with inflammatory bowel diseases and an elevated risk of deep vein thrombosis. Inflamm Bowel Dis 2016; 22 (07) 1631-1638
    CrossrefPubMedGoogle Scholar
  • 102 Pellino G, Sciaudone G, Caprio F. et al. Hormonal contraceptives and venous thromboembolism: are inflammatory bowel disease patients at increased risk? A retrospective study on a prospective database. Ann Med Surg (Lond) 2015; 4 (04) 462-466
    CrossrefPubMedGoogle Scholar
  • 103 Curtis KM, Tepper NK, Jatlaoui TC. et al. U.S. Medical Eligibility Criteria for Contraceptive Use, 2016. MMWR Recomm Rep 2016; 65 (03) 1-103
    CrossrefPubMedGoogle Scholar
  • 104 Lobo JL, Garcia-Fuertes JA, Trujillo-Santos J. et al; RIETE Investigators. Anticoagulant therapy for venous thromboembolism in patients with inflammatory bowel disease. Eur J Gastroenterol Hepatol 2018; 30 (05) 526-530
    CrossrefPubMedGoogle Scholar
  • 105 Comerota AJ. Pharmacologic and pharmacomechanical thrombolysis for acute deep vein thrombosis: focus on ATTRACTCME . Methodist DeBakey Cardiovasc J 2018; 14 (03) 219-227
    CrossrefPubMedGoogle Scholar
  • 106 Campello E, Spiezia L, Simion C. et al. Direct oral anticoagulants in patients with inherited thrombophilia and venous thromboembolism: a prospective cohort study. J Am Heart Assoc 2020; 9 (23) e018917
    CrossrefPubMedGoogle Scholar
  • 107 Viola A, Chiappetta MF, Scolaro M, Bignoli F, Versace A, Fries W. Direct oral anticoagulants increase the risk of anaemia and hospitalization in IBD patients with active intestinal disease. Dig Liver Dis 2020; 52 (12) 1525-1526
    CrossrefPubMedGoogle Scholar
  • 108 Cai TQ, Wu W, Shin MK. et al. Factor XII full and partial null in rat confers robust antithrombotic efficacy with no bleeding. Blood Coagul Fibrinolysis 2015; 26 (08) 893-902
    CrossrefPubMedGoogle Scholar
  • 109 Larsson M, Rayzman V, Nolte MW. et al. A factor XIIa inhibitory antibody provides thromboprotection in extracorporeal circulation without increasing bleeding risk. Sci Transl Med 2014; 6 (222) 222ra17
    CrossrefPubMedGoogle Scholar
  • 110 Nourse J, Danckwardt S. A novel rationale for targeting FXI: insights from the hemostatic microRNA targetome for emerging anticoagulant strategies. Pharmacol Ther 2021; 218: 107676
    CrossrefPubMedGoogle Scholar
  • 111 Al-Horani RA. Factor XI(a) inhibitors for thrombosis: an updated patent review (2016-present). Expert Opin Ther Pat 2020; 30 (01) 39-55
    CrossrefPubMedGoogle Scholar
  • 112 DeLoughery EP, Olson SR, Puy C, McCarty OJT, Shatzel JJ. The safety and efficacy of novel agents targeting factors XI and XII in early phase human trials. Semin Thromb Hemost 2019; 45 (05) 502-508
    Article in Thieme ConnectPubMedGoogle Scholar