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54 Chapter 5 Pathogenesis and new insights into acute and chronic venous thrombosis
https://t.me/med1917
REFERENCES
★ Review ♦ Guidelines
1. Heit JA, Cohen AT and Anderson FA. Estimated annual number of incident and recurrent, non-fatal and fatal venous thromboembolism (VTE) events in the US. Blood. 2005;106:267a.
2. Mahan CE, Borrego ME, Woersching AL, Federici R, Downey R, Tiongson J, Bieniarz MC, Cavanaugh BJ and Spyro­poulos AC. Venous thromboembolism: Annualised United States models for total, hospital-acquired and preventable costs utilising long-term attack rates. Thromb Haemost. 2012;108:291–302.
3. Yeh CH, Gross PL and Weitz JI. Evolving use of new oral anticoagulants for treatment of venous thromboembolism. Blood. 2014;124:1020–28.
4. Tepper PG, Mardekian J, Masseria C, Phatak H, Kamble S, Abdulsattar Y, Petkun W and Lip GYH. Real-world comparison of bleeding risks among non-valvular atrial brillation patients prescribed apixaban, dabigatran, or riva­roxaban. PLoS One. 2018;13:e0205989.
5. Delis KT, Bountouroglou D and Manseld AO. Venous claudication in iliofemoral thrombosis: Long-term effects on venous hemodynamics, clinical status, and quality of life. Ann Surg. 2004;239:118–26.
6. Palabrica T, Lobb R, Furie BC, Aronovitz M, Benjamin C, Hsu YM, Sajer SA and Furie B. Leukocyte accumulation pro­moting brin deposition is mediated in vivo by P-selectin on adherent platelets. Nature. 1992;359:848–51.
7. Andre P, Hartwell D, Hrachovinova I, Saffaripour S and Wagner DD. Pro-coa­gulant state resulting from high levels of soluble P-selectin in blood. Proc Natl Acad Sci U S A. 2000;97:13835–40.
8. Celi A, Pellegrini G, Lorenzet R, De Blasi A, Ready N, Furie BC and Furie B. P-selectin induces the expression of tissue factor on monocytes. Proc Natl Acad Sci U S A. 1994;91:8767–71.
9. Jamaly S, Basavaraj MG, Starikova I, Olsen R, Braekkan SK and Hansen JB. Elevated plasma levels of P-selectin glycoprotein ligand-1-positive microve­sicles in patients with unprovoked venous thromboembolism. J Thromb Haemost. 2018;16:1546–54.
10. Merten M and Thiagarajan P. P-selectin expression on platelets determines size and stability of platelet aggregates. Circu- lation. 2000;102:1931–6.
11. Myers DD, Hawley AE, Farris DM, Wrobleski SK, Thanaporn P, Schaub RG, Wagner DD, Kumar Aand Wakeeld TW. P-selectin and leukocyte microparticles are associated with venous thrombogene­sis. J Vasc Surg. 2003;38:1075–89.
12. Etulain J, Martinod K, Wong SL, Cifuni SM, Schattner M and Wagner DD. P-selec­tin promotes neutrophil extracellular trap formation in mice. Blood. 2015;126: 242–6.
13. Yago T, Liu Z, Ahamed J and McEver RP. Cooperative PSGL-1 and CXCR2 signaling in neutrophils promotes deep vein thrombosis in mice. Blood. 2018;132:1426–37.
14. Obi AT, Andraska E, Kanthi Y, Luke CE, Eline M, Madathilparambil S, Siahaan TJ, Jaffer FA, Wakeeld TW, Raghaven­dran K and Henke PK. Gram-negative pneumonia alters large-vein cell-adhesion molecule prole and potentiates experi­mental stasis venous thrombosis. J Vasc Res. 2016;53:186–95.
15. Obi AT, Andraska E, Kanthi Y, Kessin­ger CW, Eline M, Luke C, Siahaan TJ, Jaffer FA, Wakeeld TW and Henke PK. Endotoxaemia-augmented murine venous thrombosis is dependent on TLR-4 and ICAM-1, and potentiated by neutropenia. Thromb Haemost. 2017;117:339–48.
16. Panicker SR, Mehta-D’souza P, Zhang N, Klopocki AG, Shao B and McEver RP. Circulating soluble P-selectin must dime­rize to promote inammation and coagu­lation in mice. Blood. 2017;130:181–91.
17. Morikis VA, Hernandez AA, Magnani JL, Sperandio M and Simon SI. Targeting neutrophil adhesive events to address vaso-occlusive crisis in sickle cell patients. Front Immunol. 2021;12:663886.
18. Vandy FC, Stabler C, Eliassen AM, Hawley AE, Guire KE, Myers DD, Henke PK and Wakeeld TW. Soluble P-selectin for the diagnosis of lower extremity deep venous thrombosis. J Vasc Surg Venous Lymphat Disord. 2013;1:117–25.
19. Ramacciotti E, Blackburn S, Hawley AE, Vandy F, Ballard-Lipka N, Stabler C, Baker N, Guire KE, Rectenwald JE, Henke PK, Myers DD, Jr. and Wakeeld TW. Evaluation of soluble P-selectin as a marker for the diagnosis of deep venous thrombosis. Clin Appl Thromb Hemost. 2011;17:425–31.
20. Antonopoulos CN, Sfyroeras GS, Kakisis JD, Moulakakis KG and Liapis CD. The role of soluble P-selectin in the diagnosis of venous thromboembolism. Thromb Res. 2014;133:17–24.
21. Gremmel T, Ay C, Seidinger D, Pabinger I, Panzer S and Koppensteiner R. Soluble p-selectin, D-dimer, and high-sensitivity C-reactive protein after acute deep vein thrombosis of the lower limb. J Vasc Surg. 2011;54:48S–55S.
22. Kyrle PA, Hron G, Eichinger S and Wagner O. Circulating P-selectin and the risk of recurrent venous thromboembo­lism. Thromb Haemost. 2007;97:880–3.
23. Myers DD, Jr., Rectenwald JE, Bedard PW, Kaila N, Shaw GD, Schaub RG, Farris DM, Hawley AE, Wrobleski SK, Henke PK and Wakeeld TW. Decreased venous thrombosis with an oral inhibitor of P selectin. J Vasc Surg. 2005;42:329–36.
24. Wakeeld TW, Strieter RM, Schaub R, Myers DD, Prince MR, Wrobleski SK, Londy FJ, Kadell AM, Brown SL, Henke PK and Greeneld LJ. Venous thrombosis prophylaxis by inammatory inhibition without anticoagulation therapy. J Vasc Surg. 2000;31:309–24.
25. Myers DD, Jr., Schaub R, Wrobleski SK,
26. Myers D, Wrobleski S, Londy F, Fex B,
27. Meier TR, Myers DD, Jr., Wrobleski SK,
28. Myers DD, Jr., Wrobleski SK, Longo C,
29. Ramacciotti E, Myers DD, Jr., Wrobleski
30. Diaz JA, Wrobleski SK, Alvarado CM,
31. Wong DJ, Park DD, Park SS, Haller CA,
32. Evangelista V, Manarini S, Sideri R,
33. Gross PL. Along-half-life, high-af-
34. McEver RP. Selectins: Initiators of
35. Myers D, Jr., Farris D, Hawley A,
Londy FJ, 3rd, Fex BA, Chapman AM, Greeneld LJ and Wakeeld TW. P-se­lectin antagonism causes dose-dependent venous thrombosis inhibition. Thromb Haemost. 2001;85:423–29.
Hawley A, Schaub R, Greeneld L and Wakeeld T. New and effective treatment of experimentally induced venous throm­bosis with anti-inammatory rPSGL-Ig. Thromb Haemost. 2002;87:374–82.
Zajkowski PJ, Hawley AE, Bedard PW, Ballard NE, Londy FJ, Kaila N, Vlasuk GP, Schaub RG and Wakeeld TW. Prophylactic P-selectin inhibition with PSI-421 promotes resolution of venous thrombosis without anticoagulation. Thromb Haemost. 2008;99:343–51.
Bedard PW, Kaila N, Shaw GD, Londy FJ, Rohrer SE, Fex BA, Zajkowski PJ, Meier TR, Hawley AE, Farris DM, Ballard NE, Henke PK, Schaub RG and Wakeeld TW. Resolution of venous thrombo­sis using a novel oral small-molecule inhibitor of P-selectin (PSI-697) without anticoagulation. Thromb Haemost. 2007;97:400–7.
SK, Deatrick KB, Londy FJ, Rectenwald JE, Henke PK, Schaub RG and Wakeeld TW. P-selectin/PSGL-1 inhibitors versus enoxaparin in the resolution of venous thrombosis: Ameta-analysis. Thromb Res. 2010;125:e138–e142.
Hawley AE, Doornbos NK, Lester PA, Lowe SE, Gabriel JE, Roelofs KJ, Henke PK, Schaub RG, Wakeeld TW and Myers DD, Jr. P-selectin inhibition thera­peutically promotes thrombus resolution and prevents vein wall brosis better than enoxaparin and an inhibitor to von Willebrand factor. Arterioscler Thromb Vasc Biol. 2015;35:829–37.
Chen J, Dai E, Liu L, Mandhapati AR, Eradi P, Dhakal B, Wever WJ, Hanes M, Sun L, Cummings RD and Chaikof EL. APSGL-1 glycomimetic reduces throm­bus burden without affecting hemostasis. Blood. 2021;138:1182–93.
Rotondo S, Martelli N, Piccoli A, Totani L, Piccardoni P, Vestweber D, de Gaetano G and Cerletti C. Platelet/polymorpho­nuclear leukocyte interaction: P-selectin triggers protein-tyrosine phosphoryla­tion-dependent CD11b/CD18 adhesion: Role of PSGL-1 as a signaling molecule. Blood. 1999;93:876–85.
nity P-selectin inhibitor. Blood. 2021;138:1096–7.
leucocyte adhesion and signalling at the vascular wall. Cardiovasc Res. 2015;107:331–9.
Wrobleski S, Chapman A, Stoolman L, Knibbs R, Strieter R and Wakeeld T.
References 55
https://t.me/med1917
Selectins inuence thrombosis in a mouse model of experimental deep venous thrombosis. J Surg Res. 2002;108:212–21.
36. Chase SD, Magnani JL and Simon SI. E-se­lectin ligands as mechanosensitive recep­tors on neutrophils in health and disease. Ann Biomed Eng. 2012;40:849–59.
37. Morikis VA, Chase S, Wun T, Chaikof EL, Magnani JL and Simon SI. Selectin catch-bonds mechanotransduce integrin activation and neutrophil arrest on inamed endothelium under shear ow. Blood. 2017;130:2101–110.
38. Jilma B, Marsik C, Kovar F, Wagner OF, Jilma-Stohlawetz P and Endler G. The single nucleotide polymorphism Ser128Arg in the E-selectin gene is associated with enhanced coagulation during human endotoxemia. Blood. 2005;105:2380–83.
39. Jilma B, Kovar FM, Hron G, Endler G, Marsik CL, Eichinger S and Kyrle PA. Homozygosity in the single nucleotide polymorphism Ser128Arg in the E-selec­tin gene associated with recurrent venous thromboembolism. Arch Intern Med. 2006;166:1655–9.
40. Bittar LF, Silva LQD, Orsi FLA, Zapponi KCS, Mazetto BM, Paula EV, Montal­vao SAL and Annichino-Bizzacchi JM. Increased inammation and endothelial markers in patients with late severe post-thrombotic syndrome. PLoS One. 2020;15:e0227150.
41. Dzikowska-Diduch O, Domienik-Ka­rlowicz J, Gorska E, Demkow U, Pruszczyk P and Kostrubiec M. E-selectin and sICAM-1, biomarkers of endo­thelial function, predict recurrence of venous thromboembolism. Thromb Res. 2017;157:173–80.
42. Torres C, Matos R, Morais S, Campos M and Lima M. Soluble endothelial cell molecules and circulating endothelial cells in patients with venous throm­boembolism. Blood Coagul Fibrinolysis. 2017;28:589–95.
43. Mosevoll KA, Lindas R, Wendelbo O, Bruserud O and Reikvam H. Systemic levels of the endothelium-derived soluble adhesion molecules endocan and E-selec­tin in patients with suspected deep vein thrombosis. Springerplus. 2014;3:571.
44. Bucek RA, Reiter M, Quehenberger P, Minar E and Baghestanian M. The role of soluble cell adhesion molecules in patients with suspected deep vein thrombosis. Blood Coagul Fibrinolysis. 2003;14:653–7.
45. Cushman M, Callas PW, Allison MA and Criqui MH. Inammation and peripheral venous disease. The San Diego Population Study. Thromb Haemost. 2014;112:566–72.
46. Oliva A, Rando E, Al Ismail D, De Ange­lis M, Cancelli F, Miele MC, Aronica R, Mauro V, Di Timoteo F, Loffredo L and Mastroianni CM. Role of serum E-Selec­tin as a biomarker of infection severity in coronavirus disease 2019. J Clin Med. 2021;10.
47. Chirinos JA, Heresi GA, Velasquez H, Jy W, Jimenez JJ, Ahn E, Horstman LL, Soriano AO, Zambrano JP and Ahn YS. Elevation of endothelial microparticles,
platelets, and leukocyte activation in patients with venous thromboembolism. J Am Coll Cardiol. 2005;45:1467–71.
48. Toth B, Nikolajek K, Rank A, Nieuwland R, Lohse P, Pihusch V, Friese K and Thaler CJ. Gender-specic and menstrual cycle dependent differences in circulating microparticles. Platelets. 2007;18:515–
21.
49. Culmer DL, Dunbar ML, Hawley AE, Sood S, Sigler RE, Henke PK, Wakeeld TW, Magnani JL and Myers DD, Jr. E-selectin inhibition with GMI-1271 decreases venous thrombosis without profoundly affecting tail vein bleeding in a mouse model. Thromb Haemost. 2017;117:1171–81.
50. Devata S, Angelini DE, Blackburn S, Hawley A, Myers DD, Schaefer JK, Hemmer M, Magnani JL, Thackray HM, Wakeeld TW and Sood SL. Use of GMI­1271, an E-selectin antagonist, in healthy subjects and in 2 patients with calf vein thrombosis. Res Pract Thromb Haemost. 2020;4:193–204.
51. Myers D, Jr., Lester P, Adili R, Hawley A, Durham L, Dunivant V, Reynolds G, Crego K, Zimmerman Z, Sood S, Sigler R, Fogler W, Magnani J, Holinstat M and Wakeeld T. Anew way to treat proximal deep venous thrombosis using E-selectin inhibition. J Vasc Surg Venous Lymphat Disord. 2020;8:268–78.
52. Li J, Zhang F, Liang C, Ye Z, Chen S and Cheng J. The diagnostic efcacy of age-adjusted D-Dimer cutoff value and pretest probability scores for deep venous thrombosis. Clin Appl Thromb Hemost. 2019;25:1076029619826317.
53. Reardon PM, Patrick S, Taljaard M, Thavorn K, Nemnom MJ, Mukarram M, Kim SM, Le Gal G, Huang L and Thiru­ganasambandamoorthy V. Diagnostic accuracy and nancial implications of age-adjusted D-dimer strategies for the diagnosis of deep venous thrombosis in the emergency department. J Emerg Med. 2019;56:469–77.
54. Wells PS, Anderson DR, Rodger M, Forgie M, Kearon C, Dreyer J, Kovacs G, Mitchell M, Lewandowski B and Kovacs MJ. Evaluation of D-dimer in the diagno­sis of suspected deep-vein thrombosis. N Engl J Med. 2003;349:1227–35.
55. Adam SS, Key NS and Greenberg CS. D-di­mer antigen: Current concepts and future prospects. Blood. 2009;113:2878–87.
56. Cesarman-Maus G and Hajjar KA. Molecular mechanisms of brinolysis. Br J Haematol. 2005;129:307–21.
57. Fuchs TA, Brill A, Duerschmied D, Schatzberg D, Monestier M, Myers DD, Jr., Wrobleski SK, Wakeeld TW, Hartwig JH and Wagner DD. Extracellular DNA traps promote thrombosis. Proc Natl Acad Sci U S A. 2010;107:15880–5.
58. Onishi H, Kaniyu K, Iwashita M, Tanaka A, Watanabe T. Fibrin monomer complex in normal pregnant women: a potential thrombotic marker in pregnancy. Ann Clin Biochem 2007; 44(5):449–454.
59. Yoshioka K, Kitajima I, Kabata T, Tani M, Kawahara N, Murakami H, Demura A, Tsubokawa T, Tomita K. Venous thromboembolism after spine surgery:
changes of the brin monomer complex and D-dimer level during the periope­rative period. J Neurosurg Spine 2010; 13:594–9.
60. Mitani G, Takagaki T, Hamahashi K, Serigano K, Nakamura Y, Sato Y, Mochida J. Associations between venous thromboembolism onset, D-dimer, and soluble brin monomer complex after total knee arthroplasty. J Orthop Surg Res 2015;10:172.
61. Bittar LF, Paula EV, Montalvao SA, Mello TB, Annichino-Bizzacchi JM. Severe post-thrombotic syndrome is associated with higher levels of factor VIII. Clin Appl Thromb Hemost 2013;19:570–3.
62. Roberts LN, Patel RK, Goss DE, Paradzai C, Bonner L, Arya R. Relationship between development of post-thrombotic syndrome and serial ultrasound, D-dimer, and factor VIII activity after a rst deep venous thrombosis. J Vasc Surg Venous Lymphat Disord 2016; 4(1):28–35.
63. Bittar LF, Mazetto BdM, Orsi FLA, Collela MP, De Paula EV, Annichino-Biz­zacchi JM. Long-term increased factor VIII levels are associated to interleukin-6 levels but not to post-thrombotic syndrome in patients with deep venous thrombosis. Thromb Res 2015; 135(3): 497–501.
64. Audu CO, Gordon AE, Obi AT, Wakeeld TW and Henke PK. Inammatory bio­markers in deep venous thrombosis orga­nization, resolution, and post-thrombotic syndrome. J Vasc Surg Venous Lymphat Disord. 2020;8:299–305.
65. Rabinovich A, Cohen JM, Cushman M, Wells PS, Rodger MA, Kovacs MJ, Anderson DR, Tagalakis V, Lazo-Langner A, Solymoss S, Miron MJ, Yeo E, Smith R, Schulman S, Kassis J, Kearon C, Cha­gnon I, Wong T, Demers C, Hanmiah R, Kaatz S, Selby R, Rathbun S, Desmarais S, Opatrny L, Ortel TL, Ginsberg JS and Kahn SR. Inammation markers and their trajectories after deep vein throm­bosis in relation to risk of post-throm­botic syndrome. J Thromb Haemost. 2015;13:398–408.
66. Shbaklo H, Holcroft CA and Kahn SR. Levels of inammatory markers and the development of the post-thrombotic syndrome. Thromb Haemost. 2009;101: 505–12.
67. van Aken BE, den Heijer M, Bos GM, van Deventer SJ and Reitsma PH. Recur­rent venous thrombosis and markers of inammation. Thromb Haemost. 2000;83:536–9.
68. Downing LJ, Strieter RM, Kadell AM, et al. IL-10 regulates thrombus-induced vein wall inammation and thrombosis. J Immunol. 1998;161:1471–6.
69. Proctor MC, Sullivan V, Zajkowski P, Wolk SW, Pomerantz RA, Wake­eld TW, Greeneld LJ. A role for interleukin-10 in the assessment of venous thromboembolism risk in injured patients. J Trauma 2006; 60(1):147–51.
70. Elmoamly S, Mattar M, Yacoub MF and Af A. Can Biomarkers of coagulation, platelet activation, and inammation pre­dict venous thromboembolism in patients
5
56 Chapter 5 Pathogenesis and new insights into acute and chronic venous thrombosis
https://t.me/med1917
with haematological malignancies? Acta Haematol. 2019;141:245–53.
71. Marchena Yglesias PJ, Nieto Rodriguez JA, Serrano Martinez S, Belinchon Moya O, Cortes Carmona A, Diaz de Tuesta A, Bruscas Alijarde MJ and Ruiz Ribo MD. [Acute-phase reactants and markers of inammation in venous thromboembolic disease: Correlation with clinical and evolution parameters]. An Med Interna. 2006;23:105–10.
72. Luxembourg B, Schmitt J, Humpich M, Glowatzki M, Dressler D, Seifried E and Lindhoff-Last E. Cardiovascular risk fac­tors in idiopathic compared to risk-asso­ciated venous thromboembolism: Afocus on brinogen, factor VIII, and high-sen­sitivity C-reactive protein (hs-CRP). Thromb Haemost. 2009;102:668–75.
73. Wang TF, Wong CA, Milligan PE, Thoelke MS, Woeltje KF and Gage BF. Risk factors for inpatient venous throm­boembolism despite thromboprophylaxis. Thromb Res. 2014;133:25–29.
74. Kushnir M, Cohen HW and Billett HH. Persistent neutrophilia is a marker for an increased risk of venous thrombosis. J Thromb Thrombolysis. 2016;42:545–51.
75. Liu Y, Meng X, Feng J, Zhou X and Zhu H. Hypereosinophilia with concurrent venous thromboembolism: Clinical features, potential risk factors, and short­term outcomes in a chinese cohort. Sci Rep. 2020;10:8359.
76. Demelo-Rodriguez P, Galeano-Valle F, Marcelo-Ayala A, Fernandez-Carracedo E, Cuenca-Zarzuela A, Gomez-Morales M, Alvarez-Sala-Walther LA, Bel­lon-Cano JM and Del-Toro-Cervera J. C-reactive protein level predicts 30-day mortality and bleeding in patients with venous thromboembolism: Aprospective single-center study. Med Clin (Barc). 2020;155:51–6.
77. Krieger E, van Der Loo B, Amann-Vesti BR, Rousson V and Koppensteiner R. C-reactive protein and red cell aggrega­tion correlate with late venous function after acute deep venous thrombosis. J Vasc Surg. 2004;40:644–9.
78. Abul Y, Karakurt S, Ozben B, Toprak Aand Celikel T. C-reactive protein in acute pulmonary embolism. J Investig Med. 2011;59:8–14.
79. Brill A, Fuchs TA, Chauhan AK, Yang JJ, De Meyer SF, Kollnberger M, Wakeeld TW, Lammle B, Massberg S and Wagner DD. von Willebrand factor-mediated platelet adhesion is critical for deep vein thrombosis in mouse models. Blood. 2011;117:1400–7.
80. Koster T, Blann AD, Briet E, Vanden­broucke JP and Rosendaal FR. Role of clotting factor VIII in effect of von Wille­brand factor on occurrence of deep-vein thrombosis. Lancet. 1995;345:152–5.
81. Edwardson MA, Zhong X, Fiandaca MS, Federoff HJ, Cheema AK and Dromerick AW. Plasma microRNA markers of upper limb recovery following human stroke. Sci Rep. 2018;8:12558.
82. Timp JF, Lijfering WM, Flinterman LE, van Hylckama Vlieg A, le Cessie S, Rosendaal FR and Cannegieter SC. Predictive value of factor VIII levels for
recurrent venous thrombosis: Results from the MEGA follow-up study. J Thromb Haemost. 2015;13:1823–32.
83. Wagner DD and Frenette PS. The vessel wall and its interactions. Blood. 2008;111:5271–81.
84. Mohri H, Fujimura Y, Shima M, Yoshioka A, Houghten RA, Ruggeri ZM and Zimmerman TS. Structure of the von Willebrand factor domain interac­ting with glycoprotein Ib. J Biol Chem. 1988;263:17901–4.
85. Nuyttens BP, Thijs T, Deckmyn H and Broos K. Platelet adhesion to collagen. Thromb Res. 2011;127(Suppl 2):S26–29.
86. Zhang X, Halvorsen K, Zhang CZ, Wong WP and Springer TA. Mechanoenzyma­tic cleavage of the ultralarge vascular protein von Willebrand factor. Science. 2009;324:1330–4.
87. Cho JS and Ouriel K. Differential throm­bogenicity of artery and vein: The role of von Willebrand factor. Ann Vasc Surg. 1995;9:60–70.
88. Chauhan AK, Kisucka J, Lamb CB, Berg­meier W and Wagner DD. von Willebrand factor and factor VIII are independently required to form stable occlusive thrombi in injured veins. Blood. 2007;109: 2424–9.
89. Michels A, Dwyer CN, Mewburn J, Nes­bitt K, Kawecki C, Lenting P, Swystun LL and Lillicrap D. von Willebrand factor is a critical mediator of deep vein throm­bosis in a mouse model of diet-induced obesity. Arterioscler Thromb Vasc Biol. 2020;40:2860–74.
90. Michels A, Lillicrap D and Yacob M. Role of von Willebrand factor in venous thromboembolic disease. JVS Vasc Sci. 2022;3:17–29.
91. Mann KG, van’t Veer C, Cawthern K and Butenas S. The role of the tissue factor pathway in initiation of coagulation. Blood Coagul Fibrinolysis. 1998;9(Suppl
1):S3–S7.
92. Nemerson Y. Tissue factor and hemosta­sis. Blood. 1988;71:1–8.
93. Drake TA, Morrissey JH and Edgington TS. Selective cellular expression of tissue factor in human tissues. Implications for disorders of hemostasis and thrombosis. Am J Pathol. 1989;134:1087–97.
94. Parry GC, Erlich JH, Carmeliet P, Luther T and Mackman N. Low levels of tissue factor are compatible with development and hemostasis in mice. J Clin Invest. 1998;101:560–9.
95. Osterud B and Bjorklid E. Sources of tissue factor. Semin Thromb Hemost. 2006;32:11–23.
96. Steffel J, Luscher TF and Tanner FC. Tissue factor in cardiovascular diseases: Molecular mechanisms and clinical impli­cations. Circulation. 2006;113:722–31.
97. Khorana AA, Francis CW, Menzies KE, Wang JG, Hyrien O, Hathcock J, Mackman N and Taubman MB. Plasma tissue factor may be predictive of venous thromboembolism in pancreatic cancer. J Thromb Haemost. 2008;6: 1983–5.
98. Zhou J, May L, Liao P, Gross PL and Weitz JI. Inferior vena cava ligation rapidly induces tissue factor expression
and venous thrombosis in rats. Arterios- cler Thromb Vasc Biol. 2009;29:863–9.
99. von Bruhl ML, Stark K, Steinhart A, Chandraratne S, Konrad I, Lorenz M, Khandoga A, Tirniceriu A, Coletti R, Kollnberger M, Byrne RA, Laitinen I, Walch A, Brill A, Pfeiler S, Manukyan D, Braun S, Lange P, Riegger J, Ware J, Eckart A, Haidari S, Rudelius M, Schulz C, Echtler K, Brinkmann V, Schwaiger M, Preissner KT, Wagner DD, Mack­man N, Engelmann B and Massberg S. Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo. J Exp Med. 2012;209:819–35.
100. Day SM, Reeve JL, Pedersen B, Farris DM, Myers DD, Im M, Wakeeld TW, Mackman N and Fay WP. Macrovascu­lar thrombosis is driven by tissue factor derived primarily from the blood vessel wall. Blood. 2005;105:192–8.
101. Hassouna HI. Laboratory evaluation of hemostatic disorders. Hematol Oncol Clin North Am. 1993;7:1161–249.
102. Krishnamurti C, Tang DB, Barr CF and Alving BM. Plasminogen activator and plasminogen activator inhibitor activities in a reference population. Am J Clin Pathol. 1988;89:747–52.
103. Konkle BA, Schick PK, He X, Liu RJ and Mazur EM. Plasminogen activator inhibi­tor-1 mRNA is expressed in platelets and megakaryocytes and the megakaryoblas­tic cell line CHRF-288. Arterioscler Thromb. 1993;13:669–74.
104. Akhter MS, Biswas A, Ranjan R, Meena A, Yadav BK, Sharma Aand Saxena R. Plasminogen activator inhibitor-1 (PAI-1) gene 4G/5G promoter polymorphism is seen in higher frequency in the Indian patients with deep vein thrombosis. Clin Appl Thromb Hemost. 2010;16:184–8.
105. Sartori MT, Danesin C, Saggiorato G, Tormene D, Simioni P, Spiezia L, Patrassi GM and Girolami A. The PAI-1 gene 4G/5G polymorphism and deep vein thrombosis in patients with inherited thrombophilia. Clin Appl Thromb Hemost. 2003;9:299–307.
106. Tang J, Zhu W, Mei X and Zhang Z. Plasminogen activator inhibitor-1: Arisk factor for deep vein thrombosis after total hip arthroplasty. J Orthop Surg Res. 2018;13:8.
107. Obi AT, Diaz JA, Ballard-Lipka NL, Roelofs KJ, Farris DM, Lawrence DA, Wakeeld TW and Henke PK. Plas­minogen activator-1 overexpression decreases experimental postthrombotic vein wall brosis by a non-vitronectin-de­pendent mechanism. J Thromb Haemost. 2014;12:1353–63.
108. Baldwin JF, Sood V, Eline MA, Luke CE, Dewyer NA, Diaz JA, Myers DD, Wakeeld T and Henke PK. The role of urokinase plasminogen activator and plasmin activator inhibitor-1 on vein wall remodeling in experimental deep vein thrombosis. J Vasc Surg. 2012;56: 1089–97.
109. Baxi S, Crandall DL, Meier TR, Wrobleski S, Hawley A, Farris D, Elok­dah H, Sigler R, Schaub RG, Wakeeld T and Myers D. Dose-dependent throm-
References 57
https://t.me/med1917
bus resolution due to oral plaminogen activator inhibitor (PAI)-1 inhibition with tiplaxtinin in a rat stenosis model of venous thrombosis. Thromb Haemost. 2008;99:749–58.
110. Singh I, Burnand KG, Collins M, Luttun A, Collen D, Boelhouwer B and Smith A. Failure of thrombus to resolve in urokinase-type plasminogen activator gene-knockout mice: Rescue by normal bone marrow-derived cells. Circulation. 2003;107:869–75.
111. Moir E, Booth NA, Bennett B and Rob­bie LA. Polymorphonuclear leucocytes mediate endogenous thrombus lysis via a u-PA-dependent mechanism. Br J Haema- tol. 2001;113:72–80.
112. Zhu YK, MD, Liu X, MD, Wang H, MD, Kohyama T, MD, Wen F-Q, MD, PhD, Skold CM, MD, PhD and Rennard SI, MD. Interactions between monocytes and smooth-muscle cells can lead to extracel­lular matrix degradation. J Allergy Clin Immunol. 2001;108:989–96.
113. Diaz JA, Hawley AE, Alvarado CM, Berguer AM, Baker NK, Wrobleski SK, Wakeeld TW, Lucchesi BR and Myers DD, Jr. Thrombogenesis with continuous blood ow in the inferior vena cava. Anovel mouse model. Thromb Haemost. 2010;104:366–75.
114. Diaz JA, Wrobleski SK, Hawley AE, Lucchesi BR, Wakeeld TW and Myers DD, Jr. Electrolytic inferior vena cava model (EIM) of venous thrombosis. J Vis Exp. 2011:e2737.
115. Diaz JA, Alvarado CM, Wrobleski SK, Slack DW, Hawley AE, Farris DM, Henke PK, Wakeeld TW and Myers DD, Jr. The electrolytic inferior vena cava model (EIM) to study thrombogenesis and thrombus resolution with continuous blood ow in the mouse. Thromb Hae- most. 2013;109:1158–69.
★116. Diaz JA, Obi AT, Myers DD, Jr.,
Wrobleski SK, Henke PK, Mackman N and Wakeeld TW. Critical review of mouse models of venous throm­bosis. Arterioscler Thromb Vasc Biol. 2012;32:556–62.
117. Varma MR, Varga AJ, Knipp BS, Sukheepod P, Upchurch GR, Kunkel SL, Wakeeld TW and Henke PK. Neutrope­nia impairs venous thrombosis resolution in the rat. J Vasc Surg. 2003;38:1090–8.
118. Stewart GJ. Neutrophils and deep venous thrombosis. Haemostasis. 1993;23(Suppl
1):127–40.
119. Humphries J, McGuinness CL, Smith A, Waltham M, Poston R and Burnand KG. Monocyte chemotactic protein-1 (MCP-1) accelerates the organization and resolution of venous thrombi. J Vasc Surg. 1999;30:894–9.
120. Henke PK, Pearce CG, Moaveni DM, Moore AJ, Lynch EM, Longo C, Varma M, Dewyer NA, Deatrick KB, Upchurch GR, Wakeeld TW, Hogaboam C, and Kunkel SL. Targeted deletion of CCR2 impairs deep vein thombosis resolu­tion in a mouse model. J Immunol. 2006;177:3388–97.
121. Ali T, Humphries J, Burnand K, Sawyer B, Bursill C, Channon K, Greaves D, Rollins B, Charo IF and Smith A. Mono-
cyte recruitment in venous thrombus resolution. J Vasc Surg. 2006;43: 601–8.
122. Nathan C and Ding A. Nonresolving Inammation. Cell. 2010;140:871–82.
123. Fuchs TA, Brill A, Duerschmied D, Schatzberg D, Monestier M, Myers DD, Wrobleski SK, Wakeeld TW, Hartwig JH and Wagner DD. Extracellular DNA traps promote thrombosis. Proc Natl Acad Sci U.S.A. 2010;107:15880–85.
124. Stark K, Philippi V, Stockhausen S, Busse J, Antonelli A, Miller M, Schubert I, Hoseinpour P, Chandraratne S, Von Bruhl ML, Gaertner F, Lorenz M, Agresti A, Coletti R, Antoine DJ, Heermann R, Jung K, Reese S, Laitinen I, Schwaiger M, Walch A, Sperandio M, Nawroth PP, Reinhardt C, Jäckel S, Bianchi ME and Massberg S. Disulde HMGB1 derived from platelets coordinates venous throm­bosis in mice. Blood. 2016;128:2435–49.
125. Chang CF, Goods BA, Askenase MH, Hammond MD, Renfroe SC, Steinsch­neider AF, Landreneau MJ, Ai Y, Beatty HE, Da Costa LHA, Mack M, Sheth KN, Greer DM, Huttner A, Coman D, Hyder F, Ghosh S, Rothlin CV, Christopher Love J and Sansing LH. Erythrocyte efferocy­tosis modulates macrophages towards recovery after intracerebral hemorrhage. J. Clin. Investig. 2018;128:607–24.
126. Saha P, Andia ME, Modarai B, Blume U, Humphries J, Patel AS, Phinikaridou A, Evans CE, Mattock K, Grover SP, Ahmad A, Lyons OT, Attia RQ, Renne T, Premaratne S, Wiethoff AJ, Botnar RM, Schaeffter T, Waltham M and Smith A. Magnetic resonance T1 relaxation time of venous thrombus is determined by iron processing and predicts susceptibility to lysis. Circulation. 2013;128: 729–36.
127. Singh I, Burnand KG, Collins M, Luttun A, Collen D, Boelhouwer B and Smith A. Failure of thrombus to resolve in urokinase-type plasminogen activator gene-knockout mice: Rescue by normal bone marrow-derived cells. Circulation. 2003;107:869–75.
128. Meznarich J, Malchodi L, Helterline D, Ramsey SA, Bertko K, Plummer T, Plawman A, Gold E and Stempien-Otero A. Urokinase plasminogen activator induces Pro-Fibrotic/M2 phenotype in murine cardiac macrophages. PLoS One. 2013;8:e57837.
129. Fleetwood AJ, Achuthan A, Schultz H, Nansen A, Almholt K, Usher P and Hamilton JA. Urokinase plasminogen activator is a central regulator of macro­phage three-dimensional invasion, matrix degradation, and adhesion. J Immunol. 2014;192:3540–7.
130. Jager NA, Wallis de Vries BM, Hille­brands JL, Harlaar NJ, Tio RA, Slart RHJA, van Dam GM, Boersma HH, Zeebregts CJ and Westra J. Distribution of matrix metalloproteinases in human atherosclerotic carotid plaques and their production by smooth muscle cells and macrophage subsets. Mol Imaging Biol. 2016;18:283–91.
131. Henke PK, Varga A, De S, Deatrick CB, Eliason J, Arenberg DA, Sukheepod P,
Thanaporn P, Kunkel SL, Upchurch GR and Wakeeld TW. Deep vein thrombosis resolution is modulated by monocyte CXCR2-mediated activity in a mouse model. Arterioscler Thromb Vasc Biol. 2004;24:1130–7.
132. Modarai B, Guiver Burnand K, Hum­phries J, Waltham M and Smith A. The role of neovascularisation in the resolution of venous thrombus. J Thromb Haemost. 2005;93:801–9.
133. Henke PK, Pearce CG, Moaveni DM, Moore AJ, Lynch EM, Longo C, Varma M, Dewyer NA, Deatrick KB, Upchurch GR, Wakeeld TW, Hogaboam C and Kunkel SL. Targeted deletion of CCR2 impairs deep vein thombosis resolu­tion in a mouse model. J Immunol. 2006;177:3388–97.
134. Varma MR, Moaveni DM, Dewyer NA, Varga AJ, Deatrick KB, Kunkel SL, Upchurch GR, Wakeeld TW and Henke PK. Deep vein thrombosis resolution is not accelerated with increased neovascu­larization. J Vasc Surg. 2004;40: 536–42.
135. Alias S, Redwan B, Panzenböck A, Winter MP, Schubert U, Voswinckel R, Frey MK, Jakowitsch J, Alimohammadi A, Hobohm L, Mangold A, Bergmeis­ter H, Sibilia M, Wagner EF, Mayer E, Klepetko W, Hölzenbein TJ, Preissner KT and Lang IM. Defective angiogenesis delays thrombus resolution: Apotential pathogenetic mechanism underlying chronic thromboembolic pulmonary hypertension. Arterioscler Thromb Vasc Biol. 2014;34:810–9.
136. Comerota AJ, Oostra C, Fayad Z, Gun­ning W, Henke P, Luke C, Lynn Aand Lurie F. Ahistological and functional description of the tissue causing chronic postthrombotic venous obstruction. Thromb Res. 2015;135:882–7.
137. Ali T, Humphries J, Burnand K, Sawyer B, Bursill C, Channon K, Greaves D, Rollins B, Charo IF and Smith A. Mono­cyte recruitment in venous thrombus resolution. J Vasc Surg. 2006;43:601–8.
138. Nosaka M, Ishida Y, Kimura A, Kuni­naka Y, Inui M, Mukaida N and Kondo T. Absence of IFN-γ accelerates thrombus resolution through enhanced MMP-9 and VEGF expression in mice. J Clin Invest. 2011;121:2911–20.
139. Kimball AS, Obi AT, Luke CE, Dowling AR, Cai Q, Adili R, Jankowski H, Schaller M, Holinstadt M, Jaffer FA, Kunkel SL, Gallagher KA and Henke PK. Ly6CLo Monocyte/Macrophages are essential for thrombus resolution in a murine model of venous thrombosis. J Thromb Haemost. 2020; 120(2): 289–99.
140. Shahneh F, Christian Probst H, Wies­mann SC, N AG, Ruf W, Steinbrink K, Raker VK and Becker C. Inammatory monocyte counts determine venous blood clot formation and resolution. Arterioscler Thromb Vasc Biol. 2022;42:145–55.
141. Cherpokova D, Jouvene CC, Libreros S, DeRoo EP, Chu L, De La Rosa X, Norris PC, Wagner DD and Serhan CN. Resolvin D4 attenuates the severity of
5
58 Chapter 5 Pathogenesis and new insights into acute and chronic venous thrombosis
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pathological thrombosis in mice. Blood. 2019;134:1458–8.
142. Henke PK, Mitsuya M, Luke CE, Eline MA, Baldwin JF, Deatrick KB, Diaz JA, Sood V, Upchurch GR, Wakeeld TW, Hogaboam C and Kunkel SL. Toll-like receptor 9 signaling is critical for early experimental deep vein thrombosis reso­lution. Arterioscler Thromb Vasc Biol. 2011;31:43–9.
143. Varma MR, Moaveni DM, Dewyer NA, Varga AJ, Deatrick KB, Kunkel SL, Upchurch GR, Jr., Wakeeld TW and Henke PK. Deep vein thrombo­sis resolution is not accelerated with increased neovascularization. J Vasc Surg. 2004;40:536–42.
144. Waltham M, Burnand KG, Collins M, McGuinness CL, Singh Iand Smith A. Vascular endothelial growth factor enhances venous thrombus recanalisation and organisation. Thromb Haemost. 2003;89:169–76.
145. Wakeeld TW, Strieter RM, Wilke CA, Kadell AM, Wrobleski SK, Burdick MD, Schmidt R, Kunkel SL and Greeneld LJ. Venous thrombosis-associated inamma­tion and attenuation with neutralizing antibodies to cytokines and adhesion molecules. Arterioscler Thromb Vasc Biol. 1995;15:258–68.
146. Du T and Tan Z. Relationship between deep venous thrombosis and inamma­tory cytokines in postoperative patients with malignant abdominal tumors. Braz J Med Biol. 2014;47:1003–7.
147. Rabinovich A, Cohen JM, Cushman M, Wells PS, Rodger MA, Kovacs MJ, Anderson DR, Tagalakis V, Lazo-Langner A, Solymoss S, Miron MJ, Yeo E, Smith R, Schulman S, Kassis J, Kearon C, Cha­gnon I, Wong T, Demers C, Hanmiah R, Kaatz S, Selby R, Rathbun S, Desmarais S, Opatrny L, Ortel TL, Ginsberg JS and Kahn SR. Inammation markers and their trajectories after deep vein throm­bosis in relation to risk of post-throm­botic syndrome. J Thromb Haemost. 2015;13:398–408.
148. Zhang Y, Zhang Z, Wei R, Miao X, Sun S, Liang G, Chu C, Zhao L, Zhu X, Guo Q, Wang B and Li X. IL (Interleukin)-6 contributes to deep vein thrombosis and is negatively regulated by miR­338–5p. Arterioscler Thromb Vasc Biol. 2020;40:323–34.
149. Nosaka M, Ishida Y, Kimura A, Kuni­naka Y, Taruya A, Ozaki M, Tanaka A, Mukaida N and Kondo T. Crucial involvement of IL-6 in thrombus resolution in mice via macrophage recruitment and the induction of proteolytic enzymes. Front Immunol. 2019;10:3150.
150. Scheller J, Chalaris A, Schmidt-Arras D and Rose-John S. The pro- and anti-in­ammatory properties of the cytokine interleukin-6. Biochim Biophys Acta, Mol CellRes. 2011;1813:878–88.
♦151. Murray PJ, Allen JE, Biswas SK, Fisher
EA, Gilroy DW, Goerdt S, Gordon S, Hamilton JA, Ivashkiv LB, Lawrence T, Locati M, Mantovani A, Martinez FO, Mege JL, Mosser DM, Natoli G, Saeij JP, Schultze JL, Shirey KA, Sica A, Suttles J,
Udalova I, VanGinderachter JA, Vogel SN and Wynn TA. Macrophage activation and polarization: Nomenclature and experimental guidelines. Immunity. 2014;41:14–20.
152. Casella G, Garzetti L, Gatta AT, Finardi A, Maiorino C, Rufni F, Martino G, Muzio L and Furlan R. IL4 induces IL6-producing M2 macrophages asso­ciated to inhibition of neuroinammation in vitro and in vivo. J Neuroinamma- tion. 2016:13:139.
153. Metz AK, Luke CE, Dowling Aand Henke PK. Acute experimental venous thrombosis impairs venous relaxation but not contraction. J Vasc Surg 2020; 71(3):1006–1012.e1
154. Wojcik BM, Wrobleski SK, Hawley AE, Wakeeld TW, Myers DD and Diaz JA. Interleukin-6: Apotential target for post-thrombotic syndrome. J Vasc Surg. 2011;25:229–39.
155. Deatrick KB, Eliason JL, Lynch EM, Moore AJ, Dewyer NA, Varma MR, Pearce CG, Upchurch GR, Wakeeld TW and Henke PK. Vein wall remode­ling after deep vein thrombosis involves matrix metalloproteinases and late brosis in a mouse model. J Vasc Surg. 2005;42:140–8.
156. Myers DD, Jr., Henke PK, Wrobleski SK, Hawley AE, Farris DM, Chapman AM, Knipp BS, Thanaporn P, Schaub RG, Greeneld LJ and Wakeeld TW. P-selec­tin inhibition enhances thrombus resolu­tion and decreases vein wall brosis in a rat model. J Vasc Surg. 2002;36:928–38.
157. Thanaporn P, Myers DD, Wrobleski SK, Hawley AE, Farris DM, Wakeeld TW and Henke PK. P-selectin inhibi­tion decreases post-thrombotic vein wall brosis in a rat model. Surgery. 2003;134:365–71.
158. Deatrick KB, Luke CE, Eline MA, Sood V, Baldwin J, Upchurch GR, Jr., Jaffer FA, Wakeeld TW and Henke PK. The effect of matrix metalloproteinase 2 and matrix metalloproteinase 2/9 deletion in experimental post-thrombotic vein wall remodeling. J Vasc Surg. 2013;58:1375– 84 e2.
159. Obi AT, Diaz JA, Ballard-Lipka NL, Roelofs KJ, Farris DM, Lawrence DA, Henke PK and Wakeeld TW. Low-mo­lecular-weight heparin modulates vein wall brotic response in a plasminogen activator inhibitor 1-dependent manner. J Vasc Surg Venous Lymphat Disord. 2014;2:441–50 e1.
160. Modarai B, Burnand KG, Sawyer B and Smith A. Endothelial progenitor cells are recruited into resolving venous thrombi. Circulation. 2005;111:2645–53.
161. Hashimoto N, Jin H, Liu T, Chensue SW and Phan SH. Bone marrow-derived progenitor cells in pulmonary brosis. J Clin Invest. 2004;113:243–52.
162. Laser A, Eline M, Luke C, Slack D, Shah A, Sood V, Deatrick B, McEvoy B, Ostra C, Comerota A, Kunkel S, Hogaboam C and Henke PK. Deletion of cysteine­cysteine receptor 7 promotes brotic injury in experimental post-thrombo­tic vein wall remodeling. Arterioscler Thromb Vasc Biol. 2014;34:377–85.
163. Stein-Merlob AF, Kessinger CW, Erdem SS, Zelada H, Hilderbrand SA, Lin CP, Tearney GJ, Jaff MR, Reed GL, Henke PK, McCarthy JR and Jaffer FA. Blood accessibility to brin in venous throm­bosis is thrombus age-dependent and predicts brinolytic efcacy: An in Vivo brin molecular imaging study. Theranos- tics. 2015;5:1317–27.
164. Li W, Kessinger CW, Orii M, Lee H, Wang L, Weinberg I, Jaff MR, Reed GL, Libby P, Tawakol A, Henke PK, and Jaffer FA. Time-restricted salutary effects of blood ow restoration on venous thrombosis and vein wall injury in mouse and human subjects. Circulation. 2021;143:1224–38.
165. Li WD and Li XQ. Endothelial progeni­tor cells accelerate the resolution of deep vein thrombosis. Vascular Pharmacology. 2016;83:10–16.
166. Hobohm L, Kolmel S, Niemann C, Kum­pers P, Krieg VJ, Bochenek ML, Lukasz AH, Reiss Y, Plate KH, Liebetrau C, Wie­denroth CB, Guth S, Munzel T, Hasenfuss G, Wenzel P, Mayer E, Konstantinides SV, Schafer K and Lankeit M. Role of angio­poietin-2 in venous thrombus resolution and chronic thromboembolic disease. Eur Respir J. 2021; 58(6):p2004196.
167. Moaveni DK, Lynch EM, Luke C, Sood V, Upchurch GR, Wakeeld TW and Henke PK. Vein wall re-endothelializa­tion after deep vein thrombosis is impro­ved with low-molecular-weight heparin. J Vasc Surg. 2008;47:616–24.
168. Kong L, Hu N, Du X, Wang W, Chen H, Li W, Wei S, Zhuang H, Li X and Li C. Upregulation of miR-483–3p contributes to endothelial progenitor cells dysfunc­tion in deep vein thrombosis patients via SRF. J Transl Med. 2016; 14:23.
169. Sun LL, Xiao L, Du XL, Hong L, Li CL, Jiao J, Li WD and Li XQ. MiR-205 promotes endothelial progenitor cell angiogenesis and deep vein thrombosis recanalization and resolution by targe­ting PTEN to regulate Akt/autophagy pathway and MMP2 expression. J Cell Mol Med. 2019;23:8493–504.
170. Du X, Hong L, Sun L, Sang H, Qian A, Li W, Zhuang H, Liang H, Song D, Li C, Wang W and Li X. miR-21 induces endothelial progenitor cells proliferation and angiogenesis via targeting FASLG and is a potential prognostic marker in deep venous thrombosis. J Transl Med. 2019;17:270.
171. Wang W, Zhu X, Du X, Xu A, Yuan X, Zhan Y, Liu M and Wang S. MiR-150 promotes angiogensis and proliferation of endothelial progenitor cells in deep venous thrombosis by targeting SRCIN1. Microvasc Res. 2019;123:35–41.
172. Glynn RJ, Danielson E, Fonseca FA, Genest J, Gotto AM, Jr., Kastelein JJ, Koenig W, Libby P, Lorenzatti AJ, Macfadyen JG, Nordestgaard BG, Shepherd J, Willerson JT and Ridker PM. Arandomized trial of rosuvastatin in the prevention of venous thromboembolism. N Eng J Med 2009; 360:1851–61.
173. Patterson KA, Zhang X, Wrobleski SK, Hawley AE, Lawrence DA, Wakeeld TW, Myers DD and Diaz JA.
References 59
https://t.me/med1917
Rosuvastatin reduced deep vein thrombosis in ApoE gene deleted mice with hyperlipidemia through non-lipid lowering effects. Thromb Res. 2013;131:268–76.
174. Kessinger CW, Kim JW, Henke PK, Thompson B, McCarthy JR, Hara T, Sillesen M, Margey RJ, Libby P, Weissleder R, Lin CP and Jaffer FA. Statins improve the resolution of established murine venous thrombosis: Reductions in thrombus burden and vein wall scarring. PLoS One. 2015;10:e0116621.
175. Liu FT, Hsu DK, Zuberi RI, Hill PN, Shenhav A, Kuwabara Iand Chen SS. Modulation of functional properties of galectin-3 by monoclonal antibodies bin­ding to the non-lectin domains. Biochem. 1996;35:6073–9.
176. Cao Z, Said N, Amin S, Wu HK, Bruce A, Garate M, Hsu DK, Kuwabara I, Liu FT and Panjwani N. Galectins-3 and -7, but not galectin-1, play a role in re-epithe­lialization of wounds. J Biol Chem. 2002;277:42299–305.
177. Iacobini C, Amadio L, Oddi G, Ricci C, Barsotti P, Missori S, Sorcini M, Di Mario U, Pricci F and Pugliese G. Role
of galectin-3 in diabetic nephropathy. J Am Soc Nephrol. 2003;14:S264–70.
178. Nachtigal M, Ghaffar Aand Mayer EP. Galectin-3 gene inactivation reduces atherosclerotic lesions and adventitial inammation in ApoE-decient mice. Am J Pathol. 2008;172:247–55.
179. O’Driscoll L, Linehan R, Liang YH, Joyce H, Oglesby Iand Clynes M. Galectin-3 expression alters adhesion, motility and invasion in a lung cell line (DLKP), in vitro. Anticancer Res. 2002;22:3117–25.
180. Zuberi RI, Hsu DK, Kalayci O, Chen HY, Sheldon HK, Yu L, Apgar JR, Kawakami T, Lilly CM and Liu FT. Critical role for galectin-3 in airway inammation and bronchial hyperresponsiveness in a murine model of asthma. Am J Pathol. 2004;165:2045–53.
181. Sato S, Ouellet N, Pelletier I, Simard M, Rancourt Aand Bergeron MG. Role of galectin-3 as an adhesion molecule for neutrophil extravasation during streptococcal pneumonia. J Immunol. 2002;168:1813–22.
182. Rabinovich GA, Liu FT, Hirashima M and Anderson A. An emerging role for galectins in tuning the immune response: Lessons
from experimental models of inammatory disease, autoimmunity and cancer. Scand J Immunol. 2007;66:143–58.
183. Yang RY, Rabinovich GA and Liu FT. Galectins: Structure, function and thera­peutic potential. Expert Rev Mol Med. 2008;10:e17.
184. Ramacciotti E, Hawley AE, Wrobleski SK, Myers DD, Jr., Strahler JR, Andrews PC, Guire KE, Henke PK and Wakeeld TW. Proteomics of microparticles after deep venous thrombosis. Thromb Res. 2010;125:e269–e274.
185. Iurisci I, Cumashi A, Sherman AA, Tsvetkov YE, Tinari N, Piccolo E, D’Egidio M, Adamo V, Natoli C, Rabi­novich GA, Iacobelli S, Nifantiev NE and Consorzio Interuniversitario Nazionale Per la Bio-Oncologia. Synthetic inhibitors of galectin-1 and -3 selectively modu­late homotypic cell aggregation and tumor cell apoptosis. Anticancer Res. 2009;29:403–10.
186. DeRoo EP, Wrobleski SK, Shea EM, Al-Khalil RK, Hawley AE, Henke PK, Myers DD, Jr., Wakeeld TW and Diaz JA. The role of galectin-3 and galec­tin-3-binding protein in venous thrombo­sis. Blood. 2015;125:1813–21.
5
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CHAPTER
6
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Epidemiology, genetics, and risk
factors for chronic venous disease
Eri Fukaya
6.1 INTRODUCTION
There are multiple established risk factors for chronic venous disease and a large body of evidence implicating the existence of genetic inuences on its development. In recent years, it has become known that chronic venous dis­ease is not due to a single gene disorder, but rather, it is multifactorial with signicant epigenetic inuences, and the pathophysiology of chronic venous disease development is uniquely intertwined with genetics and environmental fac­tors. Environmental and acquired factors contribute to the complex interplay in the regulation of gene expression and lead to differences in clinical phenotypes and presentations of chronic venous disease.
This chapter will review epidemiological ndings from population studies, environmental factors that contribute to clinical presentation, traditional risk factors, genetic ndings from familial studies, and association with con­genital disorders to the more recent genome-wide associa­tion studies (GWAS).
6.2 EPIDEMIOLOGICAL FINDINGS
Chronic venous disease is quite common in the general population. Still, the true disease burden is difcult to esti­mate given the variability in its reporting and spectrum of phenotypes, which can be misclassied. As opposed to con­ditions that may result in dire health consequences such as venous thromboembolism, chronic venous disease may not routinely be picked up as a medical condition. This will be so if they are not self-reported, if they are asymptomatic, or if only mild disease is present such that both the patient and the physician label them as a cosmetic issue and incon­sequential. Also, it presents as a spectrum of disease rather than a dichotomous presence or absence, making it dif­cult to assert its presence. The trained venous expert will know that chronic venous disease phenotypes are described using the CEAP classication system [1]; however, this sys­tem is only widely implemented in vascular specialties, and therefore, phenotypic classication, including the diagnosis codes that describe a patient, can be inaccurate in many of those who have limited knowledge of the disease. For example, it is common to see patients with prominent
veins, spider veins, stasis dermatitis, or leg swelling all described as varicose veins even if they did not have classic varicose veins. Similarly, for venous leg ulcers, it is com­mon to see any lower extremity leg wound categorized as such whether the true pathology behind this is venous or not. These factors may overcount and underestimate the true chronic venous disease prevalence in many of the data­base-driven epidemiological studies reporting incidence. In addition, geographic diversity, study methodology, and self-reporting of the disease can contribute to differences in disease prevalence. With this caveat, chronic venous dis­ease is thought to affect >25million adults in the United States, with 6–7million having advanced venous disease [2]. The prevalence of varicose veins varies widely by stud­ies and is reported in 1%–73% of women and 2%–56% of men [3]. One study that included CEAP 1–6 estimated the global prevalence of chronic venous disease to be as high as 83.6% [4]. The prevalence of more advanced dis­ease (chronic venous insufciency) also varies in that it was found in up to 40% of women and 17% of men in Western countries [3].
6.3 RISK FACTORS FOR CHRONIC VENOUS DISEASE
There are well-established risk factors for chronic venous disease, including older age, female sex, pregnancy, family history, prolonged standing with work, history of deep vein thrombosis, and obesity [5]. In addition, agnostically dis­covered novel risk factors, including leg bioimpedance and increased height for varicose vein development, have been reported [6] (Figure6.1).
6.3.1 Age
The correlation between increased age and disease preva­lence is related to many of the cellular and molecular aging processes that contribute to venous aging, including vessel wall and venous valve deterioration coupled with increased venous pressure resulting from weakened calf muscles [7]. Endothelial cells in older adults have thickening due to subintimal connective tissue accumulation and increased permeability, which can promote the entry of circulating
DOI: 10.1201/9781003328971-7
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62 Chapter 6 Epidemiology, genetics, and risk factors for chronic venous disease
Number of live births
Probability of varicose veins
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0.015
Age (years)
0.010
0.005
Probability of varicose veins
40 50 60 70 0
Age (years)
Number of live births History of DVT Leg bioimpedance
0.015
0.010
0.005
0 12345
Cumulative incidenceCumulative incidence
0.6%
0.4%
0.2%
0.0%
2.0%
1.5%
1.0%
0.5%
0.0%
0
Gender
Women
Men
1000 2000
Days from baseline
History of DVT
No previous history
1000 2000
Days from baseline
6.1 Possibility of varicose vein development depending on various variables [6].
inammatory mediators and cause chronic inammation [8]. Alterations of adhesion proteins and glycosaminogly­cans on the surface of endothelial cells promote platelet adhesion and thrombus formation, as well as adhesion and transmigration of leukocytes leading to endothelial cell
secreted by the corpus luteum to relax the pelvic liga­ments and a potent vasodilator, may also contribute to the increased venous pressures in the lower extremities [15]. Supplemental estrogen may additionally alter venous wall
compliance [16]. degeneration [9]. Aged endothelial cells exhibit impaired resilience to oxidative stressors and are more sensitive to apoptosis induction. In addition, the turnover of connec­tive tissue in the venous wall decreases with advancing age, and with it the structure of elastic membranes and colla­gen bundles is altered. Ahigher level of MMP activity in aged veins contributes to the remodeling of the extracel­lular matrix [10]. Smooth muscle aging reduces contractil­ity, and connective tissue aging causes brosis, a decrease in elastin, and increased rigidity of the vessel walls. These structural changes lead to functional changes, including diminished elasticity. In the venous valve, disordered colla­gen increases rigidity and becomes thickened and less ex­ible [11]. Continued venous hypertension is a key factor in this valvular remodeling. These continuous changes in the venous valves and walls lead to decreased lower limb venous distensibility, creating higher physiological pres-
6.3.3 Obesity
Obesity is a signicant predictor of clinically signicant
venous disease in both men and women [17] and is asso-
ciated with more signicant skin changes and ulceration
[5]. It remains to be determined if obesity causes venous
disease or whether its existence exacerbates the severity of
the venous disease. Obesity raises intra-abdominal pres-
sure, which in turn increases pressure in the iliofemoral
vein and compromises lymph ow—both of which increase
the risk of venous stasis and, ultimately, venous thrombo-
sis and valve dysfunction. The calf muscle pump function
itself is not compromised in obese patients, but it has been
speculated that there may be calf muscle pump disuse
in patients with morbid obesity contributing to ongoing
venous hypertension [18]. sures in the supine position. Calf muscles play a signicant role in venous return, with one contraction moving 60% of the blood in the calf upward; however, aging reduces calf muscle pump by up to 40%–45% [12, 13]. Regular phys­ical exercise can attenuate age-related changes in venous distensibility and compliance.
6.3.4 History of deep vein thrombosis
Many studies have described a history of deep vein throm-
bosis as a risk factor for chronic venous disease or varicose
veins. Venous reux and venous hypertension can occur as
the post-thrombotic syndrome following deep vein throm-
6.3.2 Female sex
Many studies show female sex is a risk factor for chronic venous disease. Still, it is unclear if this is driven by wors­ening disease during pregnancy or other genetic, hormonal, or environmental factors. Pregnancy creates extreme physi­ological changes including increased blood volume, weight gain, elevated intra-abdominal pressures, and decreased venous return [14]. The production of relaxin, a hormone
bosis. The residual clot burden leads to venous stenosis,
obstruction, or valvular damage resulting in prolonged
increases in venous pressures and eventually chronic venous
insufciency, with post-thrombotic syndrome estimated to
affect 23%–60% of individuals with deep vein thrombo-
sis [19–21]. The inverse can also occur, as venous stasis
or turbulent ow predisposes to thrombotic events, includ-
ing supercial venous thrombosis or deep vein thrombosis
in the calf veins [22]. Aretrospective cohort study inves-
0.015
0.010
0.005
Probability of varicose veinsProbability of varicose veins
0.015
0.010
0.005
Height
150
160 170 180 190
Height (cm)
200 250 300
Leg biompedance
6.4 Genetic findings 63
and Leukoencephalopathy (CADASIL)
https://t.me/med1917
tigating >400,000 patients in Taiwan’s Health Insurance program found that varicose veins dramatically increased the incidence of deep vein thrombosis, with a hazard ratio of 5.3 [23], a nding that has been supported by multiple other epidemiological studies [24, 25].
6.3.5 Novel risk factors
A study using UK Biobank data used a machine learning approach and conrmed many of the known risk factors but also identied several new strong predictors, including leg bioimpedance and height [6]. Height had been identi­ed as a potential risk factor in an early epidemiological study several decades ago [26] but had been inconsis­tently reported since [26, 27]. The other newly identied risk factor, bioimpedance, dened as the ability of the tis­sue to impede electric current, reects the amount of uid accumulation in body tissue [28]. These novel predictors may indicate a link between high-volume venous reux, increased hydrostatic pressure, and resulting venous hyper­tension.
6.4 GENETIC FINDINGS
Genomics is the roadmap to discoveries in human biology and pathology, including discovering targets for prevention and treatment. The importance of genetics and the heri­tability of chronic venous disease have long been postu­lated based on familial studies. Genetic mutations include chromosomal abnormalities, gene mutations, single-nucle­otide polymorphisms, and differences in gene expression. Historically, different approaches have been taken to study genetic conditions, including gene expression studies and candidate gene approaches. However, with GWAS becom­ing less expensive to perform and successfully identifying important genetic variants associated with human traits and diseases, this has become the main tool to study genetic ndings. This section will summarize historical studies on what has been discovered in GWAS.
6.4.1 Familial studies
Family history is a well-known contributing factor [29, 30] to chronic venous disease, and familial clustering of varicose veins has been reported with variable prevalence. Data from the Swedish multigeneration registry showed that a family history of hospital treatment for varicose veins was associated with an increased risk of similar treat­ment among relatives [31]. AFrench study of 134 fami­lies found that the risk of developing varicose veins was 90% when both parents were affected by the disease [32]. Another study using the Swedish Hospital Discharge Reg­ister found that the standardized incidence ratio was 2.39 when patients had one affected parent and 5.52 in patients with two affected parents. Interestingly, they also observed an increased risk among spouses of affected patients (stan­dardized incidence ratio ≈1.7), suggesting a signicant life­style component to the disease [31].
6.4.2 Candidate gene approach
Prior to GWAS becoming widely available, genetic studies for chronic venous disease were mostly restricted to look­ing at congenital disease, syndromic forms, and candidate gene studies [29]. The candidate gene approach involves identifying the genes associated with the disease and is done by targeting the gene responsible for the underlying pathological process. For varicose veins, FOXC2 was the rst gene found to have a strong association with primary varicose veins [33, 34]. This gene was discovered as part of lymphedema–distichiasis syndrome, which is a condi­tion that comprises intrinsic dysfunction of the lymphatic vessels and extra eyelashes. In a study of 74 affected indi­viduals, there was a 49% prevalence of varicose veins, and a genetic analysis revealed an association between the chromosome 16q24 region and the transcription factor FOXC2 [33]. This study, for the rst time, suggested a pos­sible candidate gene for the development of varicose veins. Several other disorders, genes, and specic mutations have been associated with varicose vein development [29, 35] (Figure 6.2). Although the candidate gene approach is
6
Classification
Choromsimal defects
Gene mutations
Single Nucleotide
Polymorophisms
6.2 Genetic abnormalities that have been associated with varicose vein formation [29, 35].
Specific Abnormalities Associated Syndrome
Translocation at 8:14 or 5:11 Klippel-Trenaunay syndrome
Trisomies 7,12,18
Monosomies 14
FOXC2
G6PC3
COL3A1
Von Hippel Lindau
Lymphoedema distichiasis
Severe Congentital Neutropenis Type 4
Ehlers-Danlos Syndrome
Chuvash Polycythemia
Thrombomodulin
Desmuslin
Cerebral Autosomal Dominant
Notch3
Arteriopathy with Subcortical Infarcts
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