Download PDF
Semin Thromb Hemost 2015; 41(06): 615-620
DOI: 10.1055/s-0035-1556726
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Postsurgical Inflammation as a Causative Mechanism of Venous Thromboembolism

Mostafa A. Albayati
1   Cardiovascular Division, Academic Department of Vascular Surgery, King's College London, London, United Kingdom
,
Steven P. Grover
1   Cardiovascular Division, Academic Department of Vascular Surgery, King's College London, London, United Kingdom
,
Prakash Saha
1   Cardiovascular Division, Academic Department of Vascular Surgery, King's College London, London, United Kingdom
,
Bashir A. Lwaleed
2   Department of Health Sciences, University of Southampton, Southampton, United Kingdom
,
Bijan Modarai
1   Cardiovascular Division, Academic Department of Vascular Surgery, King's College London, London, United Kingdom
,
Alberto Smith
1   Cardiovascular Division, Academic Department of Vascular Surgery, King's College London, London, United Kingdom
› Author Affiliations
Further Information

Publication History

Publication Date:
15 August 2015 (online)

    Permissions and Reprints

Abstract

Surgery is associated with an increased risk of venous thromboembolic events (VTE) including deep vein thrombosis and pulmonary embolism. Although the current treatment regiments such as mechanical manipulation and administration of pharmacological prophylaxis significantly reduced the incidence of postsurgical VTE, they remain a major cause of postoperative morbidity and mortality worldwide. The pathophysiology of venous thrombosis traditionally emphasizes the series of factors that constitute Virchow triad of factors. However, inflammation can also be a part of this by giving rise to a hypercoagulable state and endothelial damage. The inflammatory response after surgery, which is initiated by a cytokine “storm” and occurs within hours of surgery, creates a prothrombotic environment that is further accentuated by several cellular processes including neutrophil extracellular traps formation, platelet activation, and the generation of tissue factor–bearing microparticles. Although such inflammatory markers are elevated in undergoing surgery, the precise mechanism by which they give rise to venous thrombosis is poorly understood. Here, we discuss the potential mechanisms linking inflammation to thrombosis, and highlight strategies that may minimize surgical inflammation and reduce the incidence of postoperative VTE.

Keywords

surgery - inflammation - thromboembolism
 

  • References

  • 1 White RH, Zhou H, Romano PS. Incidence of symptomatic venous thromboembolism after different elective or urgent surgical procedures. Thromb Haemost 2003; 90 (3) 446-455
    Thieme ConnectPubMedSearch in Google Scholar
  • 2 Heit JA. The epidemiology of venous thromboembolism in the community. Arterioscler Thromb Vasc Biol 2008; 28 (3) 370-372
    CrossrefPubMedSearch in Google Scholar
  • 3 Nicholas M. European Cardiovascular Disease Statistics 2012: European Heart Network. Sophia Antipolis. France: Brussels and European Society of Cardiology; 2012
    Search in Google Scholar
  • 4 The prevention of venous thromboembolism in hospitalised patients. House of Commons Health Committee. 2005: 11-12
    PubMedSearch in Google Scholar
  • 5 Anderson Jr FA, Spencer FA. Risk factors for venous thromboembolism. Circulation 2003; 107 (23) (Suppl. 01) I9-I16
    CrossrefPubMedSearch in Google Scholar
  • 6 Sachdeva A, Dalton M, Amaragiri SV, Lees T. Elastic compression stockings for prevention of deep vein thrombosis. Cochrane Database Syst Rev 2010; (7) CD001484
    PubMedSearch in Google Scholar
  • 7 Koch A, Bouges S, Ziegler S, Dinkel H, Daures JP, Victor N. Low molecular weight heparin and unfractionated heparin in thrombosis prophylaxis after major surgical intervention: update of previous meta-analyses. Br J Surg 1997; 84 (6) 750-759
    CrossrefPubMedSearch in Google Scholar
  • 8 Agnelli G. Prevention of venous thromboembolism in surgical patients. Circulation 2004; 110 (24) (Suppl. 01) IV4-IV12
    CrossrefPubMedSearch in Google Scholar
  • 9 Wakefield TW, Myers DD, Henke PK. Mechanisms of venous thrombosis and resolution. Arterioscler Thromb Vasc Biol 2008; 28 (3) 387-391
    CrossrefPubMedSearch in Google Scholar
  • 10 Saha P, Humphries J, Modarai B , et al. Leukocytes and the natural history of deep vein thrombosis: current concepts and future directions. Arterioscler Thromb Vasc Biol 2011; 31 (3) 506-512
    CrossrefPubMedSearch in Google Scholar
  • 11 Brivio F, Perego M, Mauri E , et al. Variations in interleukin-2 and interleukin-6 due to surgical trauma in cancer patients [in Italian]. G Chir 1998; 19 (10) 377-380
    PubMedSearch in Google Scholar
  • 12 Rumbaut RETP. Platelet-Vessel Wall Interactions in Hemostasis and Thrombosis. San Rafael, CA: Morgan & Claypool Life Sciences; 2010
    Search in Google Scholar
  • 13 Stewart GJ. Neutrophils and deep venous thrombosis. Haemostasis 1993; 23 (Suppl. 01) 127-140
    PubMedSearch in Google Scholar
  • 14 Fox EA, Kahn SR. The relationship between inflammation and venous thrombosis. A systematic review of clinical studies. Thromb Haemost 2005; 94 (2) 362-365
    PubMedSearch in Google Scholar
  • 15 Sakon M, Maehara Y, Yoshikawa H, Akaza H. Incidence of venous thromboembolism following major abdominal surgery: a multi-center, prospective epidemiological study in Japan. J Thromb Haemost 2006; 4 (3) 581-586
    CrossrefPubMedSearch in Google Scholar
  • 16 Grignani G, Maiolo A. Cytokines and hemostasis. Haematologica 2000; 85 (9) 967-972
    PubMedSearch in Google Scholar
  • 17 Mutlu GM, Green D, Bellmeyer A , et al. Ambient particulate matter accelerates coagulation via an IL-6-dependent pathway. J Clin Invest 2007; 117 (10) 2952-2961
    CrossrefPubMedSearch in Google Scholar
  • 18 Chiarella SE, Soberanes S, Urich D , et al. β2-Adrenergic agonists augment air pollution-induced IL-6 release and thrombosis. J Clin Invest 2014; 124 (7) 2935-2946
    CrossrefPubMedSearch in Google Scholar
  • 19 Stouthard JM, Levi M, Hack CE , et al. Interleukin-6 stimulates coagulation, not fibrinolysis, in humans. Thromb Haemost 1996; 76 (5) 738-742
    PubMedSearch in Google Scholar
  • 20 Montes-Worboys A, Rodriguez-Portal JA, Arellano-Orden E, Digón-Pereiras J, Rodriguez-Panadero F. Interleukin-8 activates coagulation and correlates with survival after talc pleurodesis. Eur Respir J 2010; 35 (1) 160-166
    CrossrefPubMedSearch in Google Scholar
  • 21 van Aken BE, Reitsma PH, Rosendaal FR. Interleukin 8 and venous thrombosis: evidence for a role of inflammation in thrombosis. Br J Haematol 2002; 116 (1) 173-177
    CrossrefPubMedSearch in Google Scholar
  • 22 Baggiolini M, Walz A, Kunkel SL. Neutrophil-activating peptide-1/interleukin 8, a novel cytokine that activates neutrophils. J Clin Invest 1989; 84 (4) 1045-1049
    CrossrefPubMedSearch in Google Scholar
  • 23 von Brühl ML, Stark K, Steinhart A , et al. Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo. J Exp Med 2012; 209 (4) 819-835
    CrossrefPubMedSearch in Google Scholar
  • 24 Downing LJ, Strieter RM, Kadell AM , et al. IL-10 regulates thrombus-induced vein wall inflammation and thrombosis. J Immunol 1998; 161 (3) 1471-1476
    PubMedSearch in Google Scholar
  • 25 Pajkrt D, van der Poll T, Levi M , et al. Interleukin-10 inhibits activation of coagulation and fibrinolysis during human endotoxemia. Blood 1997; 89 (8) 2701-2705
    PubMedSearch in Google Scholar
  • 26 Witsell AL, Schook LB. Tumor necrosis factor alpha is an autocrine growth regulator during macrophage differentiation. Proc Natl Acad Sci U S A 1992; 89 (10) 4754-4758
    CrossrefPubMedSearch in Google Scholar
  • 27 van der Poll T, Büller HR, ten Cate H , et al. Activation of coagulation after administration of tumor necrosis factor to normal subjects. N Engl J Med 1990; 322 (23) 1622-1627
    CrossrefPubMedSearch in Google Scholar
  • 28 Nawroth PP, Stern DM. Modulation of endothelial cell hemostatic properties by tumor necrosis factor. J Exp Med 1986; 163 (3) 740-745
    CrossrefPubMedSearch in Google Scholar
  • 29 Pircher J, Merkle M, Wörnle M , et al. Prothrombotic effects of tumor necrosis factor alpha in vivo are amplified by the absence of TNF-alpha receptor subtype 1 and require TNF-alpha receptor subtype 2. Arthritis Res Ther 2012; 14 (5) R225
    CrossrefPubMedSearch in Google Scholar
  • 30 Cambien B, Bergmeier W, Saffaripour S, Mitchell HA, Wagner DD. Antithrombotic activity of TNF-alpha. J Clin Invest 2003; 112 (10) 1589-1596
    CrossrefPubMedSearch in Google Scholar
  • 31 Hurlimann J, Thorbecke GJ, Hochwald GM. The liver as the site of C-reactive protein formation. J Exp Med 1966; 123 (2) 365-378
    CrossrefPubMedSearch in Google Scholar
  • 32 Bisoendial RJ, Kastelein JJ, Levels JH , et al. Activation of inflammation and coagulation after infusion of C-reactive protein in humans. Circ Res 2005; 96 (7) 714-716
    CrossrefPubMedSearch in Google Scholar
  • 33 Cermak J, Key NS, Bach RR, Balla J, Jacob HS, Vercellotti GM. C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor. Blood 1993; 82 (2) 513-520
    PubMedSearch in Google Scholar
  • 34 Devaraj S, Dasu MR, Singh U, Rao LV, Jialal I. C-reactive protein stimulates superoxide anion release and tissue factor activity in vivo. Atherosclerosis 2009; 203 (1) 67-74
    CrossrefPubMedSearch in Google Scholar
  • 35 Cirillo P, Golino P, Calabrò P , et al. C-reactive protein induces tissue factor expression and promotes smooth muscle and endothelial cell proliferation. Cardiovasc Res 2005; 68 (1) 47-55
    CrossrefPubMedSearch in Google Scholar
  • 36 Li YD, Ye BQ, Zheng SX , et al. NF-kappaB transcription factor p50 critically regulates tissue factor in deep vein thrombosis. J Biol Chem 2009; 284 (7) 4473-4483
    CrossrefPubMedSearch in Google Scholar
  • 37 Danenberg HD, Szalai AJ, Swaminathan RV , et al. Increased thrombosis after arterial injury in human C-reactive protein-transgenic mice. Circulation 2003; 108 (5) 512-515
    CrossrefPubMedSearch in Google Scholar
  • 38 Matsuda S, Yamashita A, Sato Y , et al. Human C-reactive protein enhances thrombus formation after neointimal balloon injury in transgenic rabbits. J Thromb Haemost 2011; 9 (1) 201-208
    CrossrefPubMedSearch in Google Scholar
  • 39 Brinkmann V, Reichard U, Goosmann C , et al. Neutrophil extracellular traps kill bacteria. Science 2004; 303 (5663) 1532-1535
    CrossrefPubMedSearch in Google Scholar
  • 40 Wang Y, Li M, Stadler S , et al. Histone hypercitrullination mediates chromatin decondensation and neutrophil extracellular trap formation. J Cell Biol 2009; 184 (2) 205-213
    CrossrefPubMedSearch in Google Scholar
  • 41 Fuchs TA, Brill A, Duerschmied D , et al. Extracellular DNA traps promote thrombosis. Proc Natl Acad Sci U S A 2010; 107 (36) 15880-15885
    CrossrefPubMedSearch in Google Scholar
  • 42 Brill A, Fuchs TA, Savchenko AS , et al. Neutrophil extracellular traps promote deep vein thrombosis in mice. J Thromb Haemost 2012; 10 (1) 136-144
    CrossrefPubMedSearch in Google Scholar
  • 43 Martinod K, Demers M, Fuchs TA , et al. Neutrophil histone modification by peptidylarginine deiminase 4 is critical for deep vein thrombosis in mice. Proc Natl Acad Sci U S A 2013; 110 (21) 8674-8679
    CrossrefPubMedSearch in Google Scholar
  • 44 McIlroy DJ, Jarnicki AG, Au GG , et al. Mitochondrial DNA neutrophil extracellular traps are formed after trauma and subsequent surgery. J Crit Care 2014; 29 (6) 1133.e1-1133.e5
    CrossrefPubMedSearch in Google Scholar
  • 45 Schafer AI. Vascular endothelium: in defense of blood fluidity. J Clin Invest 1997; 99 (6) 1143-1144
    CrossrefPubMedSearch in Google Scholar
  • 46 Babin-Ebell J, Gimpel-Henning K, Sievers HH, Scharfschwerdt M. Influence of clamp duration and pressure on endothelial damage in aortic cross-clamping. Interact Cardiovasc Thorac Surg 2010; 10 (2) 168-171
    CrossrefPubMedSearch in Google Scholar
  • 47 Nieswandt B, Watson SP. Platelet-collagen interaction: is GPVI the central receptor?. Blood 2003; 102 (2) 449-461
    CrossrefPubMedSearch in Google Scholar
  • 48 White-Adams TC, Berny MA, Patel IA , et al. Laminin promotes coagulation and thrombus formation in a factor XII-dependent manner. J Thromb Haemost 2010; 8 (6) 1295-1301
    CrossrefPubMedSearch in Google Scholar
  • 49 Clahsen T, Schaper F. Interleukin-6 acts in the fashion of a classical chemokine on monocytic cells by inducing integrin activation, cell adhesion, actin polymerization, chemotaxis, and transmigration. J Leukoc Biol 2008; 84 (6) 1521-1529
    CrossrefPubMedSearch in Google Scholar
  • 50 Romano M, Sironi M, Toniatti C , et al. Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment. Immunity 1997; 6 (3) 315-325
    CrossrefPubMedSearch in Google Scholar
  • 51 Gerszten RE, Garcia-Zepeda EA, Lim YC , et al. MCP-1 and IL-8 trigger firm adhesion of monocytes to vascular endothelium under flow conditions. Nature 1999; 398 (6729) 718-723
    CrossrefPubMedSearch in Google Scholar
  • 52 DiVietro JA, Smith MJ, Smith BR, Petruzzelli L, Larson RS, Lawrence MB. Immobilized IL-8 triggers progressive activation of neutrophils rolling in vitro on P-selectin and intercellular adhesion molecule-1. J Immunol 2001; 167 (7) 4017-4025
    CrossrefPubMedSearch in Google Scholar
  • 53 Samama CM, Thiry D, Elalamy I , et al. Perioperative activation of hemostasis in vascular surgery patients. Anesthesiology 2001; 94 (1) 74-78
    CrossrefPubMedSearch in Google Scholar
  • 54 Rinder CS, Bohnert J, Rinder HM, Mitchell J, Ault K, Hillman R. Platelet activation and aggregation during cardiopulmonary bypass. Anesthesiology 1991; 75 (3) 388-393
    CrossrefPubMedSearch in Google Scholar
  • 55 Oleksowicz L, Mrowiec Z, Zuckerman D, Isaacs R, Dutcher J, Puszkin E. Platelet activation induced by interleukin-6: evidence for a mechanism involving arachidonic acid metabolism. Thromb Haemost 1994; 72 (2) 302-308
    PubMedSearch in Google Scholar
  • 56 Pignatelli P, De Biase L, Lenti L , et al. Tumor necrosis factor-alpha as trigger of platelet activation in patients with heart failure. Blood 2005; 106 (6) 1992-1994
    CrossrefPubMedSearch in Google Scholar
  • 57 Pearce AC, Wilde JI, Doody GM , et al. Vav1, but not Vav2, contributes to platelet aggregation by CRP and thrombin, but neither is required for regulation of phospholipase C. Blood 2002; 100 (10) 3561-3569
    CrossrefPubMedSearch in Google Scholar
  • 58 Myers Jr DD, Schaub R, Wrobleski SK , et al. P-selectin antagonism causes dose-dependent venous thrombosis inhibition. Thromb Haemost 2001; 85 (3) 423-429
    PubMedSearch in Google Scholar
  • 59 Nieuwland R, Berckmans RJ, Rotteveel-Eijkman RC , et al. Cell-derived microparticles generated in patients during cardiopulmonary bypass are highly procoagulant. Circulation 1997; 96 (10) 3534-3541
    CrossrefPubMedSearch in Google Scholar
  • 60 Johnson GJ, Leis LA, Bach RR. Tissue factor activity of blood mononuclear cells is increased after total knee arthroplasty. Thromb Haemost 2009; 102 (4) 728-734
    PubMedSearch in Google Scholar
  • 61 Owens III AP, Mackman N. Microparticles in hemostasis and thrombosis. Circ Res 2011; 108 (10) 1284-1297
    CrossrefPubMedSearch in Google Scholar
  • 62 Ramacciotti E, Hawley AE, Farris DM , et al. Leukocyte- and platelet-derived microparticles correlate with thrombus weight and tissue factor activity in an experimental mouse model of venous thrombosis. Thromb Haemost 2009; 101 (4) 748-754
    PubMedSearch in Google Scholar
  • 63 Wang JG, Geddings JE, Aleman MM , et al. Tumor-derived tissue factor activates coagulation and enhances thrombosis in a mouse xenograft model of human pancreatic cancer. Blood 2012; 119 (23) 5543-5552
    CrossrefPubMedSearch in Google Scholar
  • 64 Biró E, Sturk-Maquelin KN, Vogel GM , et al. Human cell-derived microparticles promote thrombus formation in vivo in a tissue factor-dependent manner. J Thromb Haemost 2003; 1 (12) 2561-2568
    CrossrefPubMedSearch in Google Scholar
  • 65 Collins R, Scrimgeour A, Yusuf S, Peto R. Reduction in fatal pulmonary embolism and venous thrombosis by perioperative administration of subcutaneous heparin. Overview of results of randomized trials in general, orthopedic, and urologic surgery. N Engl J Med 1988; 318 (18) 1162-1173
    CrossrefPubMedSearch in Google Scholar
  • 66 Nguyen NT, Hinojosa MW, Fayad C , et al. Laparoscopic surgery is associated with a lower incidence of venous thromboembolism compared with open surgery. Ann Surg 2007; 246 (6) 1021-1027
    CrossrefPubMedSearch in Google Scholar
  • 67 Odegård A, Lundbom J, Myhre HO , et al. The inflammatory response following treatment of abdominal aortic aneurysms: a comparison between open surgery and endovascular repair. Eur J Vasc Endovasc Surg 2000; 19 (5) 536-544
    CrossrefPubMedSearch in Google Scholar
  • 68 Swartbol P, Truedsson L, Norgren L. The inflammatory response and its consequence for the clinical outcome following aortic aneurysm repair. Eur J Vasc Endovasc Surg 2001; 21 (5) 393-400
    CrossrefPubMedSearch in Google Scholar
  • 69 Schmidt M, Christiansen CF, Horváth-Puhó E, Glynn RJ, Rothman KJ, Sørensen HT. Non-steroidal anti-inflammatory drug use and risk of venous thromboembolism. J Thromb Haemost 2011; 9 (7) 1326-1333
    CrossrefPubMedSearch in Google Scholar
  • 70 Ridker PM, Thuren T, Zalewski A, Libby P. Interleukin-1β inhibition and the prevention of recurrent cardiovascular events: rationale and design of the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS). Am Heart J 2011; 162 (4) 597-605
    CrossrefPubMedSearch in Google Scholar
  • 71 Glynn RJ, Danielson E, Fonseca FA , et al. A randomized trial of rosuvastatin in the prevention of venous thromboembolism. N Engl J Med 2009; 360 (18) 1851-1861
    CrossrefPubMedSearch in Google Scholar
  • 72 Owens III AP, Passam FH, Antoniak S , et al. Monocyte tissue factor-dependent activation of coagulation in hypercholesterolemic mice and monkeys is inhibited by simvastatin. J Clin Invest 2012; 122 (2) 558-568
    CrossrefPubMedSearch in Google Scholar
  • 73 Ridker PM, Cannon CP, Morrow D , et al; Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) Investigators. C-reactive protein levels and outcomes after statin therapy. N Engl J Med 2005; 352 (1) 20-28
    CrossrefPubMedSearch in Google Scholar
  • 74 Rodriguez AL, Wojcik BM, Wrobleski SK, Myers Jr DD, Wakefield TW, Diaz JA. Statins, inflammation and deep vein thrombosis: a systematic review. J Thromb Thrombolysis 2012; 33 (4) 371-382
    CrossrefPubMedSearch in Google Scholar
  • 75 Kato M, Honda I, Suzuki H, Murakami M, Matsukawa S, Hashimoto Y. Interleukin-10 production during and after upper abdominal surgery. J Clin Anesth 1998; 10 (3) 184-188
    CrossrefPubMedSearch in Google Scholar
  • 76 Roth-Isigkeit A, Borstel TV, Seyfarth M, Schmucker P. Perioperative serum levels of tumour-necrosis-factor alpha (TNF-alpha), IL-1 beta, IL-6, IL-10 and soluble IL-2 receptor in patients undergoing cardiac surgery with cardiopulmonary bypass without and with correction for haemodilution. Clin Exp Immunol 1999; 118 (2) 242-246
    CrossrefPubMedSearch in Google Scholar
  • 77 Neumaier M, Metak G, Scherer MA. C-reactive protein as a parameter of surgical trauma: CRP response after different types of surgery in 349 hip fractures. Acta Orthop 2006; 77 (5) 788-790
    CrossrefPubMedSearch in Google Scholar