CC BY 4.0 · TH Open 2023; 07(03): e244-e250
DOI: 10.1055/a-2159-9957
Original Article

Surgery As a Trigger for Incident Venous Thromboembolism: Results from a Population-Based Case-Crossover Study

Dana Meknas
1   Department of Clinical Medicine, Thrombosis Research Group, UiT—The Arctic University of Norway, Tromsø, Norway
2   Department of Orthopedic Surgery, University Hospital of North Norway, Tromsø, Norway
,
Sigrid K. Brækkan
1   Department of Clinical Medicine, Thrombosis Research Group, UiT—The Arctic University of Norway, Tromsø, Norway
3   Division of Internal Medicine, Thrombosis Research Center, University Hospital of North Norway, Tromsø, Norway
,
John-Bjarne Hansen
1   Department of Clinical Medicine, Thrombosis Research Group, UiT—The Arctic University of Norway, Tromsø, Norway
3   Division of Internal Medicine, Thrombosis Research Center, University Hospital of North Norway, Tromsø, Norway
,
Vânia M. Morelli
1   Department of Clinical Medicine, Thrombosis Research Group, UiT—The Arctic University of Norway, Tromsø, Norway
3   Division of Internal Medicine, Thrombosis Research Center, University Hospital of North Norway, Tromsø, Norway
› Author Affiliations

Abstract

Background Surgery is a major transient risk factor for venous thromboembolism (VTE). However, the impact of major surgery as a VTE trigger has been scarcely investigated using a case-crossover design.

Aim To investigate the role of major surgery as a trigger for incident VTE in a population-based case-crossover study while adjusting for other concomitant VTE triggers.

Methods We conducted a case-crossover study with 531 cancer-free VTE cases derived from the Tromsø Study cohort. Triggers were registered during the 90 days before a VTE event (hazard period) and in four preceding 90-day control periods. Conditional logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for VTE according to major surgery and after adjustment for other VTE triggers.

Results Surgery was registered in 85 of the 531 (16.0%) hazard periods and in 38 of the 2,124 (1.8%) control periods, yielding an OR for VTE of 11.40 (95% CI: 7.42–17.51). The OR decreased to 4.10 (95% CI: 2.40–6.94) after adjustment for immobilization and infection and was further attenuated to 3.31 (95% CI: 1.83–5.96) when additionally adjusted for trauma, blood transfusion, and central venous catheter. In a mediation analysis, 51.4% (95% CI: 35.5–79.7%) of the effect of surgery on VTE risk could be mediated through immobilization and infection.

Conclusions Major surgery was a trigger for VTE, but the association between surgery and VTE risk was in part explained by other VTE triggers often coexisting with surgery, particularly immobilization and infection.

Author's Contributions

D. Meknas analyzed data, interpreted the results, and drafted the manuscript. S. K. Brækkan and J.B. Hansen designed the study, organized data collection, interpreted the results, and revised the manuscript. V.M. Morelli designed the study, analyzed data, interpreted the results, contributed to the manuscript draft, and revised the manuscript. All authors reviewed and approved the final version of the manuscript.




Publication History

Received: 21 April 2023

Accepted: 14 July 2023

Accepted Manuscript online:
24 August 2023

Article published online:
20 September 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Wolberg AS, Rosendaal FR, Weitz JI. et al. Venous thrombosis. Nat Rev Dis Primers 2015; 1: 15006
  • 2 Heit JA, Ashrani A, Crusan DJ, McBane RD, Petterson TM, Bailey KR. Reasons for the persistent incidence of venous thromboembolism. Thromb Haemost 2017; 117 (02) 390-400
  • 3 Arshad N, Isaksen T, Hansen JB, Brækkan SK. Time trends in incidence rates of venous thromboembolism in a large cohort recruited from the general population. Eur J Epidemiol 2017; 32 (04) 299-305
  • 4 Heit JA, O'Fallon WM, Petterson TM. et al. Relative impact of risk factors for deep vein thrombosis and pulmonary embolism: a population-based study. Arch Intern Med 2002; 162 (11) 1245-1248
  • 5 World Health Organization (WHO). Fact sheet: ageing and health. 2022 . Accessed March 29, 2023 at: https://www.who.int/news-room/fact-sheets/detail/ageing-and-health
  • 6 Gangireddy C, Rectenwald JR, Upchurch GR. et al. Risk factors and clinical impact of postoperative symptomatic venous thromboembolism. J Vasc Surg 2007; 45 (02) 335-341 , discussion 341–342
  • 7 Roderick P, Ferris G, Wilson K. et al. Towards evidence-based guidelines for the prevention of venous thromboembolism: systematic reviews of mechanical methods, oral anticoagulation, dextran and regional anaesthesia as thromboprophylaxis. Health Technol Assess 2005; 9 (49) iii-iv , ix–x, 1–78
  • 8 Wilson S, Chen X, Cronin M. et al. Thrombosis prophylaxis in surgical patients using the Caprini Risk Score. Curr Probl Surg 2022; 59 (11) 101221
  • 9 White RH, Zhou H, Romano PS. Incidence of symptomatic venous thromboembolism after different elective or urgent surgical procedures. Thromb Haemost 2003; 90 (03) 446-455
  • 10 Albayati MA, Grover SP, Saha P, Lwaleed BA, Modarai B, Smith A. Postsurgical inflammation as a causative mechanism of venous thromboembolism. Semin Thromb Hemost 2015; 41 (06) 615-620
  • 11 Cofrancesco E, Cortellaro M, Leonardi P, Corradi A, Ravasi F, Bertocchi F. Markers of hemostatic system activation during thromboprophylaxis with recombinant hirudin in total hip replacement. Thromb Haemost 1996; 75 (03) 407-411
  • 12 Arnesen H, Dahl OE, Aspelin T, Seljeflot I, Kierulf P, Lyberg T. Sustained prothrombotic profile after hip replacement surgery: the influence of prolonged prophylaxis with dalteparin. J Thromb Haemost 2003; 1 (05) 971-975
  • 13 Grimnes G, Isaksen T, Tichelaar YIGV, Brækkan SK, Hansen JB. Acute infection as a trigger for incident venous thromboembolism: Results from a population-based case-crossover study. Res Pract Thromb Haemost 2017; 2 (01) 85-92
  • 14 Bjøri E, Johnsen HS, Hansen JB, Brækkan SK. Hospitalization as a trigger for venous thromboembolism - results from a population-based case-crossover study. Thromb Res 2019; 176: 115-119
  • 15 Rolston JD, Han SJ, Bloch O, Parsa AT. What clinical factors predict the incidence of deep venous thrombosis and pulmonary embolism in neurosurgical patients?. J Neurosurg 2014; 121 (04) 908-918
  • 16 Yang SS, Yu CS, Yoon YS, Yoon SN, Lim SB, Kim JC. Symptomatic venous thromboembolism in Asian colorectal cancer surgery patients. World J Surg 2011; 35 (04) 881-887
  • 17 Mangwani J, Sheikh N, Cichero M, Williamson D. What is the evidence for chemical thromboprophylaxis in foot and ankle surgery? Systematic review of the English literature. Foot 2015; 25 (03) 173-178
  • 18 Sebastian AS, Currier BL, Clarke MJ, Larson D, Huddleston III PM, Nassr A. Thromboembolic disease after cervical spine surgery: a review of 5,405 surgical procedures and matched cohort analysis. Global Spine J 2016; 6 (05) 465-471
  • 19 Keller K, Hobohm L, Barco S. et al. Venous thromboembolism in patients hospitalized for hip joint replacement surgery. Thromb Res 2020; 190: 1-7
  • 20 Monn MF, Haut ER, Lau BD. et al. Is venous thromboembolism in colorectal surgery patients preventable or inevitable? One institution's experience. J Am Coll Surg 2013; 216 (03) 395.e1-401.e1
  • 21 Monn MF, Hui X, Lau BD. et al. Infection and venous thromboembolism in patients undergoing colorectal surgery: what is the relationship?. Dis Colon Rectum 2014; 57 (04) 497-505
  • 22 Heit JA, Silverstein MD, Mohr DN, Petterson TM, O'Fallon WM, Melton III LJ. Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch Intern Med 2000; 160 (06) 809-815
  • 23 Rogers MA, Levine DA, Blumberg N, Flanders SA, Chopra V, Langa KM. Triggers of hospitalization for venous thromboembolism. Circulation 2012; 125 (17) 2092-2099
  • 24 Maclure M. The case-crossover design: a method for studying transient effects on the risk of acute events. Am J Epidemiol 1991; 133 (02) 144-153
  • 25 Caron A, Depas N, Chazard E. et al. Risk of pulmonary embolism more than 6 weeks after surgery among cancer-free middle-aged patients. JAMA Surg 2019; 154 (12) 1126-1132
  • 26 Jacobsen BK, Eggen AE, Mathiesen EB, Wilsgaard T, Njølstad I. Cohort profile: the Tromso Study. Int J Epidemiol 2012; 41 (04) 961-967
  • 27 Braekkan SK, Borch KH, Mathiesen EB, Njølstad I, Wilsgaard T, Hansen JB. Body height and risk of venous thromboembolism: the Tromsø Study. Am J Epidemiol 2010; 171 (10) 1109-1115
  • 28 Morelli VM, Sejrup JK, Småbrekke B. et al. The role of stroke as a trigger for incident venous thromboembolism: results from a population-based case-crossover study. TH Open 2019; 3 (01) e50-e57
  • 29 Sejrup JK, Børvik T, Grimnes G. et al. Myocardial infarction as a transient risk factor for incident venous thromboembolism: results from a population-based case-crossover study. Thromb Haemost 2019; 119 (08) 1358-1364
  • 30 Kearon C, Ageno W, Cannegieter SC, Cosmi B, Geersing GJ, Kyrle PA. Subcommittees on Control of Anticoagulation, and Predictive and Diagnostic Variables in Thrombotic Disease. Categorization of patients as having provoked or unprovoked venous thromboembolism: guidance from the SSC of ISTH. J Thromb Haemost 2016; 14 (07) 1480-1483
  • 31 Anderson Jr FA, Spencer FA. Risk factors for venous thromboembolism. Circulation 2003; 107 (23, Suppl 1): I9-I16
  • 32 Iorio A, Kearon C, Filippucci E. et al. Risk of recurrence after a first episode of symptomatic venous thromboembolism provoked by a transient risk factor: a systematic review. Arch Intern Med 2010; 170 (19) 1710-1716
  • 33 Breen R, Karlson KB, Holm A. Total, direct, and indirect effects in logit and probit models. Sociol Methods Res 2013; 42 (02) 164-191
  • 34 Cassidy MR, Rosenkranz P, McAneny D. Reducing postoperative venous thromboembolism complications with a standardized risk-stratified prophylaxis protocol and mobilization program. J Am Coll Surg 2014; 218 (06) 1095-1104
  • 35 Geerts WH, Bergqvist D, Pineo GF. et al. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133 (6, Suppl): 381S-453S
  • 36 European Centre for Disease Prevention and Control. Healthcare-associated infections: surgical site infections. In: ECDC Annual Epidemiological Report for 2017 Stockholm. Solna: ECDC; 2019
  • 37 Samama CM, Thiry D, Elalamy I. et al. Perioperative activation of hemostasis in vascular surgery patients. Anesthesiology 2001; 94 (01) 74-78
  • 38 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