Balancing the risks of venous thromboembolism and bleeding in abdominal surgery: factors to consider in personalising thromboprophylaxis

Patients undergoing abdominal surgery are at risk of both venous thromboembolic (VTE) and bleeding complications perioperatively. To reduce VTE risk, the routine administration of pharmacologic thromboprophylaxis has been recommended by certain regulatory bodies (1). As a result, many institutions have adopted a one-size fits all approach to thromboprophylaxis prescription (2) which protects against VTE but may risk increased bleeding events. It is clear that there remains significant variation in both the use and timing of thromboprophylaxis prescription across healthcare, with much of this attributed to individual experiences and surgical dogma (3). This unrationalised variation in practice has been well demonstrated to confer harm (4-6) and clearly a personalised approach to VTE prophylaxis prescription balancing an individual’s risks of VTE and bleeding is required.

We read with interest the comprehensive systematic review and meta-analysis performed on this subject by Lavikainen et al. (7). The authors set out to quantify procedure-specific risks of both VTE and bleeding complications for patients undergoing a wide range of general abdominal, colorectal, upper-gastrointestinal (UGI) and hepatopancreaticobiliary (HPB) surgery. In addition, they utilised patient-related VTE risk factors to further stratify VTE risk; providing estimates for the cumulative incidence at four weeks post-surgery for both VTE and bleeding events, with and without pharmacologic thromboprophylaxis prescription. The review clearly demonstrates that at a population level, the routine prescription of pharmacologic thromboprophylaxis for certain general surgical procedures including elective laparoscopic cholecystectomy confers harm. The results and subsequent infographics generated by the authors are invaluable, and allow clinicians to begin to quantify risks and benefits of thromboprophylaxis prescription for selected procedures. The results will help inform further clinical trials and facilitate patient centred discussions. The authors should be applauded for their work and substantial contribution to the literature.

In addition to balancing absolute risks of clotting versus bleeding as advocated in this paper, there are many other factors that need to be considered when tailoring thromboprophylaxis decisions to each patient.

Lavikainen et al. (7) looked at median or absolute risk at a population level, however there are multiple patient and procedural factors not assessed within the review that significantly alter the patient’s procedure-specific baseline incidence of symptomatic VTE or major bleeding. Many of which are utilised by risk calculators like the Caprini score (8), and the Risk of BIMS (9) to generate a more personalised calculation. This raises the question—how can Lavikainen et al.’s findings be married up with these more personalised calculators to help inform decision-making processes for the patient in front of us?

The actual consequences of major bleeding and VTE complications also need to be further considered. For example, with respect to bleeding complications, intra-abdominal bleeding post-minimally invasive colectomy for cancer is likely to concern the surgeon (and patient) more than subcutaneous bleeding post elective open ventral hernia repair. In these scenarios, both procedures have a comparable bleeding risk of 1.5% and a similar risk of VTE (5) yet the consequences of bleeding may impact on thromboprophylaxis prescription practices. Similarly, the morbidity associated with VTE varies significantly depending on clot burden, clot location and other patient and procedural factors.

Like many other studies, Lavikainen et al. quantified VTE incidence at four weeks following surgery. It is important to consider that perioperative VTE risk extends to 3 months post-surgery (10). Conversely, as highlighted in their article (7), 86% of all bleeding events occurred within the first week postoperatively. This, along with the asymptomatic nature of some VTE makes it difficult to characterise the true procedure-specific rate of VTE. Therefore, it is important to recognise that the true rate of VTE is likely underestimated by systematic reviews.

The timing and type of pharmacologic thromboprophylaxis is also an important consideration. We know that pre-operative and intra-operative use of thromboprophylaxis increases the risk of bleeding events, whereas postoperative use within 24 h of skin closure mitigates bleeding risk without increasing VTE incidence (4,5,11,12). It is also not clear whether the thromboprophylaxis agent matters, though our data suggest that unfractionated heparin is associated with higher rates of bleeding than low molecular weight heparin (13).

The clinical setting is also important. Patients undergoing emergency surgery may be in a hypercoagulable state due to the nature of their acute pathology. Moreover, compared with elective procedures, emergency operations have higher rates of complications including bleeding. Therefore, findings derived from the elective setting may not translate to emergency situations. Indeed, in their study Lavikainen et al. (7) demonstrated that the incidence of VTE in patients undergoing emergency surgery, particularly in the high-risk VTE group, was noticeably higher than in their elective counterparts.

Lastly, there is significant variability in thromboprophylaxis compliance, with failure to prescribe or administer being the most common contributing factors (14). As such, strategies to improve the appropriate use of thromboprophylaxis amongst patients, especially those at high risk for VTE are necessary to improve patient outcomes. Standardising timing of administration to set time points within a clinical roster may improve thromboprophylaxis uptake, and the use of automated and integrated systems that facilitate risk stratification and prescription have been shown to improve thromboprophylaxis compliance (15).

In summary, optimising thromboprophylaxis requires consideration of multiple patient and procedural factors as well as their care environment. Having comprehensive point estimates of VTE and bleeding risk for each operation is an excellent start to facilitating a patient-centred approach to thromboprophylaxis usage. Risk calculators can also be used to help guide decision making when considering the risk and potential impacts of bleeding versus symptomatic VTE. This personalised approach must be combined with appropriate VTE thromboprophylaxis timing and type, utilising appropriate strategies or systems to facilitate compliance.

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, HepatoBiliary Surgery and Nutrition. The article did not undergo external peer review.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-24-602/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Australian Commission on Safety and Quality in Health Care. Venous Thromboembolism Prevention Clinical Care Standard. Sydney: 2020.
2. Allaway MGR, Eslick GD, Kwok GTY, et al. Improving Venous Thromboembolism Prophylaxis Administration in an Acute Surgical Unit. J Patient Saf 2021;17:e1341-5. [Crossref] [PubMed]
3. Liu DS, Wong E, Fong J, et al. Perioperative thromboprophylaxis is highly variable in general surgery: results from a multicentre survey. ANZ J Surg 2020;90:2401-3. [Crossref] [PubMed]
4. Liu DS, Stevens SG, Watson DI, et al. Optimal Timing of Perioperative Chemoprophylaxis in Patients With High Thromboembolic Risk Undergoing Major Abdominal Surgery: A Multicenter Cohort Study. Ann Surg 2023;277:79-86. [Crossref] [PubMed]
5. Klonis C, Ashraf H, Cabalag CS, et al. Optimal Timing of Perioperative Chemical Thromboprophylaxis in Elective Major Abdominal Surgery: A Systematic Review and Meta-analysis. Ann Surg 2023;277:904-11. [Crossref] [PubMed]
6. Liu DS, Newbold R, Stevens S, et al. Early Versus Postoperative Chemical Thromboprophylaxis Is Associated with Increased Bleeding Risk Following Abdominal Visceral Resections: a Multicenter Cohort Study. J Gastrointest Surg 2022;26:1495-502. [Crossref] [PubMed]
7. Lavikainen LI, Guyatt GH, Sallinen VJ, et al. Systematic Reviews and Meta-analyses of the Procedure-specific Risks of Thrombosis and Bleeding in General Abdominal, Colorectal, Upper Gastrointestinal, and Hepatopancreatobiliary Surgery. Ann Surg 2024;279:213-25. [PubMed]
8. Caprini JA. Thrombosis risk assessment as a guide to quality patient care. Dis Mon 2005;51:70-8. [Crossref] [PubMed]
9. Roshanov PS, Guyatt GH, Tandon V, et al. Preoperative prediction of Bleeding Independently associated with Mortality after noncardiac Surgery (BIMS): an international prospective cohort study. Br J Anaesth 2021;126:172-80. [Crossref] [PubMed]
10. Spencer FA, Lessard D, Emery C, et al. Venous thromboembolism in the outpatient setting. Arch Intern Med 2007;167:1471-5. [Crossref] [PubMed]
11. Liu DS, Stevens S, Wong E, et al. Pre-operative and intra-operative chemical thromboprophylaxis increases bleeding risk following elective cholecystectomy: a multicentre (PROTECTinG) study. ANZ J Surg 2020;90:2449-55. [Crossref] [PubMed]
12. PROTECTinG investigators. Chemical thromboprophylaxis before skin closure increases bleeding risk after major ventral hernia repair: A multicenter cohort study. Surgery 2022;172:198-204. [Crossref] [PubMed]
13. Liu DS, Wong DJ, Goh SK, et al. Quantifying Perioperative Risks for Antireflux and Hiatus Hernia Surgery: A Multicenter Cohort Study of 4301 Patients. Ann Surg 2024;279:796-807. [Crossref] [PubMed]
14. PROTECTinG investigators. VERITAS Collaborative. Postoperative Timing of Chemoprophylaxis and Its Impact on Thromboembolism and Bleeding Following Major Abdominal Surgery: A Multicenter Cohort Study. World J Surg 2023;47:1174-83. [Crossref] [PubMed]
15. Liu DSH, Lee MMW, Spelman T, et al. Medication chart intervention improves inpatient thromboembolism prophylaxis. Chest 2012;141:632-41. [Crossref] [PubMed]