Abtin Alvand, Raja Bhaskara Rajasekaran, Adolph J. Yates, Jr.
Response/Recommendation: The most optimal thromboprophylaxis in patients on strict bed rest is not known. Any combination of chemical and/or mechanical (i.e., intermittent compression devices) prophylaxis may be considered in patients who will be on prolonged and strict bed rest.
Strength of Recommendation: Limited.
Rationale: Prolonged bed rest is well-known to increase the risk of venous thromboembolism (VTE)1. Strict bed rest for more than 7 days, especially after a fracture, is a significant risk factor in developing VTE2,3. Despite the recognized risk, there is a paucity of literature recommending the optimal prophylaxis for these patients4. Chemical prophylaxis, including low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH), and mechanical measures (such as graduated compression stockings [GCS], and intermittent pneumatic compression [IPC]) have been suggested by some authors5,6.
Paucity in the literature regarding optimal prophylaxis often results in clinicians prescribing aggressive or long-term anticoagulation for patients on strict bed rest. The United Kingdom’s National Institute of Clinical Excellence (NICE) guidelines7, and the American Society of Hematology (ASH) guidelines8 do not provide precise recommendations on how to prevent VTE in patients who are restricted to bed rest. LMWH is advised up to 12 hours from surgery in hip fractures if surgery is delayed beyond the day of admission8. In patients where pharmacological prophylaxis is contraindicated, mechanical prophylaxis, including IPC, or GCS is advised7,9. One of the common limitations of these guidelines is that they do not focus specifically on the issue of “strict bed rest” during the pre-or post-surgery period.
For patients who are bedbound/bedridden due to acute medical illness, LMWH is an effective prophylactic option6,10 and reduces VTE-related events but does not reduce mortality11. Studies have also shown the use of IPC, and GCS to be efficacious in hospitalized patients with prolonged immobilization12-14. Ho et al., reviewed this in a meta-analysis and concluded that combining IPC with pharmacological prophylaxis to be more effective than IPC alone13. It must be noted that their sub-analysis was not limited to patients on strict bed rest but involved hospitalized patients. A multicenter randomized clinical trial RCT analyzing dose-specific prophylaxis in bedridden patients due to acute illness found that a 20 mg daily dose of subcutaneous LMWH (enoxaparin) for 10 days to be effective in preventing VTE15.
Although it is widely recognized that bed rest increases the risk of deep venous thrombosis (DVT), and pulmonary embolism (PE), there is only limited evidence that addresses the most optimal VTE prophylactic agent in this group of patients, especially with regards to orthopaedic surgery. Nevertheless, despite the proven efficacy of LMWH in reducing VTE risk in patients with immobilization and evidence from a multicenter RCT, there is limited evidence to suggest that subcutaneous LMWH is effective in the prevention of VTE. The role of combined prophylaxis, including chemical and mechanical prophylaxis, including IPC in this subset of patients, needs to be analyzed in well-designed prospective studies in the future.
References:
1. Kyrle PA, Eichinger S. Deep vein thrombosis. Lancet. 2005;365(9465):1163-1174. doi:10.1016/S0140-6736(05)71880-8
2. Liu Z, Tao X, Chen Y, Fan Z, Li Y. Bed rest versus early ambulation with standard anticoagulation in the management of deep vein thrombosis: a meta-analysis. PLoS One. 2015;10(4):e0121388. Published 2015 Apr 10. doi:10.1371/journal.pone.0121388
3. Xia ZN, Xiao K, Zhu W, et al. Risk assessment and management of preoperative venous thromboembolism following femoral neck fracture. J Orthop Surg Res. 2018;13(1):291. Published 2018 Nov 20. doi:10.1186/s13018-018-0998-4
4. Struijk-Mulder MC, Ettema HB, Heyne RA, Rondhuis JJ, Büller HR, Verheyen CC. Venous thromboembolism during hip plaster cast immobilisation: review of the literature. Neth J Med. 2014;72(1):17-19.
5. 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. doi:10.1001/archinte.162.11.1245
6. Ettema HB, Kollen BJ, Verheyen CC, Büller HR. Prevention of venous thromboembolism in patients with immobilization of the lower extremities: a meta-analysis of randomized controlled trials. J Thromb Haemost. 2008;6(7):1093-1098. doi:10.1111/j.1538-7836.2008.02984.x
7. Venous thromboembolism in over 16s: reducing the risk of hospital-acquired deep vein thrombosis or pulmonary embolism. London: National Institute for Health and Care Excellence (UK); August 13, 2019.
8. Ktistakis I, Giannoudis V, Giannoudis PV. Anticoagulation therapy and proximal femoral fracture treatment: An update. EFORT Open Rev. 2017;1(8):310-315. Published 2017 Mar 13. doi:10.1302/2058-5241.1.160034
9. Holger J. Schünemann, Mary Cushman, Allison E. Burnett, Susan R. Kahn, Jan Beyer-Westendorf, Frederick A. Spencer, Suely M. Rezende, Neil A. Zakai, Kenneth A. Bauer, Francesco Dentali, Jill Lansing, Sara Balduzzi, Andrea Darzi, Gian Paolo Morgano, Ignacio Neumann, Robby Nieuwlaat, Juan J. Yepes-Nuñez, Yuan Zhang, Wojtek Wiercioch; American Society of Hematology 2018 guidelines for management of venous thromboembolism: prophylaxis for hospitalized and nonhospitalized medical patients. Blood Adv 2018; 2 (22): 3198–3225. doi: https://doi.org/10.1182/bloodadvances.2018022954
10. Jacobs, B. N., Cain-Nielsen, A. H., Jakubus, J. L., Mikhail, J. N., Fath, J. J., Regenbogen, S. E., & Hemmila, M. R. (2017). Unfractionated heparin versus low-molecular-weight heparin for venous thromboembolism prophylaxis in trauma. The journal of trauma and acute care surgery, 83(1), 151–158. https://doi.org/10.1097/TA.0000000000001494
11. Mahé I, Bergmann JF, d’Azémar P, Vaissie JJ, Caulin C. Lack of effect of a low-molecular-weight heparin (nadroparin) on mortality in bedridden medical in-patients: a prospective randomised double-blind study. Eur J Clin Pharmacol. 2005;61(5-6):347-351. doi:10.1007/s00228-005-0944-3
12. Sachdeva A, Dalton M, Amaragiri SV, Lees T. Elastic compression stockings for prevention of deep vein thrombosis. Cochrane Database Syst Rev. 2010;(7):CD001484. Published 2010 Jul 7. doi:10.1002/14651858.CD001484.pub2
13. Ho, K. M., & Tan, J. A. (2013). Stratified meta-analysis of intermittent pneumatic compression of the lower limbs to prevent venous thromboembolism in hospitalized patients. Circulation, 128(9), 1003–1020. https://doi.org/10.1161/CIRCULATIONAHA.113.002690
14. Sachdeva A, Dalton M, Amaragiri SV, Lees T. Graduated compression stockings for prevention of deep vein thrombosis. Cochrane Database Syst Rev. 2014;(12):CD001484. Published 2014 Dec 17. doi:10.1002/14651858.CD001484.pub3
15. Bergmann, J. F., & Neuhart, E. (1996). A multicenter randomized double-blind study of enoxaparin compared with unfractionated heparin in the prevention of venous thromboembolic disease in elderly in-patients bedridden for an acute medical illness. The Enoxaparin in Medicine Study Group. Thrombosis and haemostasis, 76(4), 529–534.