99 – If a patient is in an “increased risk” group for the development of VTE, are there certain agents which have increased efficacy over other anticoagulants?

99 – If a patient is in an “increased risk” group for the development of VTE, are there certain agents which have increased efficacy over other anticoagulants?

Dennis Sievers, William Jiranek, Ronald Navarro.

Response/Recommendation: There is limited evidence to support that certain anticoagulants have increased efficacy over other anticoagulants. The specific factor that increases a patient’s risk for venous thromboembolism (VTE) must be considered and treatment tailored to that specific cause, after considering drug class, and dosing regimen.

Strength of Recommendation: Limited.

Rationale: The presence of certain conditions are known to increase a patient’s risk for venous thromboembolism (VTE), such as cancer1,2, older age3, cystic fibrosis4, chronic kidney disease (CKD)5, and obesity6. Surgery can also increase a patient’s risk for VTE, especially many types of orthopaedic surgeries which tend to limit a patient’s ability to be physically active for a period of time following a procedure7. While there are many drug regimens to combat the increased risk from surgery and the above comorbidities, there lacks a consensus as to which drugs, if any, have increased efficacy in the setting of orthopaedic surgery performed on patients with increased risk for VTE8,9.

Two studies examined VTE prophylaxis in the setting of cancer. Key et al., compared direct oral anticoagulants (DOAC) and low-molecular-weight heparin (LMWH) for VTE prophylaxis in patients with cancer2. Their results showed that both categories of drugs were effective VTE prophylaxis, but the DOAC had a higher risk of bleeding compared to LMWH. The authors recommended apixaban, rivaroxaban, or LMWH in high-risk cancer patients and advised for the start of pharmacotherapy prior to surgery and to continue 7-10 days after surgery. A systematic review by Lex et al., was performed regarding VTE prophylaxis in orthopaedic oncology patients10. The authors concluded that there is limited evidence to guide clinicians in VTE prophylaxis in this population. They suggest that both mechanical and pharmacologic techniques can be utilized. They also report that no specific pharmacological agent has been shown to be superior to others as VTE prophylaxis.

A study by Krantz et al., compared the incidence of VTE in high-risk elderly trauma patients receiving either unfractionated heparin (UFH) or the LMWH (enoxaparin)11. They found similar incidence of VTE between the two groups but concluded that further research is required to determine the noninferiority of UFH compared to enoxaparin in this population of older individuals.

CKD has been shown to increase the risk of VTE12. Shorr et al., performed a study of VTE and bleeding incidence in patients undergoing total hip arthroplasty (THA) with stage 3B CKD receiving either desirudin or enoxaparin5. The results showed similar rates of bleeding events, but a markedly increased incidence of VTE in the enoxaparin group compared to the desirudin group.

The use of aspirin (ASA) as a form of VTE prophylaxis in an obese population was examined by Tang et al.13. This study compared VTE incidence in obese patients versus nonobese patients receiving ASA following revision THA or total knee arthroplasty. The study revealed similar rates of VTE between the two groups and the authors concluded that ASA was safe and effective for VTE prophylaxis in obese patients as compared to non-obese patients, although this study does not include another drug for comparison. Other studies of VTE prophylaxis in obese populations have revealed better outcomes with high dose regimens of LMWH compared to standard dosing regimens, but these too did not compare the efficacy against a different drug14,15.

At this time when outpatient surgery especially in surgical centers remote from main hospitals is increasing and accelerated with the 2020 pandemic, it is important to consider that this venue may create a potential differential risk group. Venclauskas et al., published guidelines for perioperative VTE prophylaxis in the setting of outpatient surgery16. They recommend that patients with additional risk factors for VTE undergoing a lower risk surgery receive general measures of thromboprophylaxis and offer a suggestion of LMWH. In patients with additional risk factors for VTE undergoing a higher risk surgery, they suggest preferential administration of LMWH over other drugs.

Further work needs to be done to conclude if certain anticoagulants are more effective than others for VTE prophylaxis in patients at increased risk of VTE. Attention must be given to the specific cause of increased risk along with the dosing regimen of the chosen mechanical and chemoprophylaxis.


1.         Ay C, Pabinger I, Cohen AT. Cancer-associated venous thromboembolism: Burden, mechanisms, and management. Thromb Haemost. 2017;117(2):219-230. doi:10.1160/TH16-08-0615

2.         Key NS, Khorana AA, Kuderer NM, et al. Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: ASCO Clinical Practice Guideline Update. J Clin Oncol. 2020;38(5):496-520. doi:10.1200/JCO.19.01461

3.         Kozek-Langenecker S, Fenger-Eriksen C, Thienpont E, Barauskas G, ESA VTE Guidelines Task Force. European guidelines on perioperative venous thromboembolism prophylaxis: Surgery in the elderly. Eur J Anaesthesiol. 2018;35(2):116-122. doi:10.1097/EJA.0000000000000705

4.         Takemoto CM. Venous thromboembolism in cystic fibrosis. Pediatr Pulmonol. 2012;47(2):105-112. doi:10.1002/ppul.21566

5.         Shorr AF, Eriksson BI, Jaffer AK, Smith J. Impact of stage 3B chronic kidney disease on thrombosis and bleeding outcomes after orthopedic surgery in patients treated with desirudin or enoxaparin: insights from a randomized trial. J Thromb Haemost. 2012;10(8):1515-1520. doi:10.1111/j.1538-7836.2012.04803.x

6.         Shaikh S, Boneva D, Hai S, McKenney M, Elkbuli A. Venous thromboembolism chemoprophylaxis regimens in trauma and surgery patients with obesity: A systematic review. J Trauma Acute Care Surg. 2020;88(4):522-535. doi:10.1097/TA.0000000000002538

7.         Anderson FA, Spencer FA. Risk factors for venous thromboembolism. Circulation. 2003;107(23 Suppl 1):I9-16. doi:10.1161/01.CIR.0000078469.07362.E6

8.         Lieberman JR, Heckmann N. Venous Thromboembolism Prophylaxis in Total Hip Arthroplasty and Total Knee Arthroplasty Patients: From Guidelines to Practice. J Am Acad Orthop Surg. 2017;25(12):789-798. doi:10.5435/JAAOS-D-15-00760

9.         Kepler CK, McKenzie J, Kreitz T, Vaccaro A. Venous Thromboembolism Prophylaxis in Spine Surgery. J Am Acad Orthop Surg. 2018;26(14):489-500. doi:10.5435/JAAOS-D-17-00561

10.       Lex JR, Evans S, Cool P, et al. Venous thromboembolism in orthopaedic oncology. Bone Joint J. 2020;102-B(12):1743-1751. doi:10.1302/0301-620X.102B12.BJJ-2019-1136.R3

11.       Krantz EN, Philpott CD, Droege ME, et al. Retrospective Evaluation of Venous Thromboembolism Prophylaxis in Elderly, High-Risk Trauma Patients. J Surg Res. 2020;249:225-231. doi:10.1016/j.jss.2019.12.024

12.       Wattanakit K, Cushman M. Chronic kidney disease and venous thromboembolism: epidemiology and mechanisms. Curr Opin Pulm Med. 2009;15(5):408-412. doi:10.1097/MCP.0b013e32832ee371

13.       Tang A, Sicat CS, Singh V, Rozell JC, Schwarzkopf R, Long WJ. Aspirin Use for Venous Thromboembolism Prevention Is Safe and Effective in Overweight and Obese Patients Undergoing Revision Total Hip and Knee Arthroplasty. J Arthroplasty. 2021;36(7S):S337-S344. doi:10.1016/j.arth.2020.12.006

14.       Wang T-F, Milligan PE, Wong CA, Deal EN, Thoelke MS, Gage BF. Efficacy and safety of high-dose thromboprophylaxis in morbidly obese inpatients. Thromb Haemost. 2014;111(1):88-93. doi:10.1160/TH13-01-0042

15.       Tran VN, Varfolomeev I, Hill G. Prophylactic Enoxaparin Dosing in Obese Orthopedic Patients: A Literature Search. Hosp Pharm. 2020;55(6):366-372. doi:10.1177/0018578719848732

16.       Venclauskas L, Llau JV, Jenny J-Y, Kjaersgaard-Andersen P, Jans Ø, ESA VTE Guidelines Task Force. European guidelines on perioperative venous thromboembolism prophylaxis: Day surgery and fast-track surgery. Eur J Anaesthesiol. 2018;35(2):134-138. doi:10.1097/EJA.0000000000000706

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