George Komnos, Theofilos Karachalios, Eugénia Cruz, Farideh Najafi, Neusha Hollingworth, Javad Parvizi.
Response/Recommendation: It is generally known that the severe acute respiratory syndrome-related coronavirus (SARS-CoV [COVID – 19]) infection predisposes individuals to a higher risk of thromboembolism. However, there is not sufficient data to suggest that a previous COVID – 19 infection increases the risk of venous thromboembolism (VTE) after an orthopaedic procedure. Thus, the VTE prophylaxis of patients with prior COVID – 19 does not need to be altered.
Strength of Recommendation: Limited.
Rationale: It has been demonstrated that COVID – 19 infection can result in coagulopathy and thromboembolic disease1 with a high risk of VTE2. This can be explained by the association between COVID – 19 and inflammation, increased clot firmness and decreased clot formation time3. Similar to the effects of COVID – 192,4,5 orthopaedic injuries cause a hyperinflammatory and hypercoagulable response, increasing VTE risk. The additive effects of these factors can amplify inflammatory response to the traumatic insult and pose an even greater VTE risk, while lowering survival rates6. Because of the latter concern and the potential for increased risk for mortality, some studies have proposed that elective surgical intervention be delayed in patients with active COVID – 19 infection7,8. On the other hand, there is also some data to suggest that patients who had a delay in receiving their total joint arthroplasty due to COVID – 19 protocols may be at risk of VTE9.
Appropriate thromboprophylaxis is essential to prevent venous thrombotic complications associated with orthopaedic procedures, whether surgeries are elective (as hip and knee arthroplasties) or due to trauma10–13. Extended prophylaxis (for up to 45 days) can be considered for patients with elevated risk of VTE (e.g., immobility, presence of comorbidities such as active cancer or prior VTE)14-16. It is also important to include the assessment of bleeding risk in this decision. However, anticoagulant choice, dosage, and the duration in patients undergoing orthopaedic procedures who have previously been infected with COVID – 19 are not yet well studied. Several factors, such as the severity and length of the COVID – 19 infection, and the comorbidities of the individual seem to lead to a high heterogeneity of VTE presentation among this population17. The issue of VTE prophylaxis for patients with COVID – 19 infection was discussed by the International Consensus Group (ICM) and in their published guidelines of July 2020, the recommendation was to administer some form of VTE prophylaxis for this patient group undergoing orthopedic procedures18.
In a recent study by Perazzo et al,19. 16 patients with fracture of proximal femur who also had COVID – 19 infection were evaluated. The first seven patients received a single daily dose of low-molecular-weight heparin (LMWH), among whom four patients died of cardiovascular complications (four deaths). In the following nine patients with COVID – 19 and proximal femoral fracture, the dose of LMWH was doubled. There was only one death in that group. None of the patients died of VTE related complications and the sample size was so small that no conclusive deductions could be drawn from the study.
In a review paper, some investigators attempted to evaluate the potential implications of commonly prescribed medications in orthopaedic surgery for COVID – 19 patients, including VTE prophylaxis20. In one letter, some authorities recommended that injectable VTE prophylaxis be used in lieu of oral anticoagulant21. The authors felt that patients with COVID – 19 infection exhibited high variability in prothrombin time and international normalized ratio (INR) due to the issues with vitamin K metabolism in patients with acute viral infection. They also felt that patients with COVID – 19 receiving other oral anticoagulants may be exposed to under/over treatment caused by significant pharmacological interferences. Similar recommendations were made by other authorities in a follow-up publication22. There is some data to suggest that aspirin may be useful in preventing critical illness associated with COVID – 1923 and it is also stipulated that oral anticoagulants may help decrease the hyperinflammatory effects of COVID – 19 in general24.
In conclusion, and based on current data, there is no need to change the VTE prophylaxis of patients with prior COVID – 19 undergoing orthopedic procedures. The decision to choose one agent versus other should rely on the risk-benefit ratio for these patients like others.
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2. Fogarty H, Townsend L, Ni Cheallaigh C, et al. COVID19 coagulopathy in Caucasian patients. Br J Haematol. 2020;189(6):1044-1049. doi:10.1111/bjh.16749
3. The Procoagulant Effect of COVID-19 on the Thrombotic Risk of Patients with Hip Fractures Due to Enhanced Clot Strength and Fibrinolysis Shutdown – PubMed. Accessed September 30, 2021. https://pubmed.ncbi.nlm.nih.gov/34362178/
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6. Puzzitiello RN, Pagani NR, Moverman MA, Moon AS, Menendez ME, Ryan SP. Inflammatory and Coagulative Considerations for the Management of Orthopaedic Trauma Patients With COVID-19: A Review of the Current Evidence and Our Surgical Experience. J Orthop Trauma. 2020;34(8):389-394. doi:10.1097/BOT.0000000000001842
7. Iyengar K, Vaish A, Vaishya R. Revisiting conservative orthopaedic management of fractures during COVID-19 pandemic. J Clin Orthop Trauma. 2020;11(4):718-720. doi:10.1016/j.jcot.2020.05.010
8. Mi B, Chen L, Xiong Y, Xue H, Zhou W, Liu G. Characteristics and Early Prognosis of COVID-19 Infection in Fracture Patients. J Bone Joint Surg Am. 2020;102(9):750-758. doi:10.2106/JBJS.20.00390
9. Khan SA, Logan P, Asokan A, et al. The incidence of venous thromboembolism in total joint replacement during COVID-19 pandemic: has lockdown had an influence? Bone Jt Open. 2020;1(12):751-756. doi:10.1302/2633-1462.112.BJO-2020-0144.R1
10. Johanson NA, Lachiewicz PF, Lieberman JR, et al. Prevention of symptomatic pulmonary embolism in patients undergoing total hip or knee arthroplasty. J Am Acad Orthop Surg. 2009;17(3):183-196. doi:10.5435/00124635-200903000-00007
11. 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. doi:10.1378/chest.08-0656
12. Falck-Ytter Y, Francis CW, Johanson NA, et al. Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e278S-e325S. doi:10.1378/chest.11-2404
13. Warren JA, Sundaram K, Anis HK, Kamath AF, Higuera CA, Piuzzi NS. Have Venous Thromboembolism Rates Decreased in Total Hip and Knee Arthroplasty? J Arthroplasty. 2020;35(1):259-264. doi:10.1016/j.arth.2019.08.049
14. Spyropoulos AC, Levy JH, Ageno W, et al. Scientific and Standardization Committee communication: Clinical guidance on the diagnosis, prevention, and treatment of venous thromboembolism in hospitalized patients with COVID-19. J Thromb Haemost. 2020;18(8):1859-1865. doi:10.1111/jth.14929
15. Moores LK, Tritschler T, Brosnahan S, et al. Prevention, Diagnosis, and Treatment of VTE in Patients With Coronavirus Disease 2019: CHEST Guideline and Expert Panel Report. Chest. 2020;158(3):1143-1163. doi:10.1016/j.chest.2020.05.559
16. Bikdeli B, Madhavan MV, Jimenez D, et al. COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-Up: JACC State-of-the-Art Review. J Am Coll Cardiol. 2020;75(23):2950-2973. doi:10.1016/j.jacc.2020.04.031
17. Goshua G, Lee AI. Harmonizing hypercoagulable heterogeneity: Baseline VTE risk in COVID-19. Res Pract Thromb Haemost. 2021;5(1):9-10. doi:10.1002/rth2.12448
18. Parvizi J, Gehrke T, Krueger CA, et al. Resuming Elective Orthopaedic Surgery During the COVID-19 Pandemic: Guidelines Developed by the International Consensus Group (ICM). J Bone Joint Surg Am. 2020;102(14):1205-1212. doi:10.2106/JBJS.20.00844
19. Perazzo P, Giorgino R, Briguglio M, et al. From Standard to Escalated Anticoagulant Prophylaxis in Fractured Older Adults With SARS-CoV-2 Undergoing Accelerated Orthopedic Surgery. Front Med (Lausanne). 2020;7:566770. doi:10.3389/fmed.2020.566770
20. Tan SHS, Hong CC, Saha S, Murphy D, Hui JH. Medications in COVID-19 patients: summarizing the current literature from an orthopaedic perspective. Int Orthop. 2020;44(8):1599-1603. doi:10.1007/s00264-020-04643-5
21. Testa S, Paoletti O, Giorgi-Pierfranceschi M, Pan A. Switch from oral anticoagulants to parenteral heparin in SARS-CoV-2 hospitalized patients. Intern Emerg Med. 2020;15(5):751-753. doi:10.1007/s11739-020-02331-1
22. Piazza G, Morrow DA. Diagnosis, Management, and Pathophysiology of Arterial and Venous Thrombosis in COVID-19. JAMA. 2020;324(24):2548-2549. doi:10.1001/jama.2020.23422
23. Sayed Ahmed HA, Merrell E, Ismail M, et al. Rationales and uncertainties for aspirin use in COVID-19: a narrative review. Fam Med Community Health. 2021;9(2):e000741. doi:10.1136/fmch-2020-000741
24. Paar V, Wernly B, Zhou Z, et al. Anti-coagulation for COVID-19 treatment: both anti-thrombotic and anti-inflammatory? J Thromb Thrombolysis. 2021;51(1):226-231. doi:10.1007/s11239-020-02212-6