Adolfo Llinás, Mustafa Citak, Mustafa Akkaya, Juan Sebastián Sánchez-Osorio.
Response/Recommendation: Patients with thrombophilia should receive venous thromboembolism (VTE) prophylaxis for major orthopaedic surgery. We recommend a combination of mechanical and pharmacological interventions for up to 35 days after the procedure to address the variability of VTE risk, which is difficult to estimate in frequency and magnitude. For less invasive musculoskeletal procedures, the VTE prophylaxis should be tailored according to the prothrombotic risk of each procedure, with emphasis on those of lower extremities.
Strength of Recommendation: Limited.
Rationale: The prevalence of thrombophilic abnormalities ranges from 0.02% up to 14.5%1-4 and is known to be an independent risk factor for spontaneous VTE events providing a 2-fold up to a 50-fold increased risk5, depending on the underlying disease and its severity. However, thrombotic events attributed to thrombophilia, in the absence of additional risk factors, do not surpass half of the VTE events6. This reflects the requirement for several thrombotic risk factors or high-risk situations to be present, for a clinical event to occur in patients with inherited thrombophilia7, such as surgery. Performing surgery in a patient with inherited thrombophilia supposes a 13-fold increased risk of VTE within 1 year (odds ratio [OR], 13.3 95% confidence interval [CI]; 7.2 – 24.7)8. Furthermore, VTE risk was highest within the first 30-days following surgery (OR adj 17.5; 95% CI, 9.2 – 33.4) and remained high up to 90-days postoperatively in this population8-13.
In terms of VTE risk, thromboprophylaxis guidelines stratify orthopaedic procedures in low-, intermediate-, and high-risks groups. All patients with thrombophilia should be classified in the high-risk VTE groups independently from the underlying procedure8.
The safety and effectiveness of anticoagulants or mechanical interventions on specific subtypes of thrombophilia evaluating the frequency of VTE events after surgery as a primary outcome has not been established. According to the 2016 guidelines on antithrombotic therapy by the American College of Chest Physicians (ACCP) recommend that the choice of anticoagulant should be individualized considering patient factors such as renal/liver/coronary artery diseases, adherence, and preference, however no specific mechanical and/or pharmacological protocol for patients with thrombophilia has been specified14. The low prevalence of thrombophilia, as well as the high economic burden on screening for its subtypes, would require extensive resources to answer this complex clinical question. Intuitively, one might consider a higher dose of antithrombotic medication will result in a higher protection against VTE events, however, this would affect the safety window of anticoagulants increasing the bleeding rate.
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- Nizankowska-Mogilnicka E, Adamek L, Grzanka P, et al: Genetic polymorphisms associated with acute pulmonary embolism and deep venous thrombosis. Eur Respir J 21:25–30, 2003 doi: 10.1183/09031936.03.00034302
- Makris M: Hyperhomocysteinemia and thrombosis. Clin Lab Haematol 22:133–143, 2000. doi: 10.1046/j.1365-2257.2000.00301.x
- Salvati EA, Della Valle AG, Westrich GH, Rana AJ, Specht L, Weksler BB, Wang P, Glueck CJ. The John Charnley Award: heritable thrombophilia and development of thromboembolic disease after total hip arthroplasty. Clin Orthop Relat Res. 2005 Dec;441:40-55. doi: 10.1097/01.blo.0000192366.61616.81.
- Martinelli, I., De Stefano, V. & Mannucci, P. Inherited risk factors for venous thromboembolism. Nat Rev Cardiol 11, 140–156 (2014) doi: 10.1038/nrcardio.2013.211
- Wu O, Robertson L, Twaddle S, Lowe G, Clark P. Screening for thrombophilia in high-risk situations: systematic review and cost-effectiveness analysis. The Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) study. Health Technol Assess 2006;10(11) doi: 10.3310/hta10110.
- Zambelli R, Nemeth B, Touw CE, Rosendaal FR, Rezende SM, Cannegieter SC. High risk of venous thromboembolism after orthopedic surgery in patients with thrombophilia. J Thromb Haemost. 2021 Feb;19(2):444-451. doi: 10.1111/jth.15163. doi: 10.1111/jth.15163.
- Tsantes AG, et al. Higher coagulation activity in hip fracture patients: A case-control study using rotational thromboelastometry. Int J Lab Hematol. 2021 Jun;43(3):477-484. doi: 10.1111/ijlh.13409
- Jetty V, Glueck CJ, Freiberg RA, Wang P. Venous Thromboembolism After Knee Arthroscopy in Undiagnosed Familial Thrombophilia. Orthopedics. 2016 Nov 1;39(6):e1052-e1057. doi: 10.3928/01477447-20160719-02.
- Glueck CJ, Freiberg RA, Wang P. Medical treatment of osteonecrosis of the knee associated with thrombophilia-hypofibrinolysis. Orthopedics. 2014 Oct;37(10):e911-6. doi: 10.3928/01477447-20140924-59
- Chotanaphuti T, Ongnamthip P, Silpipat S, Foojareonyos T, Roschan S, Reumthantong A. The prevalence of thrombophilia and venous thromboembolism in total knee arthroplasty. J Med Assoc Thai. 2007 Jul;90(7):1342-7. PMID: 17710975.
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- Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest 2016;149:315-352. doi: 10.1016/j.chest.2015.11.026