Karsten Keller, Lukas Hobohm.
Response/Recommendation: Increasing age is associated with an increased risk of postoperative venous thromboembolism (VTE) in patients undergoing orthopaedic procedures.
Strength of Recommendation: Strong.
Rationale: Increasing age is an important risk factor for the development of VTE1–9 as well as for a poor outcome following an acute VTE8,10–15. The incidence of this complication has been shown to increase exponentially with age9,16 and this increase in risk is similar in both male and female individuals9. Studies have revealed that the prevalence of established VTE risk factors also varies with age17. In addition to major surgery, malignancy accounts for approximately 20% of the overall incidence of VTE18,19. Familial and genetic factors are also important for the development of VTE, although the relative contribution of familial factors declines with age9. Several epidemiologic studies have shown that the rate of VTE events following knee or hip joint replacements increases significantly with a patient’s age20–38.
The results of some key studies are presented as follows: White et al., demonstrated that patients‘ age was independently associated with a thromboembolic complication (odds ratio [OR] 1.15 for each 10-year increase in age over 50 years and a 95% confidence interval [CI], 1.1-1.3) among 19,586 patients who underwent primary hip arthroplasties and 24,059 who underwent primary knee arthroplasties24. In a large nationwide study on hip replacements including 1’885,839 patients from 2005-2016 in Germany, Keller at al., reported that the number of VTE events increased with age (β 0.33 per age decade [95% CI 0.30-0.35])21. A second study including 1’804,496 hospitalized patients who had elective primary knee joint replacement demonstrated that VTE risk was age-dependent (β 0.14 [95% CI 0.12 to 0.15], per age decade)22. In accordance with these findings, in the Danish Knee Arthroplasty Registry, Pedersen et al., identified 37,223 primary knee arthroplasties performed from 1997 to 2007 in patients who received pharmacological thromboprophylaxis31. The risk of hospitalization with VTE increased with increasing age, and this risk was highest in patients >80 years old (adjusted relative risk [RR] 1.58 [95% CI 1.01 to 2.47]) compared to patients <50 years31. Yhim et al., analyzed 306,912 patients with total joint replacement (261,260 total knee and 45,652 total hip replacements) in the Health Insurance Review and Assessment Service (HIRA) database35. Patients ≥60 years (OR 2.20 [95% CI 1.98–2.45]) showed a higher risk of postoperative VTE compared to patients <60 years35. In the New York State database from 1985 to 2003, Lyman et al., analyzed 152,461 patients who had total hip arthroplasties (THA) and 162,085 who had total knee arthroplasty (TKA)38. Increased age was associated with a higher number of VTE events (TKA: OR 1.03 per 10-year increase in age [95% CI 1.00-1.06]; THA: OR 1.10 per 10-year increase in age [95% CI 1.07-1.13])38. In a separate study, Wu et al., analyzed 114,026 patients undergoing hip (n=61,460) or knee (n=52,566) replacement surgery between 2002 and 2006 using the National Health Insurance database of Taiwan and found that VTE rates in patients aged 60–69 (OR 2.33 [95% CI 1.34-4.06]) and 70–79 (OR 1.90 [95% CI 1.15-3.16]) years were higher compared to those who were younger than 50 years30.
In contrast, only a very few studies have reported no relationship between age and the incidence of VTE39–41. Furthermore, others have reported divergent results for hip and knee arthroplasty32,34. Data from the Spanish National Discharge Database in 2005–2006 revealed that age >70 years was associated with VTE in THA (OR 1.5 [95% CI 1.1–1.9]), but not associated with VTE in TKA33. When analyzing 93,071 THA and 223,600 TKA in the Nationwide Inpatient Sample (NIS) database from 2003 to 2006, Kapoor et al., observed that age ≥80 years was accompanied by a higher postoperative VTE rate following THA compared to patients aged 65-69 years (OR 1.30 [95% CI 1.05-1.60]), but advanced age was not associated with a higher VTE rate in patients who underwent TKA32.
Although the rate of VTE after orthopedic surgeries of the upper limb is substantially lower than after orthopedic surgeries of the lower extremities42, an age-dependent increase was also found in most of these studies38,43–45. In the study by Lyman et al., including 13,759 patients who underwent shoulder arthroplasty, an increase in VTE occurrence (OR 1.19 [95% CI 1.02-1.37]) was seen with every 10-year increase in age38. Consistent with this, Kunutsor et al., conducted a large study of 672,495 primary shoulder and elbow replacements, observing that age ≥70 years was associated with an elevated risk for VTE (RR 1.15 [95% CI 1.08-1.22])43. Jameson et al., similarly found an increased VTE risk after arthroscopy of the shoulder in 65,302 patients aged ≥70 years versus <60 years, but this association was not demonstrated in 10,229 patients undergoing elective shoulder replacement and 4,696 patients undergoing proximal humeral fracture surgery44.
The influence of age on VTE risk in patients with fractures of the lower extremity and oncologic orthopedic surgeries were not consistent46–55. In patients undergoing surgical treatment of fractures below the hip, age ≥60 years was identified as a risk factor for VTE (RR 1.85 [95% CI 1.34-2.55]) in 191,294 patients46. Similarly, Park et al., showed that advanced age of ≥60 years was associated with higher risk of VTE (OR 3.1 [1.3-7.4]) in 901 patients who underwent surgical treatment of fractures below the hip49. In addition, Zhang et al., reported that patients ≥65 years of age had a higher risk of preoperative deep vein thrombosis following closed distal femur fractures (OR 4.39 [95% CI 1.73-11.16)56(p65). In contrast, the study by McNamara et al., that analyzed 5,300 hip fracture patients revealed no age-dependent impact on VTE occurrence48.
A study by Congiusta et al., utilized the NIS database to determine the VTE rate after benign as well as malignant musculoskeletal tumor surgery55. After analyzing more than 18,000 patients with benign tumors and more than 69,000 patients with malignant musculoskeletal tumors, all age groups except for patients ≥80 years had a higher frequency of VTE following malignant tumor surgery compared to the <30 years age group55. In patients who had surgery for benign musculoskeletal tumors, only patients ≥80 years had a higher VTE risk55. Fu et al., showed that in patients who had surgery for musculoskeletal tumors, an age of >60 years was associated with a higher VTE rate in comparison to patients aged <60 years (26.4% vs. 21.2%)47. The study by Yamaguchi et al., identified age >70 years as a risk factor for VTE events in 94 patients undergoing musculoskeletal tumor resection52. In contrast, other studies were not able to detect an association between age and VTE occurrence50,51,53,54.
In view of the wealth of national registry-based studies with large cohorts undergoing primary major joint replacements, fracture surgeries, and orthopedic tumor surgeries, there is ample evidence demonstrating an association between increasing age and a higher risk of VTE after orthopedic surgery20–36,38,43–46,49,55. This association was stronger for patients who underwent THA20–36 compared to TKA32–34. Although a patient’s age seems to be a weaker risk factor compared to other VTE risk factors (e.g., immobilization), it should be recognized that the prevalence of important concomitant VTE risk factors (e.g., malignancy) also increases with advanced age18,19,23,25,29,57.
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