Very few sets of guidelines have addressed the ageing issue. No recommendations are directly dedicated to the elderly, especially in the perioperative setting. However, if the venous thromboembolism (VTE) risk is known to increase with age, the bleeding risk is also increasing. Therefore, it was of utmost importance to address the elderly issue in these guidelines.
Risk factors for venous thromboembolism in the elderly
Large population-based epidemiological studies globally show that VTE is predominantly a disease of older age, and it rarely occurs prior to late adolescence.1–8 Incidence rates increase markedly with age for men and women, as well as for deep vein thrombosis (DVT) and pulmonary embolism.2,4,6
Cushman et al.2 conducted a longitudinal investigation of VTE cause in a cohort of middle-aged (>45 years) and older patients in the United States (n = 21 680), and followed them for 7.6 years. The age-standardised incidence of first-time VTE was 1.92 per 1000 person-years. The incidence of first lifetime VTE increased with age, with rates among patients more than 65 years old more than three times those in patients aged 45 to 54 years. The researchers reported that incidence was similar in men and women. However, above the age of 75 years, the rate in men was twice that in women [5.5 (95% confidence interval (CI) 3.8 to 8.0) per 1000 person-years vs. 2.7 (95% CI 1.7 to 4.3) per 1000 person-years]. There was no antecedent trauma, surgery, immobilisation or diagnosis of cancer for 48% (175/366) of events.
Naess et al.4 conducted a case–controlled population-based study in a county of 91 194 residents aged more than 20 years in Norway. The incidence rate for all first VTE events was 1.43 per 1000 person-years (95% CI 1.33 to 1.54); for DVT, it was 0.93 per 1000 person-years (95% CI 0.85 to 1.02) and for pulmonary embolism it was 0.50 per 1000 person-years (95% CI 0.44 to 0.56). The incidence rates increased exponentially with age and were slightly higher in women than in men.
Silverstein et al.6 followed a population of a county in the United States (106 470 inhabitants) during a time period of 25 years and found that the incidence of VTE rose markedly with increasing age for both sexes, with pulmonary embolism accounting for most of the increase. Significantly, the researchers found that the rate of pulmonary embolism decreased markedly during the study; it was approximately 45% lower during the last 15 years of the study. This effect was seen for both men and women, and it was seen for all age strata. The incidence of DVT, however, remained constant for men across all age strata, decreased for women younger than 55 years and increased for women older than 60 years.
More evidence for the relevance of age as a risk factor for VTE was published by Oger5 in a study of the incidence of VTE in a French community population. The researchers found that the rate of VTE increased with age. For patients older than 75 years, an incidence of more than 1% was found. This study also reported that the rate of pulmonary embolism as a proportion of total VTE increased with age.
A recent population-based study of residents of a large New England metropolitan area has revealed that the magnitude of VTE increases even more dramatically to 885/100 000 of the population in those who are 85 years and older.9
Anderson and Spencer10 have identified and categorised risk factors for VTE into
- strong [odds ratio (OR) >10] – hip or leg fracture/replacement, major general surgery, major trauma, spinal cord injury
- moderate (2 < OR < 9) – arthroscopic knee surgery, central venous lines, chemotherapy, congestive heart or respiratory failure, HRT, malignancy, paralytic stroke, previous VTE, thrombophilia
- weak (OR < 2) – bed rest for more than 3 days, increasing age, laparoscopic surgery, obesity, varicose veins.
In a prospective cohort study in four US communities involving 4859 participants aged 65 years and older, 52% of the sample were classified as having intermediate or definite frailty.11 After adjustment for age, race, sex, BMI and diabetes, the relative risk (RR) of total VTE for people who were frail compared with no frailty was 1.31 (95% CI 0.93 to 1.84). The comparably adjusted RR for idiopathic VTE was 1.79 (95% CI 1.02 to 3.13).
Similarly, Leibson et al.12 found in a population-based nested case–control study that, contrary to previous assumptions, most VTE risk factors identified in non-nursing home populations do not apply to the nursing home residents who may be characterised as frail. Nursing home residents with infection, substantial mobility limitations or recent general surgery should be considered potential candidates for VTE prophylaxis.
Tsai et al.13 have shown that among hospitalisations of adults, age, sex, race and other variables were important determinants of VTE. Each of the following pre-existing co-morbid conditions – AIDS, anaemia, arthritis, congestive heart failure, coagulopathy, hypertension, lymphoma, metastatic cancer, other neurological disorders, obesity, paralysis, pulmonary circulation disorders, renal failure, solid tumour without metastasis and weight loss – was associated independently with 1.04 (95% CI 1.02 to 1.06) to 2.91 (95% CI 2.81 to 3.00) times increased likelihood of VTE diagnosis. The presence of two or more such conditions was associated with a 180 to 450% increased likelihood of a VTE diagnosis.
Post-menopausal oestrogen replacement is associated with an increased risk of VTE, and this risk may be highest in the first year of use.14 An estimated OR of 3.5 for VTE amongst users of HRT compared with controls suggests that this medical population as an at-risk population for VTE.1 Similarly, another study has revealed in multi-variate analysis that the risk for VTE was even more increased among women who had lower extremity fractures [relative hazard, 18.1 (CI 5.4 to 60.4)] or cancer [relative hazard, 3.9 (CI 1.6 to 9.4)] and for 90 days after inpatient surgery [relative hazard, 4.9 (CI 2.4 to 9.8)] or non-surgical hospitalisation [relative hazard, 5.7 (CI 3.0 to 10.8)].15 In addition, post-menopausal therapy with oestrogen and progestin increases risk for VTE in women with coronary artery disease. These risks should be considered when the risks and benefits of therapy are being weighed up.
Diabetes remains a debatable risk factor for VTE in the elderly as well as in the younger population. In a population-based case–control study from the United States, diabetes mellitus and diabetes complications were shown not to be independent risk factors of incident VTE.16 On the contrary, the most recent Taiwan longitudinal nationwide cohort study indicated that type 2 diabetes mellitus patients carried greater risks of developing VTE than did the general population.17 Further studies are needed to develop sufficiently sound conclusions.
Risk factors for venous thromboembolism and pulmonary embolism in the elderly undergoing surgery
Limited physiological reserves of older patients make them more vulnerable to postoperative stress and illness.18 Frailty is broadly defined as a state of increased vulnerability resulting from age-associated declines in reserve and function across multiple physiological systems, such that the ability to cope with everyday or acute stressors is compromised.19 Lee et al.20 found that age at least 70 years (OR 5.61), at least two co-morbidities (OR 13.42) and white blood cell count of more than 10 000 μl−1 (OR 17.43) were independent risk factors for postoperative VTE in a cohort of Korean patients undergoing major abdominal surgery for colorectal cancer.
Zhang et al. undertook a systematic review to assess the risk factors for VTE after total hip arthroplasty (THA) and total knee arthroplasty (TKA). They included level I and level II studies published between 2003 and 2013 on risk factors for VTE of total joint arthroplasty.21,22 In total, 45 articles were included in their review. Risk factors found to be associated with VTE after both THA and TKA included older age, female sex, higher BMI, bilateral surgery and surgery time more than 2 h. The researchers did not provide a (pooled) risk estimate. Sun et al.23 retrospectively assessed a cohort of 537 Chinese patients who underwent knee arthroscopy and found age a strongly significant risk factor for DVT.
Saleh et al.24 conducted a systematic review to assess the incidence of VTE after shoulder arthroplasty. They included 14 studies and reported a cumulative incidence of 0.2 to 16%. The most prominent risk factors for development of VTE were previous VTE, thrombophilia, major surgery, advanced age (>60 years), current malignant disease, immobility and bed confinement.
Akpinar et al.25 retrospectively assessed a cohort of 1206 patients who had undergone THA, TKA or trauma surgery and found advanced age (≥65 years) [OR 4.9 (95% CI 1.1 to 22.0)] and immobility a high risk for developing postoperative VTE.
In a population-based historical cohort study in the United States, all (n = 4833) residents undergoing a first arthroscopic knee operation during the 18-year period of 1988 to 2005 were followed for the incidence of deep venous thrombosis or pulmonary embolism. In total, 18 developed postoperative VTE, all within the first 6 weeks after surgery. Risks for postoperative VTE were significantly increased for advanced patient age [hazard ratio 1.34 for each 10-year increase in patient age (P = 0.03)] and hospitalisation either before or after knee arthroscopy (hazard ratio 14.1; P < 0.001).26
Because pulmonary embolism risk rises faster than that of DVT, the relative incidence of pulmonary embolism and, therefore, the fatal impact of VTE, also increases with age.27–29 It has been argued, however, that the association between age and VTE and pulmonary embolism might be mediated by underlying co-morbidities that could be the actual risk factors.1,30
It has to be noted that age may be a proxy of immobility and coagulation activation.31–33 Dagrosa et al.34 assessed 12123 patients who underwent robotic-assisted laparoscopic radical prostatectomy (RALRP) in the timeframe 2009 to 2012. Univariate analysis demonstrated that nine co-morbidities were associated with age: history of congestive heart failure, myocardial infarction (MI), cerebrovascular attack (CVA), transient ischaemic attack, bleeding disorder, chronic obstructive pulmonary disease, percutaneous coronary intervention, cardiac surgery and American Society of Anesthesiologists’ physical status (P < 0.05). Postoperatively, five medical complications were associated with age-related co-morbidities: MI, CVA, pneumonia (PNA), DVT, pulmonary embolism and urinary tract infection (UTI). On multi-variate analysis, age was found to be an independent risk factor for postoperative PNA (P < 0.05), but not for MI (P = 0.09), UTI (P = 0.3), CVA (P = 0.2) or DVT/pulmonary embolism (P = 0.7). The researchers concluded that although patient age may generate concern for medical complications following surgery, the results suggested that age is not an independent risk factor for these medical complications after RALRP.
Are risk factors still important if the elderly are going through a perioperative early mobilisation programme?
Pearse et al.35 carried out a level III study on the result of achieving early walking following total knee replacement after implementation of a rapid rehabilitation protocol. They assessed the influence of the protocol on the development of DVT as determined by Doppler ultrasound scanning on the fifth postoperative day. Early mobilisation was defined as beginning to walk less than 24 h after knee replacement. Sample size was 97 patients who received 122 knee replacements. A historical cohort was used for comparison (98 patients, 125 TKAs). All the patients received low molecular weight heparin (LMWH) thromboprophylaxis and wore compression stockings postoperatively. In the early mobilisation group, 90 patients (92.8%) began walking successfully within 24 h of their operation. The incidence of DVT decreased from 27.6% in the control group to 1.0% in the early mobilisation group (P < 0.001).
Husted et al.36 conducted a level IV study and assessed 1977 consecutive, un-selected patients who were operated on for primary THA, TKA or bilateral simultaneous TKA (BSTKA) in a fast-track setting between 2004 and 2008. All patients received DVT prophylaxis with LMWH starting 6 to 8 h after surgery until discharge. An overall risk of death potentially related to the operation of 0.15% was found, which was deemed to compare favourably with the literature. During the last 2 years (854 patients), when patients were mobilised within 4 h postoperatively, and the duration of DVT prophylaxis was shortest (1 to 4 days), the mortality was 0% (95% CI 0 to 0.5). The incidence of DVT in TKA was 0.60% (0.2 to 2.2), in THA it was 0.51% (0.1 to 1.8) and in BSTKA it was 0% (0 to 2.9). The incidence of pulmonary embolism in TKA was 0.30% (0.1 to 1.7), in THA it was 0% (0 to 1.0) and in BSTKA it was 0% (0 to 2.9).
In 2013, a group of researchers published results from a study including 4659 arthroplasty procedures.37 They found 90-day postoperative rates of symptomatic pulmonary embolism events and VTE of 0.84 and 0.41%, respectively, in patients with length of stay (LOS) 5 days or less and in-hospital thromboprophylaxis only. They compared their rates with literature: two Danish nationwide studies found symptomatic VTE in more than 1% of THA and TKA procedures despite prolonged prophylaxis, and the incidence was increasing across the study period (1995 to 2007). The researchers attributed the difference between their data and the literature to the fast-track set-up including early mobilisation in their study, and as LOS in Denmark was about 11 days in year 2000.
Chandrasekaran et al.38 published a rather small level III study in which 50 patients who underwent mobilisation on the first postoperative day were compared with 50 patients who had strict bed rest on the first postoperative day. There was a significant reduction in the incidence of VTE complications in the mobilisation group (seven in total) compared with the control group (16 in total) (P = 0.03). Furthermore, in the mobilisation group, the odds of developing a thromboembolic complication was significantly reduced the greater the distance the patient mobilised (P = 0.005).
Pertaining to the field of cardiac surgery, Freeman and Maley39 previously observed that, if ICU patients on mechanical circulatory support were kept in bed, their probability of VTE increased, alongside poorer/reduced pulmonary function that increased risk of PNA, longer LOS, further deconditioning and a greater need for postoperative rehabilitation. To counteract these risks, the researchers introduced a protocol including early extubation and early mobilisation. This protocol included a range of motion exercises on the day of surgery, dangling at the bedside and being out of bed to a chair. The postoperative protocol included being out of bed to a chair two to three times per day, and walking in the room/hall. Both protocols of early extubation/mobilisation successfully reduced the number of complications and LOS for this patient population.
When do we start venous thromboembolism prophylaxis and at what dose in the elderly?
Recommendations for VTE prophylaxis in elderly patients are typically extrapolated from non-age-specific VTE prophylaxis trials. There are relatively few high-quality studies to guide decisions concerning the timing of VTE prophylaxis in the elderly population.
Ramanathan et al.40 investigated the impact of delayed initiation/interruption of chemical prophylaxis on VTE rates in 9961 surgical patients. Interrupted prophylaxis (interruption for >24 h) was associated with more VTE compared with complete prophylaxis (started within 24 h of admission, no interruptions) (10.2 vs. 2.0 per 1000, P < 0.01) and 5.2 greater odds. Admission to a surgical service and prolonged hospital stay were independently associated with increased likelihood of VTE.
Nunez et al.41 observed in a single-institution prospective non-randomised study that weight-adjusted dosing of enoxaparin had resulted in an increase of goal anti-Xa levels from 19 to 59% (P < 0.0001).
There are limited high-quality data comparing different LMWH with each other or with UFH in elderly patients. In a single-centre retrospective study, 210 patients (median age 81 years) were treated with fondaparinux 1.5 or 2.5 mg daily. The authors concluded that, in elderly acutely ill-hospitalised medical patients, thromboprophylaxis with fondaparinux 2.5 or 1.5 mg daily was well tolerated and effective in preventing VTE without significantly increasing bleeding risk.42
Another group has observed that preoperative subcutaneous heparin has significantly reduced postoperative VTE events (17.6 vs. 2.6%, P = 0.035) when compared with intermittent compression boots and postoperative pharmacoprophylaxis.43
The DIRECT (Dalteparin's Influence on the Renally Compromised: Anti-Ten-A) trial included critically ill patients (n = 138) with a creatinine clearance less than 30 ml min−1 given dalteparin (5000 IU daily) in the prophylactic setting. No bioaccumulation of dalteparin was observed.44 Another randomised clinical trial that enrolled patients with a median creatinine clearance of 34.7 ± 11.4 ml min−1 randomised to receive enoxaparin (40 mg) or tinzaparin once daily in the prophylactic setting found that factor Xa did not accumulate significantly in patients who were given tinzaparin but did accumulate in the enoxaparin group (P < 0.0001).45 Tinzaparin might, therefore, be preferable in patients with renal insufficiency.
A recent Canadian consensus stated there is no high-level evidence to recommend one LMWH or UFH over another in elderly patients with active malignancy46. In contrast, Tincani et al.47 recommend UFH to be the anti-coagulant of choice in the treatment of patients with renal failure, at high risk of bleeding, and in whom rapid reversal of anti-coagulation may be required.
Limongelli et al.48 have conducted analysis on 1018 consecutive patients who had undergone total thyroidectomy for benign and malignant diseases with/without preoperative prophylaxis and found the risk of developing VTE was eight times less than developing a postoperative bleed.
The most recent Cochrane Database Systematic Review, although not specifically addressing the elderly, concludes that multi-faceted interventions (graduated compression stockings, sequential compression devices and anti-coagulant medications such as LMWH) are well tolerated and can prevent blood clotting in patients at risk of these complications.11
A recent meta-analysis included nine phase 3 randomised controlled trials comparing direct oral anticoagulants (DOACs) against LMWH in the prevention of VTE in 29 403 elective post-arthroplasty patients.49 The elderly population was defined as adults aged at least 75 years. The risk of VTE or VTE-related deaths in elderly patients after elective arthroplasty was similar with DOACs compared with LMWH (OR 0.62, 95% CI 0.30 to 1.26; P = 0.18; I = 44%) but bleeding risk was significantly lower (OR 0.71, 95% CI 0.53 to 0.94; P = 0.02; I = 0%). Analysis of individual DOACs showed superior efficacy but similar safety for apixaban when compared with LMWH. Efficacy and safety profiles of rivaroxaban and dabigatran were similar to LMWH. In elderly patients, after elective arthroplasty, DOACs have demonstrated similar efficacy but superior safety when compared with enoxaparin for VTE prophylaxis.
Statins are currently under investigation as anti-thrombotic therapies.50 They have been shown to demonstrate an anti-inflammatory effect via reduction of pro-inflammatory cytokines, chemokines and inflammation-sensitive plasma markers, importantly C-reactive protein.51 A positive effect of statins significantly reducing symptomatic VTE was shown in a randomised trial52 and a Cochrane Systematic Review.53 In contrast to other lipid-lowering drugs, statins are therapeutic and also preventive against VTE among at-risk medical inpatients and also the general population in a dose-dependent manner, although this effect has not been observed in the elderly population, as was shown in the PROSPER study.54 Further, interpreting the JUPITER trial results, Perez and Bartholomew55 caution against substitution of proven prophylaxis and anti-coagulation with statins, especially for patients at high risk of VTE. The most recent meta-analysis by Sardar et al.56 concluded that, in participants of clinical trials aged 75 and older, DOACs did not cause excess bleeding and were associated with equal or greater efficacy than conventional therapy.
- Age over 70 years is a risk factor for postoperative VTE (Grade B).
- In elderly patients, we suggest identification of co-morbidities increasing the risk for VTE (e.g. congestive heart failure, pulmonary circulation disorder, renal failure, lymphoma, metastatic cancer, obesity, arthritis, post-menopausal oestrogen therapy) and correction if present (e.g. anaemia, coagulopathy) (Grade 2C).
- We suggest against bilateral knee replacement in elderly and frail patients (Grade 2C).
- We suggest timing and dosing of pharmacological VTE prophylaxis as in the non-aged population (Grade 2C).
- In elderly patients with renal failure, low-dose un-fractionated heparin may be used or weight-adjusted dosing of LMWH (Grade 2C).
- In the elderly, we recommend careful prescription of postoperative VTE prophylaxis and early postoperative mobilisation (Grade 1C).
- We recommend multi-faceted interventions for VTE prophylaxis in elderly and frail patients, including pneumatic compression devices, LMWH (and/or direct oral anti-coagulants after knee or hip replacement) (Grade 1C).
Acknowledgements relating to this article
Assistance with the guideline chapter: none.
Financial support and sponsorship: expenses for two meetings of the VTE Task Force (Brussels and Berlin) were covered by the ESA for the ESA members.
Conflicts of interest: none.
1. Anderson FA Jr, Wheeler HB, Goldberg RJ, et al. A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism. The Worcester DVT study. Arch Intern Med
2. Cushman M, Tsai AW, White RH, et al. Deep vein thrombosis and pulmonary embolism in two cohorts: the longitudinal investigation of thromboembolism etiology. Am J Med
3. Heit JA. Venous thromboembolism: disease burden, outcomes and risk factors. J Thromb Haemost
4. Naess IA, Christiansen SC, Romundstad P, et al. Incidence and mortality of venous thrombosis: a population-based study. J Thromb Haemost
5. Oger E. Incidence of venous thromboembolism: a community-based study in Western France. EPI-GETBP Study Group. Groupe d’Etude de la Thrombose de Bretagne Occidentale. Thromb Haemost
6. Silverstein MD, Heit JA, Mohr DN, et al. Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study. Arch Intern Med
7. Spencer FA, Emery C, Lessard D, et al. The Worcester Venous Thromboembolism study: a population-based study of the clinical epidemiology of venous thromboembolism. J Gen Intern Med
8. White RH. The epidemiology of venous thromboembolism. Circulation
2003; 107 (23 Suppl 1):I-4–I-8.
9. Spencer FA, Gore JM, Lessard D, et al. Venous thromboembolism in the elderly. A community-based perspective. Thromb Haemost
10. Anderson FA, Spencer FA. Risk factors for venous thromboembolism. Circulation
2003; 107 (23 Suppl 1):I9–16.
11. Kahn SR, Morrison DR, Cohen JM, et al. Interventions for implementation of thromboprophylaxis in hospitalized medical and surgical patients at risk for venous thromboembolism. Cochrane Database Syst Rev
12. Leibson CL, Petterson TM, Smith CY, et al. Rethinking guidelines for VTE risk among nursing home residents: a population-based study merging medical record detail with standardized nursing home assessments. Chest
13. Tsai J, Grant AM, Beckman MG, et al. Determinants of venous thromboembolism among hospitalizations of US adults: a multilevel analysis. PLoS One
14. Miller J, Chan BK, Nelson HD. Postmenopausal estrogen replacement and risk for venous thromboembolism: a systematic review and meta-analysis for the U.S. Preventive Services Task Force. Ann Intern Med
15. Grady D, Wenger NK, Herrington D, et al. Postmenopausal hormone therapy increases risk for venous thromboembolic disease. The Heart and Estrogen/progestin Replacement Study. Ann Intern Med
16. Heit JA, Leibson CL, Ashrani AA, et al. Is diabetes mellitus an independent risk factor for venous thromboembolism?: a population-based case–control study. Arterioscler Thromb Vasc Biol
17. Chung WS, Lin CL, Kao CH. Diabetes increases the risk of deep-vein thrombosis and pulmonary embolism. A population-based cohort study. Thromb Haemost
18. Kim S, Brooks AK, Groban L. Preoperative assessment of the older surgical patient: honing in on geriatric syndromes. Clin Interv Aging
19. Xue QL. The frailty syndrome: definition and natural history. Clin Geriatr Med
20. Lee E, Kang SB, Choi SI, et al. Prospective study on the incidence of postoperative venous thromboembolism in Korean patients with colorectal cancer. Cancer Res Treat
21. Zhang J, Chen Z, Zheng J, et al. Risk factors for venous thromboembolism after total hip and total knee arthroplasty: a meta-analysis. Arch Orthop Trauma Surg
22. Zhang ZH, Shen B, Yang J, et al. Risk factors for venous thromboembolism of total hip arthroplasty and total knee arthroplasty: a systematic review of evidence in ten years. BMC Musculoskelet Disord
23. Sun Y, Chen D, Xu Z, et al. Incidence of symptomatic and asymptomatic venous thromboembolism after elective knee arthroscopic surgery: a retrospective study with routinely applied venography. Arthroscopy
24. Saleh HE, Pennings AL, El Maraghy AW. Venous thromboembolism after shoulder arthroplasty: a systematic review. J Shoulder Elbow Surg
25. Akpinar EE, Hosgun D, Akan B, et al. Does thromboprophylaxis prevent venous thromboembolism after major orthopedic surgery? J Bras Pneumol
26. Mauck KF, Froehling DA, Daniels PR, et al. Incidence of venous thromboembolism after elective knee arthroscopic surgery: a historical cohort study. J Thromb Haemost
27. Heit JA. Epidemiology of venous thromboembolism. Nat Rev Cardiol
28. Machlus KR, Aleman MM, Wolberg AS. Update on venous thromboembolism: risk factors, mechanisms, and treatments. Arterioscler Thromb Vasc Biol
29. Silverstein RL, Bauer KA, Cushman M, et al. Venous thrombosis in the elderly: more questions than answers. Blood
30. Anderson FA Jr, Wheeler HB, Goldberg RJ, et al. The prevalence of risk factors for venous thromboembolism among hospital patients. Arch Intern Med
31. Ageno W, Agnelli G, Imberti D, et al. Risk factors for venous thromboembolism in the elderly: results of the master registry. Blood Coagul Fibrinolysis
32. Lowe GD, Rumley A, Woodward M, et al. Epidemiology of coagulation factors, inhibitors and activation markers: the Third Glasgow MONICA Survey. I. Illustrative reference ranges by age, sex and hormone use. Br J Haematol
33. Lowe GD, Rumley A, Woodward M, et al. Activated protein C resistance and the FV: R506Q mutation in a random population sample – associations with cardiovascular risk factors and coagulation variables. Thromb Haemost
34. Dagrosa LM, Gorlov IP, Hyams ES. Is age an independent risk factor for medical complications following robotic-assisted laparoscopic radical prostatectomy? An evaluation of National Surgical Quality Improvement Program (NSQIP) data. Paper presented at the New England Section of the American Urological Association, Newport, Rhode Island, 16–19 October 2014.
35. Pearse EO, Caldwell BF, Lockwood RJ, et al. Early mobilisation after conventional knee replacement may reduce the risk of postoperative venous thromboembolism. J Bone Joint Surg Br
36. Husted H, Otte KS, Kristensen BB, et al. Low risk of thromboembolic complications after fast-track hip and knee arthroplasty. Acta Orthop
37. Jorgensen CC, Jacobsen MK, Soeballe K, et al. Thromboprophylaxis only during hospitalisation in fast-track hip and knee arthroplasty, a prospective cohort study. BMJ Open
38. Chandrasekaran S, Ariaretnam SK, Tsung J, et al. Early mobilization after total knee replacement reduces the incidence of deep venous thrombosis. ANZ J Surg
39. Freeman R, Maley K. Mobilization of intensive care cardiac surgery patients on mechanical circulatory support. Crit Care Nurs Q
40. Ramanathan R, Gu Z, Limkemann AJ, et al. Association between interruptions in chemical prophylaxis and VTE formation. Am Surg
41. Nunez JM, Becher RD, Rebo GJ, et al. Prospective evaluation of weight-based prophylactic enoxaparin dosing in critically ill trauma patients: adequacy of anti-Xa levels is improved. Am Surg
42. Silvestri F, Pasca S, Labombarda A, et al. Safety of fondaparinux in the prevention of venous thromboembolism in elderly medical patients: results of a single-center, retrospective study. Minerva Med
43. Reinke CE, Drebin JA, Kreider S, et al. Timing of preoperative pharmacoprophylaxis for pancreatic surgery patients: a venous thromboembolism reduction initiative. Ann Surg Oncol
44. Douketis J, Cook D, Meade M, et al. Prophylaxis against deep vein thrombosis in critically ill patients with severe renal insufficiency with the low-molecular-weight heparin dalteparin: an assessment of safety and pharmacodynamics: the DIRECT study. Arch Intern Med
45. Mahe I, Aghassarian M, Drouet L, et al. Tinzaparin and enoxaparin given at prophylactic dose for eight days in medical elderly patients with impaired renal function: a comparative pharmacokinetic study. Thromb Haemost
46. Easaw JC, Shea-Budgell MA, Wu CM, et al. Canadian consensus recommendations on the management of venous thromboembolism in patients with cancer. Part 1: Prophylaxis. Curr Oncol
47. Tincani E, Crowther MA, Turrini F, et al. Prevention and treatment of venous thromboembolism in the elderly patient. Clin Interv Aging
48. Limongelli P, Tolone S, Gubitosi A, et al. Relationship between postoperative venous thromboembolism and hemorrhage in patients undergoing total thyroidectomy without preoperative prophylaxis. Int J Surg
2014; 12 (suppl 1):S198–S201.
49. Pathak R, Giri S, Karmacharya P, et al. Meta-analysis on efficacy and safety of new oral anticoagulants for venous thromboembolism prophylaxis in elderly elective postarthroplasty patients. Blood Coagul Fibrinolysis
50. Saghazadeh A, Hafizi S, Rezaei N. Inflammation in venous thromboembolism: cause or consequence? Int Immunopharmacol
51. Adams NB, Lutsey PL, Folsom AR, et al. Statin therapy and levels of hemostatic factors in a healthy population: the Multi-Ethnic Study of atherosclerosis. J Thromb Haemost
52. Glynn RJ, Danielson E, Fonseca FA, et al. A randomized trial of rosuvastatin in the prevention of venous thromboembolism. N Engl J Med
53. Li L, Zhang P, Tian JH, et al. Statins for primary prevention of venous thromboembolism. Cochrane Database Syst Rev
54. Freeman DJ, Robertson M, Brown EA, et al. Incident venous thromboembolic events in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER). BMC Geriatr
55. Perez A, Bartholomew JR. Interpreting the JUPITER trial: statins can prevent VTE, but more study is needed. Cleve Clin J Med
56. Sardar P, Chatterjee S, Chaudhari S, et al. New oral anticoagulants in elderly adults: evidence from a meta-analysis of randomized trials. J Am Geriatr Soc