J Orthop Sci (2014) 19:471–477 DOI 10.1007/s00776-014-0553-z
ORIGINAL ARTICLE
The incidence and the risk factors of venous thromboembolism in Korean patients with pelvic or acetabular fractures Joon-Woo Kim • Chang-Wug Oh • Jong-Keon Oh • Seung-Gil Baek • Byoung-Joo Lee • Han-Pyo Hong • Woo-Kie Min
Received: 18 June 2013 / Accepted: 22 February 2014 / Published online: 14 March 2014 Ó The Japanese Orthopaedic Association 2014
Abstract Background Pelvic ring and acetabular fractures are the results of high energy trauma, but there is a paucity of information available regarding the incidence and risk factors of venous thromboembolism (VTE) after these injuries in Asians. This study was undertaken to evaluate the incidence of VTE after a pelvic or an acetabular fracture and to identify predictive factors. Methods A prospective evaluation was performed by indirect computed tomography (CT) venography in patients with pelvic or acetabular fractures. Ninety-five patients were examined by indirect CT venography. Fiftyfive patients suffered from a pelvic ring injury (anteroposterior compression 5, lateral compression 25, vertical shear 25), and the remaining 40 from acetabular fractures (simple 18, complex 22). Indirect CT venography was performed within 1–2 weeks of initial trauma. Relationships between VTE and sex, age, fracture pattern, body mass index, injury severity score, period of immobilization, and need for surgical treatment were analyzed. Deep vein thrombosis (DVT) in a more proximal to popliteal vein and the existence of PE were considered clinically significant. Results Thirty-two patients (33.7 %) were found to have VTE at an average of 11 days after initial injury. Clinically
J.-W. Kim C.-W. Oh (&) S.-G. Baek B.-J. Lee H.-P. Hong W.-K. Min Department of Orthopaedic Surgery, Kyungpook National University Hospital, 50, 2-Ga, Samdok, Chung-gu, Daegu 700-721, Republic of Korea e-mail: [email protected] J.-K. Oh Department of Orthopaedic Surgery, Korea University Guro Hospital, 97, Gurodong-gil, Guro-gu, Seoul 152-703, Republic of Korea
significant DVT was found 20 cases (21.1 %). No statistical difference was found between pelvic ring injuries and acetabular fractures with respect to the development of VTE. For those with pelvic ring injury, the incidence of VTE in those with a vertical shear injury (52 %) was significantly greater than in others with a pelvic ring injury (p = 0.014). Patients with an age [50 were found to be at greater risk of VTE (p = 0.032). Conclusion Our findings demonstrate that Korean patients with pelvic or acetabular fractures have a higher risk of VTE than is generally believed, and caution should be taken to prevent and treat VTE, especially in high energy pelvic ring injury and elderly patients.
Introduction Pelvic ring or acetabular fractures are caused by highenergy trauma, and can be risk factors for the development of thromboembolism [1, 2]. The rate of deep vein thrombosis (DVT) after fracture of the pelvis has been reported to be up to 61 % [3], and the rate of pulmonary embolism (PE) after pelvic trauma up to 10 %. Furthermore, a fatal event was reported in half of this population [4, 5]. The first clinical manifestation of venous thromboembolism (VTE) is often PE-related sudden death, as has been established by epidemiologic and autopsy studies in Western populations [1]. However, in Asian populations, VTE is considered a rare disease entity and its prophylaxis after major orthopedic problems is occasionally overlooked [6, 7]. Recently, many investigators have emphasized that the incidence of VTE in Asians is similar to that in Caucasians, especially after total joint replacement surgery [8, 9]. Piovella et al. [10] reported the results of the AIDA (Assessment of the Incidence of Deep vein thrombosis in
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Asia) investigation and concluded that incidence of DVT by postoperative screening using bilateral venography is higher than generally believed. However, despite the above mentioned reports, decision making regarding VTE after pelvic trauma is problematic because of a lack of data. In particular, published information regarding the incidence and the risk factors of VTE in patients with a pelvic or acetabular fracture in the Asian population is scant. Accordingly, the objectives of this study were; (1) to determine the incidence of VTE after pelvic and acetabular fractures, and (2) to identify influencing factors and their significances based on statistical analysis of variance. To the best of our knowledge, this is one of the largest series conducted to examine the incidence of VTE and to identify the risk factors responsible after pelvic-acetabular trauma in an Asian cohort.
Patients and methods From January 2009 through December 2010, we prospectively evaluated a cohort of patients with pelvic or acetabular fractures. The design and protocol of this study were approved by the Institutional Review Board. The study group consisted of 95 skeletally mature patients. There were 40 men and 55 women of median age 57 years (range, 18–79) and of median body mass index (BMI) 23.6 kg/m2 (range, 17.2–35.8). Pelvic ring fractures were classified using the Young-Burgess classification [11] and acetabular fractures were classified as described by Letournel [12]. Fracture patterns were analyzed using pelvic anteroposterior, both oblique, and inlet and outlet views, and 3-dimensional computed tomography (CT) scans by two orthopedic surgeons, unaware of the existence of VTE to avoid selection bias. Injury severity scores (ISS) were used to grade injury severity. There were 55 cases of pelvic ring fracture [5 cases of anteroposterior compression (APC), 25 cases of lateral compression (LC) and 25 cases of vertical shear (VS) injury] and 40 acetabular fracture cases (18 cases of simple and 22 cases of complex fractures). Indirect CT venography was performed using a 64-channel multi-directional CT scanner (GE Healthcare, Milwaukee, Wisconsin, United States). Briefly, with a patient supine, feet were elevated to avoid calf compression. A scout CT image was then obtained to position subsequent fast acquisition images. Undiluted nonionic contrast media [120 ml; Optiray (ioversol) Millinckrodt, Pointe-Claire, Quebec, Canada] was administered to all patients using a power injector through an 18- or 20-gauge intravenous catheter in an antecubital vein, at a flow rate of 3 ml/s with a delay of 20–25 s before scanning. Helical CT of the pulmonary arteries was performed from the
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diaphragm to 2 cm above the aortic arch, 20 s after starting the contrast injection, using the following parameters; collimation 1.25 mm in fast mode, table speed 7.5 mm per gantry rotation, and pitch 6.0. Three minutes after starting the contrast injection, an indirect CT venography scan was performed from the ankle to the mid-abdomen, at a collimation of 4 9 2.5 mm, a 7.5 mm/s table speed, and a pitch of 3.0. Depending on patient height, 250–300 venous images were typically acquired. CT venography scans took approximately 80–90 s. The total examination time (including scanner programming, image acquisition, and delay time after starting contrast injection), including pulmonary CT angiography, was approximately 5–7 min. The criteria used to diagnose DVT were the presence of an intramural filling defect or localized non-opacification of a vein segment, venous expansion, and wall enhancement, as described by Loud et al. [13]. Indirect CT venography was scheduled within 7–14 days after injury, which was assumed as the stabilization period before operation. But, we also performed it promptly when any symptom suggesting DVT or PE presented. However, 5 patients were referred from other institutions at [2 weeks post-injury, and thus CT scans were delayed. Average time from injury to indirect CT venography was 11.8 days (range, 3–26). An anti-embolic stocking was applied to all patients, but no patient received chemoprophylaxis. However, when a patient exhibited a clinical manifestation of VTE, or DVT was confirmed by DVT-CT, low molecular weight heparin was started. If definitive stabilization was planned in patients with DVT, an inferior vena cava (IVC) filter was inserted prior to operation. We considered the presence of proximal DVT (in the popliteal or a more proximal vein) or PE as clinically significant VTE. The possible risk factors for VTE that we assessed were; age, sex, ISS, BMI, fracture pattern, duration of immobilization, and need for surgery. Associations between potential risk factors and VTE were analyzed using Pearson’s chi-square test and Fisher’s exact test. Statistical significance was accepted for p values of \0.05.
Results Thirty-two of the 95 patients (33.7 %) developed VTE at an average of 11 days (range, 3–26) post initial injury. Proximal DVT was present in 16 cases (16.8 %) and distal DVT in 13 (13.7 %). Bilateral distal DVT was found in 6 cases, but no case of bilateral proximal DVT was encountered. Furthermore, no mortality due to PE occurred in this series, but pulmonary CT angiography revealed 9 cases of PE, 5 of which developed from proximal DVT and 1 from distal DVT. The other 3 showed PE without
VTE in Koreans after pelvic trauma
thrombosis in the lower extremity. The incidence of clinically significant VTE was 21.1 % (20 cases). Eighty-one patients (85.3 %) underwent surgery at a median of 26 days (range, 0–42) after initial injury and VTE developed in 26 of these patients (32.1 %), and 9 of them had clinically significant VTE (13.6 %). On the other hand, 6 of the 14 patients that did not undergo surgery had VTE (42.9 %), and 5 had clinically significant VTE (35.7 %). There was no statistical significance between surgically and conservatively treated patients with respect to the incidence of VTE (p = 0.43) and clinically significant VTE (p = 0.14). In 17 of the patients, VTE was found before surgery, and all underwent inferior vena cava filter insertion before operative management. Fifty-five patients (57.9 %) had pelvic ring injuries (APC: 5, LC: 25, VS: 25) and 40 (42.1 %) had acetabular fractures (simple acetabular fractures: 18, complex acetabular fractures: 22). In the pelvic ring injury group, the incidence of VTE was 32.7 %, and in the acetabular fracture group, its incidence was 35 % (p = 0.81). With respect to clinically significant VTE, the incidences were 20 % in the pelvic ring injury group and 21.8 % in the acetabular fracture group (p = 0.83). However, these incidences were not significantly different (Pearson’s chi-square test). In patients with APC injury, no VTE was found, although 5 patients with LC injury (20 %) and 13 patients with VS injury (52 %) developed VTE. Clinically significant VTE was found in 2 cases (8 %) of LC injury and 10 cases (40 %) of VS injury. Patients with VS injury (Figs. 1, 2, 3, 4) had higher incidences of VTE and clinically significant VTE than other patients with APC or LC injuries (p = 0.014 and 0.011 respectively, Pearson’s chi-square test). Four (22.2 %) of the patients with a simple acetabular fracture developed VTE, and 2 (11.1 %) developed clinically significant VTE. On the other hand, 10 of the 22 patients (45.5 %) with complex acetabular fractures developed VTE (p = 0.125) and 6 (27.3 %) developed clinically significant VTE (p = 0.204). However, these incidences were not significantly different (Pearson’s chisquare test). The incidence of VTE in each group was summarized at Table 1. Median ISS was 26 (range, 1–48) in the total study subjects. Median ISS was 39 (range, 1–48) in the VTE group and 20 (range, 1–43) in the non-VTE group. Median ISS for the proximal DVT was 38 (range, 1–48). However, no significant relation was found between ISS and the development of VTE. Furthermore, no relation was found between other possible risk factors (sex, BMI, immobilization period, and the need for surgical intervention) and the development of VTE. However, patients aged more than 50 showed a high risk of VTE development (p = 0.032, Fisher’s exact test).
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Fig. 1 A 54-year-old female patient suffered from a vertical shear injury of the pelvic ring. She was treated conservatively at another hospital
Discussion Pelvic ring and acetabular fractures are major high energy trauma injuries, and are often associated with other injuries or fractures. In particular, VTE is an important common complication in trauma patients with pelvic or acetabular fractures [12, 14–17]. However, the importance of VTE has been underestimated and overlooked in Asian patients. In the Western literature, the incidence of DVT after major orthopedic trauma varies from 30 to 80 %. For acetabular fractures, the incidence of DVT was reported to be up to 34 %, although all were silent [14]. More recently, Moed and colleagues [18] reported that 15 % of patients with acetabular or pelvic fractures treated operatively developed DVT. Nevertheless, there appears to be a belief that VTE is rare in Asian patients, and for this reason, some investigators do not recommend routine chemoprophylaxis [19–21]. On the other hand, other authors have drawn attention to the fact that the incidence of DVT after major
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Fig. 2 At 3 weeks after injury, chest pain, dyspnea, and cold sweating suddenly developed and the patient was transferred to our institution. Pulmonary CT-angiography revealed emboli on both
pulmonary arteries (a, b), and multiple thrombi at right femoral vein, left peroneal vein, and left posterior tibial vein were detected by indirect CT venography (c, d, e)
orthopedic surgery in Asian populations is not low, and is entirely consistent with incidences observed in Western countries [8, 22, 23]. The present study confirms that VTE is considerably more common than is generally believed, in fact, our cohort showed a VTE incidence of 33.7 %, and a clinically significant VTE incidence of 21.1 %, although there was no mortality related to PE. Greets and colleagues [1] reported that the prevalence of VTE among trauma patients is higher than that among those undergoing an elective orthopedic procedure, such as arthroplasty. Furthermore, the pathophysiology of VTE in trauma cases is known to differ from that in those that have undergone elective surgery, and that the majority of thrombi in these patients are proximal [3, 14, 24]. Pelvic and acetabular fractures are the result of high velocity trauma, and are invariably associated with injury to vascular structures around the hip [3, 14], and subsequent manipulation during surgery further damages the vascular endothelium [3] and probably increases the risk of PE development. We presume that APC and LC injuries in the pelvic ring and simple acetabular fractures are due to lower energy injuries than VS injury and complex acetabular fractures. In the present series, patients with VS pelvic ring injuries had a VTE incidence of 52 %, which is higher than that
experienced by patients with APC or LC injuries (p = 0.014). However, no difference was observed between the incidences of VTE in patients with complex and simple acetabular fractures (p = 0.186). Accordingly, we emphasize that care should be taken when diagnosing and considering VTE prophylaxis in patients with high energy pelvic ring injuries. One should consider chemoprophylaxis as well as mechanical prophylaxis, such as anticoagulant agents, in patients with high energy pelvic ring injuries. Nevertheless, it has been well established that elderly patients with pelvic ring or acetabular fractures are at greater risk of thrombosis. In the present study, statistical analysis revealed that an age greater than 50 was associated with an increased risk of VTE (p = 0.032), which is somewhat younger than that reported by previous investigators. However, Montgomery and coworkers [25] reported that patients of 30 years and older showed an increased prevalence of VTE, which is considerably younger than that previously reported. On the other hand, some authors have reported that the incidence of VTE is independent of age [8, 23], but it should be added that the majority of reports on the subject have concluded that age significantly affects the development of VTE [3, 10, 14, 18, 25]. Accordingly, despite some controversy, age
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VTE in Koreans after pelvic trauma
475 Table 1 The incidence of venous thromboembolism (VTE) Kinds of injury (No. of patients)
% of VTE
% of clinically significant VTE
Pelvic ring injuries (55)
32.7
20
APC (5)
0
0
LC (25)
20
8
VS (25)
52
40
35
21.8
Simple (18)
22.2
11.1
Complex (22)
45.5
27.3
Acetabular fractures (40)
VTE venous thromboembolism, APC anteroposterior compression injury, LC lateral compression injury, VS vertical shear injury
Fig. 3 After 2 weeks of thrombolytic therapy, venous thrombi on her legs were dissolved (a, b)
Fig. 4 Post 6 weeks initial injury, surgical treatment was performed (a) after IVC filter insertion (b)
appears to be an important cause of VTE. Thus, the use of chemoprophylaxis may be appropriate for elderly patients.
In the present study, no significant association was found between the immobilization period and the prevalence of VTE, which concurs with the findings of Steel et al. [26]. However, others [14, 16] have reported a significant correlation between the development of DVT and prolonged immobilization. Furthermore, we found no correlation between surgery and VTE risk, although Napolitano et al. [24] reported that surgery and subsequent manipulation in trauma patients increases risk. In addition, we found no correlation between VTE development and sex, ISS, or BMI. Similarly, others have reported poor correlations between standard thrombosis risk factors and the development of VTE in trauma patients [3, 14, 27]. Thus, it appears that these factors have little effect on VTE development in trauma patients because the high baseline prevalence of thrombosis in these patients tends to overwhelm other influences. Nonetheless, the message that we wish to convey is that major trauma patients should be considered at high risk of thrombosis regardless of other risk factors. Duplex ultrasonography has been widely used to detect venous thrombosis, presumably, because it is readily applied, is non-invasive, and presents no radiation risk, but its efficacy is limited in the trauma setting, because bulky leg dressings, compromised skin and soft tissue statuses, wounds, and pain often limit studies. Moreover, duplex ultrasonography cannot be used to evaluate deep veins of the pelvis, which can be an important reservoir of occult venous thrombosis, and its efficacy as a screening tool in patients with suspected PE is limited. For this reason, and its superior ability to image proximal thigh and pelvic veins, we chose to use pulmonary CT angiography and indirect CT venography to screen for DVT. Several studies [28, 29] have shown that indirect CT venography produces results comparable to those of sonographic studies, but that it also has the following benefits: (1) both PE and DVT can be evaluated during a single examination, (2) indirect CT venography can detect DVT in the intra-abdominal and
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pelvic cavity areas whereas ultrasonography cannot, (3) indirect CT venography is not as invasive as conventional venography and more cost-effective than magnetic resonance venography. In the present study, the rate of proximal DVT or PE was 59.4 % in the VTE population (19 in 32), and this is difficult to diagnose by ultrasonography. Sen et al. [23] conducted a similar study by using pulmonary CT angiography and indirect CT venography, and found a proximal DVT or PE of 28.6 % in Indian patients. Although direct comparisons are difficult, because they studied the rate of VTE postoperatively, the rate reported was similar to ours (21.1 %), which reinforces our finding that VTE is common in Asian patients. The major concerns regarding CT venography are the additional radiation exposure required and the adverse effect of contrast. Furthermore, it is difficult to obtain a CT venography scan whenever a thrombotic symptom is suspected. In the present study, patients were evaluated prospectively, and all cases of DVT and PE were identified preoperatively. Furthermore, thrombolytic therapy was initiated and IVC filter insertion was performed before surgery, and no mortality occurred. The facts that the present study was conducted at a single institute and that the sample size was small are limitations. Accordingly, we suggest that a larger-scale, randomized, multicenter trial be undertaken with the objectives of determining the prevalence of VTE more precisely and of proposing guidelines for the prevention of VTE in Asian patients with pelvic or acetabular fractures.
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Conclusion Our findings demonstrate that Korean patients with pelvic or acetabular fractures are at higher risk of VTE development than most believe. Furthermore, because commonly believed risk factors are poor predictors of VTE in trauma patients, it is vital that efforts be made to diagnose, prevent, and treat VTE. Finally, we recommend that chemoprophylaxis be considered in patients at high risk, such as elderly patients and those with high energy pelvic ring injuries.
12. 13.
14.
15. 16.
Acknowledgments This work was supported by Biomedical Research Institute grant, Kyungpook National University Hospital (2014). 17. Conflict of interest All authors have certified that they have no commercial associations (e.g., consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with this article.
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thromboembolism: American College of Chest Physicians evidence-based clinical practice guidelines (8th Edition). Chest. 2008;133(6 suppl):381S–453S. Hill J, Treasure T, Guideline Development Group. Reducing the risk of venous thromboembolism (deep vein thrombosis and pulmonary embolism) in patients admitted to hospital: summary of the NICE guideline. Heart. 2010;96:879–82. Greets WH, Code KI, Jay RM, Chen E, Szalai JP. A prospective study of venous thromboembolism after major trauma. N Eng J Med. 1994;331:1601–6. O’Malley KF, Ross SE. Pulmonary embolism in major trauma patients. J Trauma. 1990;30:748–50. Webb LX, Rush PT, Fuller SB, Meredith JW. Greenfield filter prophylaxis of pulmonary embolism in patients undergoing surgery for acetabular fracture. J Orthop Trauma. 1992;6: 139–45. White RH, Zhou H, Romano PS. Incidence of idiopathic deep venous thrombosis and secondary thromboembolism among ethnic groups in California. Ann Intern Med. 1998;128:737–40. Klatsky AL, Armstrong MA, Poggi J. Risk of pulmonary embolism and/or deep venous thrombosis in Asian-Americans. Am J Cardiol. 2000;85:1334–7. Dhillon KS, Askander A, Doraismay S. Postoperative deep vein thrombosis in Asian patients is not a rarity: a prospective study of 88 patients with no prophylaxis. J Bone Joint Surg Br. 1996;78:427–30. Wang CJ, Wang JW, Chen LM, Chen HS, Yang BY, Cheng SM. Deep vein thrombosis after total knee arthroplasty. J Formos Assoc. 2000;99:848–53. Piovella F, Wang CJ, Lu H, Lee K, Lee LH, Lee WC, Turpie AG, Gallus AS, Plane`s A, Passera R, Rouillon A, AIDA investigators. Deep vein thrombosis rates after major orthopedic surgery in Asia. An epidemiological study based on postoperative screening with centrally adjudicated bilateral venography. J Thromb Haemost. 2005;3:2664–70. Young JWR, Burgess AR. Radiologic management of pelvic ring fractures: systematic radiographic diagnosis. Baltimore: Urban & Schwarzenberg; 1987. Letournel E, Judet R. Fractures of the acetabulum. 2nd ed. New York: Springer; 1993. Loud PA, Grossman ZD, Klippenstein DL, Ray CE. Combined CT venography and pulmonary angiography: a new diagnostic technique for suspected thromboembolic disease. AJR Am J Roentgenol. 1998;170:951–4. Montgomery KD, Geerts WH, Potter HG, Helfet DL. Thromboembolic complications in patients with pelvic trauma. Clin Orthop Relat Res. 1996;329:68–87. Rogers FB. Venous thromboembolism in trauma patients: a review. Surgery. 2001;130:1–12. Stannard JP, Lopez-Ben RR, Volgas DA, Anderson ER, Busbee M, Karr DK, McGwin GR Jr, Alonso JE. Prophylaxis against deep-vein thrombosis following trauma: a prospective, randomized comparison of mechanical and pharmacologic prophylaxis. J Bone Joint Surg Am. 2006;88:261–6. Slobogean GP, Lefaivre KA, Nicolaou S, O’Brien PJ. A systematic review of thromboprophylaxis for pelvic and acetabular fractures. J Orthop Trauma. 2009;23:379–84. Moed BR, Miller JR, Tabaie SA. Sequential duplex ultrasound screening for proximal deep venous thrombosis in asymptomatic patients with acetabular and pelvic fractures treated operatively. J Trauma Acute Care Surg. 2012;72:443–7. Mavalankar AP, Majmundar D, Rani S. Routine chemoprophylaxis for deep venous thrombosis in Indian patients: is it really justified? Indian J Orthop. 2007;41:188–93. Chan YK, Chiu KY, Cheng SW, Ho P. The incidence of deep vein thrombosis in elderly Chinese suffering hip fractures is low
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without prophylaxis: a prospective study using serial duplex ultrasound. J Orthop Surg. 2004;12:178–83. Mitra AK, Khoo TK, Ngan CC. Deep vein thrombosis following hip surgery for fracture of the proximal femur. Singap Med J. 1989;30:530–4. Leizorovicz A. SMART Venography Study Steering Committee. Epidemiology of post-operative venous thromboembolism in Asian patients. Results of the SMART venography study. Haematologica. 2007;92:1194–200. Sen RK, Kumar A, Tripathy SK, Aggarwal S, Khandelwal N, Manoharan SR. Risk of postoperative venous thromboembolism in Indian patients sustaining pelvi-acetabular injury. Int Orthop. 2011;35:1057–63. Napolitano LM, Garlapati VS, Heard SO, Silva WE, Cutler BS, O’Neill AM, Anderson FA Jr, Wheeler HB. Asymptomatic deep venous thrombosis in the trauma patient: is an aggressive screening protocol justified? J Trauma. 1995;39:651–7. Montgomery KD, Potter HG, Helfet DL. The detection and management of proximal deep venous thrombosis in patients with acute acetabular fractures: a follow-up report. J Orthop Trauma. 1997;11:330–6.
477 26. Steel N, Dodenhoff RM, Ward AJ. Thromboprophylaxis in pelvic and acetabular trauma surgeries. J Bone Joint Surg Br. 2005; 87:209–12. 27. Dennis JW, Menawat S, Von Thron J, Fallon WF Jr, Vinsant GO, Laneve LM, Jagger C, Frykberg ER. Efficacy of deep venous thrombosis prophylaxis in trauma patients and identification of high risk groups. J Trauma. 1993;35:132–9. 28. Cham MD, Yankelevitz DF, Shaham D, Shah AA, Sherman L, Lewis A, Rademaker J, Pearson G, Choi J, Wolff W, Prabhu PM, Galanski M, Clark RA, Sostman HD, Henschke CI. Deep venous thrombosis: detection by using indirect CT venography. Radiology. 2000;216:744–51. 29. Baldt MM, Zontsich T, Stu¨mpflen A, Fleischmann D, Schneider B, Minar E, Mostbeck GH. Deep venous thrombosis of the lower extremity: efficacy of spiral CT venography compared with conventional venography in diagnosis. Radiology. 1996;200: 423–8.
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ORIGINAL ARTICLE
The incidence and the risk factors of venous thromboembolism in Korean patients with pelvic or acetabular fractures Joon-Woo Kim • Chang-Wug Oh • Jong-Keon Oh • Seung-Gil Baek • Byoung-Joo Lee • Han-Pyo Hong • Woo-Kie Min
Received: 18 June 2013 / Accepted: 22 February 2014 / Published online: 14 March 2014 Ó The Japanese Orthopaedic Association 2014
Abstract Background Pelvic ring and acetabular fractures are the results of high energy trauma, but there is a paucity of information available regarding the incidence and risk factors of venous thromboembolism (VTE) after these injuries in Asians. This study was undertaken to evaluate the incidence of VTE after a pelvic or an acetabular fracture and to identify predictive factors. Methods A prospective evaluation was performed by indirect computed tomography (CT) venography in patients with pelvic or acetabular fractures. Ninety-five patients were examined by indirect CT venography. Fiftyfive patients suffered from a pelvic ring injury (anteroposterior compression 5, lateral compression 25, vertical shear 25), and the remaining 40 from acetabular fractures (simple 18, complex 22). Indirect CT venography was performed within 1–2 weeks of initial trauma. Relationships between VTE and sex, age, fracture pattern, body mass index, injury severity score, period of immobilization, and need for surgical treatment were analyzed. Deep vein thrombosis (DVT) in a more proximal to popliteal vein and the existence of PE were considered clinically significant. Results Thirty-two patients (33.7 %) were found to have VTE at an average of 11 days after initial injury. Clinically
J.-W. Kim C.-W. Oh (&) S.-G. Baek B.-J. Lee H.-P. Hong W.-K. Min Department of Orthopaedic Surgery, Kyungpook National University Hospital, 50, 2-Ga, Samdok, Chung-gu, Daegu 700-721, Republic of Korea e-mail: [email protected] J.-K. Oh Department of Orthopaedic Surgery, Korea University Guro Hospital, 97, Gurodong-gil, Guro-gu, Seoul 152-703, Republic of Korea
significant DVT was found 20 cases (21.1 %). No statistical difference was found between pelvic ring injuries and acetabular fractures with respect to the development of VTE. For those with pelvic ring injury, the incidence of VTE in those with a vertical shear injury (52 %) was significantly greater than in others with a pelvic ring injury (p = 0.014). Patients with an age [50 were found to be at greater risk of VTE (p = 0.032). Conclusion Our findings demonstrate that Korean patients with pelvic or acetabular fractures have a higher risk of VTE than is generally believed, and caution should be taken to prevent and treat VTE, especially in high energy pelvic ring injury and elderly patients.
Introduction Pelvic ring or acetabular fractures are caused by highenergy trauma, and can be risk factors for the development of thromboembolism [1, 2]. The rate of deep vein thrombosis (DVT) after fracture of the pelvis has been reported to be up to 61 % [3], and the rate of pulmonary embolism (PE) after pelvic trauma up to 10 %. Furthermore, a fatal event was reported in half of this population [4, 5]. The first clinical manifestation of venous thromboembolism (VTE) is often PE-related sudden death, as has been established by epidemiologic and autopsy studies in Western populations [1]. However, in Asian populations, VTE is considered a rare disease entity and its prophylaxis after major orthopedic problems is occasionally overlooked [6, 7]. Recently, many investigators have emphasized that the incidence of VTE in Asians is similar to that in Caucasians, especially after total joint replacement surgery [8, 9]. Piovella et al. [10] reported the results of the AIDA (Assessment of the Incidence of Deep vein thrombosis in
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Asia) investigation and concluded that incidence of DVT by postoperative screening using bilateral venography is higher than generally believed. However, despite the above mentioned reports, decision making regarding VTE after pelvic trauma is problematic because of a lack of data. In particular, published information regarding the incidence and the risk factors of VTE in patients with a pelvic or acetabular fracture in the Asian population is scant. Accordingly, the objectives of this study were; (1) to determine the incidence of VTE after pelvic and acetabular fractures, and (2) to identify influencing factors and their significances based on statistical analysis of variance. To the best of our knowledge, this is one of the largest series conducted to examine the incidence of VTE and to identify the risk factors responsible after pelvic-acetabular trauma in an Asian cohort.
Patients and methods From January 2009 through December 2010, we prospectively evaluated a cohort of patients with pelvic or acetabular fractures. The design and protocol of this study were approved by the Institutional Review Board. The study group consisted of 95 skeletally mature patients. There were 40 men and 55 women of median age 57 years (range, 18–79) and of median body mass index (BMI) 23.6 kg/m2 (range, 17.2–35.8). Pelvic ring fractures were classified using the Young-Burgess classification [11] and acetabular fractures were classified as described by Letournel [12]. Fracture patterns were analyzed using pelvic anteroposterior, both oblique, and inlet and outlet views, and 3-dimensional computed tomography (CT) scans by two orthopedic surgeons, unaware of the existence of VTE to avoid selection bias. Injury severity scores (ISS) were used to grade injury severity. There were 55 cases of pelvic ring fracture [5 cases of anteroposterior compression (APC), 25 cases of lateral compression (LC) and 25 cases of vertical shear (VS) injury] and 40 acetabular fracture cases (18 cases of simple and 22 cases of complex fractures). Indirect CT venography was performed using a 64-channel multi-directional CT scanner (GE Healthcare, Milwaukee, Wisconsin, United States). Briefly, with a patient supine, feet were elevated to avoid calf compression. A scout CT image was then obtained to position subsequent fast acquisition images. Undiluted nonionic contrast media [120 ml; Optiray (ioversol) Millinckrodt, Pointe-Claire, Quebec, Canada] was administered to all patients using a power injector through an 18- or 20-gauge intravenous catheter in an antecubital vein, at a flow rate of 3 ml/s with a delay of 20–25 s before scanning. Helical CT of the pulmonary arteries was performed from the
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diaphragm to 2 cm above the aortic arch, 20 s after starting the contrast injection, using the following parameters; collimation 1.25 mm in fast mode, table speed 7.5 mm per gantry rotation, and pitch 6.0. Three minutes after starting the contrast injection, an indirect CT venography scan was performed from the ankle to the mid-abdomen, at a collimation of 4 9 2.5 mm, a 7.5 mm/s table speed, and a pitch of 3.0. Depending on patient height, 250–300 venous images were typically acquired. CT venography scans took approximately 80–90 s. The total examination time (including scanner programming, image acquisition, and delay time after starting contrast injection), including pulmonary CT angiography, was approximately 5–7 min. The criteria used to diagnose DVT were the presence of an intramural filling defect or localized non-opacification of a vein segment, venous expansion, and wall enhancement, as described by Loud et al. [13]. Indirect CT venography was scheduled within 7–14 days after injury, which was assumed as the stabilization period before operation. But, we also performed it promptly when any symptom suggesting DVT or PE presented. However, 5 patients were referred from other institutions at [2 weeks post-injury, and thus CT scans were delayed. Average time from injury to indirect CT venography was 11.8 days (range, 3–26). An anti-embolic stocking was applied to all patients, but no patient received chemoprophylaxis. However, when a patient exhibited a clinical manifestation of VTE, or DVT was confirmed by DVT-CT, low molecular weight heparin was started. If definitive stabilization was planned in patients with DVT, an inferior vena cava (IVC) filter was inserted prior to operation. We considered the presence of proximal DVT (in the popliteal or a more proximal vein) or PE as clinically significant VTE. The possible risk factors for VTE that we assessed were; age, sex, ISS, BMI, fracture pattern, duration of immobilization, and need for surgery. Associations between potential risk factors and VTE were analyzed using Pearson’s chi-square test and Fisher’s exact test. Statistical significance was accepted for p values of \0.05.
Results Thirty-two of the 95 patients (33.7 %) developed VTE at an average of 11 days (range, 3–26) post initial injury. Proximal DVT was present in 16 cases (16.8 %) and distal DVT in 13 (13.7 %). Bilateral distal DVT was found in 6 cases, but no case of bilateral proximal DVT was encountered. Furthermore, no mortality due to PE occurred in this series, but pulmonary CT angiography revealed 9 cases of PE, 5 of which developed from proximal DVT and 1 from distal DVT. The other 3 showed PE without
VTE in Koreans after pelvic trauma
thrombosis in the lower extremity. The incidence of clinically significant VTE was 21.1 % (20 cases). Eighty-one patients (85.3 %) underwent surgery at a median of 26 days (range, 0–42) after initial injury and VTE developed in 26 of these patients (32.1 %), and 9 of them had clinically significant VTE (13.6 %). On the other hand, 6 of the 14 patients that did not undergo surgery had VTE (42.9 %), and 5 had clinically significant VTE (35.7 %). There was no statistical significance between surgically and conservatively treated patients with respect to the incidence of VTE (p = 0.43) and clinically significant VTE (p = 0.14). In 17 of the patients, VTE was found before surgery, and all underwent inferior vena cava filter insertion before operative management. Fifty-five patients (57.9 %) had pelvic ring injuries (APC: 5, LC: 25, VS: 25) and 40 (42.1 %) had acetabular fractures (simple acetabular fractures: 18, complex acetabular fractures: 22). In the pelvic ring injury group, the incidence of VTE was 32.7 %, and in the acetabular fracture group, its incidence was 35 % (p = 0.81). With respect to clinically significant VTE, the incidences were 20 % in the pelvic ring injury group and 21.8 % in the acetabular fracture group (p = 0.83). However, these incidences were not significantly different (Pearson’s chi-square test). In patients with APC injury, no VTE was found, although 5 patients with LC injury (20 %) and 13 patients with VS injury (52 %) developed VTE. Clinically significant VTE was found in 2 cases (8 %) of LC injury and 10 cases (40 %) of VS injury. Patients with VS injury (Figs. 1, 2, 3, 4) had higher incidences of VTE and clinically significant VTE than other patients with APC or LC injuries (p = 0.014 and 0.011 respectively, Pearson’s chi-square test). Four (22.2 %) of the patients with a simple acetabular fracture developed VTE, and 2 (11.1 %) developed clinically significant VTE. On the other hand, 10 of the 22 patients (45.5 %) with complex acetabular fractures developed VTE (p = 0.125) and 6 (27.3 %) developed clinically significant VTE (p = 0.204). However, these incidences were not significantly different (Pearson’s chisquare test). The incidence of VTE in each group was summarized at Table 1. Median ISS was 26 (range, 1–48) in the total study subjects. Median ISS was 39 (range, 1–48) in the VTE group and 20 (range, 1–43) in the non-VTE group. Median ISS for the proximal DVT was 38 (range, 1–48). However, no significant relation was found between ISS and the development of VTE. Furthermore, no relation was found between other possible risk factors (sex, BMI, immobilization period, and the need for surgical intervention) and the development of VTE. However, patients aged more than 50 showed a high risk of VTE development (p = 0.032, Fisher’s exact test).
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Fig. 1 A 54-year-old female patient suffered from a vertical shear injury of the pelvic ring. She was treated conservatively at another hospital
Discussion Pelvic ring and acetabular fractures are major high energy trauma injuries, and are often associated with other injuries or fractures. In particular, VTE is an important common complication in trauma patients with pelvic or acetabular fractures [12, 14–17]. However, the importance of VTE has been underestimated and overlooked in Asian patients. In the Western literature, the incidence of DVT after major orthopedic trauma varies from 30 to 80 %. For acetabular fractures, the incidence of DVT was reported to be up to 34 %, although all were silent [14]. More recently, Moed and colleagues [18] reported that 15 % of patients with acetabular or pelvic fractures treated operatively developed DVT. Nevertheless, there appears to be a belief that VTE is rare in Asian patients, and for this reason, some investigators do not recommend routine chemoprophylaxis [19–21]. On the other hand, other authors have drawn attention to the fact that the incidence of DVT after major
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Fig. 2 At 3 weeks after injury, chest pain, dyspnea, and cold sweating suddenly developed and the patient was transferred to our institution. Pulmonary CT-angiography revealed emboli on both
pulmonary arteries (a, b), and multiple thrombi at right femoral vein, left peroneal vein, and left posterior tibial vein were detected by indirect CT venography (c, d, e)
orthopedic surgery in Asian populations is not low, and is entirely consistent with incidences observed in Western countries [8, 22, 23]. The present study confirms that VTE is considerably more common than is generally believed, in fact, our cohort showed a VTE incidence of 33.7 %, and a clinically significant VTE incidence of 21.1 %, although there was no mortality related to PE. Greets and colleagues [1] reported that the prevalence of VTE among trauma patients is higher than that among those undergoing an elective orthopedic procedure, such as arthroplasty. Furthermore, the pathophysiology of VTE in trauma cases is known to differ from that in those that have undergone elective surgery, and that the majority of thrombi in these patients are proximal [3, 14, 24]. Pelvic and acetabular fractures are the result of high velocity trauma, and are invariably associated with injury to vascular structures around the hip [3, 14], and subsequent manipulation during surgery further damages the vascular endothelium [3] and probably increases the risk of PE development. We presume that APC and LC injuries in the pelvic ring and simple acetabular fractures are due to lower energy injuries than VS injury and complex acetabular fractures. In the present series, patients with VS pelvic ring injuries had a VTE incidence of 52 %, which is higher than that
experienced by patients with APC or LC injuries (p = 0.014). However, no difference was observed between the incidences of VTE in patients with complex and simple acetabular fractures (p = 0.186). Accordingly, we emphasize that care should be taken when diagnosing and considering VTE prophylaxis in patients with high energy pelvic ring injuries. One should consider chemoprophylaxis as well as mechanical prophylaxis, such as anticoagulant agents, in patients with high energy pelvic ring injuries. Nevertheless, it has been well established that elderly patients with pelvic ring or acetabular fractures are at greater risk of thrombosis. In the present study, statistical analysis revealed that an age greater than 50 was associated with an increased risk of VTE (p = 0.032), which is somewhat younger than that reported by previous investigators. However, Montgomery and coworkers [25] reported that patients of 30 years and older showed an increased prevalence of VTE, which is considerably younger than that previously reported. On the other hand, some authors have reported that the incidence of VTE is independent of age [8, 23], but it should be added that the majority of reports on the subject have concluded that age significantly affects the development of VTE [3, 10, 14, 18, 25]. Accordingly, despite some controversy, age
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VTE in Koreans after pelvic trauma
475 Table 1 The incidence of venous thromboembolism (VTE) Kinds of injury (No. of patients)
% of VTE
% of clinically significant VTE
Pelvic ring injuries (55)
32.7
20
APC (5)
0
0
LC (25)
20
8
VS (25)
52
40
35
21.8
Simple (18)
22.2
11.1
Complex (22)
45.5
27.3
Acetabular fractures (40)
VTE venous thromboembolism, APC anteroposterior compression injury, LC lateral compression injury, VS vertical shear injury
Fig. 3 After 2 weeks of thrombolytic therapy, venous thrombi on her legs were dissolved (a, b)
Fig. 4 Post 6 weeks initial injury, surgical treatment was performed (a) after IVC filter insertion (b)
appears to be an important cause of VTE. Thus, the use of chemoprophylaxis may be appropriate for elderly patients.
In the present study, no significant association was found between the immobilization period and the prevalence of VTE, which concurs with the findings of Steel et al. [26]. However, others [14, 16] have reported a significant correlation between the development of DVT and prolonged immobilization. Furthermore, we found no correlation between surgery and VTE risk, although Napolitano et al. [24] reported that surgery and subsequent manipulation in trauma patients increases risk. In addition, we found no correlation between VTE development and sex, ISS, or BMI. Similarly, others have reported poor correlations between standard thrombosis risk factors and the development of VTE in trauma patients [3, 14, 27]. Thus, it appears that these factors have little effect on VTE development in trauma patients because the high baseline prevalence of thrombosis in these patients tends to overwhelm other influences. Nonetheless, the message that we wish to convey is that major trauma patients should be considered at high risk of thrombosis regardless of other risk factors. Duplex ultrasonography has been widely used to detect venous thrombosis, presumably, because it is readily applied, is non-invasive, and presents no radiation risk, but its efficacy is limited in the trauma setting, because bulky leg dressings, compromised skin and soft tissue statuses, wounds, and pain often limit studies. Moreover, duplex ultrasonography cannot be used to evaluate deep veins of the pelvis, which can be an important reservoir of occult venous thrombosis, and its efficacy as a screening tool in patients with suspected PE is limited. For this reason, and its superior ability to image proximal thigh and pelvic veins, we chose to use pulmonary CT angiography and indirect CT venography to screen for DVT. Several studies [28, 29] have shown that indirect CT venography produces results comparable to those of sonographic studies, but that it also has the following benefits: (1) both PE and DVT can be evaluated during a single examination, (2) indirect CT venography can detect DVT in the intra-abdominal and
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pelvic cavity areas whereas ultrasonography cannot, (3) indirect CT venography is not as invasive as conventional venography and more cost-effective than magnetic resonance venography. In the present study, the rate of proximal DVT or PE was 59.4 % in the VTE population (19 in 32), and this is difficult to diagnose by ultrasonography. Sen et al. [23] conducted a similar study by using pulmonary CT angiography and indirect CT venography, and found a proximal DVT or PE of 28.6 % in Indian patients. Although direct comparisons are difficult, because they studied the rate of VTE postoperatively, the rate reported was similar to ours (21.1 %), which reinforces our finding that VTE is common in Asian patients. The major concerns regarding CT venography are the additional radiation exposure required and the adverse effect of contrast. Furthermore, it is difficult to obtain a CT venography scan whenever a thrombotic symptom is suspected. In the present study, patients were evaluated prospectively, and all cases of DVT and PE were identified preoperatively. Furthermore, thrombolytic therapy was initiated and IVC filter insertion was performed before surgery, and no mortality occurred. The facts that the present study was conducted at a single institute and that the sample size was small are limitations. Accordingly, we suggest that a larger-scale, randomized, multicenter trial be undertaken with the objectives of determining the prevalence of VTE more precisely and of proposing guidelines for the prevention of VTE in Asian patients with pelvic or acetabular fractures.
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2.
3.
4. 5.
6.
7.
8.
9.
10.
11.
Conclusion Our findings demonstrate that Korean patients with pelvic or acetabular fractures are at higher risk of VTE development than most believe. Furthermore, because commonly believed risk factors are poor predictors of VTE in trauma patients, it is vital that efforts be made to diagnose, prevent, and treat VTE. Finally, we recommend that chemoprophylaxis be considered in patients at high risk, such as elderly patients and those with high energy pelvic ring injuries.
12. 13.
14.
15. 16.
Acknowledgments This work was supported by Biomedical Research Institute grant, Kyungpook National University Hospital (2014). 17. Conflict of interest All authors have certified that they have no commercial associations (e.g., consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with this article.
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