Scholarly article on topic 'Thromboprophylaxis does not prevent venous thromboembolism after major surgery'

Thromboprophylaxis does not prevent venous thromboembolism after major surgery Academic research paper on "Clinical medicine"

CC BY-NC-ND
0
0
Share paper
OECD Field of science
Keywords
{Thromboprophylaxis / "Pulmonary embolism" / "Deep venous thrombosis"}

Abstract of research paper on Clinical medicine, author of scientific article — Adel Attia, Hitham Ali, Mohammed Al Amory, Hosam Othman

Abstract Pulmonary embolism (PE) is a life-threatening condition or complication and might be one of the worst nightmares for most surgeons. The aim of this study was to evaluate the incidence of venous thrombo-embolism (VTE) in patients undergoing major abdominal surgery and major orthopedic surgery who received VTE prophylaxis. Methods Between January of 2010 and September of 2013 all the patients who underwent major abdominal surgery and major orthopedic surgery who received VTE prophylaxis, at King Fahad Hospital Dammam Kingdom of Saudi Arabia, were prospectively evaluated for the incidence of DVT and PE within 30 postoperative days. Results The incidence of symptomatic DVT and PE in the patients studied was 2.23% and 2.03%, respectively. The incidences of PE and DVT following abdominal surgery were 2.44%, and the incidences of PE and DVT following orthopedic surgery were 1.62% and 2.03%, respectively. Conclusion Despite the use of thromboprophylaxis, PE and DVT were important complications of major abdominal and major orthopedic surgery.

Academic research paper on topic "Thromboprophylaxis does not prevent venous thromboembolism after major surgery"

Egyptian Journal of Chest Diseases and Tuberculosis (2015) 64, 249-254

HOSTED BY

The Egyptian Society of Chest Diseases and Tuberculosis Egyptian Journal of Chest Diseases and Tuberculosis

www.elsevier.com/locate/ejcdt www.sciencedirect.com

ORIGINAL ARTICLE

Thromboprophylaxis does not prevent venous c^Ma*

thromboembolism after major surgery

Adel Attia a *, Hitham Ali b, Mohammed Al Amory c, Hosam Othman d

a Chest Department, Faculty of Medicine, Zagazig University, Egypt b Orthopedic Department, King Fahad Hospital Dammam, Saudi Arabia c General Surgery Department, King Fahad Hospital Dammam, Saudi Arabia d Diagnostic Radiology Department, Faculty of Medicine, Al-Azhar Assuit University, Egypt

Received 22 September 2014; accepted 10 November 2014 Available online 12 December 2014

KEYWORDS

Thromboprophylaxis; Pulmonary embolism; Deep venous thrombosis

Abstract Pulmonary embolism (PE) is a life-threatening condition or complication and might be one of the worst nightmares for most surgeons.

The aim of this study was to evaluate the incidence of venous thrombo-embolism (VTE) in patients undergoing major abdominal surgery and major orthopedic surgery who received VTE prophylaxis.

Methods: Between January of 2010 and September of 2013 all the patients who underwent major abdominal surgery and major orthopedic surgery who received VTE prophylaxis, at King Fahad Hospital Dammam Kingdom of Saudi Arabia, were prospectively evaluated for the incidence of DVT and PE within 30 postoperative days.

Results: The incidence of symptomatic DVT and PE in the patients studied was 2.23% and 2.03%, respectively. The incidences of PE and DVT following abdominal surgery were 2.44%, and the incidences of PE and DVT following orthopedic surgery were 1.62% and 2.03%, respectively.

Conclusion: Despite the use of thromboprophylaxis, PE and DVT were important complications of major abdominal and major orthopedic surgery.

© 2014 The Egyptian Society of Chest Diseases and Tuberculosis. Production and hosting by Elsevier

B.V. All rights reserved.

Introduction

Pulmonary embolism (PE) is a life-threatening condition or complication and might be one of the worst nightmares for

* Corresponding author. Tel.: +20 1224733108, +20 966502591539. E-mail address: adelattia68@yahoo.com (A. Attia). Peer review under responsibility of The Egyptian Society of Chest Diseases and Tuberculosis.

most surgeons. The embolus that causes the obstruction usually travels through the venous system from a distant site. PE causes symptoms such as dyspnea, chest pain or collapse. Moreover, the clinical severity of PE can vary, ranging from asymptomatic cases to sudden death. Despite advances in diagnosis and treatment, PE remains a significant cause of morbidity and mortality and is still one of the most common preventable causes of death, which is easily overlooked [1,2]. Risk factors for deep vein thrombosis (DVT) and PE are prior

http://dx.doi.org/10.1016/j.ejcdt.2014.11.011

0422-7638 © 2014 The Egyptian Society of Chest Diseases and Tuberculosis. Production and hosting by Elsevier B.V. All rights reserved.

medical history of DVT or PE, recent surgery, general anesthesia lasting longer than 30 min, pregnancy, prolonged immobilization, age >40 years, obesity or underlying malignancy [3,4]. Moreover, gynecologic surgery, major trauma and indwelling venous catheters are risk factors for DVT at any location. Otherwise, venous thrombosis commonly involves lower limbs, affecting most frequently calf veins, which are involved in virtually 100% of symptomatic, spontaneous lower extremity DVT. Although DVT usually starts in calf veins, it is propagated above the knee in 87% of symptomatic patients before the diagnosis has been made. However, more than 35% of patients who die from PE may have isolated calf vein thrombosis [5]. Because perioperative VTE is asymptomatic in the majority of the cases (95%), this important clinical condition might be underestimated by surgeons, resulting in inadequate use of prophylactic anticoagulants [6].

The aim of this study was to evaluate the incidence of venous thromboembolism (VTE) in patients undergoing major abdominal surgery and major orthopedic surgery who received VTE prophylaxis.

Methods and subjects

The study was approved by the King Fahad Hospital Ethics and Research committee. Between January of 2010 and September of 2013 all the patients who underwent major abdominal surgery (bariatric surgery, Whipple operation, colo-rectal surgery, nephrectomy, splenectomy) and major orthopedic surgery (hip arthroplasty, knee arthroplasty, or femur fracture repair), were included in the study (Table 1). 493 patients who had been referred to the Orthopedics and General Surgery Departments of the King Fahad Hospital Dammam Kingdom of Saudi Arabia, and submitted to surgery were prospectively studied and evaluated for the incidence of DVT and PE within 30 postoperative days. The departments had a standard protocol for thromboprophylaxis (enoxaparin 40 mg/day s.c., and the use of graded compression stockings). This protocol was used during the period of the study. Patients who underwent major abdominal surgery and major orthopedic surgery in the hospital were routinely followed on postoperative day 14, and 30

after had discharged 7 days postoperative. Patients who had respiratory symptoms (pleuritic chest pain, dyspnea, hemoptysis, or cough), with or without signs and symptoms consistent with DVT (swelling, pain, tenderness, increase in the diameter of lower limbs, or local heat), were referred and evaluated by a pulmonologist as a consultation. Patients suspected of having VTE were submitted to chest CT angiography and Doppler ultrasound of the lower extremities by an expert radiologist. Chest CT angiography was performed with a 16-section multi-detector CT scanner (LightSpeed 16; GE Healthcare, Milwaukee, WI, USA) within 24 h. PE was diagnosed when an intraluminal filling defect surrounded by intravascular contrast or total occlusion of the pulmonary arterial lumen was detected at any level of the pulmonary arteries. Doppler ultrasound of the deep veins of the lower extremities was performed with a standard method using a dedicated ultrasound unit (LOGIQ 7; GE Healthcare) with a 10 L linear array transducer (bandwidth, 6-10 MHz) in order to investigate the presence/ absence of intravenous thrombi. Data on the type of surgical procedure, the type and duration of anesthesia, and other potential risk factors for VTE, including obesity, immobility (bed rest >48 h), malignancy, previous history of VTE, COPD, smoking, congestive heart failure, trauma, thrombocy-tosis, and history of hormone replacement, were also recorded (Table 2). In addition, the time of initiation and the duration of thromboprophylaxis were collected.

Statistical analysis

Data were analyzed using the Statistical Package for the Social Sciences for Windows, version 16.0 (SPSS Inc., Chicago, IL, USA). Descriptive statistical analysis results were presented as absolute and relative frequencies. Differences between groups for categorical variables were analyzed using the chi-square test or Fisher's exact test, where appropriate. The three clinically important variables among those which were found significantly effective in the development of VTE in the univar-iate analysis were evaluated by multiple logistic regression analysis in order to define independent risk factors of outcome variables.

Table 1 Demographic data, type of surgery, and incidence of PE and DVT in the patients included in the study.

Variable Result PE (N = 10) DVT (N = 11)

Age 64.46 ± 19.12

Gender

Male 229 (46.45%) 4 (40%) 4(36.36%)

Female 264 (53.55%) 6 (60%) 7(63.63%)

Type of surgery

Abdominal surgery 246 (49.89) 6 (60%) 6 (54.55%)

Orthopedic surgery 247 (50.ll) 4 (40%) 5 (45.45%)

Bariatric surgery 35 (7.10%) 1 (10%) 1 (9.09%)

Whipple operation 99 (20.08%) 2 (20%) 2 (18.18%)

Colorectal surgery 83 (16.84%) 3 (30%) 3 (27.27%)

Splenectomy 6 (1.21%) 0 0

Nephrectomy 6 (1.21%) 0 0

Knee arthroplasty 94 (19.07%) 0 0

Hip arthroplasty 67 (13.59%) 1 (10%) 1 (9.09%)

Femur fracture repair 86 (17.44%) 3 (30%) 4 (36.37%)

PE: Pulmonary Embolism, DVT: Deep Venous Thrombosis.

Table 2 Distribution of potential risk factors for pulmonary embolism and DVT.

Risk factors Study sample (n = 493)

Abdominal Surgery 246 (49.89)

Orthopedic surgery 247 (50.11)

Obesity 95 (19.27)

Immobility 145 (29.41)

Malignancy 106 (21.50)

Previous history of VTE 34 (6.09)

COPD 19 (3.85)

Congestive heart failure 39 (7.91)

Smoking 63 (12.78)

Trauma 0

Hormonal replacement 0

Thrombocytosis 0

Results

Demographic data, type of surgery, and incidence of PE and DVT in the patients included in the study are shown in Table 1. The mean age of the patients was 64.46 ± 19.12 years. Females and males accounted for 229 and 264, respectively. General anesthesia was administered to 58.9% of the patients, whereas 41.1% of the patients were treated with combined spinal-epidural anesthesia. Patients who underwent of bariat-ric surgery 35 (7.10%), Whipple operation 99 (20.08%), colorectal surgery 83 (16.84%), nephrectomy 23 (4.67%), splenectomy 6 (1.21%), knee arthroplasty 94 (19.07%), hip arthroplasty 67 (13.59%), and femur fracture repair 86 (17.44%). Of the 493 patients, 10 (2.03%) and 11 (2.23%), respectively, were diagnosed with PE and DVT. All of the patients wore compression stockings and received VTE prophylaxis. Enoxaparin (40 mg/day) was the anticoagulant used for all of the patients, who received VTE prophylaxis during 30 postoperative days. Prophylaxis was started at the tenth postoperative hour. Nearly one-half of the patients (48.68%) presented with one or more than one risk factor for VTE other than the surgery (immobility and obesity). Additional risk factors for VTE are included in Table 2.

The incidence of symptomatic DVT and PE in the patients studied was 2.23% and 2.03%, respectively. All of the patients with PE were also diagnosed with concomitant DVT. The incidences of PE and DVT following abdominal surgery were 2.44%, and the incidences of PE and DVT following orthopedic surgery were 1.62%, and 2.03%, respectively. The incidences of PE and DVT following bariatric, surgery, Whipple operation,

and colorectal surgery were 2.85%, 2.02% and 3.61% respectively, and the incidences of PE following hip arthroplasty, and femur fracture repair were 1.49% and 3.49%, respectively, and the incidence of DVT following femur fracture repair was 4.65%. Of the patients who had PE and DVT, 80% and 81.82%, respectively, developed them within the first 5 postoperative days. The time for the onset of PE and DVT in the patients is shown in Table 3 (see Fig. 1).

The majority of the patients (78.6%) who developed PE were aged P65 years (p = 0.004). No significant differences were found regarding the gender or the type of anesthesia administered in the group of patients who developed PE (p > 0.05). The multiple logistic regression analysis revealed that the patients undergoing colorectal surgery and Whipple operation were at a greater risk for the development of PE and DVT than those who underwent bariatric surgery, nephrectomy, splenectomy (OR = 3.338; 95% CI: 1.17515.39; p = 0.023) and those who underwent femur fracture repair were at a greater risk for the development of PE and DVT than those who underwent knee or hip arthroplasty (OR = 5.113; 95% CI: 1.161-17.29; p = 0.028). Patients aged P65 years also had higher rates of PE (OR = 4.856; 95% CI: 1.074-21.953; p = 0.040).

The incidence of PE and DVT was higher in bedridden patients than in those who were not (p = 0.004). However, the incidence of PE and DVT in obese patients or in patients with a previous history of VTE, COPD, congestive heart failure, trauma, smoking, hormone replacement, or thrombocytosis was not significantly higher than in the other participants (p > 0.05 for all).

Discussion

Venous thromboembolism (VTE), deep vein thrombosis (DVT) and pulmonary embolism (PE), are important causes of morbidity and mortality. The risk of VTE is highest in patients undergoing major surgery [7]. PE is the third most common cause of death in the US, with at least 650,000 cases occurring annually. Furthermore, PE represents the first or second most common cause of unexpected death in most age groups. The highest incidence of recognized PE occurs in hospitalized patients. Autopsy results are showing that up to 60% of patients who die at a hospital have PE, and that diagnosis is missed in about 70% of cases [8].

In our study, the incidence of PE and DVT in the patients following major surgery was 2.03% and 2.23%, respectively. Most of the patients developed PE or DVT within the first 5 postoperative days. The patients undergoing colorectal surgery

Table 3 Time for the onset of pulmonary embolism and deep vein thrombosis in the study sample.

Onset of PE and DVT postoperative days PE (N = 10) DVT (N = 11)

2 4 (40%) 3 (27.27%)

3 3 (30%) 4 (36.36%)

4 1 (10%) 2 (18.19%)

7 1 (10%) 1 (9.09%)

14 1 (10%) 1 (9.09%)

30 0 0

Total 10 (2.03%) 11 (2.23%)

t V V S ^ S j

mA: ' • ----..C^SCT KVp: 120 - ~ . W: 7OCT Acq no: 6 ^_-®FOV:30x30cm " compressed 11:1 Page: 33"3f-«41 P IM: 33 SE: 3

Figure 1 Showed subsegmental pulmonary embolism.

and femur fracture repair, those aged p 65 years, and those who were bedridden were at a higher risk for developing VTE. All of the patients undergoing major abdominal surgery and major orthopedic surgery in the hospital under study received VTE prophylaxis. The surgery creates an additional risk for the development of VTE. It has been previously reported that VTE can develop following colorectal surgery and hip and femur fracture surgery despite thromboprophylaxis [9]. The incidence of PE was highest in the patients submitted to femur fracture repair (3.49%) among the major orthopedic surgeries in our study population. This can be explained by the following factors: patients undergoing femur fracture repair are commonly older, and long bone fracture itself increases the risk for VTE due to prolonged immobility and increased endo-thelial injury. It has been previously reported that the low incidence of symptomatic VTE perioperatively (5%) might mislead surgeons into considering PE as a rare complication of major orthopedic surgeries [10,11]. On the contrary, the present study demonstrated that approximately 80% of symptomatic PE occurred within the first 5 postoperative days, despite the routine use of prophylaxis. It is well known that damage to vascular endothelium and venous stasis resulting in endothelial hypoxia can cause the activation of the coagulation cascade. The natural fibrinolytic activity of the body tries to overcome the formation of thrombosis. The development of PE, more commonly within 5 days after surgery, might be due to the early intense effect of endothelial injury and hypoxia because of the surgical trauma and venous stasis [12].

In one study, the incidence of PE in patients who did not receive prophylaxis was approximately 50% [11]. The use of prophylaxis decreased the incidence but did not completely resolve the problem. In one meta-analysis, it was reported that the incidence of PE within 3 months after the procedure was 3.2% in patients receiving short-term prophylaxis (7-10 days) [13]. The incidence of PE was lower in the present study than in that meta-analysis. This difference between the results might be explained by the long-term prophylaxis (30 days) and the short duration of the follow-up of the patients (30 postoperative days) in our study, in contrast to the results in the studies included in that meta-analysis. Previous studies showed that the duration of prophylaxis reduced the risk of symptomatic DVT [14,15]. However, despite the long-term use of thrombo-prophylaxis in our study population, the prevention of this

important complication was not completely achieved. Enoxap-arin was the anticoagulant therapy administered to the high-risk population for prophylaxis. The commonly used dose of the medication was 40 mg/day (4000 IU) in all of the patients despite their weight. The recommended dose of LMWH for thromboprophylaxis is >3400 IU in accordance with the ACCP guidelines, although weight-based dose adjustments ofLMWHs might provide more effective prophylaxis. ACCP recommends long-term thromboprophylaxis (30-35 days) after major surgery [16]. When we reviewed the LMWH dose in the protocol, we realized that the dose was consistent with the ACCP guidelines. In our study, the risk of PE and DVT was also higher in patients undergoing surgery for colorectal surgery (3.61%) as compared to those having other abdominal surgery. The increased risk of PE and DVT can be explained by a number of factors, such as malignancy-related hypercoagulable state, postoperative infectious complications, prolonged surgery, and pelvic dissection [17]. An increased risk of PE after colorectal surgery has also been showed by Lee et al. in a study on Chinese patients who underwent colorectal surgery without DVT prophylaxis. The authors demonstrated the occurrence of asymptomatic calf vein thrombosis in 41.7% of patients using serial Duplex ultrasound studies [18]. Kerkez et al. [19] reported that, the incidence of PE after colorectal surgery of patients who received prophylaxis was significantly lower compared to that seen among subjects with colorectal surgery without prophylaxis. White et al. reported that the incidence of VTE after hip arthroplasty was higher than that of VTE after knee arthro-plasty (2.8% vs. 2.1%) [20]. Our study showed a more striking difference between the incidence of PE following hip and knee arthroplasty (1.49% vs. 0%). Similarly to previous data [21,22], the highest incidence of PE in the present study (3.49%) occurred in the patients who underwent femur fracture repair. Shorr et al. found the incidence of PE after major orthopedic surgery in patients receiving enoxaparin to be 2.3% [23]. Although the frequency of PE increases with age, this is not an independent risk factor. Nevertheless, the accumulation of different risk factors, such as underlying illnesses and decreased mobility, increases the frequency of PE in older patients. Unfortunately, diagnosis of PE is often missed, especially in older patients. PE is diagnosed in 30% of all patients who die with massive PE, but only in 10% of those who are 70 years of age or older. Thus, PE still remains the most commonly missed

diagnosis in the elderly institutionalized patients [24]. In our study, we found that, patients aged P65 years were at a significantly higher risk for PE after major surgery. Additional risk factors other than surgery, such as malignancy and immobility, might increase with age. It is known that patients aged >40 years are at a greater risk for VTE than younger patients and that prolonged immobility, together with other major risk factors, increases the risk for VTE. Although a previous history showed VTE and obesity to be known risk factors for VTE [11], these two conditions were not found to be independent risk factors for VTE in the present study. In our study, the previous history of VTE of patients might not have been adequately documented on the medical records. Bleeding as a complication from medical prophylaxis is one of the factors that might lead to its inadequate use by the surgeons, especially following procedures such as a major orthopedic surgery. However, previous studies showed that the risk of clinically significant bleeding did not increase with medical prophylaxis [25]. In our study, patients who received prophylaxis with low dose LMWH after major surgery did not have any side effects (such as bleeding).

Conclusion

Despite the use of thromboprophylaxis, PE and DVT were important complications of major abdominal and major orthopedic surgery.

Contribution

All the authors contributed to research design, participated in the writing of the manuscript and data analysis, performed research, and contributed with analytical tools.

Conflict of interest

The authors have disclosed no conflicts of interest.

References

[1] M. Idiz, C. Konuralp, M. Ates, Under diagnosis of pulmonary embolism: a recurrent nightmare for surgeons, Eastern J. Med. 8 (2003) 1-6.

[2] T.R. Wolfe, S.C. Hartsell, Pulmonary embolism: making sense of the diagnostic evaluation, Ann. Emerg. Med. 37 (2001) 504514.

[3] G.V. Robinson, Pulmonary embolism in hospital practice, BMJ 332 (2006) 156-160.

[4] F.A. McAlister, K. Bertsch, J. Man, J. Bradley, M. Jacka, Incidence of and risk factors for pulmonary complications after nonthoracic surgery, Am. J. Respir. Crit. Care Med. 171 (2005) 514-517.

[5] J.A. Heit, The epidemiology of venous thromboembolism in the community: implications for prevention and management, J. Thromb. Thrombolysis 21 (2006) 23-29.

[6] J.I. Arcelus, J.A. Caprini, J.J. Reyna, Finding the right fit: effective thrombosis risk stratification in orthopedic patients, Orthopedics 23 (6 Suppl.) (2000) s633-s638.

[7] R.H. White, The epidemiology of venous thromboembolism, Circulation 107 (23 Suppl. 1) (2003) I4-I8, http://dx.doi.org/ 10.1161/01.CIR.0000078468.11849.66.

[8] F.A. Klok, I.C. Mos, M.V. Huisman, Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism: a systematic review and metaanalysis, Am. J. Respir. Crit. Care Med. 178 (2008) 425-430.

[9] S B. Deitelzweig, S.C. McKean, A.N. Amin, D.J. Brotman, A.K. Jaffer, A.C. Spyropoulos, Prevention of venous thromboembolism in the orthopedic surgery patient, Cleve Clin. J. Med. 75 (Suppl. 3) (2008) S27-S36, http://dx.doi.org/ 10.3949/ccjm.75.Suppl_3.S27.

[10] F.A. Anderson Jr., F.A. Spencer, Risk factors for venous thromboembolism, Circulation 107 (23 Suppl. 1) (2003) I9-I16, http://dx.doi.org/10.1161/01.CIR.0000078469.07362.E6.

[11] J.I. Arcelus, J.C. Kudrna, J.A. Caprini, Venous thromboembolism following major orthopedic surgery: what is the risk after discharge?, Orthopedics 29 (6) (2006) 506-516

[12] J.M. Enders, J.M. Burke, P.P. Dobesh, Prevention of venous thromboembolism in acute medical illness, Pharmacotherapy 22 (12) (2002) 1564-1578, http://dx.doi.org/10.1592/ phco.22.17.1564.34124.

[13] J.D. Douketis, J.W. Eikelboom, D.J. Quinlan, A.R. Willan, M.A. Crowther, Short-duration prophylaxis against venous thromboembolism after total hip or knee replacement: a meta-analysis of prospective studies investigating symptomatic outcomes, Arch. Intern. Med. 162 (13) (2002) 1465-1471, http://dx.doi.org/10.1001/archinte.162.13.1465.

[14] R.D. Hull, G.F. Pineo, P.D. Stein, A.F. Mah, S.M. MacIsaac, O.E. Dahl, et al, Extended out-of-hospital low-molecular-weight heparin prophylaxis against deep venous thrombosis in patients after elective hip arthroplasty: a systematic review, Ann. Intern. Med. 135 (10) (2001) 858-869, http://dx.doi.org/10.7326/ 0003-4819-135-10-200111200-00006.

[15] J.W. Eikelboom, D.J. Quinlan, J.D. Douketis, Extended-duration prophylaxis against venous thromboembolism after total hip or knee replacement: a meta-analysis of the randomised trials, Lancet 358 (9275) (2001) 9-15, http://dx.doi.org/10.1016/ S0140-6736(00)05249-1.

[16] G.H. Guyatt, E.A. Akl, M. Crowther, D.D. Gutterman, H.J. Schuünemann; American College of Chest Physicians Antithrombotic Therapy and Prevention of Thrombosis Panel. Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed.: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 141(2 Suppl.) (2012) 7S-47S. Erratum. In: Chest. 141(4) (2012) 1129.

[17] P.J. Shukla, R. Siddachari, S. Ahire, S. Arya, S. Ramani, S.G. Barreto, S. Gupta, S.V. Shrikhande, P. Jagannath, L.J. Desouza, Postoperative deep vein thrombosis in patients with colorectal cancer, Indian J. Gastroenterol. 27 (2008) 71-73.

[18] F.Y. Lee, W. Chu, R. Chan, Y.F. Leung, K.H. Liu, S.M. Ng, P.B. Lai, C. Metreweli, W.Y. Lau, Incidence of deep vein thrombosis after colorectal surgery in a Chinese population, ANZ J. Surg. 71 (2001) 637-640.

[19] M. Kerkez, D. Culafic, D. Mijc, V. Rankovic, N. Lekic, D. Stefanovic, A study of pulmonary embolism after abdominal surgery in patients undergoing prophylaxis, World J. Gastroentrol. 15 (3) (2009) 344-348.

[20] R.H. White, P.S. Romano, H. Zhou, J. Rodrigo, W. Bargar, Incidence and time course of thromboembolic outcomes following total hip or knee arthroplasty, Arch. Intern. Med. 158 (14) (1998) 1525-1531, http://dx.doi.org/10.1001/ archinte.158.14.1525.

[21] J. Edelsberg, D. Ollendorf, G. Oster, Venous thromboembolism following major orthopedic surgery: review of epidemiology and economics, Am. J. Health Syst. Pharm. 58 (Suppl. 2) (2001) S4-S13.

[22] W. Gillespie, D. Murray, P.J. Gregg, D. Warwick, Risks and benefits of prophylaxis against venous thromboembolism in orthopaedic surgery, J. Bone Joint Surg. Br. 82 (4) (2000) 475479, http://dx.doi.org/10.1302/0301-620X.82B4.10452.

[23] A.F. Shorr, L.M. Kwong, M. Sarnes, L. Happe, E. Farrelly, N. Mody-Patel, Venous thromboembolism after orthopedic surgery: implications of the choice for prophylaxis, Thromb. Res. 121 (1) (2007) 17-24, http://dx.doi.org/10.1016/ j.thromres.2007.02.013.

[24] S.V. Konstantinides, Massive pulmonary embolism: what level of aggression?, Semin Respir. Crit. Care Med. 29 (2008) 47-55.

[25] W.H. Geerts, G.F. Pineo, J.A. Heit, D. Bergqvist, M R. Lassen, C.W. Colwell, et al, Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy, Chest 126 (3 Suppl.) (2004) 338S-400S, http://dx.doi.org/10.1378/chest.126.3_suppl.338S.