Preoperative Prevalence of and Risk Factors for Venous Thromboembolism in Patients with a Hip Fracture: An Indirect Multidetector CT Venography Study

Shin, Won Chul MD; Woo, Seung Hun MD; Lee, Seung-Jun MD; Lee, Jung Sub MD, PhD; Kim, Choongrak PhD; Suh, Kuen Tak MD, PhD

Journal of Bone & Joint Surgery - American Volume:
doi: 10.2106/JBJS.15.01329
Scientific Articles
Abstract

Background: This retrospective cohort study investigated the prevalence of and risk factors for preoperative venous thromboembolism (VTE) in patients with a hip fracture and a delay of >24 hours from injury to surgery.

Methods: This observational study included 208 patients with a hip fracture surgically treated at 1 university hospital between December 2010 and August 2014. Patients underwent indirect multidetector computed tomographic (MDCT) venography for preoperative VTE detection after admission. Overall VTE risk and median time from injury to CT scan were calculated. Age, sex, fracture type, time from injury to CT scan, body mass index, preinjury mobility score, previous anticoagulation treatment, previous hospitalization for VTE, varicose veins, and medical comorbidities were considered potential risk factors.

Results: The prevalence of preoperative VTE was 11.1% (23 of 208 patients), including 12 patients with deep vein thrombosis alone, 7 patients with pulmonary embolism alone, and 4 patients with both. The mean time from injury to CT scan was 4.9 days. The delay from the time of injury to CT scan averaged 7.6 days for patients who developed preoperative VTE, compared with 4.2 days for patients who had not developed VTE. In the adjusted models, female sex, subtrochanteric fracture, pulmonary disease, cancer, previous hospitalization for VTE, and varicose veins were risk factors for VTE. The final multivariate logistic regression analysis demonstrated that female sex (odds ratio [OR] = 5.86; 95% confidence interval [CI] = 1.21 to 28.21), subtrochanteric fracture (OR = 22.17; 95% CI = 4.02 to 122.06), pulmonary disease (OR = 21.10; 95% CI = 5.35 to 83.21), and previous hospitalization for VTE (OR = 16.36; 95% CI = 3.41 to 78.43) increased the risk of VTE.

Conclusions: Our findings show a high prevalence of preoperative VTE in patients with a hip fracture. Therefore, preoperative investigation for VTE should be routinely considered for patients in whom surgery is delayed for >24 hours. At this time, indirect MDCT venography seems to be effective and useful.

Level of Evidence: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Author Information

1Department of Orthopedic Surgery, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea

2Department of Orthopedic Surgery, Medical Research Institute, Pusan National University School of Medicine, Yangsan, Republic of Korea

3Department of Statistics, Pusan National University, Busan, Republic of Korea

E-mail address for K.T. Suh: kuentak@pusan.ac.kr

Article Outline

Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), occurs frequently in patients with a hip fracture. A delay in surgical care for patients with acute trauma is an important factor contributing to a high prevalence of preoperative VTE1-5. However, few reports have investigated the preoperative prevalence of VTE that may already be present in these high-risk patients at the time of hospital admission2-6. Studies have shown the preoperative prevalence of DVT to be 54% to 62% for patients with acute fracture whose surgery was delayed by >48 hours4,7. Although a delay in surgery increases morbidity and mortality in patients with a hip fracture8-12, patients often present a few days after the fracture, particularly in tertiary-care hospitals. The delay may result from preoperative medical evaluation and optimization or transfer from community hospitals to tertiary-care facilities. Elderly patients tend to be sicker on admission and therefore more likely to require greater time to surgery for preoperative testing and treatment and may be more likely to experience adverse events than patients undergoing immediate surgery8. These delays in surgical intervention may predispose patients to developing thromboembolic problems. The challenge with delayed surgery is to diagnose and protect patients from VTE preoperatively to avoid undesirable and occasionally disastrous consequences intraoperatively and postoperatively.

DVT or PE diagnosis has traditionally been performed using venography or color Doppler ultrasonography, computed tomography (CT), and ventilation perfusion lung scintigraphy. Recently indirect multidetector (MD) CT venography, which combines CT pulmonary angiography and indirect venography, has been shown to facilitate rapid and objective detection of both DVT and PE in 1 acquisition13-15. No recent report, to our knowledge, has described the prevalence of preoperative VTE in patients with a hip fracture using MDCT venography, a highly sensitive and specific means of identifying VTE.

The purpose of this study was to identify, using indirect MDCT venography, the prevalence of and risk factors for preoperative VTE in patients with a hip fracture who had a delay of >24 hours from the time of injury to surgery.

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Materials and Methods

Between December 2010 and August 2014, 239 consecutive patients were admitted to our hospital with a hip fracture. Thirty-one patients were excluded: 20 patients with a displaced femoral neck fracture and emergency operation within 24 hours of injury and 11 patients who underwent ultrasonography for VTE diagnosis, including 9 with preoperative azotemia (serum creatinine of >1.5 mg/dL) for whom contrast-enhanced CT was contraindicated and 2 who were hypersensitive to contrast media. The remaining cohort of 208 patients with a hip fracture whose surgery was delayed for >24 hours from the time of injury were included in this retrospective cohort study. Patient information was reviewed by the university human subjects committee, and institutional review board approval for this study was obtained prior to commencing the study.

In principle, we performed surgery as quickly as possible within 48 hours of hospital admission for patients with a hip fracture12. Surgery was delayed if needed for acute medical comorbidities, as delaying surgery may provide an opportunity for medical optimization, thus decreasing the risk for perioperative complications. Routine preoperative investigations included a full blood-cell count, blood urea, electrolytes, chest radiograph, electrocardiography, echocardiogram, and pulmonary function test. We applied a suitable surgical procedure for each type of fracture. If a delay in surgical treatment was anticipated, the patients were started preoperatively on once-daily subcutaneous injection of enoxaparin (4,000 IU), and intermittent pneumatic compression devices were applied immediately after admission.

All patients with a delay of >24 hours from the time of injury to surgery underwent indirect MDCT venography for preoperative VTE detection after admission. The indirect MDCT venography protocol is a combination of CT pulmonary angiography and indirect venography16. This combined imaging study examines the subdiaphragmatic deep-vein system at the time of CT pulmonary angiography. CT scans were performed using MDCT scanners (SOMATOM Definition Flash; Siemens Healthineers) with 128 detector rows. Low osmolar nonionic contrast material (2 mL/kg; up to 150 mL) was injected through an antecubital vein at 3 to 4 mL/sec. Individual contrast optimization was achieved using bolus tracking within the main pulmonary artery. CT scanning of the thorax began 40 seconds after contrast injection to evaluate for PE, and lower extremity scanning, with 2.0-mm slice thickness, was performed for DVT at 4 minutes after contrast injection. CT pulmonary angiography was obtained in the craniocaudal direction, ranging from the apex to the adrenal gland, during a single inspiratory breath-hold. Indirect CT venography was performed from the kidneys to the feet to detect DVT after a thoracic scan.

The indirect MDCT venography images were interpreted by an experienced senior professor, a board-certified radiologist with fellowship training in vascular CT, who was unaware of the purpose of the study. On a CT scan, PE was diagnosed when a sharply delineated pulmonary arterial filling defect was observed in at least 2 consecutive transverse images and located centrally within the vessel or with acute angles at its interface with the vessel wall17. A DVT was defined as a low-attenuating partial or complete intraluminal filling defect surrounded by a high-attenuating ring of enhanced blood that was seen on at least 2 consecutive transverse images18. Proximal DVT was defined as a thrombosis at the level of the popliteal vein or proximal to it, and distal DVT was defined as a thrombosis affecting the axial calf veins. If a DVT or PE was identified, a therapeutic dose of enoxaparin (100 IU/kg) was administered twice a day before surgery regardless of symptoms. If a DVT was identified, patients underwent insertion of an inferior vena cava filter prior to surgery, if necessary. The time from injury to CT scan and the indirect MDCT venography findings were recorded. Recorded data also included age, sex, type of fracture, time from injury to surgery, body mass index (BMI), preinjury mobility score19, previous anticoagulation treatment, previous hospitalization for VTE, varicose veins, and medical comorbidities.

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Statistical Analysis

Age, sex, type of fracture, BMI, preinjury mobility score19, previous anticoagulation treatment, previous hospitalization for VTE, varicose veins, and medical comorbidities were included in the analysis as possible risk factors. Continuous variables were analyzed using t tests for 2 independent samples. The chi-square test (or Fisher exact test where appropriate) and the linear-by-linear association were used for analysis of categorical data. To examine the effect of specific comorbidities on the risk of preoperative VTE, we also categorized patients according to the presence of certain conditions at the time of injury—such as diabetes, hypertension, cardiac disease (including previous myocardial infarction, congestive heart failure, angina pectoris, arrhythmia, and cardiac valvular disease), previous hospitalization for DVT and/or PE, pulmonary disease (asthma and chronic obstructive pulmonary disease), cerebrovascular accident, cancer, dementia, thyroid disease, kidney and liver disease, and dehydration. We used cumulative hazard plotting to calculate the overall VTE risk and the median time from injury to CT scan. All independent variables underwent statistical analysis. Only variables that were significant at a p value of 0.10 were included in the model for adjusted analysis. A multivariate logistic regression analysis was then performed to examine the association between possible risk factors and preoperative VTE. We report odds ratios (ORs) and 95% confidence intervals (CIs) for all associations. A p value of <0.05 was considered significant.

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Results

Patient characteristics and VTE risk factors are summarized in Table I. The mean age (and standard deviation) of the patients was 75.9 ± 9.7 years (range, 27 to 97 years), with 68.8% who were >75 years old. There were 62 male (29.8%) and 146 female patients (70.2%). The preoperative diagnosis was femoral neck fracture in 94 patients (45.2%), intertrochanteric fracture in 101 patients (48.6%), and subtrochanteric fracture in 13 patients (6.3%). Surgery was delayed because of interinstitutional transfer for 25 patients (12%), delayed hospital admission for 18 patients (9%), and medical optimization in 165 patients (79%). No side effect related to contrast medium was observed in this study.

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Prevalence of VTE

The overall prevalence of preoperative VTE in patients with a hip fracture whose operation was delayed >24 hours from the time of injury was 11.1% (23 of 208 patients), occurring at a median of 5 days (25th to 75th percentile, 3 to 10.5 days). The mean time from injury to CT scan was 4.9 days (range, 1 to 28 days). The mean time from injury to surgery was 5.7 days (range, 1 to 30 days). The mean delay from injury to CT scan was 7.6 days (range, 1 to 28 days) for patients who developed a preoperative VTE compared with a mean 4.2-day delay (range, 1 to 25 days) for patients who had not developed VTE (p = 0.031). There was an increasing linear association between the occurrence of VTE and the time from injury to CT scan on cumulative hazard plotting (Fig. 1). VTE occurred in 12 patients with DVT alone, 7 patients with PE alone, and 4 patients with both DVT and PE. All patients were asymptomatic, and there were no fatal or life-threatening clinical presentations related to preoperative VTE. DVT was found in the ipsilateral extremity with the fracture in all cases. The DVT was proximal in 9 patients and distal in 7 patients. Patients with subtrochanteric fractures had a higher prevalence of VTE than patients with femoral neck or intertrochanteric fractures (p = 0.029). In the VTE group, there was a higher prevalence of cardiac disease (30.4% versus 11.4%; p = 0.020), pulmonary disease (34.8% versus 5.4%; p < 0.001), cancer (34.8% versus 10.8%; p = 0.005), and previous hospitalization for VTE (26.1% versus 3.8%; p = 0.001).

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VTE Risk Factors

The results of the unadjusted and adjusted logistic regression analyses for VTE are displayed in Table II.

There was a significant association between the time from injury to CT scan and preoperative VTE in the unadjusted model. The time from injury to CT scan was no longer a significant predictor of preoperative VTE after adjusting for the potential confounders, because the time from injury to CT scan was highly associated with other risk factors. The adjusted significance levels are calculated by multiplying the unadjusted significance values by the number of comparisons, setting the value to 1 if the product was >1. The analysis was considered to be significant if the minimum value of the 95% CI for each factor was >1.00. In the adjusted models, female sex, subtrochanteric fracture, pulmonary disease, cancer, previous hospitalization for VTE, and varicose veins were assessed as VTE risk factors. The final multivariate logistic regression analysis is shown in Table III. These results showed that, after adjustment for other risk factors, female sex was a significant risk factor for VTE (OR = 5.86; 95% CI = 1.21 to 28.21) compared with male sex. Patients with subtrochanteric fractures (OR = 22.17; 95% CI = 4.02 to 122.06) had a higher risk than patients with femoral neck fractures. Patients with pulmonary disease (OR = 21.10; 95% CI = 5.35 to 83.21) had a higher risk than patients without pulmonary disease. Patients who had previous hospitalization for VTE (OR = 16.36; 95% CI = 3.41 to 78.43) had a higher risk than patients who had no previous VTE. No significant difference in thromboembolic event rates was demonstrated with logistic regression analysis regarding the interaction between VTE and age, medical comorbidities except pulmonary disease, anticoagulation treatment before injury, preoperative mobility score, or BMI.

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Discussion

Patients with a hip fracture are at increased risk of developing VTE even before surgery because of trauma to and immobilization of the extremity as well as other factors such as old age and medical problems4. However, most studies until now have investigated postoperative VTE, and only a few investigators have documented the prevalence of VTE in these high-risk patients at the time of hospital admission2-6. Additionally, most previous studies in the orthopaedic literature used Doppler ultrasound or a venogram to diagnose VTE3,4,7. This study was a retrospective and observational study in which the prevalence of and risk factors for preoperative VTE in patients with a hip fracture were evaluated. To our knowledge, this study provides the first evidence for preoperative VTE in patients with hip fracture using 128-row indirect MDCT venography, a highly sensitive and specific means of identifying DVT and PE in 1 acquisition.

The overall prevalence of preoperative VTE in this study was 11.1%. This result is consistent with those in other studies in the literature2-6 that have shown an overall 9% to 12.7% prevalence of preoperative VTE. A delay in surgical care for patients with acute trauma is one of the most important factors contributing to the high prevalence of preoperative VTE1-5, and it increases morbidity and mortality in patients with a hip fracture8-12. Ideally, surgery should be performed as early as possible, but routine surgery within 48 hours after admission is hard to achieve in most facilities. We observed that patients experiencing a delay in surgical care for an acute hip fracture were at a relatively high risk for the development of VTE. The average delay from injury to CT scan for patients who developed a preoperative VTE was significantly longer than that for patients who did not develop VTE. There was an increasing linear association between the period of delay and the occurrence of VTE on cumulative hazard plotting, which suggests that delay alone is a risk factor for VTE regardless of prophylaxis. The prevalence of VTE in this study compared with other reports likely reflects several points of interest. We studied a sequential series of patients, and indirect MDCT venography surveillance for VTE was performed in all patients. Therefore, asymptomatic patients with VTE were identified, raising the detection rate compared with a series where only symptomatic patients were identified. In addition, this population of patients (elderly with substantial medical comorbidities and a hip fracture) represents a group at a particularly high risk for VTE development20. In addition, although the prevalence of preoperative VTE in patients with a hip fracture may be higher in cases with delayed surgery, our results show that VTE can occur at any time after a hip fracture regardless of a delay in surgery. Therefore, we think that preoperative investigation of VTE could be performed for patients with a hip fracture. In this respect, our results are considered to be more meaningful.

In the present study, we identified 4 independent predictive factors for preoperative VTE in patients with hip fracture whose surgery was delayed by >24 hours: female sex, subtrochanteric fracture, pulmonary disease, and previous hospitalization for VTE. Conversely, we found that age, medical comorbidities except for pulmonary disease, BMI, preinjury mobility score, and previous anticoagulation treatment were not significant predictors of preoperative VTE. These results are thought to differ from those in previous reports2-4,6,7 because most previous studies recruited patients with either suspected DVT or PE and used conventional venography or ultrasonography. These patients may differ from those with suspected VTE, and it is not known whether findings in patients with suspected VTE can be extrapolated to those with either suspected DVT or PE alone.

The use of 128-row indirect MDCT venography, which provides high-quality images much faster than conventional indirect MDCT venography13, was chosen for VTE evaluation in this study. All patients with a delay of >24 hours from the time of injury underwent CT scanning according to an established protocol after admission. Contrast venography has traditionally been considered the reference standard test for DVT, with nearly perfect sensitivity and specificity. Recently, because of its invasive nature, allergic reactions, 10% to 20% failure rate, and cost21,22, contrast venography has gradually been replaced by color Doppler ultrasonography, which is readily available and highly accurate in detecting proximal DVT2,23. However, ultrasound requires changing between the supine and prone positions during examination and is often limited to the inferior vena cava and iliac vein because of technical reasons. Furthermore, patients with VTE may present with both suspected DVT and PE, requiring 2 diagnostic tests. Rapid and objective detection and measurement of thrombi in both PE and DVT can now be performed using indirect MDCT venography. Combined CT pulmonary angiography and indirect venography was first reported, to our knowledge, in 199816 and has become routine clinical practice in some medical centers18,24. The procedure is easy to perform and allows concurrent evaluation for PE and DVT, with only 1 peripheral venous infusion of contrast media. The venography examination does add several minutes to the time that the patient spends in the CT scanner, but this extra time is negligible considering the accuracy and usefulness of the CT scan. Although there are concerns regarding the high equipment cost and mild invasiveness with MDCT procedures, the usefulness of this modality is supported by its high sensitivity (100%) and specificity (96.6%) and moderate-to-high interobserver agreement rates15,25. There is obviously another concern about the additional radiation exposure to the patient, but the effective radiation dose is relatively low and is comparatively safe26. In general, the side effects of radiographic contrast media range from a mild inconvenience, such as itching, to a life-threatening emergency27,28. There were no side effects related to contrast media in the patients in the present study.

In conclusion, we think that patients with a hip fracture whose surgery is delayed by >24 hours should be considered at high risk for VTE. In addition, a preoperative distal thrombosis may migrate into a proximal vein and cause intraoperative PE. As clinical examination is unreliable for the detection of VTE, preoperative investigation should be routinely performed for patients with a hip fracture in whom surgery is delayed for >24 hours. At this time, the use of indirect MDCT venography seems to be effective and useful.

Investigation performed at the Department of Orthopedic Surgery, Medical Research Institute, Pusan National University School of Medicine, Yangsan, Republic of Korea

Disclosure: There was no external source of funding for this study. The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article.

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