Venous thromboembolism prophylaxis following degenerative spine surgery: a narrative review

Introduction

Background

Venous thromboembolism (VTE) is a well-known complication of surgery within the peri-operative period. VTE consists of both proximal and distal deep vein thrombosis (DVT) and the more catastrophic condition pulmonary embolism (PE). DVT cases have been estimated to approach a frequency of 2 million per year within the United States population and fatal PE has been reported to occur in approximately 100,000 patients annually (1). Thromboembolic complications come with severe, potentially fatal implications, as PE has been estimated to have a mortality rate around 30%, leading to an estimated 50,000 deaths per year in the United States (2-5). Although the importance of prophylactic measures dedicated to lowering the risk of thromboembolic complications has long been recognized, major surgery (defined as requiring hospitalization) has still been reported to account for approximately 25% of VTE observed in population-based studies of the general public (6,7). It is important to note that the risk for post-operative VTE varies considerably across different surgical procedures, with hip and knee arthroplasty, spine and neurosurgery, and major vascular surgery carrying the highest risk (6,8). Spinal surgery patients, in particular, have been reported to undergo prolonged immobility in their perioperative care period, leading to an increased predisposition for thromboembolic complications (4,9-12). Despite the increased risk for VTE and its potential negative impact on post-operative outcomes, routine chemoprophylaxis remains highly controversial due to concerns regarding symptomatic or asymptomatic hemorrhage, spinal epidural hematoma (SEH), blood loss and potential neurologic complications, including intracranial hemorrhage (4,13). Unlike the case for other commonly performed elective procedures such as hip and knee arthroplasty, there is still no clear evidence-based consensus on optimal thromboprophylaxis regimens in spine surgery, as evinced by the lack of concrete guidelines from both the American Academy of Orthopedic Surgeons (AAOS) and the American Association of Neurological Surgeons (AANS) as well as only fair evidence in favor of mechanical prophylaxis and a consensus statement regarding the risks of chemoprophylaxis from the North American Spine Society (NASS) working group (14-16).

Rationale and knowledge gap

Although several short-term and long-term therapeutic options for thromboprophylaxis in spinal surgery exist, such as intermittent pneumatic compression (IPC) devices, elastic compressive stockings (CS), low-dose unfractionated heparin (UFH) and low molecular-weight heparin (LMWH) (enoxaparin and dalteparin), consensus does not exist across the literature regarding the most efficacious combination of mechanical and pharmaceutical thromboprophylaxis strategies. This is likely due to the lack of high-level evidence and clinical trials regarding VTE prophylaxis in degenerative spine surgery as well as the broad range of patient risk factors and variations in recommendations from the medical community (14).

Objective

Through a critical review of the current literature, we aim to determine the incidence of DVT/PE in patients undergoing degenerative spinal surgery as well as elucidate the risks, benefits and effectiveness of various mechanical and chemical thromboprophylaxis interventions in elective spine surgery. We aim to address the following clinical question: is there a consensus across the literature regarding the most appropriate combination of mechanical and/or chemical thromboprophylaxis for patients undergoing degenerative spine surgery? We present this article in accordance with the Narrative Review reporting checklist (available at https://amj.amegroups.com/article/view/10.21037/amj-23-149/rc).

Methods

A non-systematic literature search of the PubMed database was performed in August 2023 to identify studies reporting on VTE in degenerative spine surgery. The following keywords were utilized for the search: [spine surgery], [thromboembolism], [prophylaxis]. The search resulted in 249 studies published between 1980 and August 2023 and after a thorough review of their methodologies, 87 studies were included for review and analysis. The inclusion criteria included studies published in English and those reporting on DVT or PE following degenerative spine surgery. A summary of the search strategy is presented in Table 1.

VTE in spine surgery

Frequency of DVT and PE

This critical review uncovered a broad published range for the specific incidence of VTE in spine surgery, between 0.2% and 43% (4,9,15,17-34). A summary of the reviewed studies is detailed in Table 2. This variation across the literature likely exists due to differences in study design, patient population, preoperative patient-specific risk factors, surgical procedure type and method of VTE detection and prophylaxis employed (4,15). The design and type of research study utilized can impact the reported incidence in several ways: first, incidence can be impacted by differences in both inclusion and exclusion criteria between studies (4,10,35-38). Secondly, retrospectively designed studies, many of which were identified during this review, can be affected by discrepancies in patient follow-up times, VTE screening and detection strategies and guidelines for prophylactic measures in each case (15). Furthermore, any study reporting on the incidence of VTE, be it retrospective or prospective, may not capture every patient with a post-operative DVT or PE, as patients can potentially be lost during follow-up or choose to seek care at a site other than that of their index procedure, both of which can obscure the true incidence of VTE.

The patient population and surgical procedure type can also impact the observed incidence of thromboembolic events. Certain studies included in our review are internationally published, hence, screening and prophylaxis guidelines can differ in each included case leading to inaccuracies in reported VTE incidences (15,22,39-41). Additionally, the specific patient population investigated by each study can impact VTE rates. Previous literature shows a greater risk of VTE in emergent spinal surgery patients and a higher specific incidence of VTE in patients who have undergone trauma leading to acute spinal cord injury (SCI) (15,34,42,43). A recent retrospective chart review demonstrated an 11% rate of symptomatic VTE in 151 patients with acute SCI and univariable analysis showed acute SCI to be a significant risk factor for VTE occurrence (42). Prophylaxis is often automatically administered in patients who have undergone trauma and is also recommended by the American Society of Hematology (ASH) guidelines, likely due to the association between post-traumatic VTE and increased morbidity and mortality (6,15,44). Moreover, significant previous literature has been conducted comparing the efficacy of various mechanical and chemical prophylactic measures in the surgical trauma setting (45-52). In patients undergoing surgery for major trauma including acute and traumatic brain and SCI, the 2012 American College of Chest Physicians (ACCP) guidelines recommend the usage of LMWH, low-dose UFH or mechanical prophylaxis with IPC stockings for adequate VTE prophylaxis (6,53). These guidelines also recommend addition of IPC to chemical prophylaxis on the condition that mechanical prophylaxis is not contraindicated by lower extremity injury.

Previous studies have also corroborated a lower incidence of VTE in elective spine surgery for degenerative conditions compared to traumatic injury. In a multi-center retrospective cohort study, Buchanan et al. reported a 30- and 90-day post-operative VTE incidence of 0.42% and 0.62%, respectively, within a cohort of 838,507 degenerative spinal surgery cases (4). In a case-control study of 5,766 consecutive elective thoracolumbar degenerative spine surgery cases, Hohl et al. report a VTE prevalence of 1.5% overall, 0.88% for PE and 0.66% for DVT (54). Lastly, in a retrospective study of the PearlDiver database, Bui et al. demonstrate a cumulative post-operative VTE incidence of 3.10% in cervical spine surgery patients at 3-month follow up (55). The highest incidence of VTEs occurred within the first follow-up period at 1 week post-op in patients undergoing posterior cervical fusion (2.56%) (55). This study’s cohort comprised patients undergoing anterior cervical discectomy and fusion, posterior cervical fusion, discectomy and decompression (55). In light of the dearth of high-level evidence to guide general prophylactic algorithms for patients undergoing elective surgery for degenerative spine conditions, both orthopedic surgeons and neurosurgeons should look to identify risk factors in patients during the preoperative phase of care to better understand each individual’s specific need for prophylaxis.

Risk factors for VTE

VTE has been reported to be the most common preventable cause of hospital mortality, with surgical patients carrying a known increased risk of perioperative venous stasis due to prolonged immobility and induced prothrombotic states. As such, it is crucial that surgeons identify preoperative risk factors regarding surgical procedure and patient specific characteristics (advanced age, comorbidities) that may warrant consideration for more aggressive thromboprophylaxis (56-58). Significant literature has been published on VTE risk factors which have been stratified based on demographic variables including sex, age and weight/body mass index (BMI) (15,17,32,58-60). A multitude of risk factors have been identified in previous studies, including prior episodes of DVT/PE, type and duration of surgery, pre-operative malignancy, infection, immobilization, venous stasis, chronic lower extremity swelling or trauma, advanced age, obesity and sleep apnea (10,32,34,60-62).

Patients with genetic hypercoagulable conditions, including factor V Leiden, antiphospholipid antibody syndrome, antithrombin 3 deficiency and protein C or protein S deficiency, are known to have an increased predisposition for thromboembolic events and may require immediate peri-operative and potentially long-term chemical prophylaxis with low-dose subcutaneous UFH or LMWH per NASS recommendations (16,63). Further research has also demonstrated that patients being treated with estrogen replacement therapy, steroid use and red blood cell transfusion as well as patients with specific comorbidities including hypertension, atrial fibrillation, renal disease, coronary artery disease, congestive heart failure and diabetes are at an increased risk for the development of post-operative VTE (4,25,32,34,54,64-67). Although a multitude of risk factors have been attributed to an increased risk of VTE, advanced age remains the most commonly reported risk factor across the literature (15,29,57-59,63,65,66,68).

Surgical variables including multistage spinal surgery, vertebral level of spinal surgery, surgical approach and increased vertebral exposure have also been shown to be associated with an increased risk of developing post-operative VTE (15,25,60,61,69,70). In a single-institution retrospective study of patients undergoing spinal surgery through a posterior approach, Edwards et al. demonstrated that after adjusting for all covariates, patients undergoing multistage surgery were 8.17 times more likely to yield a DVT compared to patients undergoing single-stage surgery (69). In a separate retrospective study of 5,405 patients undergoing either cervical discectomy, corpectomy, laminoplasty, laminectomy or fusion between 1995 and 2012, Sebastian et al. demonstrated an increased risk of VTE in patients undergoing staged surgery (25).

Surgical approach to fusion has also been shown to impact VTE rates. A retrospective review of 430,081 spinal fusion patients from the Nationwide Inpatient Sample Database between 2002 and 2008 reported a varying overall rate of VTE based on surgical approach to spinal fusion: overall rate 0.40%, cervical fusion 0.22%, thoracic/thoracolumbar 1.90%, lumbar/lumbosacral 0.49%, re-fusion 0.64%, and fusions not otherwise specified 0.84% (61). On multivariate logistic regression analysis of thoracic/thoracolumbar fusion patients, a combined anterior/posterior spinal fusion approach was also independently associated with an increased odds ratio of VTE complications compared to a posterior-only approach (61). Furthermore, in a review of 978 patients who received spinal surgery due to traumatic injury between 1980 and 2004, VTE complications were more commonly observed in patients undergoing procedures at the lumbar spine region and in patients with anterior spinal fusion surgical approach (60). Our literature review also uncovered a recent retrospective review of clinical and radiographic data for patients undergoing anterior lumbar interbody fusion which demonstrated that increased vertebral exposure (in terms of number of levels) was associated with higher rates of postoperative DVT (P=0.0032) and higher rates of venous injuries (P=0.0251) (70). Multivariate analysis found that increased levels of vertebral exposure [relative risk (RR) =6.23, P=0.026] and a history of degenerative spinal disease (RR =0.033, P=0.033) were predictive of intraoperative venous injury (70).

As degenerative spine surgery is the main focus of this review, we specifically searched the literature for studies investigating risk factors for DVT or PE in this patient population, the results of which are detailed in Table 3. Kelly et al. performed a retrospective review of 52,458 degenerative thoracolumbar fusion patients between 2016 and 2018 from the National Surgical Quality Improvement Program database in order to develop a predictive VTE model that can be potentially integrated into a patient’s electronic health record (57). This study demonstrated that on multivariate analysis, age ≥70 years [odds ratio (OR) =1.440, P<0.001], body mass index (BMI) ≥35 kg/m² (OR =1.340, P=0.007), operative time ≥270 min (OR =2.275, P<0.001), male gender (female: OR =0.826, P=0.043), non-smokers (smoker: OR =0.702, P=0.011), disseminated cancer (OR =3.561, P<0.001), American Society of Anesthesiologists Physical Classification Scale (ASA) ≥3 (OR =1.248, P=0.032) and an open wound at the time of surgery (OR =3.280, P=0.001) were significant predictors of increased risk for postoperative VTE in degenerative spinal fusion (57). In addition, Buchanan et al. conducted a retrospective query of the Nationwide Readmission Database from 2010 to 2014 and identified a total of 838,507 spine operations for degenerative disease (4). Within this population, researchers found several procedure and patient related factors that were significantly associated with an increased likelihood of post-operative VTE including procedures of the thoracolumbar region compared to those of the cervical region (OR =1.19–1.26, P<0.001), corticosteroid use (30-days: OR =1.58, P<0.0005, and 90-days: OR =1.97, P<0.0001), advanced age (OR =1.63–1.76, P<0.0001), increased length of stay on index procedure admissions (stays ≥5 days: OR =3.42–3.68, P<0.0001), and final disposition with home health resources (OR =1.227, P<0.0001) or to institutional care (4). Lastly, in a case-control study of 5,766 elective thoracolumbar degenerative spinal surgery, Hohl et al. demonstrate a significantly increased rate of PE in patients undergoing ≥4 segment fusion, 5 segment fusion, older age >65 years, and surgery with an included osteotomy (Smith Peterson osteotomy or pedicle subtraction osteotomy) (54). In this study, use of instrumentation, sex, and revision surgery were found to not be contributory to the development of post-operative VTE (54). The identification of one or more risk factors in patients undergoing spine surgery may be a helpful indication to consider further VTE risk stratification with the use of certain pretest probability criteria, such as the Wells score or PE rule out criteria (PERC).

Diagnosis of VTE

Diagnosing VTE can be challenging for various reasons and requires providers to maintain a high index of suspicion in order to prevent cases from going undetected and untreated. First, a large proportion of hospitalized patients with DVT can present as clinically asymptomatic and classic symptomatology, such as calf swelling and leg pain, may be absent, which can delay diagnosis (71,72). Additionally, certain physical exam findings, such as erythema and swelling, can potentially present in other post-operative conditions including surgical site infection and hematoma, which can obscure the diagnosis (73). Consequently, previous literature has emphasized the importance of stratifying pretest probability for individual patients in order to identify the optimal imaging modality for confirmation of a VTE diagnosis (15,74,75). This has prompted the development of various scoring systems including the Charlotte rule, Minaiti score, Geneva Score, revised Geneva score, and Wells criteria (74,76-78). Of these options, the Wells criteria is the most commonly used scoring system and determines whether a patient has a low, intermediate, or high pretest probability of VTE development after taking into consideration the presence or absence of certain risk factors, prior history of DVT and clinical presentation of the patient (74,77). It is important to note that although the Wells criteria does appear to help predict post-operative DVT, it is inappropriate to use the scoring system as a means to provide a definitive diagnosis. This conclusion is based on the results of a review of 15 studies reporting that patients with a high pretest probability for DVT, as determined by Wells score, had a prevalence of DVT between 17% to 85%, whereas those with a moderate pretest probability had a prevalence of 0% to 38%, and those with the lowest pretest probability had a prevalence of 0% to 13% (75). Thus, the Wells score should primarily be used to assess an individual’s probability of developing a post-operative DVT or PE and to guide further diagnostic imaging and screening.

The most appropriate recommendations for imaging options following Wells score stratification differ between DVT and PE. For DVT, contrast venography has historically served as the gold standard for diagnosis; however, it has become increasingly uncommon due to its high costs and invasive nature (6,74,75,79). As a result, the current most commonly used diagnostic test for DVT is a venous compression ultrasound (CUS) (6,79,80). In a prospective evaluation of 209 spinal surgery patients, Akeda et al. concluded that ultrasound assessment for DVT is vital in the perioperative spine surgery period (81). In a separate prospective evaluation of 194 spinal surgery patients, Ikeda et al. demonstrated that perioperative application of duplex ultrasonography in the lower extremity should be performed on patients undergoing spine surgery who are female, non-ambulatory and have a higher preoperative D-dimer serum level, as these factors were significantly associated with the development a post-operative DVT (82). Duplex ultrasound, a separate imaging study, is used for a more thorough evaluation of the deep veins of the thigh, popliteal region and calf. It is comprised of venous CUS, Doppler waveforms and color Doppler of the calf veins and iliac veins (71,75). In a review article of randomized controlled trials (RCTs), observational studies and systematic reviews of RCTs, Segal et al. report an overall 97% sensitivity and 98% specificity for CUS used for the detection of proximal DVT (75). However, as many DVTs can be isolated and located distally, this high sensitivity and specificity can lead to overtreatment in these controversial scenarios, as the literature still varies on the decision to treat isolated distal DVTs.

Multidetector computed tomography (MDCT) angiograms have also been reported within the literature to be an effective and convenient imaging modality for the detection of VTE, although it is not recommended as the primary imaging modality of choice for diagnosis of DVT (19). MDCT can potentially be considered when other imaging options are inconclusive, or there is a particular need to investigate the anatomy surrounding the clot in a more thorough fashion (73,75). On the other hand, MDCT, more specifically, computed tomography pulmonary angiography (CTPA) has become the primary imaging modality for diagnosing PE in the United States, replacing conventional pulmonary angiography (15,75,78,79). Although pulmonary angiography has long been considered the gold standard for diagnosis of PE, it requires an increased amount of contrast and radiation compared to CTPA and is contraindicated in patients with severe pulmonary hypertension and heart failure (73,79). CTPA can be used in patients for whom PE is suspected in the setting of a positive D-dimer assay result, or in those who have a high pretest probability of PE regardless of D-dimer result (73). Before considering imaging, scoring systems such as the Wells criteria and the PE rule out criteria (PERC rule) should be used to determine pretest probability of PE, similar to the diagnostic process for DVT. In patients at intermediate to high risk for PE, the positive predictive value of CTPA is 92% to 96% (73). However, with only a 60% negative predictive value, it cannot be used to reliably exclude PE in patients with high clinical probability of development (83). In these patients, further imaging evaluation with CUS and possibly conventional pulmonary angiography is indicated.

Ventilation-perfusion (V/Q) scanning is another methodology reported in the literature for the diagnosis of PE, although its use has been declining due to its decreased availability compared to CT (15). While CTPA results in only a binary outcome of PE diagnosis, V/Q scan can offer more information regarding the probability of PE (73,78,84). As with CT, any disparities between a patient’s findings from V/Q scan and their preassigned clinical probability for PE should prompt further assessment for VTE (73). Lastly, as certain patients can present with contraindications to CT imaging, such as allergies to contrast material, renal disease or pregnancy, V/Q scan remains a viable option for PE detection within this patient population (15,73,84,85).

D-dimer is a plasma protein and degradation product of the plasmin-mediated lysis of crosslinked fibrin, predictability produced at the site of thrombosis. Although pathophysiology would suggest low D-dimer levels should theoretically be useful in ruling out DVT and PE, the literature has demonstrated that this test is fairly nonspecific for DVT patients, as other clinical scenarios such as sepsis, pregnancy or malignancy, can also cause an elevated D-dimer (79). Although not studied in spinal surgery patients, the AAOS has concluded that D-dimer is not a reliable screening method for post-operative DVT in arthroplasty patients (79,86). Further investigation needs to be performed to determine the effectiveness of D-dimer as a screening tool in degenerative spinal surgery.

Screening for VTE

As detailed above, the reported incidence of VTE in spine surgery varies widely across the literature as a result of variations in patient population, surgical procedure type and specific patient risk factors. Although a significant amount of risk factors for VTE have been identified, advanced age remains the most commonly reported risk factor across the literature. Furthermore, diagnosing VTE remains challenging as the clinical presentation can often be asymptomatic. As a result, several scoring systems have been developed to help preoperatively identify patients at greater risk for VTE; however, a highly sensitive and specific test does not exist for screening purposes. Future research into VTE prophylaxis in spine surgery may look to develop predictive models of preoperative risk for VTE to assist in prophylactic decision-making through the electronic health record.

Mechanical prophylaxis in spine surgery

Mechanical prophylaxis options for VTE in degenerative spine surgery include IPC devices, CS, sequential compression devices (SCDs) and inferior vena cava (IVC) filters. For primary prophylaxis against VTE, mechanical devices have remained a common choice amongst both orthopedic surgeons and neurosurgeons and the use of mechanical compression on the lower extremities is recommended by evidence-based guidelines from the NASS (14,16). In a series of 315 patients who underwent minimally invasive transforaminal lumbar interbody fusion followed by a postoperative DVT prophylaxis management protocol based on NASS guidelines, Olinger and Gardocki have demonstrated two cases of DVT (0.6%), leading the authors to conclude that mechanical DVT prophylaxis seems to be adequate in elective spine surgery (87). However, both patients in this study were elderly obese males with multiple comorbidities who did not receive any chemoprophylaxis against DVT. Additionally, the authors note that within these two cases, the mean operative time was somewhat longer than usual and a longer operative times may contribute to DVT risk (85). Additionally, the 2019 guidelines from the ASH support the use of mechanical prophylaxis over no prophylaxis, with a recommendation for IPC over graduated CS and a recommendation against IVC filters in major surgery in general (6). Through the use of the Grading of Recommendations Assessment, Development and Evaluation approach, the panel reviewed 5 systematic reviews and recommended mechanical prophylaxis over no prophylaxis, recognizing that certainty in evidence remains very low. Six systematic reviews were analyzed for the recommendation of IPC over graduated CS with a very low certainty in evidence. Finally, their recommendation against IVC filters resulted from a review of 2 systematic reviews and thus, the certainty in evidence of effects remains very low.

Although several options are available for both mechanical prophylaxis and chemoprophylactic treatment, no widely accepted protocol from the national societies yet exists to help guide clinicians in choosing the most efficacious combination of the two to prevent VTE in degenerative spine surgery (15). Preferred prophylaxis regimens vary amongst clinicians and is often chosen on a case-by-case basis after careful assessment of each patient’s comorbidities and risk factors, the risk for bleeding and wound complications and the risk for potential neurologic injury from chemoprophylaxis. For instance, in a survey study of attendees of the 2009 British Association of Spinal Surgeons Annual Meeting, it was demonstrated that neurosurgeons chose to use anti-embolism stockings more frequently than orthopedic surgeons (79% vs. 50%), while orthopedists preferred other forms of mechanical prophylaxis (26% vs. 9%) (14). Due to the significant difference in preferred thromboprophylaxis across different surgical disciplines, further research examining the risks and benefits of all existing thromboprophylaxis measures, along with the implementation of a standard set of guidelines in degenerative spine surgery is warranted.

Various authors have investigated the efficacy of different mechanical prophylactic options in spine surgery and these studies are outline in Table 4 (59,88,89,94). In a systematic review of 25 articles and a total of 9,485 patients, Glotzbecker et al. reported an overall DVT rate of 2.1% in spine surgery (9). The study investigated various thromboprophylaxis measures, including IVC filters, pharmacologic anticoagulation, CS and pneumatic sequential compression devices (PSCD). They report a rate of DVT of 2.7% with the use of CS, 4.6% with PSCD alone, 1.3% with PSCD and CS, 0.6% with chemical anticoagulants, and 22% with IVC filters (9). Thus, the use of CS with other compressive devices does appear to reduce the risk of DVT after spine surgery; however, the researchers concluded that there is insufficient evidence to support or refute the use of chemoprophylaxis in spine surgery (9). Other authors have performed investigations regarding the efficacy of PSCD and thigh length CS, yielding mixed results. Dearborn et al. conclude that although simple mechanical prophylaxis may be adequate for posteriorly approached thoracolumbar spine surgery, it may not provide sufficient protection in a combined anterior/posterior surgical approach (90). However, the authors do note that in their study, patients undergoing combined anterior/posterior fusion were significantly older (mean age, 52±14 years) than patients undergoing isolated posterior procedures (mean age, 43.9±16 years; P<0.005). Additionally, they describe that surgical location may also play a role in risk for endothelial injury as anterior procedures involving the lumbosacral spine require increased manipulation and retraction of the great vessels and as a result, may increase risk for development of DVT and subsequent PE (89). In regards to clinical decision-making, Dearborn et al. believe that patients undergoing anterior spine surgery are at greater risk for VTE than most surgical patients were previously considered to be and consequently, may require a more sensitive imaging study (magnetic resonance venography) than duplex ultrasound for DVT detection (90). Additionally, in a prospective study of 317 spine surgery patients who received thigh length CS and PSCD, Smith et al. report a VTE rate of 0.9% (3 total complications) (91). Of the three patients who suffered post-operative VTE, all three received an anterior lumbar approach for their procedure; however, this association was not clinically significant (91). However, the authors report that their study did not contain a control group as all patients were managed with the same prophylactic regimen and as a result, no conclusion can be drawn regarding the effects of any one method of prophylaxis on the overall rate of VTE (94). Furthermore, in a review of various neurosurgical studies focusing on different methods of VTE prophylaxis, Epstein concluded that mechanical prophylaxis with IPC and/or CS does seem to provide effective prophylaxis against VTE and although chemical anticoagulation does add efficacy of prophylaxis, its benefits must be weighed against the risk of major hemorrhage and neurologic injury (59). Lastly, the NASS guidelines recommend initiation of mechanical compression devices prior to or at the start of elective spine surgery (fair evidence); and continuing with the use of these devices until the patient is fully ambulatory (consensus statement).

Another form of mechanical prophylaxis is the IVC filter, an endovascular device that serves to prevent thrombi from the venous system from passing through the cardiac and systemic circulation. IVC filters are indicated for patients with VTE who have a contraindication to either mechanical or chemical anticoagulation or for those who have failed other forms of anticoagulation and are at high risk of suffering a PE (95). Within spinal surgery, IVC filters have been shown to be efficacious in reducing the incidence of VTE across multiple single institution studies. Makary et al. report an 11% rate of VTE in the post-placement period, with 1% (n=4) experiencing a PE (92). In another single-institution study of 219 spine surgery patients, the incidence of lower extremity DVT was observed as 18.7% (n=41) in 36 patients, PE incidence was 3.7% (n=8) and the paradoxical embolus rate was 0.5% (n=1) (93). Prophylactic IVC filter use reduced the odds of developing a pulmonary embolus (OR =3.7, P<0.05) compared to a population control. However, although previous studies have demonstrated that the use of IVC filters is associated with a reduction in VTE rates, they are not currently recommended by the ACCP as primary prophylaxis (93,96,97). In addition, the 2019 ASH guidelines recommend against the use of prophylactic IVC filters in patients undergoing major surgery or trauma patients (6). The authors of the ASH guidelines report that this recommendation follows review of the 2012 ACCP, 2011 AAOS, 2013 European Venous Forum, 2013 Neurocritical Care Society and 2013 British Committee for Standards in Hematology guidelines as well as the “appropriateness criteria” from the American College of Radiology. The recommendation against IVC filters follows correspondence with recommendations from many of the aforementioned reviewed guidelines. The IVC filter does carry risk for potential adverse effects including IVC thrombosis, filter migration, infection, and inability to remove the device (79,98,99). Prolonged placement of these devices has also proven to be associated with an increased risk for these adverse outcomes (79,99).

Generally, although most guidelines do recommend against prophylactic IVC filter placement, there are specific instances where its use is indicated as mechanical and pharmacological prophylaxis do not provide protection in certain high-risk patients. In a retrospective study on 129 patients with risk factors for PE who underwent prophylactic IVC filter placement for complex spine surgery, Ozturk et al. report a 1.5% rate of PE in patients receiving an IVC filter compared to 4.2% in the matched cohort control group (100). The authors describe that IVC filter placement is typically considered once a DVT forms; however, it cannot treat nor prevent the initial embolic event. In patients with any history of thromboembolism, comorbidities including diabetes and hypertension, prior spine surgery, active smoking, obesity, any contraindications to anticoagulation therapy, malignancy, prolonged bed rest >2 weeks before surgery, staged or multilevel procedures, combined anterior/posterior approaches, possibility of significant iliocaval manipulation during exposure and single stage anesthetic time >6 hours, the authors report that IVC filter prophylaxis may be considered (100). Thus, as the efficacy and general safety of mechanical prophylaxis in spine surgery is well recognized, research efforts regarding VTE prophylaxis in spine surgery have largely focused on investigating chemoprophylaxis treatments, as these options are known to carry an increased risk for bleeding complications.

Chemical prophylaxis in spine surgery

Chemical, or pharmacologic, anticoagulation as primary prophylaxis against VTE in spinal surgery patients remains a highly controversial topic within the literature, largely due to the risk of bleeding complications. As several options for pharmacologic prophylaxis exist, there remains a significant difference in selections across various disciplines. A recent survey study demonstrated that 73% of neurosurgical respondents employed LMWH compared to 31% of responding orthopaedic surgeons (P<0.001) (14). According to the 2009 NASS guidelines, Level IV evidence exists demonstrating that LMWH can be started safely on the day of elective spine surgery; however, the overall recommendation from the work group was to employ LMWH cautiously and withhold it unless risk factors for VTE exist, likely due to the risk of bleeding complications (16). Furthermore, various older studies have investigated the efficacy of LMWH and other chemoprophylaxis options in spine surgery, and these studies are summarized in Table 5.

Timing of chemoprophylaxis administration appears to play a role in the risk of bleeding complications. Strom et al. conducted a retrospective study of patients undergoing cervical and lumbar decompressive laminectomies from 2007 to 2011 with LMWH employed as primary prophylaxis beginning 24 to 36 hours after degenerative spine surgery (101). They report a VTE incidence of 3.8% (14 patients) and upon comparison to UFH, LMWH appears to be a superior option for chemoprophylaxis (101). Additionally, with only a 0.7% observed rate of hemorrhage, they conclude that when LMWH is withheld until 24–36 hours after major spinal surgery, it appears to carry a very low risk for bleeding complications (101). Although larger prospective studies are needed to assess the safety of this recommendation, it appears that delayed LMWH administration may provide the patient with sufficient hemostasis to help mitigate bleeding complications (101). This recommendation of LMWH over UFH in orthopedic patients is also supported by the 2019 ASH guidelines (6). These evidence-based guidelines from the ASH further support the recommendation from the 2012 ACCP guideline for LMWH, low-dose UFH, or mechanical prophylaxis, preferably with IPC as VTE prophylaxis in the surgical management of patients with major trauma, ASI, and traumatic spine injury (6,53).

Within certain patient populations, pharmacologic prophylaxis is universally recommended by various evidence-based guidelines. For patients with pre-operatively identified risk factors including advanced age, prior DVT or PE and staged surgery, the ACCP guidelines recommend the use of low-dose UFH, LMWH, IPCs or SCDs as primary prophylaxis and also recommend a combination of mechanical and chemical prophylaxis in high-risk patients. Spinal trauma patients are also considered at high risk for PE and DVT and are frequently chosen for pharmacologic prophylaxis, typically in combination with some form of mechanical prophylaxis (54). Lastly, the NASS guidelines comment that chemical prophylaxis should be considered in patients with thromboembolic risk factors such as hypercoagulable state, malignancy, paralysis or SCI, and in those individuals undergoing long and complex surgeries including those with an anterior or combined anterior-posterior approach.

Although substantial literature has been published demonstrating the efficacy of chemical anticoagulation as primary prophylaxis against VTE in spine surgery, its use remains controversial due to the risk for bleeding, neurological deficit and the unique risk of SEH within spinal surgery. Several studies have demonstrated that the use of certain chemoprophylaxis, including subcutaneous LMWH and UFH, can increase the risk of major postoperative SEH (59,63,103). Upon conducting a review of the literature, rates of SEH in spine surgery range between 0% to 0.9% (24,104-106). With the lack of universally accepted guidelines on chemoprophylaxis in spine surgery, providers are required to rely upon their clinical judgement to balance the risk of hemorrhage and SEH against the major benefit of prevention of catastrophic PE or DVT. Various review articles have been published regarding epidural hematoma in the setting of VTE prophylaxis in spine surgery. In a recent review of the literature, Glotzbecker et al. demonstrate that the prevalence of SEH in postoperative spinal surgery patients ranges between 0 to 1.0% amongst 16 different studies (106). The prevalence of SEH in patients receiving LMWH was observed at 0.4%, whereas in those patients with no chemoprophylaxis given, the reported SEH prevalence equaled 0.2%. Furthermore, in a review of 6 studies, Cheng et al. report only 10 symptomatic SEH amongst 2,507 spine surgery patients, leading to a SEH prevalence of 0.4% (102). Lastly, Sansone et al. report 8 out of 2,071 elective spine surgery patients (0.39%) developed post operative SEH, with 3 patients (0.14%) developing permanent neurological deficits (13).

Researchers have also conducted retrospective cohort and case-control studies investigating rates of SEH following various pharmacologic options for VTE prophylaxis. In a case-control study of patients undergoing elective thoracolumbar degenerative spine surgery, Hohl et al. report 0 cases of patients with PE developing SEH when employing the use of IVC filter and warfarin, or therapeutic LMWH and warfarin or therapeutic UFH and warfarin (54). As the debate continues on whether the benefits of chemoprophylaxis should outweigh the risk of bleeding complications, Hohl et al. explain the importance of weighing the likelihood of developing VTE in specific patient populations a provider is treating against that population’s risk for developing SEH when employing chemical anticoagulation as primary prophylaxis (54). If the rate of VTE has been shown to be significantly lower than controls in a particular group of patients, it should raise the question of whether pharmacologic prophylaxis needs to be considered within that population, given the risk for hemorrhage, SEH and adverse neurologic sequalae. McLynn et al. also conducted a retrospective analysis of 109,609 elective spine surgery patients from the National Surgical Quality Improvement Program (NSQIP) database, in which pharmacologic prophylaxis, particularly UFH, was not significantly associated with a reduction in VTE incidence (107). However, within the same study, McLynn et al. also performed a single institution retrospective cohort analysis of 2,855 elective spine surgery patients, within which 56.3% received chemical anticoagulation, 97.1% with UFH (107). In this separate population analysis, the researchers conclude that the use of chemical anticoagulation, particularly UFH, is significantly associated with an increased incidence of post-operative hematoma requiring reoperation (RR =7.37, P=0.048) (107).

Conclusions

VTE, comprising both DVT and/or PE, is a complication of spinal surgery that has been reported to cause major postoperative morbidity and mortality and leads to an appreciable burden on the healthcare system. The true incidence of these thromboembolic complications is currently unclear as literature specific to VTE in degenerative spinal surgery remains sparse. Ideal combinations of mechanical and chemical thromboprophylaxis within degenerative spine surgery remain controversial due to concerns regarding symptomatic epidural hematoma, hemorrhagic complications and catastrophic neurologic injury that can occur with the utilization of various pharmacologic anticoagulation. Spine surgeons should consider risk stratification for VTE within the preoperative phase of care through the utilization of currently available pretest probability criteria such as the Wells score or PE rule out criteria.

While there is literature to support the safety and efficacy of mechanical compressive devices for perioperative VTE prophylaxis, there remains relatively little high-level evidence to directly guide surgeons regarding the various forms of chemical prophylaxis. As such, spinal surgeons should consider guidelines published by the NASS, ACCP and ASH when determining the most appropriate combination of thromboprophylaxis for their patients. To facilitate the prevention of VTE following degenerative spine surgery, future investigations should aim to develop universally accepted guidelines for chemoprophylaxis specifically following degenerative spine surgery as well as a perioperative predictive model for VTE that may be integrated into an electronic health record. Ideally, the purpose of such a model would be to serve as a screening test for patients at risk for VTE with high specificity and sensitivity. Randomized clinical trials are also needed to help better compare the efficacy of various chemoprophylactic options in reducing risk for VTE following degenerative spine surgery.

Based on the available literature and these guidelines, in our practice we utilize mechanical prophylaxis, in the form of IPC devices, for all patients throughout the entirety of their hospital course with strong consideration of the addition of LMWH as chemical anticoagulation as early as the first post-operative day for patients deemed to be at high risk for thromboembolic complications based on underlying hypercoagulability or poor mobilization.

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: This article was commissioned by the Guest Editors (Mark Lambrechts and Brian Karamian) for the series “Degenerative Spine Disease” published in AME Medical Journal. The article has undergone external peer review.

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://amj.amegroups.com/article/view/10.21037/amj-23-149/rc

Peer Review File: https://amj.amegroups.com/article/view/10.21037/amj-23-149/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://amj.amegroups.com/article/view/10.21037/amj-23-149/coif). The series “Degenerative Spine Disease” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Haines ST. Venous thromboembolism: pathophysiology and clinical presentation. Am J Health Syst Pharm 2003;60:S3-5. [Crossref] [PubMed]
2. Chibbaro S, Cebula H, Todeschi J, et al. Evolution of Prophylaxis Protocols for Venous Thromboembolism in Neurosurgery: Results from a Prospective Comparative Study on Low-Molecular-Weight Heparin, Elastic Stockings, and Intermittent Pneumatic Compression Devices. World Neurosurg 2018;109:e510-6. [Crossref] [PubMed]
3. Simanek R, Vormittag R, Hassler M, et al. Venous thromboembolism and survival in patients with high-grade glioma. Neuro Oncol 2007;9:89-95. [Crossref] [PubMed]
4. Buchanan IA, Lin M, Donoho DA, et al. Venous Thromboembolism After Degenerative Spine Surgery: A Nationwide Readmissions Database Analysis. World Neurosurg 2019;125:e165-74. [Crossref] [PubMed]
5. Pilato E, Comentale G. Surgical treatment of acute pulmonary embolism: a modified surgical technique to avoid deep hypothermia and circulatory arrest. Curr Chall Thorac Surg 2020;2:37. [Crossref]
6. Anderson DR, Morgano GP, Bennett C, et al. American Society of Hematology 2019 guidelines for management of venous thromboembolism: prevention of venous thromboembolism in surgical hospitalized patients. Blood Adv 2019;3:3898-944. [Crossref] [PubMed]
7. Heit JA, O'Fallon WM, Petterson TM, et al. Relative impact of risk factors for deep vein thrombosis and pulmonary embolism: a population-based study. Arch Intern Med 2002;162:1245-8. [Crossref] [PubMed]
8. White RH, Zhou H, Romano PS. Incidence of symptomatic venous thromboembolism after different elective or urgent surgical procedures. Thromb Haemost 2003;90:446-55. [Crossref] [PubMed]
9. Glotzbecker MP, Bono CM, Wood KB, et al. Thromboembolic disease in spinal surgery: a systematic review. Spine (Phila Pa 1976) 2009;34:291-303. [Crossref] [PubMed]
10. Zacharia BE, Kahn S, Bander ED, et al. Incidence and risk factors for preoperative deep venous thrombosis in 314 consecutive patients undergoing surgery for spinal metastasis. J Neurosurg Spine 2017;27:189-97. [Crossref] [PubMed]
11. Chew HK, Wun T, Harvey D, et al. Incidence of venous thromboembolism and its effect on survival among patients with common cancers. Arch Intern Med 2006;166:458-64. [Crossref] [PubMed]
12. Anderson FA Jr, Wheeler HB, Goldberg RJ, et al. The prevalence of risk factors for venous thromboembolism among hospital patients. Arch Intern Med 1992;152:1660-4. [Crossref] [PubMed]
13. Sansone JM, del Rio AM, Anderson PA. The prevalence of and specific risk factors for venous thromboembolic disease following elective spine surgery. J Bone Joint Surg Am 2010;92:304-13. [Crossref] [PubMed]
14. Bryson DJ, Uzoigwe CE, Braybrooke J. Thromboprophylaxis in spinal surgery: a survey. J Orthop Surg Res 2012;7:14. [Crossref] [PubMed]
15. Solaru S, Alluri RK, Wang JC, et al. Venous Thromboembolism Prophylaxis in Elective Spine Surgery. Global Spine J 2021;11:1148-55. [Crossref] [PubMed]
16. Bono CM, Watters WC 3rd, Heggeness MH, et al. An evidence-based clinical guideline for the use of antithrombotic therapies in spine surgery. Spine J 2009;9:1046-51. [Crossref] [PubMed]
17. Bouyer B, Rudnichi A, Dray-Spira R, et al. Thromboembolic risk after lumbar spine surgery: a cohort study on 325 000 French patients. J Thromb Haemost 2018;16:1537-45. [Crossref] [PubMed]
18. Schairer WW, Pedtke AC, Hu SS. Venous Thromboembolism After Spine Surgery. Spine (Phila Pa 1976) 2014;39:911-8. [Crossref] [PubMed]
19. Inoue H, Watanabe H, Okami H, et al. The Rate of Venous Thromboembolism Before and After Spine Surgery as Determined with Indirect Multidetector CT. JB JS Open Access 2018;3:e0015.
20. Cox JB, Weaver KJ, Neal DW, et al. Decreased incidence of venous thromboembolism after spine surgery with early multimodal prophylaxis: Clinical article. J Neurosurg Spine 2014;21:677-84. [Crossref] [PubMed]
21. Du W, Zhao C, Wang J, et al. Comparison of rivaroxaban and parnaparin for preventing venous thromboembolism after lumbar spine surgery. J Orthop Surg Res 2015;10:78. [Crossref] [PubMed]
22. Guo Y, Zou Z, Jia L, et al. Safety and effectiveness of argatroban versus heparin for preventing venous thromboembolism after lumbar decompressive surgery. Int J Surg 2017;44:324-8. [Crossref] [PubMed]
23. Zeng XJ, Peng H. Prevention of Thromboembolic Complications After Spine Surgery by the Use of Low-Molecular-Weight Heparin. World Neurosurg 2017;104:856-62. [Crossref] [PubMed]
24. Cunningham JE, Swamy G, Thomas KC. Does preoperative DVT chemoprophylaxis in spinal surgery affect the incidence of thromboembolic complications and spinal epidural hematomas? J Spinal Disord Tech 2011;24:E31-4. [Crossref] [PubMed]
25. Sebastian AS, Currier BL, Clarke MJ, et al. Thromboembolic Disease after Cervical Spine Surgery: A Review of 5,405 Surgical Procedures and Matched Cohort Analysis. Global Spine J 2016;6:465-71. [Crossref] [PubMed]
26. Leon L, Rodriguez H, Tawk RG, et al. The prophylactic use of inferior vena cava filters in patients undergoing high-risk spinal surgery. Ann Vasc Surg 2005;19:442-7. [Crossref] [PubMed]
27. Matsumoto S, Suda K, Iimoto S, et al. Prospective study of deep vein thrombosis in patients with spinal cord injury not receiving anticoagulant therapy. Spinal Cord 2015;53:306-9. [Crossref] [PubMed]
28. Chung SB, Lee SH, Kim ES, et al. Incidence of deep vein thrombosis after spinal cord injury: a prospective study in 37 consecutive patients with traumatic or nontraumatic spinal cord injury treated by mechanical prophylaxis. J Trauma 2011;71:867-70; discussion 870-1. [Crossref] [PubMed]
29. Li L, Li Z, Huo Y, et al. Time-to-event analyses of lower-limb venous thromboembolism in aged patients undergoing lumbar spine surgery: a retrospective study of 1620 patients. Aging (Albany NY) 2019;11:8701-9. [Crossref] [PubMed]
30. Rokito SE, Schwartz MC, Neuwirth MG. Deep vein thrombosis after major reconstructive spinal surgery. Spine (Phila Pa 1976) 1996;21:853-8; discussion 859. [Crossref] [PubMed]
31. Lee HM, Suk KS, Moon SH, et al. Deep vein thrombosis after major spinal surgery: incidence in an East Asian population. Spine (Phila Pa 1976) 2000;25:1827-30. [Crossref] [PubMed]
32. Schulte LM, O'Brien JR, Bean MC, et al. Deep vein thrombosis and pulmonary embolism after spine surgery: incidence and patient risk factors. Am J Orthop (Belle Mead NJ) 2013;42:267-70. [PubMed]
33. Yamasaki K, Hoshino M, Omori K, et al. Prevalence and risk factors of deep vein thrombosis in patients undergoing lumbar spine surgery. J Orthop Sci 2017;22:1021-5. [Crossref] [PubMed]
34. Wang TY, Sakamoto JT, Nayar G, et al. Independent Predictors of 30-Day Perioperative Deep Vein Thrombosis in 1346 Consecutive Patients After Spine Surgery. World Neurosurg 2015;84:1605-12. [Crossref] [PubMed]
35. Oda T, Fuji T, Kato Y, et al. Deep venous thrombosis after posterior spinal surgery. Spine (Phila Pa 1976) 2000;25:2962-7. [Crossref] [PubMed]
36. Jain A, Hassanzadeh H, Puvanesarajah V, et al. Incidence of perioperative medical complications and mortality among elderly patients undergoing surgery for spinal deformity: analysis of 3519 patients. J Neurosurg Spine 2017;27:534-9. [Crossref] [PubMed]
37. De la Garza Ramos R, Goodwin CR, Abu-Bonsrah N, et al. Patient and operative factors associated with complications following adolescent idiopathic scoliosis surgery: an analysis of 36,335 patients from the Nationwide Inpatient Sample. J Neurosurg Pediatr 2016;25:730-6. [Crossref] [PubMed]
38. Yoshioka K, Murakami H, Demura S, et al. Comparative study of the prevalence of venous thromboembolism after elective spinal surgery. Orthopedics 2013;36:e223-8. [Crossref] [PubMed]
39. Wang T, Yang SD, Huang WZ, et al. Factors predicting venous thromboembolism after spine surgery. Medicine (Baltimore) 2016;95:e5776. [Crossref] [PubMed]
40. Ko BS, Cho KJ, Kim YT, et al. Does Tranexamic Acid Increase the Incidence of Thromboembolism After Spinal Fusion Surgery? Clin Spine Surg 2020;33:E71-5. [Crossref] [PubMed]
41. Gruber UF, Rem J, Meisner C, et al. Prevention of thromboembolic complications with miniheparin-dihydroergotamine in patients undergoing lumbar disc operations. Eur Arch Psychiatry Neurol Sci 1984;234:157-61. [Crossref] [PubMed]
42. Piran S, Schulman S. Incidence and risk factors for venous thromboembolism in patients with acute spinal cord injury: A retrospective study. Thromb Res 2016;147:97-101. [Crossref] [PubMed]
43. Rogers FB, Shackford SR, Horst MA, et al. Determining venous thromboembolic risk assessment for patients with trauma: the Trauma Embolic Scoring System. J Trauma Acute Care Surg 2012;73:511-5. [Crossref] [PubMed]
44. Paffrath T, Wafaisade A, Lefering R, et al. Venous thromboembolism after severe trauma: incidence, risk factors and outcome. Injury 2010;41:97-101. [Crossref] [PubMed]
45. Geerts WH, Jay RM, Code KI, et al. A comparison of low-dose heparin with low-molecular-weight heparin as prophylaxis against venous thromboembolism after major trauma. N Engl J Med 1996;335:701-7. [Crossref] [PubMed]
46. Olson EJ, Bandle J, Calvo RY, et al. Heparin versus enoxaparin for prevention of venous thromboembolism after trauma: A randomized noninferiority trial. J Trauma Acute Care Surg 2015;79:961-8; discussion 968-9. [Crossref] [PubMed]
47. Roberts I, Shakur H, Coats T, et al. The CRASH-2 trial: a randomised controlled trial and economic evaluation of the effects of tranexamic acid on death, vascular occlusive events and transfusion requirement in bleeding trauma patients. Health Technol Assess 2013;17:1-79. [Crossref] [PubMed]
48. Dennis JW, Menawat S, Von Thron J, et al. Efficacy of deep venous thrombosis prophylaxis in trauma patients and identification of high-risk groups. J Trauma 1993;35:132-8; discussion 138-9. [Crossref] [PubMed]
49. Barrera LM, Perel P, Ker K, et al. Thromboprophylaxis for trauma patients. Cochrane Database Syst Rev 2013;CD008303. [PubMed]
50. Monreal M, Lafoz E, Navarro A, et al. A prospective double-blind trial of a low molecular weight heparin once daily compared with conventional low-dose heparin three times daily to prevent pulmonary embolism and venous thrombosis in patients with hip fracture. J Trauma 1989;29:873-5. [Crossref] [PubMed]
51. Rogers FB, Shackford SR, Ricci MA, et al. Prophylactic vena cava filter insertion in selected high-risk orthopaedic trauma patients. J Orthop Trauma 1997;11:267-72. [Crossref] [PubMed]
52. Fisher CG, Blachut PA, Salvian AJ, et al. Effectiveness of pneumatic leg compression devices for the prevention of thromboembolic disease in orthopaedic trauma patients: a prospective, randomized study of compression alone versus no prophylaxis. J Orthop Trauma 1995;9:1-7. [Crossref] [PubMed]
53. Gould MK, Garcia DA, Wren SM, et al. Prevention of VTE in nonorthopedic surgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141:e227S-77S.
54. Hohl JB, Lee JY, Rayappa SP, et al. Prevalence of venous thromboembolic events after elective major thoracolumbar degenerative spine surgery. J Spinal Disord Tech 2015;28:E310-5. [Crossref] [PubMed]
55. Bui A, Lashkari N, Formanek B, et al. Incidence and Risk Factors for Postoperative Venous Thromboembolic Events in Patients Undergoing Cervical Spine Surgery. Clin Spine Surg 2021;34:E458-65. [Crossref] [PubMed]
56. Kahn SR, Morrison DR, Cohen JM, et al. Interventions for implementation of thromboprophylaxis in hospitalized medical and surgical patients at risk for venous thromboembolism. Cochrane Database Syst Rev 2013;CD008201. [Crossref] [PubMed]
57. Kelly M, Speciale A, Patton C, et al. A predictive model of preoperative risk factors for venous thromboembolism after fusion for degenerative conditions of the thoracolumbar spine. J Orthop 2020;22:598-601. [Crossref] [PubMed]
58. Tominaga H, Setoguchi T, Tanabe F, et al. Risk factors for venous thromboembolism after spine surgery. Medicine (Baltimore) 2015;94:e466. [Crossref] [PubMed]
59. Epstein NE. A review of the risks and benefits of differing prophylaxis regimens for the treatment of deep venous thrombosis and pulmonary embolism in neurosurgery. Surg Neurol 2005;64:295-301; discussion 302. [Crossref] [PubMed]
60. Platzer P, Thalhammer G, Jaindl M, et al. Thromboembolic complications after spinal surgery in trauma patients. Acta Orthop 2006;77:755-60. [Crossref] [PubMed]
61. Gephart MG, Zygourakis CC, Arrigo RT, et al. Venous thromboembolism after thoracic/thoracolumbar spinal fusion. World Neurosurg 2012;78:545-52. [Crossref] [PubMed]
62. Lippi G, Mattiuzzi C, Franchini M. Sleep apnea and venous thromboembolism. A systematic review. Thromb Haemost 2015;114:958-63. [Crossref] [PubMed]
63. Brambilla S, Ruosi C, La Maida GA, et al. Prevention of venous thromboembolism in spinal surgery. Eur Spine J 2004;13:1-8. [Crossref] [PubMed]
64. Cloney M, Dhillon ES, Roberts H, et al. Predictors of Readmissions and Reoperations Related to Venous Thromboembolic Events After Spine Surgery: A Single-Institution Experience with 6869 Patients. World Neurosurg 2018;111:e91-7. [Crossref] [PubMed]
65. Yang SD, Ding WY, Yang DL, et al. Prevalence and Risk Factors of Deep Vein Thrombosis in Patients Undergoing Lumbar Interbody Fusion Surgery: A Single-Center Cross-Sectional Study. Medicine (Baltimore) 2015;94:e2205. [Crossref] [PubMed]
66. Yang SD, Liu H, Sun YP, et al. Prevalence and risk factors of deep vein thrombosis in patients after spine surgery: a retrospective case-cohort study. Sci Rep 2015;5:11834. [Crossref] [PubMed]
67. Dong HY, Tong MS, Wang J, et al. Risk factors for pulmonary embolism in lung cancer patients with lower limb deep venous thrombosis: a case-control study. Transl Lung Cancer Res 2023;12:1539-48. [Crossref] [PubMed]
68. Swann KW, Black PM. Deep vein thrombosis and pulmonary emboli in neurosurgical patients: a review. J Neurosurg 1984;61:1055-62. [Crossref] [PubMed]
69. Edwards CC 2nd, Lessing NL, Ford L, et al. Deep Vein Thrombosis After Complex Posterior Spine Surgery: Does Staged Surgery Make a Difference? Spine Deform 2018;6:141-7. [Crossref] [PubMed]
70. Ho VT, Martinez-Singh K, Colvard B, et al. Increased vertebral exposure in anterior lumbar interbody fusion associated with venous injury and deep venous thrombosis. J Vasc Surg Venous Lymphat Disord 2021;9:423-7. [Crossref] [PubMed]
71. Hansrani V, Khanbhai M, McCollum C. The Diagnosis and Management of Early Deep Vein Thrombosis. Adv Exp Med Biol 2017;906:23-31. [Crossref] [PubMed]
72. Kolokotroni SM. Deep vein thrombosis and pulmonary embolism following lung resection. Shanghai Chest 2021;5:30. [Crossref]
73. Wilbur J, Shian B. Diagnosis of deep venous thrombosis and pulmonary embolism. Am Fam Physician 2012;86:913-9. [PubMed]
74. Modi S, Deisler R, Gozel K, et al. Wells criteria for DVT is a reliable clinical tool to assess the risk of deep venous thrombosis in trauma patients. World J Emerg Surg 2016;11:24. [Crossref] [PubMed]
75. Segal JB, Eng J, Tamariz LJ, et al. Review of the evidence on diagnosis of deep venous thrombosis and pulmonary embolism. Ann Fam Med 2007;5:63-73. [Crossref] [PubMed]
76. Lee CH, Hankey GJ, Ho WK, et al. Venous thromboembolism: diagnosis and management of pulmonary embolism. Med J Aust 2005;182:569-74. [Crossref] [PubMed]
77. Wells PS, Ginsberg JS, Anderson DR, et al. Use of a clinical model for safe management of patients with suspected pulmonary embolism. Ann Intern Med 1998;129:997-1005. [Crossref] [PubMed]
78. Le Gal G, Righini M, Roy PM, et al. Prediction of pulmonary embolism in the emergency department: the revised Geneva score. Ann Intern Med 2006;144:165-71. [Crossref] [PubMed]
79. Saleh J, El-Othmani MM, Saleh KJ. Deep Vein Thrombosis and Pulmonary Embolism Considerations in Orthopedic Surgery. Orthop Clin North Am 2017;48:127-35. [Crossref] [PubMed]
80. Schellong SM. Complete compression ultrasound for the diagnosis of venous thromboembolism. Curr Opin Pulm Med 2004;10:350-5. [Crossref] [PubMed]
81. Akeda K, Matsunaga H, Imanishi T, et al. Prevalence and countermeasures for venous thromboembolic diseases associated with spinal surgery: a follow-up study of an institutional protocol in 209 patients. Spine (Phila Pa 1976) 2014;39:791-7. [Crossref] [PubMed]
82. Ikeda T, Miyamoto H, Hashimoto K, et al. Predictable factors of deep venous thrombosis in patients undergoing spine surgery. J Orthop Sci 2017;22:197-200. [Crossref] [PubMed]
83. Stein PD, Fowler SE, Goodman LR, et al. Multidetector computed tomography for acute pulmonary embolism. N Engl J Med 2006;354:2317-27. [Crossref] [PubMed]
84. Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). JAMA 1990;263:2753-9. [Crossref] [PubMed]
85. Anderson DR, Barnes DC. Computerized tomographic pulmonary angiography versus ventilation perfusion lung scanning for the diagnosis of pulmonary embolism. Curr Opin Pulm Med 2009;15:425-9. [Crossref] [PubMed]
86. McRae SJ, Ginsberg JS. Update in the diagnosis of deep-vein thrombosis and pulmonary embolism. Curr Opin Anaesthesiol 2006;19:44-51. [Crossref] [PubMed]
87. Olinger CR, Gardocki RJ. Deep Venous Thrombosis and Pulmonary Embolism After Minimally Invasive Transforaminal Lumbar Interbody Fusion: Report of 2 Cases in 315 Procedures. Orthop Clin North Am 2020;51:423-5. [Crossref] [PubMed]
88. Ferree BA, Wright AM. Deep venous thrombosis following posterior lumbar spinal surgery. Spine (Phila Pa 1976) 1993;18:1079-82. [Crossref] [PubMed]
89. Epstein NE. Intermittent pneumatic compression stocking prophylaxis against deep venous thrombosis in anterior cervical spinal surgery: a prospective efficacy study in 200 patients and literature review. Spine (Phila Pa 1976) 2005;30:2538-43. [Crossref] [PubMed]
90. Dearborn JT, Hu SS, Tribus CB, et al. Thromboembolic complications after major thoracolumbar spine surgery. Spine (Phila Pa 1976) 1999;24:1471-6. [Crossref] [PubMed]
91. Smith MD, Bressler EL, Lonstein JE, et al. Deep venous thrombosis and pulmonary embolism after major reconstructive operations on the spine. A prospective analysis of three hundred and seventeen patients. J Bone Joint Surg Am 1994;76:980-5. [Crossref] [PubMed]
92. Makary MS, Koso M, Yoder M. Utility and Clinical Outcomes of Perioperative Inferior Vena Cava Filter Prophylaxis in Spine Surgery Patients. Spine (Phila Pa 1976) 2024;49:569-76. [Crossref] [PubMed]
93. McClendon J Jr. Comprehensive assessment of prophylactic preoperative inferior vena cava filters for major spinal reconstruction in adults. Spine (Phila Pa 1976) 2012;37:1122-9. [Crossref] [PubMed]
94. Andreshak TG, An HS, Hall J, et al. Lumbar spine surgery in the obese patient. J Spinal Disord 1997;10:376-9. [Crossref] [PubMed]
95. Molvar C. Inferior vena cava filtration in the management of venous thromboembolism: filtering the data. Semin Intervent Radiol 2012;29:204-17. [Crossref] [PubMed]
96. Hamidi S, Riazi M. Cutoff values of plasma d-dimer level in patients with diagnosis of the venous thromboembolism after elective spinal surgery. Asian Spine J 2015;9:232-8. [Crossref] [PubMed]
97. Brooks F, Lau S, Baddour E, et al. Thromboprophylaxis in Spinal Surgery – Current UK Practice. J Spine 2013;1:4. [Crossref]
98. Seshadri T, Tran H, Lau KK, et al. Ins and outs of inferior vena cava filters in patients with venous thromboembolism: the experience at Monash Medical Centre and review of the published reports. Intern Med J 2008;38:38-43. [Crossref] [PubMed]
99. Berczi V, Bottomley JR, Thomas SM, et al. Long-term retrievability of IVC filters: should we abandon permanent devices? Cardiovasc Intervent Radiol 2007;30:820-7. [Crossref] [PubMed]
100. Ozturk C, Ganiyusufoglu K, Alanay A, et al. Efficacy of prophylactic placement of inferior vena cava filter in patients undergoing spinal surgery. Spine (Phila Pa 1976) 2010;35:1893-6. [Crossref] [PubMed]
101. Strom RG, Frempong-Boadu AK. Low-molecular-weight heparin prophylaxis 24 to 36 hours after degenerative spine surgery: risk of hemorrhage and venous thromboembolism. Spine (Phila Pa 1976) 2013;38:E1498-502. [Crossref] [PubMed]
102. Cheng JS, Arnold PM, Anderson PA, et al. Anticoagulation risk in spine surgery. Spine (Phila Pa 1976) 2010;35:S117-24. [Crossref] [PubMed]
103. Gerlach R, Raabe A, Beck J, et al. Postoperative nadroparin administration for prophylaxis of thromboembolic events is not associated with an increased risk of hemorrhage after spinal surgery. Eur Spine J 2004;13:9-13. [Crossref] [PubMed]
104. Massaro AM, Frier S, Strot SM, et al. Revisiting Anticoagulation in Spine Surgery: Balancing Venous Thromboembolic Events and Epidural Hematoma. Global Spine J 2023; Epub ahead of print. [Crossref] [PubMed]
105. Yi S, Yoon DH, Kim KN, et al. Postoperative spinal epidural hematoma: risk factor and clinical outcome. Yonsei Med J 2006;47:326-32. [Crossref] [PubMed]
106. Glotzbecker MP, Bono CM, Wood KB, et al. Postoperative spinal epidural hematoma: a systematic review. Spine (Phila Pa 1976) 2010;35:E413-20. [Crossref] [PubMed]
107. McLynn RP, Diaz-Collado PJ, Ottesen TD, et al. Risk factors and pharmacologic prophylaxis for venous thromboembolism in elective spine surgery. Spine J 2018;18:970-8. [Crossref] [PubMed]