Risk Factors for Venous Thrombosis after Spinal Surgery: A Systematic Review and Meta-analysis

Background Venous thrombosis, comprising DVT and PE, is an orthopedic condition that may be fatal after surgery. This study's purpose was to analyze risk factors for venous thrombosis following spine surgery to help guide treatment prophylaxis. Methods A computer searched English databases such as PubMed, Web of Science, Embase, Cochrane Library, and Google Academic for relevant publications after spinal surgery. Preoperative walking difficulties, hypertension, diabetes, heart disease, preoperative bleeding volume, etc., were all examined using the NOS scale. Data were analyzed using Review Manager 5.3 software. An analysis was done. Due to the study's differences, the data was compiled using fixed effects or random effects models. Results A total of 25 studies were considered, with a total of 1,927,781 individuals after spine surgery, including 7843 patients with venous thrombosis. The included literatures had NOS scores ranging from 5 to 8. According to the findings of the meta-analysis, the age of patients with venous thrombosis after spinal surgery (OR = 7.53, 95% CI (6.73, 8.33)), blood loss (OR = −141.79, 95% CI (-154.68, -128.9), P = 0.00001), and operation time (OR = 76.93, 95% CI (73.17, 80.86), P = 0.00001) were higher than those without; diabetes mellitus (OR =1.23, 95% CI (1.12, 1.34), P = 0.00001) and walking disability history (OR = 2.97, 95% CL (1.77, 4.98), P = 0.0001) increased the incidence of postoperative venous thrombosis. Conclusion High age, female, spinal fusion, big volume blood loss patients, operation time, and hypertension, diabetes, and walking issue are all risk factors for venous thrombosis following surgery.


Introduction
Patients having major orthopedic surgery (DVT) have an increased risk of venous thromboembolism, which may include pulmonary embolism (PE) and deep venous thrombosis [1]. VTE is a well-known and feared surgical complication, as well as a leading cause of death [2]. Acute thromboembolic illness (VTE) may result in substantial morbidity, poor quality of life, and even death [3]. It may also lead to increased medical costs and a considerable financial burden on individuals and their families [4]. The use of pharmacological prophylaxis is well established in a variety of surgical procedures, most notably hip and knee replacements, for which there are wellestablished criteria and dosing guidelines [5]. Chemoprophylaxis recommendations in spinal surgery are less well defined, and there are currently no clear evidence-based standards in this discipline [6]. Because there is no consensus on the effi-cacy and safety of chemoprophylaxis in spine surgery, a wide range of treatment options are available, many of which are dependent on the surgeon's personal experiences with the medication [7]. As a consequence, spine surgeons must be aware of the prevalence of VTE as well as the risk factors that contribute to the development of this condition [8].
An epidural hematoma, a devastating but rare complication of spinal surgery, may occur from bleeding issues [9]. As a consequence, spine surgeons should use caution when prescribing anticoagulants. To balance VTE morbidity and mortality with epidural hematomas' potential of permanent neurological disability, they must decide [10]. Many researchers have looked at the VTE risk factors following spine surgery [11]. Due to the limited sample sizes and varying detection technology, the incidence varies [12]. These studies found that older patients on prolonged bed rest for paralysis or pain had a higher incidence of VTE than younger patients [13]. Although variables such as the presence or absence of D-dimer in the blood [14], the length of the operation, intraoperative blood loss, and surgical procedures all have an effect on the frequency of VTE after spine surgery, the incidence remains consistent and never paradoxical [15].
A comprehensive review of the available literature was conducted in order to get a better understanding of VTE incidence and risk factors in patients undergoing spine surgery. In order to assist surgeons in making well-informed therapy choices, evidence-based information about this subject will be presented in a straightforward way.

Materials and Methods
2.1. Search Strategy. Search the computer for PubMed, Web of Science, Embase, Cochrane Library, and other English databases. The English search terms are "Spinal surgery", "Venous thrombosis", and "spine", all from the medical topic word list (mesh). The retrieval term for all databases is from the time the database was created until December 30, 2021. In addition, in order to completely include the literature, several references were manually gathered.

Inclusion and Exclusion Criteria.
All of the studies that were included were studies that were based on what people saw and did on the incidence of venous thrombosis after spine surgery. The following factors are included: (1) age, (2) gender, (3) BMI, (4) history of hypertension, (5) diabetes history, (6) history of heart disease, (7) preoperative D-dimer level, (8) history of preoperative walking problem, (9) mode of surgery, (10) mode of anesthesia, (11) surgical location, (12) duration of operation, (13) blood loss, (14) smoking history, (15) alcohol history, and (16) postoperative infection. At least one of the aforementioned signs may be found in the included literature. Criteria for exclusion include (1) a summary study, (2) an expert opinion, (3) a case report or case series report, (4) preoperative or coagulation function abnormal and clinically significant, (5) venous thrombosis occurred before the procedure, (6) blood system illnesses, (7) various thrombus prevention techniques were utilized both before and after the operation, and (8) after contacting the author, the relevant information could not be obtained.

Selection of Studies.
Two investigators independently reviewed all of the subjects, abstracts, and full texts of the literature that had been chosen. Following that, the eligible studies were selected in accordance with the inclusion criteria. Discussion and consensus were used to address any disagreements that arose among the investigators. A third author was sought to help settle the situation when no agreement could be obtained.

Data
Extraction and Quality Assessment. Two researchers independently extracted the data, which included the name of the original author, the year of publication, the country of origin of the subjects, and information on numerous inclusion indicators indicated in the inclusion criteria. If there are disagreements, they must be handled by conversation; if the dispute cannot be resolved, the third researcher must be consulted. Two researchers extracted the data independently, including the first author's name, the year of publication, the country of the study population, and the details on numerous inclusion indicators indicated in the inclusion criteria. If there are disagreements, they must be handled by conversation; if the dispute cannot be resolved, the third researcher must be consulted.

Statistical Analysis.
For meta-analysis, Review Manager 5.3 software was employed. The analysis statistics were odds ratio (OR) or relative risk (RR); the measurement data analysis statistics were weighted mean difference (WMD) or standardized mean difference (SMD), and each effect quantity was given by a 95% confidence interval (95% CI). The Q test and I 2 were used to quantify the heterogeneity of the research. When P > 0:1 and I 2 > 50%, it is assumed that the heterogeneity is not significant, and the fixed effect model is used to combine the data. When P < 0:1, which is 50%, it is assumed that the heterogeneity is substantial, and the fixed effect model is used to integrate the data. The model with a random effect is used, and the cause of heterogeneity is identified as thoroughly as feasible for subgroup analysis. If the reason for heterogeneity cannot be determined, the random effect model is utilized in meta-analysis. There was a statistically significant difference between the two groups (P < 0:05).

Selected Study
Results. The approach for screening and selecting articles for inclusion in this study is shown in Figure 1. Initially, a total of 2139 studies were discovered. 491 were eliminated for duplicate entries, and 1600 were excluded following a title/abstract assessment. The remaining 48 papers were then subjected to a full-text review. 23 of them were rejected because they did not match the qualifying requirements. Finally, 25 papers satisfied the inclusion criteria and were included in our meta-analysis; the features of these studies are shown in Table 1. One of the 25 studies was meant to be prospective, while the other 24 were planned to be retrospective. The entire number of participants in the study was 3,215,173, of which 1038 were difficult to deal with VTE, and the overall occurrence of VTE following spine surgery was 0.35% (the original studies' occurrence of VTE was 0.15-29.38%). VTE occurred in 8.43% of patients from Asians and 0.33% of Western patients; the difference is statistically significant (P < 0:0001).
3.2. Data Quality Assessment. All 14 studies were critically appraised independently by the two reviewers. The study design and outcome measure were valid and appropriate to the research questions. The risk of bias in the study design and results was assessed by the revised Cochrane risk of bias in randomized trials (RoB 2) latest version 22 August 2019 ( Figure 2).

BMI.
Five studies [16][17][18][19][20]35] found a link between BMI and postoperative venous thrombosis. There are two for Chinese and two for foreigners. In the study sample, there were 378 instances of VTE (+) and 5196 cases of VTE (-). Because the studies had considerable statistical heterogeneity (I 2 = 87 percent, P0.00001), the random effect model was employed for meta-analysis. Those with VTE (+) had a lower mean BMI than patients with VTE (-) ( Figure 5).

Operation Methods.
Six studies comprising 49,389 patients found an association between surgical procedures and the prevalence of venous thrombosis following spine surgery, including 32,032 patients with nonfusion and 17,357 patients without fusion [23][24][25][26][27][28][29]. Because there was no significant heterogeneity across the studies, the model with a fixed effect was adopted for meta-analysis. The findings revealed that the frequency of VTE in patients with nonfusion was greater than that in patients with fusion. There was a statistically significant difference between the two (OR = 1:67, 95% CI (1.40, 1.99), P = 0:00001, Figure 6).

Operative
Approach. Three studies comprising 461 patients found a relationship between surgical approach and the frequency of venous thrombosis following spine surgery [21][22][23], including 328 instances of posterior surgery, 133 cases of anterior/posterior mixed surgery, 34 cases of VTE (+), and 427 cases of VTE (-). The fixed effect model was adopted for meta-analysis since there was no statistical heterogeneity across the studies. The data revealed that the incidence of VTE was higher in patients undergoing simple posterior surgery than in patients undergoing anterior/   Figure 7).
3.3.6. Operative Site. Four investigations including 1617 patients found a link between the surgical site and the incidence of venous thrombosis following spinal surgery [12][13][14][15][16], including 285 instances of cervical surgery, 1332 cases of thoracolumbar surgery, 75 instances of VTE (+), and 1542 instances of VTE (-), because there was no statistically significant difference between the studies (I 2 = 0, P = 0:59). In this meta-analysis, the fixed effect model was used as a basis. The findings revealed that the incidence of VTE was lower in cervical surgery patients than in thoracolumbar surgery patients (OR = 1:17, 95% CI (0.66, 2.08), P = 0:59, Figure 8).
3.3.7. Duration of Surgery. A total of 8 investigations comprising 46,840 patients, including 680 instances of VTE (+) and 46,160 cases of VTE (-) [12][13][14][15][16][17][18][19]35], indicated that the length of surgery was associated with the incidence of The surgical billing database at our institution was queried for inpatients discharged between 2008 and 2015 after the following procedures: atlantoaxial fusion, anterior cervical fusion, posterior cervical fusion, anterior lumbar fusion, posterior lumbar fusion, lateral lumbar fusion Transfusion using a liberal trigger is associated with increased morbidity, even after controlling for possible confounders. Our results suggest that modification of transfusion practice may be a potential area for improving patient outcomes and reducing costs 5 Computational and Mathematical Methods in Medicine venous thrombosis following spine surgery. Because there was statistical heterogeneity in each research question (I 2 = 98%, P = 0:00001), the random effect model was utilized for meta-analysis. The findings of the study revealed that the mean operation time of VTE (+) patients following spinal surgery was greater than that of VTE (-), and the dif-ference was statistically significant (OR = 76:93, 95% CI (73.17, 80.86), P = 0:00001, Figure 9).
3.3.11. Heart Disease. Heart disease has been linked to a higher risk of postsurgical blood clots in four studies [20][21][22][23][24], involving 5718 patients, including 1550 cases of heart disease, 4168 cases of nonheart disease, 453 cases of VTE (+), and 5265 cases of VTE (-), which were not available due to statistical heterogeneity (P = 0:95). As a result, for the meta-analysis, a fixed effect model was adopted. The findings revealed that the incidence of VTE following spinal surgery was greater in patients with nonheart disease than in patients with heart disease; the difference was statistically significant (OR = 0:96, 95% CI (0.78, 1.20), P = 0:74, Figure 13).
3.3.14. Publication Bias. Begg and Egger tests revealed no evidence of publication bias in any of the papers included in this review ( Figure 16).

Discussion
Complications from spine surgery cause people bodily, emotional, and social distress. These two incidents have diminished        [34]. Although medications may effectively prevent venous thrombosis, the risk of venous thrombosis following spine surgery is significantly smaller than after joint surgery [37]. However, several investigations have demonstrated that deadly PE has much more severe repercussions and medical risks than epidural hematoma [38]. If surgical patients' venous thrombosis prevention and treatment are ignored, preventable PE will endanger the patient's life. Indicator measurement is difficult due to various aspects such as    9 Computational and Mathematical Methods in Medicine research design, sample size, and subject inclusion/exclusion criteria [39]. The incidence of venous thrombosis following spinal surgery varies between 0.31% and 31%, showing that there is no unanimity on the occurrence. Moreover, the existing system assessment findings vary. So, through meta-analysis/systematic review, in line with the inclusion and exclusion criteria, a more extensive qualitative and quantitative synthesis of previous research is required to investigate the risk factors for thrombosis following spine surgery.
In terms of surgery, fusion vs. nonfusion, blood loss (big), operation duration (long), past history face, hypertension (+), diabetes (+), preoperative walking problem (+), and thrombosis risk following spinal surgery [40], thrombosis in spinal surgery is linked to the following variables, with close correlation to (1) trauma, blood loss, and blood transfusion caused by operation damaging intima of blood vessels and making the body hypercoagulable; (2) compression of the venous system caused by long-lying posture during operation, such as inferior vena cava, iliac vein, and femoral vein; (3) implantation of metal and other artificial materials, such as pedicle screw system, bone cement, and artificial bone; (4) anesthesia, especially general anesthesia; (5) lower limb paralysis occurrence. Lower limbs lose muscular pump and vasomotor reflex function; (6) changes in body fluid balance, electrolyte imbalance, and fluctuation of the internal environment during the perioperative period; and (7) staying in bed or break for a long time after surgery. These are connected to the three pathogenic components of venous thrombosis: vascular wall damage, sluggish blood flow, and hypercoagulable condition. The beginning of any fac-tor may result in thrombosis. A high quantity of glucose in the blood might cause blood. Meta-analysis research found that vascular endothelial damage increased the risk of blood coagulation (OR = 1:49, 95% CI (1.40, 1.58), P = 0:00011); the result of this research is comparable [41].
Studies on the occurrence of venous thrombosis after column surgery have been reported; however, the results are mixed [42]. Compare this study's results to prior studies' findings on hypertension (+), diabetes (+), preoperative walking difficulty (+),surgery (fusion), age, gender, blood loss, and operation time (long). This study found a statistically significant difference in the incidence of venous thrombosis after spine surgery due to these variables [43]. This is because, in terms of age-related venous thrombosis incidence, this investigation included five previously published studies that complimented the results and increased the sample size. The data suggest that age may be a risk factor for postsurgery thrombosis. In terms of gender and venous thrombosis incidence, this study excluded case-control studies (the researchers believe the control selection is not representative) and studies utilizing prophylactic methods in favor of three newly published studies [44]. Gender may be a risk factor for thrombosis following spine surgery. However, it is unclear if gender (for example, men) is a risk or protective factor for thrombosis. Based on Zacharia et al., this study comprised five investigations on the impact of blood loss on venous thrombosis incidence [45]. Because blood loss varies widely, SMD was used in this study. The number of fused segments and hand operation method may be linked to heterogeneity. This study included  seven studies on the impact of operation time on venous thrombosis incidence, increasing sample size, and statistical accuracy. However, the included studies are quite varied, maybe related to surgical method, bleeding volume, or other factors. The patient's condition and personal will, as well as the doctor's evidence-based decision-making, impact the operation time and amount of bleeding, as well as the hemostasis caused by intraoperative bleeding. The comparison of BMI and the incidence of venous thrombosis after spinal surgery revealed that the heterogeneity of the included studies was substantial, and the difference was not statistically significant [46]. The source of heterogeneity was investigated using subgroups of the study population. Following subgroup analysis, the heterogeneity of each subgroup fell dramatically, suggesting that the population may be the cause of the considerable heterogeneity across groups. The mean value of BMI difference in various Asian populations is demonstrated to be in the other direction. It implies that BMI may not be a direct cause of venous thrombosis following spine surgery but may have an indirect effect on the establishment of postoperative thrombosis. Intermediate elements include vascular elasticity, blood viscosity, and the degree of vascular wall damage. This research also discovered that there was no significant difference in preoperative D-dimer levels between the postoperative VTE (+) group and the VTE (-) group. It is stated that the present data are insufficient to show that the difference in preoperative D-dimer levels has a statistically significant influence on the incidence of venous thrombosis following spine surgery. Large sample size and multicenter research are required. At the same time, consider the influence of the dynamic shift in postoperative D-dimer level on thrombosis.

Limitations
Age, gender, BMI, surgery time, and blood loss were all taken into account. They propose that where there is little or no heterogeneity, analytical meta-analysis may help determine effect sizes or test hypotheses. Methodological, clinical, or statistical variables may all contribute to heterogeneity. The majority of the papers in this study are retrospective NOS score investigations. Biases exist in certain literatures, such as (1) research bias due to disparities in inquiry methods between venous and nonvenous thrombosis situations; responders and   Figure 15: Forest diagram of preoperative walking disorder and the incidence of venous thrombosis after spinal surgery.
investigators may make systematic mistakes. Concern about the patient's medical history, for example, varies. (2) The study's major result and measurement bias were not addressed, and there were no consistent diagnostic criteria across trials; neither are preoperative diagnostic criteria for walking dysfunction or hypertension. Variable and method heterogeneity may be included in the meta-analysis. Oral vitamin E, pregnancy-preventive medicines, aspirin, postoperative functional activity, postoperative braking, and other factors contributed to clinical variability. These signs have not received much attention. Their absence might result in phenotypic differences. As a consequence, age and gender are exaggerated or minimized, resulting in clinical diversity. Clinical variability may emerge as a result of surgical skill, competency, and illness severity, all of which influence operation duration and blood loss. The unequal distribution of these components causes variation in study outcomes. There was insufficient data in the included trials, and there was no subgroup analysis to determine the cause of heterogeneity.

Conclusion
However, there is no strong evidence that these characteristics are independent risk factors for postoperative thrombosis. Diabetes may be caused by vascular endothelial damage, which is an indirect risk factor for venous thrombosis and poor cardiac function. Insufficient energy may restrict activities and produce lower extremity venous stasis (nonindependent risk variables). Large-scale multicenter prospective research is needed to evaluate the incidence of venous thrombosis following spine surgery. Regardless, this investigation found venous thrombosis following spine surgery. Birth-related risks need the spinal surgeon to focus on the postoperative period. Venous thrombosis is deadly for screening and surveillance of people with venous thrombosis. Concerning postoperative venous thrombosis prevention and therapy, a systematic review and meta-analysis based on high-quality original research are still required.

Data Availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.