Analysis of Risk Factors for Deep Venous Thrombosis in Patients With Achilles Tendon Rupture: A Retrospective Study of 247 Patients

The high incidence of deep venous thrombosis (DVT) was presented in patients with Achilles tendon rupture (ATR), and affects the prognosis of patients signicantly. The purpose of this study was to identify and quantify the risk factors for perioperative DVT and the role of DVT in clinical outcomes, which may provide a guideline for DVT prevention and Achilles tendon repair. The study was conducted on 247 patients who underwent surgical treatment for ATR at our institution from 2009 to 2019. Ultrasound results from injury to 4 weeks after operation were collected to diagnose DVT. Odds ratios (OR) were calculated using logistic regression to describe factors associated with DVT diagnosis including sex, age, body mass index (BMI), nicotine usage, mechanism of injury, rupture side, types of rupture, medical morbidity (hypertension, diabetes, coronary heart disease, stroke), time to operation, operative time and blood loss. The outcomes were assessed using the Achilles tendon Total Rupture Score (ATRS) and American Orthopaedic Foot and Ankle Society (AOFAS) Ankle Hind-Foot Scale Score at postoperative 3, 6, and 12 months.


Conclusions
Routine thromboprophylaxis should be encouraged in patients with ATR requiring surgery, which was caused by trauma. Age > 40 years and BMI > 26 were important risk factors for perioperative DVT. This study also showed that the presence of DVT of patients with ATR in the perioperative period has clear impairment of outcome within one year after surgery, which may postpone the return of athletes to the eld severely.
Background Page 3/16 Deep venous thrombosis (DVT) of the lower extremities is a common complication in patients with Achilles tendon rupture (ATR). Aside from the fatal risk of DVTs causing a pulmonary embolism (PE), long-term morbidity of impaired subjective outcome may be caused considerably by symptoms such as chronic pain, secondary varicose veins, and ulcers [1]. Many previous studies have demonstrated that the highest risk of DVT associated with ATR was 35-50% approximately, irrespective of surgical or nonsurgical treatment [2][3][4]. Despite chemoprophylaxis with low molecular weight heparin (LMWH) effectively prevents venous thromboembolism (VTE) in lower extremity trauma, an unsatisfactory effect was demonstrated on patients with ATR [5]. The same result was also been reported by Calder JDF et al. and considered that the insu cient blood circulation caused by the retraction of the ruptured tendon and immobilization of the limb may be the main reason for the high incidence of DVT and the poor preventive effect of LMWH [2].
Plenty of researches have been identi ed that increasing the venous return of lower limbs in patients with ATR prevents the occurrence of DVT effectively. Craik JD et al. demonstrated that the venous return of injured limb can be increased in patients with a partial or full weight-bearing compared to non-weightbearing [6]. Besides, active ankle and toe range of motion was also an effective method to prevent vascular stasis during the postoperative exercises [7,8]. Furthermore, a randomized controlled trial conducted by Aufwerber S et al. Illustrated that the risk of DVT could be minimized by an early exercise with more than 50% of body weight [9].
Although weight-bearing and active ankle motion as an effective method to prevent the occurrence of DVT during the period of leg immobilization have been con rmed, there are rare researches on the risk factors of perioperative DVT in patients with ATR. Therefore, the purpose of this retrospective study was to review the incidence and risk factors of perioperative DVT in patients who underwent surgical treatment to repair the Achilles tendon via the collection of the basic demographics, inter-operative data, and written questionnaires, which may guide the prevention of DVT after ATR, and the repair of the Achilles tendon.

Patients
This study was a retrospective assessment of 247 patients treated by the same surgery team for ATR between 2009, and 2019. The inclusion criteria in the studies were as follows: patients with an age between 16 and 75 years, acute ATR treated by minimally invasive approach, availability of ultrasonography results. Other patients with chronic ATR (acute ATR with delayed treatment more than 4 weeks), open ATR, current anticoagulation treatment, known kidney failure, heart failure with pitting edema, thrombophlebitis, a thromboembolic event during the previous 3 months, known malignancy, known hemophilia or thrombophilia, pregnancy, other severe trauma, and poor compliance to follow-up were excluded. Finally, 216 males and 31 females were assessed in this study according to inclusion criteria with a mean age of 37 years (range 20-75 years). The study was conducted following the Declaration of Helsinki, approved by our hospital institutional review board. The analyzed medical and ultrasonic data came from hospital records.

Surgical procedure
The operation was performed with the patient kept under spinal anesthesia. During the operation, two separate longitudinal incisions were made with 3-4 cm distance from the rupture site [10]. Careful dissection and complete release of tissue adhesions around the Achilles tendon, and the osteophytes with calcaneal tubercle hyperplasia were removed. In the extreme plantar exion of the ankle joint, the1-0 PDS-II suture material (Ethicon, Somerville, NJ) can be used as the traction line twice, respectively, through the distal incision of the Achilles tendon, and continuous traction for more than ten minutes.
From the distal incision, 3-6 longitudinal holes, approximate 2.0cm deep, were drilled in the calcaneus within the calcaneal insertion using a 2.5mm (in diameter) Kirschner wire to ensure the regenerated tendon attached to the bone rmly. After that, a transverse percutaneous calcaneal bone tunnel was drilled with a 3.0mm (in diameter) Kirschner wire to prepare for percutaneous "Yurt bone" suturing [11,12]. The plantar tendon was considered to be the most ideal biological suture graft material for strengthening the repair of the Achilles tendon. And the plantar tendon was used to bridge the ends of the distal and proximal Achilles tendon stump which plays a dual role in tendon transplantation and bridging suture.

Postoperative management
Following surgery, all patients were encouraged to do early postoperative rehabilitation without any xation [10]. These patients were advised to lie prone or lateral on the bed without xation or orthosis and with the knee at ~60° exion and the ankle joint at ~45° plantar exion. In addition, patients were instructed for the early active motion of the ankle and knee joints by a detailed physical rehabilitation regimen from postoperative day 1. In this program, the increasing intensity of motion exercises was initiated at postoperative day 10, followed by another increasing at week 3. Full weight-bearing exercise, standing on the toes, and squatting were initiated at postoperative week 4 [13]. It should be noted that the exercise of tiptoe stepping on the operated side of the tendon on the balance 3~9 kg from postoperative day 3 was a novel component of the present program, which was greatly useful not only for reducing the patient's fear of early motion of the ankle joint but also for the surgeon to determine the time of walking with weight-bearing exercises according to the increase in tiptoe stepping.

Data collection
At admission, 2 and 4 weeks postoperatively, all patients were screened for DVT in the injured leg using unilateral compression duplex ultrasound (CDU). The basic demographics data were obtained by standardized self-administrated questionnaires at the beginning of in-patient treatment and complemented by extracting relevant data from hospital records, included: age, sex, body mass index (BMI = weight (kg) / height (m 2 )), nicotine usage (continuous smoking for more than 3 months), rupture side (left or right), mechanism of injury (sports injury or trauma), types of rupture (total or partial), medical morbidity (hypertension, diabetes, coronary heart disease, and stroke), time to surgery, operative time and blood loss in operation.
Patient-subjective and functional outcomes were assessed at 3, 6, and 12 months postoperatively by completing the questionnaires or telephone interview, and all patients were evaluated by the Achilles tendon Total Rupture Score (ATRS) and American Orthopaedic Foot and Ankle Society (AOFAS) Ankle Hind-Foot Scale Score.

Potential risk factors
Continuous variables included age, time from injury to operation, operative time, and blood loss in operation. And sex, body mass index (normal weight=BMI<26kg/m 2 , overweight=BMI>26kg/m 2 ), nicotine usage, mechanism of injury (sports injury or trauma), rupture side (left or right), types of rupture (total or partial rupture), medical morbidity (hypertension, diabetes, coronary heart disease, and stroke) were attributed to the categorical variables.

Statistical analysis
Statistical analysis was performed using SPSS (Version 22.0; IBM). The measurement data were assessed for normal or non-normal distribution. Continuous variables were analyzed by independentsamples T-test and expressed as the mean and standard deviation. For the categorical data, the chisquare test was used, expressing as number. Statistically signi cant difference was set at P<0.05.
The variable with a P-value of 0.05 or less in the chi-square test or T-test was entered to in the multivariate logistic regression model the relationship between the explanatory variable and the DVT and control the potential confusion of any included variables. The difference was statistically signi cant (P<0.05).

Results
In total, 247 patients with ATR were included in this study after applying the inclusion and exclusion criteria. Of these patients, no one died, refused, or did not participate in the follow-up. Out of 247 patients, 113 patients were diagnosed with DVT according to the results of CDU, accounting for 46 % of total patients. For these patients with DVT, LMWH (0.4ml, once a day) was used to subcutaneously inject to prevent VTE. 5 patients were recommended using the inferior vena cava lter (IVCF) to prevent fatal PE according to the evaluation performed by vascular surgeons. In one year follow-up, the tendon re-rupture appeared in 16 cases, tendon infection was presented in 6 cases, and tendon exposure occurred in 1 case. Sixteen tendon re-ruptures were repaired by additional surgery. Six tendon infections were treated by debridement and oral antibiotic therapy. One tendon exposure was covered with a random pattern skin ap.

Risk Factors For Dvt
Comparison of the demographic data between the DVT group and non-DVT group revealed that there was on signi cant difference concerning the sex, rupture side, and medical morbidity (hypertension, diabetes, and stroke) ( Table 1). In the univariate logistic regression analysis, the following were associated signi cantly with a higher incidence of perioperative DVT: age > 40 years, BMI > 26, traumatic ATR, total ATR, coronary heart disease, time to operation, blood loss, operative time, and postoperative immobilization (     (Fig. 1). Moreover, more symptoms in 1 year after surgery were detected in patients with a DVT compared to patients devoid of it.

Discussion
Patients with Achilles tendon rupture (ATR) had the highest incidence to suffer deep venous thrombosis (DVT) compared to other common lower limb injuries, which may lead to various symptoms, even pulmonary embolism (PE) [13]. It has been con rmed by various studies that patients with leg immobilization were more likely to suffer from DVT, and early functional exercise after surgery was preferred to prevent the occurrence of DVT and promote early function recovery [14][15][16][17] 95% CI 1.03-1.14) were the independent risk factors for perioperative DVT in the multivariate logistic regression analyses.
The incidence of DVT in this study was 46%, which is in good agreement with previous researches that demonstrated a 36-50% DVT rate in patients with ATR irrespective of operation or conservative management [18,19]. Although aging (older than 40 years) is an independent risk factor for DVT, it is noteworthy that the incidence of DVT was 35.9% in young patients (< 40 years) in our cohort and this rate was much higher than other common lower limb injuries. [20][21][22]. This phenomenon may be related to the reductions in tendon stiffness and resistance to loads after the tendon rupture [23]. Additionally, the disappearance or weakening of the muscle pump may be another reason leading to the decrease of venous return in the lower extremity, then contributing to the occurrence of DVT.
An almost threefold increased odds for sustaining a DVT was found in overweight patients (BMI > 26kg/m 2 ) in previous studies [9,18]. In the present study, a high incidence of perioperative DVT (about 59%) was also presented in overweight patients (BMI > 26kg/m 2 ). Obese patients may be at increased risk for DVT after ATR as a result of lower postoperative mobility, the ineffectiveness of mechanical prophylaxis, and elevated procoagulant in ammatory markers. There was a consensus that early full weight-bearing can not only prevent the occurrence of DVT, but also promote the early functional recovery of the ruptured tendon, and help athletes to return to the sports eld earlier [9] [24,25]. Furthermore, a randomized controlled trial conducted by Susanna Aufwerber et al. demonstrated that a low amount of weight-bearing ≤ 50% in postoperative rehabilitation was an independent risk factor for DVT, and recommended that patients with the tendon surgery should be encouraged to load at least 50% of body weight in postoperative exercise [9]. However, in our observation, obese patients were more di cult to carry out the early full-weight exercise, which may be related to the increased cardiac load and the decreased exercise tolerance caused by obesity.
Sports injury is the main reason for ATR, and it occurs more frequently in young athletes, but it should be noted that the higher risk was associated with traumatic ATR ( Additionally, the operation itself is the introducing factor of the hypercoagulation state [31]. In the multivariate analysis, operative time (OR 0.95; 95% CI 0.91-1.01) and blood loss (OR 1.09; 95% CI 1.03-1.14) both were the independent risk factors contributing to DVT. Patients with DVT exhibited more blood loss (153.98 ml ± 39.65 ml) than patients who avoid DVT (99.33 ml ± 38.75 ml). The same result has also been reported in other operations of the lower limb [22,32]. Moreover, the operative time may be increased by greater blood loss. In a previous study, a prolonged duration of operative time of more than 60 min increases the risk of thrombosis according to National Institute for Health and Clinical Excellence (NICE) [33].
The patient-subjective and functional outcomes were evaluated by ARTS and AOFAS at postoperative months 3, 6, and 12 in patients with and without DVT. The results demonstrated that patients who were not a icted by a DVT exhibited better outcomes in one year after surgery. The poorer clinical outcomes in patients with DVT may be related to insu ciently postoperative exercise due to chronic pain and swelling in the lower extremity caused by DVT. Furthermore, older age and higher obesity have been con rmed to have a negative impact on Achilles tendon repair [34][35][36][37][38]. However, the effect of surgical and nonsurgical treatment on the outcome of ATR has been debated. In this study, we found that surgery-related factors such as trauma, blood loss, and operative time were independent risk factors for DVT and may further in uence the outcome of ATR.
Yet, certain limitations existed in this study. Firstly, given its retrospective nature and small sample size, caution should be taken regarding the interpretation of our analytical results. In fact, the factors responsible for the occurrence of DVT are complex, and there may be more confounding factors in the analysis results. Secondly, insu cient postoperative management instruction could give rise to higher numbers of DVT. Thirdly, to get control of the limitations of our study, further studies with larger sample size, longer follow-up period, and multicenter design should be designed.

Conclusions
The study was performed for demonstrating the quanti cation of risk factors for DVT and their role allows one to determine the patient-subjective and functional outcomes, which is important for both clinicians and patients. Almost 46% of patients with ATR were diagnosed with DVT based on ultrasound ndings. Age > 40 years, BMI > 26, traumatic ATR, blood loss, and operative time were the independent risk factors. A routine thromboprophylaxis should be encouraged for patients with these risk factors to achieve better outcomes. All methods in this retrospective study were carried out in accordance with the Declaration of Helsinki. This study was approved by the Ethics Committee of The First Aliated Hospital of Xinjiang Medical University. Written informed consent was obtained from all patients for their data to be recorded in our study.

Consent for publication
Informed consent was obtained from all patients for their data to be published in our study.

Availability of data and materials
The datasets generated during and analyzed during the current study are available from the corresponding author on reasonable request.