Early incidence of deep venous thrombosis and its risk factors after knee arthroscopic surgery in patients with anticoagulant and non-anticoagulant

Purpose: To investigated the early incidence of deep venous thrombosis (DVT) and its risk factors after knee arthroscopic surgery in patients with anticoagulant and non-anticoagulant. Methods: 272 patients were reviewed who have undergone knee arthroscopic surgery in our hospital from January 2018 to October 2019. Color doppler ultrasound was performed for every patient at 24h preoperatively and three days after operation. On the rst day after surgery, low molecular weight heparin (LMWH) was randomly administered to some patients and not in others. The following factors were recorded: gender, age, body mass index (BMI), preoperative platelet and D-dimer level, D-dimer level three days after surgery, anesthetic technique, tourniquet time, whether to use LMWH after operation, and type of surgical procedures. Chi-square test or Student t test was used to preliminarily screen out suspected risk factors. Then, multiple logistic regression analysis was utilized to further determine the risk factors of DVT after knee arthroscopic surgery. Results: The incidence of DVT in the postoperative anticoagulant group was 7.5%, and 7.4% in the non-anticoagulant group. An increased incidence was found among higher D-dimer level postoperatively. There was no signicant difference in the incidence of DVT between use of LMWH and non-use of LMWH in three days after surgery. Conclusion: The early incidence of DVT in the group of patients without LMWH was 7.4%. The incidence of DVT in patients with knee arthroscopy surgery could not be reduced by using LMWH within three days, and high D-dimer level was a risk factor for DVT after knee arthroscopic surgery.


Introduction
With the improvement of arthroscopy technology, more and more therapeutic operations can be performed under arthroscopy [1]. However, the incidence of deep vein thrombosis (DVT) after arthroscopy surgery has also increased due to the improved accuracy of thrombosis diagnosis, which has caused concerns of orthopedic surgeons. The incidence has been reported between 1.8-41.2% [2], and in patients undergoing high-energy knee trauma, the incidence of preoperative DVT was as high as 50% [3].
The study of Bohensky et al. [4] showed that DVT had become the most common complication after arthroscopic surgery. But even worse, DVT may occasionally developed into a fatal complication: pulmonary embolism (PE) [5,6]. Currently, there is still a big debate about whether prophylaxis should be a criterion after arthroscopic surgery. For instance, the American College of Chest Physicians indicated that it is not recommended to use thrombosis prevention measures for patients unless risk factors are present [7]. Several studies suggested that gender, age, BMI and other factors may be the potential risk factors of DVT [8][9][10][11][12]. Based on evidence existed, our purpose is to study the incidence of DVT in the two groups of anticoagulation and non-anticoagulation patients, as well as the risk factors of DVT formation after knee arthroscopic surgery.

Operative Procedure
The choice of anesthesia was determined by patient and anesthesiologist, and the procedure was performed by two experienced surgeons. Tourniquet time was routinely set for 90 minutes, if the time needed to be extended, the tourniquet would be in ated for 10 minutes and re lled again. All tendons used in ligament reconstruction surgeries were autografts. After the operation, ice was routinely applied to the wound until the third day. 24 hours later, the patients begun to do some exercise like isometric contraction of the quadriceps, and no other physical preventive measures were taken. All patients were not given drugs to prevent thrombosis before surgery, but the patients were randomly divided into two groups on the rst day after surgery, one group was injected subcutaneously with low molecular weight heparin (LMWH, enoxaparin, 0.2 ml) once a day, and another group was not.

Diagnosis of DVT
All patients underwent color doppler arteriovenous ultrasound of the lower extremities within 24 hours preoperatively and on the third day postoperatively to determine whether thrombosis was existed, and all patients were operated by the same ultrasound doctor and diagnosed by another doctor. The speci c diagnostic criteria [13] are as follows: hypoechoic masses appear in venous vein, or venous vein cannot be compressed, or venous blood ow was absent. DVT was classi ed as proximal DVT (occurred in popliteal vein and above) and distal DVT (occurred in deep vein below the knee joint plane). As long as the patient had symptoms such as local pain and obvious swelling in the lower extremities, an ultrasound examination was performed immediately to determine whether DVT was formed. When patients had chest pain, dyspnea, decreased oxygen saturation and other PE symptoms, computed tomographic pulmonary angiography (CTPA) should be performed instantly to determine whether PE occurred. Once diagnosed with DVT or PE, the patients rested in bed strictly and received relevant treatment based on the consultation of the thoracic and cardiovascular surgeon.

Statistical analysis
Each patient underwent a routine preoperative examination after admission and the following factors were recorded: gender, age, body mass index (BMI), preoperative platelet and D-dimer level, D-dimer level three days after surgery, anesthetic technique, tourniquet time, whether to use LMWH after surgery, and type of surgical procedures. All patients were categorized into two subgroups according to the occurrence and absence of DVT. SPSS 22.0 (IBM Corp. Released 2013. IBM SPSS Statistics for Windows. Armonk, NY: IBM Corp) software was used for statistical analysis. Using Chi-square test or Student t test for the comparison of data, so as to preliminarily screen out suspected risk factors. Then multiple logistic regression analysis was utilized to further determine the risk factors (P < 0.05 was considered statistically signi cant).

Results
A total of 272 patients underwent knee arthroscopic surgery were enrolled in this study, and postoperative ultrasound examination of lower extremity veins showed that 21 (7.7%) of them had DVT, two of which were identi ed as symptomatic thrombosis. The incidence of DVT in the postoperative anticoagulant group was 7.5% [14/(14 + 163)], which in the non-anticoagulant group was 7.4% [7/(7 + 88)].The locations of the thrombosis is shown in Table 1, DVT mainly occurred in the distal extremity of the lower limbs (90.5%, 19/21), among which the thrombosis in the muscular vein was the most common. No serious complications such as PE occurred, and no patients died due to PE or DVT. The patients were divided in two groups according to whether postoperative DVT occurred. The distribution of DVT occurred in each observation factor is shown in Table 2. There was no statistically signi cant difference between the two groups in age, gender, BMI, preoperative D-dimer and platelet counts, anesthetic technique and whether LMWH was used after surgery (p > 0.05), but was signi cant in the D-dimer level three days after surgery, duration of tourniquet application and surgical procedures, which were considered as potential risk factors (p < 0.05). The results of multivariate regression analysis of DVT group and non-DVT group patients are shown in Table 3. The results indicated that only postoperative D-dimer was an independent risk factor for predicting early DVT formation after knee arthroscopy (OR = 3.773, 95% CI: 1.775-8.023, χ2 = 11.906, P = 0.001), and the operation method and tourniquet time are not related risk factors.

Discussion
This study showed that for knee arthroscopy surgery, the incidence of DVT in patients without anticoagulation was 7.4%, which is very close to the result of Delis et al. [14], although the incidence was not as high as major operations such as arthroplasty [15], but its importance cannot be ignored. In contrast, the incidence of DVT in the anticoagulation patients group was 7.5%, which indicated that the use of LMWH may not reduce the probability of DVT in patients within three days after knee arthroscopic surgery. Kessler [16] noted that it is suitable to use LMWH for ve to seven days after arthroscopic knee surgery. Another randomized controlled trial has revealed that prophylaxis should last seven to ten days [17], as other studies have shown poor results for short-term preventive treatment of only three to six days [18,19]. Although LMWH did not increase the risk of perioperative bleeding, it was not a protective factor to prevent the formation of postoperative DVT in three days. In some previous studies, it was shown that thromboprophylaxis was not recommended after arthroscopic surgery [20][21][22]. A recent systematic review suggested that they against routine use of thromboprophylaxis even after anterior cruciate ligament reconstruction surgery [23]. In arthroplasty operations, the use of LMWH has become an industry guideline [24], however, among patients undergoing arthroscopic surgery, a short-term use of LMWH is not recommended to prevent the formation of DVT in patients without risk factors according to our study.
D-dimer as a brin degradation product, generally assumed has a tendency to decline to normal level within three to ten days after tissue injury [25,26], and has a high sensitivity for predicting the formation of postoperative DVT [27]. Although D-dimer is affected by pregnancy, trauma, tumor and surgery [28,29], this study excluded possible in uencing factors except for surgery, we tried our best to minimize its effects. D-dimer is a sensitive but non-speci c marker of DVT, so the positive result of D-dimer cannot be used for diagnosis, on the contrary, the possibility of thrombosis can be excluded when D-dimer is negative [30,31]. Our results also demonstrated that for every unit increase in D-dimer, the probability of patients suffering from DVT increased by 3.7 times, so anticoagulation is necessary for patients with high D-dimer after knee arthroscopic surgery. Meanwhile, D-dimer provides a characteristic of quick and convenient. It can also be used as a routine examination to screen the formation of DVT in hospitals without ultrasound or venography, and unnecessary examination can be avoided for some low-risk patients.
The incidence of non-symptomatic DVT is very high (19/21, 90.5%), which was similar to those of sun et al. [32], so adequate attention should be paid to the latent DVT, and it is not reliable to diagnose the occurrence of DVT solely by clinical symptoms. At present, there are more and more diagnostic measures for thrombosis. Color doppler ultrasound as the preferred detection method has the advantages of quickness, convenience, non-invasiveness, and radiation-free, and has relatively high sensitivity and accuracy [33][34][35]. In this study, a high incidence of DVT was detected by color doppler ultrasound 3 days after surgery. Therefore, it is suggested that early ultrasound examination is necessary for each patient with increased D-dimer level after knee arthroscopic surgery.

Limitations
Our research still has some limitations. First of all, this study was limited to the early assessment of the incidence of DVT after surgery in patients with knee arthroscopic surgery, and there was no continuous monitoring of the occurrence of subsequent thrombosis in patients. Some patients may develop DVT after discharge, which probably underestimate the incidence of DVT. Secondly, although doppler ultrasound has been used as the main monitoring method for DVT, venography is still the gold standard [30,36], which may also reduce the incidence of DVT in this research. Furthermore, this research was a retrospective study with a limited sample size, which cannot fully incorporate the risk factors that may affect the formation of DVT. Therefore, the conclusions of this study need to be further veri ed by a larger sample size and multi-center randomized controlled study. Finally, although D-dimer was a risk factor for postoperative DVT in patients with knee arthroscopic surgery, this study did not point out that the threshold for D-dimer to predict the occurrence of DVT, which may be the study we need to carry out in the later stage.

Conclusion
To conclude the early incidence of DVT in the group of patients without LMWH was 7.45%. The incidence of DVT in patients with knee arthroscopy could not be reduced by using LMWH within three days postoperatively, and high D-dimer level was a risk factor for DVT after knee arthroscopic surgery. Therefore, attention should be paid to these patients and individualized anticoagulant therapy should be given appropriately.