Predictive Factors for Post-Thrombotic Syndrome in Patients with Deep Vein Thrombosis Treated with AngioJet Pharmacomechanical Thrombectomy: A Retrospective Single-Center Study

Introduction

Deep venous thrombosis (DVT) remains a major public health concern, with an estimated annual incidence of 1 to 2 cases per 1000 population [1,2]. Anticoagulation remains the first-line treatment strategy for DVT, and new oral anticoagulant agents have proven to be safe and beneficial [3,4]. However, anticoagulant drugs have little effect on the prevention and treatment of post-thrombotic syndrome (PTS) [5]. PTS is a long-term complication of DVT that can cause pain, swelling, heaviness, and cramping in the legs. It is reported that 20% to 50% patients with DVT would develop PTS despite adequate anticoagulation [6–8]. Previous studies have confirmed the negative effect of PTS on patient quality of life, as well as the economic burden [9,10]. Current therapeutic options for PTS are limited, highlighting a critical need for treatment modalities that more effectively manage thrombus resolution to prevent PTS.

AngioJet pharmacomechanical thrombectomy offers a promising solution by using a suction catheter combined with a power-pulsed spray technique to mechanically disrupt and remove thrombi. This approach is advantageous, as it facilitates rapid thrombus removal, which is crucial for preserving venous valve function and preventing the long-term complications associated with PTS. Several studies have showed that AngioJet thrombectomy has strong clearance ability for acute and subacute lower extremity DVT, with a lower dosage of thrombolytic agents and infusion time [11,12]. Since it is suggested that the quick removal of a thrombus contributes to the preservation of venous valve and vein function [13], AngioJet pharmacomechanical thrombectomy would benefit DVT patients in terms of prevention of PTS. However, only a few studies have focused on the role of Angiojet thrombectomy in reducing the incidence of PTS. In addition, with the wide application of pharmacomechanical thrombectomy, it is important to define risk factors for PTS after its use. Therefore, we did a retrospective study to establish risk factors determining prognosis of patients with DVT after AngioJet pharmacomechanical thrombectomy.

Material and Methods

STUDY PARTICIPANTS:

The study adhered to the tenets of the Declaration of Helsinki and was approved by the Ethics Committee of the Second Affiliated Hospital of Nantong University and the Second Affiliated Hospital of Soochow University. Written informed consent was obtained from each patient enrolled in this study. Patients with a diagnosis of DVT in each department were reviewed from July 2018 to May 2020. Inclusion criteria were as follows: confirmed lower extremity DVT, received AngioJet pharmacomechanical thrombectomy, and had complete clinical and follow-up data. Exclusion criteria were recurrent DVT, presence of PTS before initial treatment, and patients undergoing catheter-directed thrombolysis or anticoagulation alone. Medical records were retrospectively collected and analyzed for demographic information, duration and severity of symptoms, dosage of thrombolytic agents, length of hospital stay, adverse events, postinterventional imaging, vessel patency, incidence of PTS, and postoperative Villalta score (Supplementary Table 1).

ENDOVASCULAR TREATMENT:

DVT diagnosis was verified by routine ultrasound or venography. Initial anticoagulation was applied to all patients with subcutaneous low-molecular-weight heparin before thrombectomy. A retrievable inferior vena cava filter was implanted to prevent pulmonary embolism prior to Angiojet thrombectomy. Endovascular interventions were performed in a hybrid operating room, using the AngioJet thrombectomy system (Boston Scientific, Natick, MA, USA), which uses multiple high-pressure saline jets that cause fragmentation of targeted clots, while simultaneously delivering thrombolytic agent into the clot. Briefly, the tip of the Angiojet catheter was placed at one end of the thrombus section and then withdrawn at a speed of 1 mm/s, while urokinase (Livzon Pharmaceutical Group. GuangZhou, China) was delivered throughout the thrombus segment. After a thrombolytic duration of 10 to 15 min, a mechanical rheolytic thrombectomy was performed to remove the thrombus as much as possible. The thrombectomy was repeated until most of the thrombus was cleared (residual thrombus <20%). After endovascular intervention, standard anticoagulation was started with subcutaneous low-molecular-weight heparin in the hospital, and oral anticoagulant rivaroxaban after discharge for at least 3 months. All the patients were recommended to wear compression stockings (class II 30–40 mmHg) as standard adjunctive treatment.

CLINICAL OUTCOMES ASSESSMENT:

Technical success was defined as the successful completion of the AngioJet pharmacomechanical thrombectomy procedure, without immediate procedural complications and with confirmation of significant clot removal, as evidenced by post-procedure imaging. The primary efficacy outcome was the development of PTS, which was evaluated by the Villalta score. The Villalta score evaluates the signs and symptoms of PTS. It includes a set of criteria that rates the severity of 5 symptoms (pain, cramps, heaviness, pruritus, and paresthesia) and 6 signs (edema, skin induration, hyperpigmentation, redness, venous ectasia, and pain during calf compression) in the affected limb. Each item is scored from 0 to 3, where 0 represents absence and 3 represents severe presence. The total score can range from 0 to 33, with higher scores indicating more severe PTS. A score of 5 or more is typically used to diagnose PTS, and scores can also be categorized into mild, moderate, or severe levels, to assist in clinical assessments and guide treatment decisions. The Villalta score is widely used in clinical trials and practice, owing to its simplicity, reproducibility, and validated effectiveness in measuring the severity and impact of PTS [14,15]. The second outcome variable was vessel patency, which was evaluated according to the Society of Interventional Radiology grading system following thrombolysis: grade I indicated <50% lysis; grade II indicated 50% to 90% lysis; and grade III indicated 100% lysis, without residual thrombus [16]. Adverse events were recorded during the hospital stay and after discharge. A major bleeding event was defined as intracranial bleeding or bleeding severe enough to result in death, surgery, cessation of therapy, or blood transfusion. Other bleeding events were regarded as minor bleeding. Local ecchymoma and ecchymosis on the skin around the puncture site were defined as puncture site bleeding. Other endovascular treatment-related complications included acute kidney injury, allergic reaction, cardiac event, and bacteremia, among others.

Follow-up duplex ultrasonography was performed at 1 month, 3 months, and 6 months, and then every half a year. Re-interventions were performed when there was a reduction in vessel diameter of >50% or occlusion along with recurrence of symptoms.

STATISTICAL ANALYSIS:

The data were analyzed by SPSS version 29.0 for Mac (IBM Corp, Armonk, NY, USA). The frequencies of categorical variables were compared using Pearson χ² or Fisher’s exact test, when appropriate. Non-normally distributed variables were reported as median (interquartile range [IQR]), and the Mann-Whitney U test and Kruskal-Wallis test were used. A P value of less than 0.05 was deemed statistically significant. Survival analysis of vessel patency and incidence of PTS were performed using the Kaplan-Meier test. To explore the association between potential risk factors and the development of PTS, logistic regression analysis was used. Potential risk factors were selected based on previous literature and our clinical experiences. The logistic regression modeling began with a univariate analysis to identify factors with statistically significant differences. Variables that demonstrated significance at a P value less than 0.05 were considered for further analysis. Subsequently, significant factors from the univariate analysis were included in a multivariate logistic regression model to adjust for potential confounders and identify the independent predictors of the outcome. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated to assess the strength and direction of associations.

Results

PATIENT CHARACTERISTICS:

We screened 767 potentially eligible patients from July 2018 to May 2020, and 89 patients with DVT were finally enrolled in the study. A flow chart detailing the selection of study participants is shown in Figure 1. Table 1 shows the baseline characteristics of patients. Of these patients, 40 were men, and 49 were women, with a median age of 59 years (range, 22–77 years). Prevalent comorbidities were hypertension in 24 patients (26.96%), coronary heart disease in 11 patients (12.36%), and diabetes in 9 patients (10.11%). Median time from onset of DVT to treatment was 6 days. Most affected limbs were on the left side (59 patients). The patients were divided into 2 groups according to the presence of PTS: 22 patients who developed PTS were categorized into group A (poor prognosis) and the remaining 67 patients were classified as group B (good prognosis).

CLINICAL OUTCOMES:

Technical success was achieved in all patients. Pre- and postoperative images were acquired to assess the efficacy of AngioJet pharmacomechanical thrombectomy (Figure 2). No immediately procedure-related complications were observed. The median dosage of thrombolytic agents per patient was 260 million units (range, 160–440 million units). Median duration of hospital stay was 5 days (range, 2–15 days). No major bleeding or serious adverse events happened, while 6 minor bleeding were recorded. Table 2 presents the clinical outcomes for each group during the hospital stay. The median dosage of thrombolytic agents was 260 million units (IQR=80) for group A and 300 million units (IQR=80) for group B, with no statistically significant difference (P=0.210). The duration of hospital stay was also similar between groups, with a median of 6 days (IQR 5.5) for group A and 5 days (IQR 4) for group B (P=0.542). There was no significant difference of adverse events between the groups. After discharge, the incidence of PTS and the Villalta scores were measured. A notable difference was observed in the Villalta scores, with group A recording a median score of 7 (IQR 3), significantly higher than group B’s median of 2 (IQR 2) (P<0.001). At the end of follow-up, 18 patients had mild PTS, 3 had moderate PTS, and 1 had severe PTS (Figure 2). The overall freedom from PTS is shown in Figure 3. Also, vessel patency was evaluated at each visit during follow-up. Grade III, grade II, and grade I lysis was achieved in 30, 41, and 18 patients, respectively (Figure 3). In comparison with group A, the vessel patency was significantly higher in group B (P=0.016).

PREDICTIVE FACTORS FOR PTS AFTER ANGIOJET TREATMENT:

To identify predictive factors for PTS after AngioJet pharmacomechanical thrombectomy, we chose 6 potential factors based on previous retrospective studies and our experience: age, sex, DVT location, affected limb, time from onset to treatment, and leg varicosities at baseline. Univariate analysis showed statistical significance between the 2 patient groups in the laterality of the affected limb, with 86.36% (n=19) of patients in group A and 62.68% (n=42) of patients in group B affected on the left side (P=0.038). Additionally, the time from onset to treatment showed a notable variance, with group A reporting a median of 8 days (IQR 5.25), compared with 5 days (IQR 4) for group B (P<0.001). Differences in DVT location were also significant. Iliofemoral and popliteal DVTs were more prevalent in group A (19 iliofemoral, 1 popliteal) than in group B (46 iliofemoral, 18 popliteal), P=0.040 (Table 3). The logistic regression model consisted of DVT location, affected limb, and time from onset to treatment. The further analyses revealed only 1 independent significant prognostic factor for PTS: time from onset to treatment (OR=1.745; 95% CI=1.316–2.315).

Discussion

LIMITATIONS:

The limitations of the present study include its small sample size and retrospective design, which can affect the generalizability and statistical power of the findings. The potential for selection bias and information bias due to reliance on retrospective data also exists. Additionally, the relatively short follow-up period may not adequately capture long-term outcomes, such as late recurrence of DVT or chronic PTS. Operator variability in performing the AngioJet pharmacomechanical thrombectomy could also influence the results. Prospective, multicenter studies with larger cohorts and longer follow-up are recommended to validate these findings in the future.

Conclusions

AngioJet pharmacomechanical thrombectomy is an effective therapeutic approach for DVT. Time from onset to treatment was an independent factor in predicting the development of PTS. Thus, adequate anticoagulation treatment should be considered in patients undergoing AngioJet pharmacomechanical thrombectomy.