Local thrombotic complications of endovenous ablation: ablation-related thrombus extension

Introduction

The introduction of modern treatment methods for superficial vein insufficiency, particularly minimally invasive techniques, has significantly reduced the incidence of numerous complications associated with traditional surgical treatment, including the risks of hemorrhagic and infectious complications. However, in place of these complications, new types of adverse effects have emerged, typically associated with specific treatment modalities.
In the literature on endovenous thermal ablation, the term endovenous heat-induced thrombosis (EHIT) has been introduced to describe thrombotic changes occurring at the saphenofemoral or saphenopopliteal junctions, induced by thermal energy sources such as radiofrequency ablation (RFA) and endovenous laser ablation (EVLA). Studies focusing on the morphological and histopathological assessment of EHIT-related changes have documented characteristics that differ somewhat from purely thrombotic lesions. A notable feature of EHIT-related changes is their stronger adhesion to the vessel wall and their tendency for spontaneous regression. The etiology of these changes differs from that of a “stan­dard” thrombus. In classical thrombosis, the endothelium exerts an anticoagulant effect, and thrombus formation at sites of excessive blood stasis consists mainly of red blood cells trapped within a forming fibrin network. In the case of EHIT, the high temperature during the procedure damages the vascular endothelium. Blood cells infiltrate the vessel wall and the remaining endothelium. This leads to the formation of a structure resembling scar tissue [1]. Recent research on the efficacy and, more importantly, the safety of endovenous treatment has introduced a new term to describe local complications in the treated area. This broader term, ablation-related thrombus extension (ARTE), is now used instead of EHIT and encompasses cases related not only to thermal techniques (TT) but also non-thermal techniques (NTNT), such as cyanoacrylate glue, mechanochemical ablation (MOCA), and ultrasound-guided sclerotherapy.
When discussing EHIT-related complications, it is essential to first address the classification system for these complications. This is not only diagnostically relevant but also influences the selection of the optimal management strategy, including determining whether anticoagulation treatment is necessary. Currently, several classification systems for EHIT are in use. The first available classification of EHIT-related changes was the Kabnick classification, introduced by L. Kabnick in 2006 (Table 1) [2].
As an alternative classification system, Lawrence’s classification has been proposed, as illustrated in Table 2 [3].
An updated classification proposal for EHIT-related changes can be found in the American Venous Forum (AVF) guidelines, published in 2021 (Table 3) [4].
When analyzing the issue of EHIT, a key question arises: Is this complication frequent and severe enough to pose a threat to patients’ health and lives? It is generally accepted that the overall incidence of thrombotic complications, including EHIT, deep vein thrombosis (DVT), and/or pulmonary embolism (PE) following thermal ablation, ranges from 1.5% to 1.7% [5]. Studies that have identified EHIT as a distinct thrombotic complication estimate its incidence between 1% and 7%. When interpreting these results, it is crucial to consider the different EHIT classes and the varying levels of risk associated with each classification (Table 4).

Risc factors

Given the variation in EHIT incidence across different studies and scientific publications, it is important to analyze the potential factors influencing the higher occurrence of this complication. According to the literature, risk factors associated with EHIT include: male gender, large diameter of the treated vein at the junction, proximity of the catheter tip to the junction, history of previous thrombotic episodes, confirmed thrombophilia, high Caprini score, and simultaneous additional phlebological procedures (e.g., miniphlebectomy). Although varicose veins and chronic venous disease are more prevalent in women, the risk of EHIT is higher in men. According to Rhee et al., the odds ratio (OR) for EHIT occurrence in men compared to women is 5.98. This observation has also been confirmed by Chi et al., who reported an OR of 2.6 [6].
A history of venous thromboembolism (VTE) does not necessarily indicate a high risk of EHIT [7]. However, some researchers suggest it may increase the likelihood of developing EHIT. For example, Chi et al. reported that patients with a previous thrombotic episode had an OR of 3.6 for EHIT [8]. Additionally, some clinical observations suggest that a prior episode of EHIT may be associated with a higher recurrence rate in future procedures [9]. An elevated risk of VTE, as assessed using the widely used Caprini Score, may also contribute to the development of EHIT. According to Rhee et al., a high Caprini Score significantly increases the likelihood of EHIT occurrence [6]. It is well known that the larger the diameter of the treated vessel is, the lower is the efficacy of thermal ablation. Effective use of tumescent anesthesia can help contract the vessel walls around the working fiber, allowing for a significant reduction in diameter, even in very large veins. Similarly, in the case of wide proximal segments of the great or small saphenous vein (GSV/SSV) near their junctions, an increase in vessel diameter may also correlate with a higher risk of EHIT [10, 11]. It is important to note that EHIT can also occur in veins with a small diameter. In such cases, its development may be linked to other risk factors, including those directly related to the procedure itself. Although studies have documented the efficacy of thermal ablation even in cases of very large saphenous vein junctions, in clinical practice, it is crucial to consider alternative treatment options for such cases. Surgical interventions, such as ligation of the saphenous-femoral junction, remain a valuable option for patients with excessively wide junctions. This approach not only ensures permanent vessel closure through surgical ligation but may also reduce the risk of EHIT development.
Factors related to both the type of procedure and its execution play a key role in EHIT prevention. One critical factor is the positioning of the working fiber tip at the start of thermal ablation. If the ablation begins too proximally, with the fiber tip extending into the deep venous system (e.g., femoral or popliteal vein), it may lead to thermal damage of the deep vein wall, resulting in thrombosis or EHIT. To minimize this risk, it is recommended to perform ultrasound monitoring at key moments during the procedure, including: fiber or patient position changes and after tumescent anesthesia administration [12]. Leaving a patent tributary near the junction of the great saphenous vein (GSV) and the femoral vein (e.g., the epigastric vein) is one of the mechanisms that prevent thrombotic complications at the junction through the washout effect. However, if incompetent tributaries are left untreated at the GSV junction, they may lead to varicose vein recurrence in the groin area, ultimately compromising the procedure’s efficacy. For this reason, some practitioners aim to perform laser crossectomy, meaning complete closure of the treated vein up to the femoral vein wall. Although multiple studies have demonstrated the safety of this approach, it has not yet become a standard practice. Research is ongoing to determine whether this technique reduces the risk of reflux recurrence at the junction. In 2022, a study compared two approaches to closing the junction between the treated vein and the deep venous system: Group 1 (EVLAf) – laser crossectomy; Group 2 (EVLAs) – classical endovenous laser ablation. The study did not report major complications such as venous thrombosis, pulmonary embolism, skin or nerve damage, or hematomas. However, one case of EHIT type 2 was detected in Group 1. At the end of the 900-day follow-up period, the reflux rate in the GSV stump was: 3.56% in EVLAf (Group 1), and 22.22% in EVLAs (Group 2). For the accessory great saphenous vein, reflux occurred in: 7.14% of patients in EVLAf (Group 1), and 17.46% of patients in EVLAs (Group 2) [13].
Manufacturer recommendations for fiber positioning during thermal ablation should also be considered. There is a clear relationship between the distance of the fiber tip from the junction and the risk of EHIT – the greater the distance, the lower the risk. Studies have proposed various optimal fiber distances from the saphenous-femoral junction, typically ranging between 1 cm and 3 cm, as summarized in Table 5.
One of the factors that increase the risk of thrombotic complications in ablation procedures is the addition of adjunctive treatments. Performing simultaneous complementary procedures, particularly extensive miniphlebectomy, bilateral interventions, or procedures involving multiple veins – which typically require longer procedure times and prolonged intraoperative immobilization – may lead to an increased risk of thrombosis associated with the treatment [7].
Currently, there are no definitive pharmacological guidelines for EHIT prophylaxis. Existing recommendations emphasize the individual assessment of thromboembolic risk and the use of anticoagulant prophylaxis in justified cases [5]. Preventing EHIT, a localized thrombotic complication induced by thermal energy, should involve: assessing the EHIT risk based on local anatomical factors (e.g., the diameter of the treated vein), considering procedural factors, such as the positioning of the fiber tip, and evaluating the patient’s overall risk for VTE. There is still a lack of well-designed and adequately conducted studies confirming the effectiveness of pharmacological prophylaxis in EHIT prevention. An increased risk of EHIT may necessitate consideration of pharmacological prophylaxis, particularly in patients undergoing thermal ablation who have an elevated risk of VTE. In most cases, EHIT is completely asymptomatic. Therefore, a follow-up venous ultrasound, commonly used as a standard post-procedure evaluation in many centers following thermal ablation, remains the primary diagnostic method. The 2021 AVF guidelines suggest that thrombus formation at the junction typically occurs between the first and third day, up to about seven days after the procedure. This influences the timing of Doppler ultrasound examinations. However, it is important to note that EHIT-related complications can also develop beyond seven days after the procedure. In 2016, Ryer EJ conducted a study involving 842 patients, confirming 43 cases (5.1%) of saphenous vein junction thrombosis induced by high temperatures. Notably, in this study, Doppler ultrasound performed within the first 24 hours after the procedure detected EHIT in 47% of cases, and an additional 44% of cases were identified on the seventh day [10]. A literature review revealed that most studies assessing EHIT focus on the early post-procedure period. However, the time frame for follow-up ultrasound varies significantly among different studies (Table 6).
Thus, the decision remains regarding the appropriate strategy and timing for post-procedural evaluation. The 2021 AVF guidelines suggest performing the ultrasound within seven days after the procedure but do not specify the optimal post-procedure day for assessment [4].
Earlier guidelines from the First International Consensus Conference on Endovenous Thermal Ablation for Varicose Vein Disease (2012) – published in 2015 in “Phlebology” – recommended a more cautious approach to EHIT detection. The authors advised conducting at least two follow-up ultrasounds within 10 days after the procedure. Additionally, a long-term follow-up Doppler ultrasound at 3-6 months was suggested – not only for EHIT detection but also for comprehensive post-procedure evaluation and treatment efficacy assessment [14].
Due to the relatively low incidence of EHIT and its limited clinical significance (as it is often asymptomatic), many researchers question the necessity of routine duplex Doppler ultrasound in the post-procedural period. The most extreme stance on routine Doppler surveillance is presented in the 2020 guidelines by Bozkurt et al., which suggest that routine ultrasound after thermal ablation is not recommended (recommendation level 2b, evidence level C). However, this recommendation is based on weak evidence. The justification for this approach includes the low incidence of EHIT, which rarely leads to symptomatic VTE, and the high cost of routine follow-up ultrasound [15]. The cost of routine duplex Doppler ultrasound for venous assessment can vary significantly between countries and healthcare systems, further influencing the decision on post-procedural imaging protocols.
The current 2023 guidelines from the Society for Vascular Surgery (SVS), AVF, and American Vein and Lymphatic Society (AVLS) align with the previously mentioned guidelines by Bozkurt et al. However, they point out the varying risk of thrombotic complications, including ARTE, in patients undergoing venous ablation. Early Doppler ultrasound screening is not recommended for asymptomatic, moderate-risk patients following thermal ablation (guideline 11.1.1), in contrast to high-risk patients (guideline 11.1.3) and symptomatic patients (guideline 11.1.4), regardless of the ablation method. For asymptomatic, moderate-risk patients who have undergone non-thermal vein ablation, routine Doppler ultrasound may be performed (guideline 11.1.2) [5].
When performing follow-up examinations after thermal ablation, it is also important to assess the proper closure of the treated vein and the presence of post-procedural thrombus near the junction. The occurrence of classic thrombosis in another location (e.g., in the calf muscles), although rare (< 1%), is also possible.

Treatment

The management of EHIT has been thoroughly described in the 2021 published guidelines [4]. The therapeutic guidelines are based on a relatively low level of recommendations, mostly derived from clinical practice. The treatment approach is correlated with specific EHIT classes and the severity of the thrombotic process at the saphenous vein junction. A major issue in EHIT treatment is the lack of sufficient evidence to support strong recommendations. Treatment guidelines for EHIT classes 1 and 2 are of low quality (2C), while strong recommendations are available only for EHIT class 4 (1A).
For EHIT class 1, where the thrombus does not extend beyond the junction, pharmacological treatment is not required (SVS and AVP 2021, guideline 3.2). In class 2, the authors propose two different approaches, both of which emphasize strict Doppler ultrasound monitoring every seven days until treatment completion. For low-risk patients, risk assessment (e.g., using the Caprini scale) is recommended, along with a watchful waiting approach and ultrasound surveillance until the thrombus resolves within the deep venous system. High-risk patients are advised to undergo pharmacological treatment. However, there is no consensus on the intensity of treatment.
A wide range of treatment options is suggested, ranging from anticoagulant medications to prophylactic doses of low-molecular-weight heparin (LMWH) and standard anticoagulation therapy. Treatment is continued until the thrombus retracts to the junction of the treated vein with the deep venous system (AVF 2021, guideline 3.3) [4,5].
In EHIT class 3, the thrombus extends into the deep venous system, occupying approximately 50% of its diameter. This is a potentially dangerous situation, as despite the different morphology of the thrombus in EHIT, there is a risk of embolization and complications, including pulmonary embolism. In this case, full anticoagulation therapy is suggested, such as a therapeutic dose of LMWH. As in class 2, weekly clinical monitoring and Doppler ultrasound follow-ups are required. Treatment continues until the thrombus retracts to the saphenofemoral (GSV) or saphenopopliteal (SSV) junction (SVS and AVF 2021, guideline 3.4) [4].
For class 4, the 2021 SVS and AVF guidelines recommend an individualized treatment approach for each patient while also implementing management similar to that of classic deep vein thrombosis. In this case, treatment does not end once the thrombus retracts to the junction but follows the standard approach for provoked thrombosis, lasting at least three months (4,16). L.S. Kabnick and the AVF 2021 guideline authors suggest the same therapeutic approach for EHIT involving both the saphenofemoral and saphenopopliteal junctions (AVF 2021, guideline 4.1) [4]. The 2023 SVS, AVF, and AVLS guidelines present a slightly different approach to this issue, partly due to the recommended limitation of routine post-procedural Doppler ultrasound examinations. In symptomatic ARTE patients, anticoagulant therapy is advised, with a preference for direct oral anticoagulants (DOACs) over vitamin K antagonists (VKAs) (guideline 11.3.4). Similarly, in asymptomatic patients with ARTE type III and IV after endovenous ablation, DOACs should be used as first-line treatment instead of VKAs. The treatment should continue until the thrombus retracts beyond the deep venous system into the lumen of the treated vessel (guidelines 11.4.1 and 11.4.2) [5].
Not only thermal methods of endovascular ablation for incompetent lower limb veins can lead to thrombotic complications, such as thrombus extension into the deep venous system at the junction of the treated vessel. The use of endovenous glue for ablation can also be associated with the presence of thrombus at the vein junction, and in some cases, with migration of the glue to the vein junction and further proximally into the deep venous system [17].
A potential cause of this issue is considered to be an insufficient distance between the tip of the adhesive delivery catheter and the saphenofemoral junction at the initial stage of adhesive application. Studies have shown the presence of thrombus in this location in 21% of patients when the catheter tip was placed 2 cm from the junction. However, available research does not provide a definitive answer on whether the amount of used glue plays a significant role [18]. Procedures in which the catheter tip was placed at a distance of 5 cm from the junction, as reported in publications by Proebstle, did not show thrombus formation or its progression into the deep venous system [19].
Regarding pharmacomechanical methods, the literature indicates a potentially higher risk of thrombosis at the saphenofemoral junction compared to thermal methods, ranging from 0.2% to 1.8%. Therefore, methods using cyanoacrylate glue or mechanochemical ablation catheters should not be planned for procedures aimed at performing endovenous crossectomy of the saphenofemoral or saphenopopliteal junction [20,21]. Studies have also reported a significantly higher risk of thrombotic changes at the junction of the treated vein when using mechanochemical ablation methods. In a study by Rebuffatti in 2021, ARTE was found in 14% of 73 patients treated with the Clarivein/MOCA method, including one case corresponding to EHIT type 4 according to the Kabnick classification [22]. Similarly, in a 2018 study by Chan, ARTE was diagnosed in 19% of patients treated with the MOCA method [23]. Rebuffatti points out differences in perioperative management protocols that may contribute to such discrepancies in study results. Strict early follow-up ultrasound examinations performed within 2-3 days after the procedure may bring different Doppler ultrasound findings compared to examinations conducted immediately post-procedure or on day 30 when most thrombi have regressed. Additionally, Rebuffatti’s study protocol did not include pharmacological prophylaxis. Chan suggests considering techniques to reduce the risk of thrombus propagation to the junction, such as increasing the distance from the saphenofemoral junction and reducing the initial amount of sclerosant used.
Until now, there have been no definitive guidelines for managing ARTE (thrombosis near the saphenofemoral junction) caused by adhesive-based treatments or pharmacomechanical methods. The approach has been similar to that used for classic EHIT (endovenous heat-induced thrombosis) caused by high temperatures. However, the 2023 SVS, AVF, and AVLS guidelines have specifically addressed this issue, as discussed earlier in this article. Despite this, authors of studies evaluating cases of junctional thrombosis following pharmacomechanical methods argue that early Doppler ultrasound follow-ups should not be abandoned or limited solely to symptomatic patients [24].

Conclusions

The previously used concept of EHIT, which refers to thrombosis at the junction of the treated vein following thermal methods, is now being replaced by the broader term ARTE, encompassing both thermal and non-thermal techniques. The course of this condition is generally milder than typical deep vein thrombosis, and treatment duration usually does not exceed 2-4 weeks. Ultrasound-confirmed regression of the thrombus into the superficial venous system, except in EHIT class 4 cases, allows for treatment discontinuation. However, it is important to acknowledge that despite the low tendency for thrombus progression, ARTE remains a potentially serious complication. If not properly diagnosed and managed, it can lead to deep vein thrombosis and, under certain conditions, even pulmonary embolism.

Disclosures

1. Institutional review board statement: Not applicable.
2. Financial support and sponsorship: None.
3. Conflicts of interest: None.

References