Coagulation function changes after high-intensity focused ultrasound therapy for uterine fibroids and adenomyosis: a large retrospective cohort study

Objective High-intensity focused ultrasound (HIFU) therapy is increasingly used in the management of various solid tumors. However, limited data are available regarding the association between HIFU treatment and coagulation function.

A total of 1,189 patients diagnosed with uterine fibroids or adenomyosis who underwent HIFU therapy at Shanghai First Maternal and Infant Hospital between August 2015 and November 2020 were included. Paired t-tests were conducted to compare coagulation indicators measured before and after HIFU treatment. Multiple logistic regression models were used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the association between the risk of elevated D-dimer/fibrinogen degradation products (FDP) and HIFU treatment parameters categorized into tertiles.

A total of 1,148 eligible patients were included in the final analysis. After HIFU treatment, 61.8% and 55.7% of patients showed elevated D-dimer and FDP levels, respectively, and 54.6% exhibited simultaneous elevation of both on the first day after treatment. Other post-treatment coagulation indicators also demonstrated a hypercoagulable state, including prolonged prothrombin time and thrombin time, shortened activated partial thromboplastin time, and decreased platelet count. During follow-up, no patients developed thromboembolism. Several HIFU parameters were associated with increased D-dimer and FDP levels. The highest tertile of exposure energy was significantly associated with a greater risk of simultaneous elevation of both D-dimer and FDP (adjusted OR [95% CI]: 4.58 [3.17, 6.66]).

Higher exposure energy during HIFU treatment may induce alterations in coagulation function, resulting in a transient post-treatment hypercoagulable state.

High-intensity focused ultrasound (HIFU) is a minimally invasive therapeutic approach increasingly applied in the management of solid tumors [Citation1–5] including breast adenocarcinoma, benign solid thyroid nodules, prostate cancer, pancreatic cancer and osteoid osteoma, as well as in the treatment of essential tremor, Parkinson’s disease [Citation6] and glaucoma [Citation7]. In gynecology, HIFU has been proposed as a uterine-sparing option for the treatment of uterine fibroids and adenomyosis, with its effectiveness and safety being widely recognized [Citation8,Citation9]. Compared with traditional surgery, HIFU offers advantages such as faster recovery and a lower risk of venous thromboembolism (VTE) [Citation10]. The incidence of VTE after gynecologic surgery for benign indications has been reported to range from 15% to 40% in the absence of thromboprophylaxis [Citation11]. Postoperative VTE is associated with prolonged hospitalization, substantial morbidity, increased mortality, and elevated healthcare costs [Citation12]. Compared with conventional surgery, HIFU has shown comparable effectiveness in improving clinical symptoms such as abnormal uterine bleeding, while thrombotic events have been rarely reported [Citation13,Citation14]. Hou et al. [Citation15] followed 36 patients with uterine fibroids measuring 10 cm or larger who underwent HIFU treatment for seven days, and found no changes in coagulation function indicators, including prothrombin time (PT) and platelet count (PLT). In a retrospective analysis of 27,053 patients with gynecologic and obstetric benign lesions treated with HIFU across 19 centers in China, Liu et al. [Citation10] reported only two VTE cases, corresponding to an incidence of 0.007%. However, the risk factors for these two cases were unclear. Notably, whether the incidence of VTE is directly related to HIFU treatment remains uncertain. Indeed, during HIFU treatment, the ultrasound beams are focused at a specific point where the highest energy intensity is deposited [Citation16]. Through thermal and mechanical effects on the target tissue, this energy deposition leads to microvessel destruction and coagulative necrosis and may result in microthrombus formation [Citation17]. Despite this possibility and the general awareness of thromboprophylaxis in perioperative management, data remain limited regarding the association between HIFU and coagulation function. In this context, using data from a large retrospective cohort, we systematically analyzed changes in the coagulation function following HIFU treatment in patients with uterine fibroids or adenomyosis and explored risk factors associated with these changes, aiming to provide evidence-based insights and practical recommendations for perioperative thromboprophylaxis in HIFU procedures.

Study population This retrospective study was approved by the Scientific and Ethical Committee of the Shanghai First Maternity and Infant Hospital affiliated with Tongji University (protocol code: KS20256), which waived the requirement for informed consent. The study was conducted in accordance with the principles of the Declaration of Helsinki. Patients diagnosed with uterine fibroids or adenomyosis at the Shanghai First Maternal and Infant Hospital who underwent HIFU treatment between August 2015 and November 2020 were included. All clinical data used in this study were de-identified to protect patient privacy, and no identifiable personal information or images were included in the manuscript. This study adhered to the reporting requirements of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement [Citation18]. The inclusion criteria were as follows: (1) diagnosis of uterine fibroids or adenomyosis based on clinical manifestations and imaging examinations; (2) declined expectant management, laparotomy, or laparoscopic surgery; and (3) absence of coagulation disorders. The exclusion criteria were as follows: (1) history of previous thrombosis or coagulation disorders; (2) use of medications affecting the coagulation system, such as heparin, aspirin, rivaroxaban, or bivalirudin, within the past three months; (3) history of surgery within the past six months or a history of radiotherapy; and (4) incomplete surgical records, coagulation indicator results before or after HIFU treatment or missing baseline patient information. Clinical data collection Demographic data, including age, height, weight, body mass index (BMI), complete blood count, and biochemical examination results, were collected from patients upon admission. In our institution, coagulation function tests are routinely performed as part of the standard pre- and postoperative clinical workflow for HIFU treatment. Specifically, coagulation indicators were measured preoperatively to identify preexisting coagulation abnormalities and postoperatively to monitor treatment-related changes in hemostatic function. The coagulation indicators included activated partial thromboplastin time (APTT), PT, thrombin time (TT), fibrinogen, fibrinogen degradation products (FDP), D-dimer, international normalized ratio (INR), and PLT. These parameters were tested using the Cismecan-6000 coagulation factor analyzer. APTT, PT, and TT were assessed using the coagulation method, whereas FDP, fibrinogen, and D-dimer were measured using the immunoturbidimetric method. Elevated plasma D-dimer levels were defined as >1 mg/L and elevated FDP levels as >5 μg/L [Citation19,Citation20]. HIFU ablation was performed using an ultrasound-guided HIFU therapeutic system (JC200, Haifu Medical Technology Co., Chongqing, China). The HIFU procedure was carried out as described previously [Citation21]. HIFU parameters, including sonication time, treatment time, treatment volume, average power, and exposure energy, were recorded during the procedure and collected after treatment. Treatment time was defined as the duration between the first and last sonications. Therapeutic intensity was expressed as the sonication time per hour and calculated using the formula: Therapeutic intensity = sonication time (seconds) × 60 / treatment time (minutes) [Citation22]. Ultrasonography of the lower extremity veins and computed tomography pulmonary angiography (CTPA) were performed for patients whose D-dimer levels were five times higher than the normal value (> 2.75 mg/L) [Citation23,Citation24]. All patients with abnormal coagulation indicators were followed for 14 days until these indicators returned to normal. The frequency of follow-up varied depending on each patient’s clinical condition; however, reassessments were typically conducted on postoperative days 1, 3, 7, and 14 to ensure the stabilization and normalization of coagulation indicators. Written informed consent was waived by the Institutional Review Board after a thorough review and discussion. Strict privacy and confidentiality measures were implemented to protect participants’ identities and personal information. Statistical analysis Baseline clinical characteristics were summarized as counts and percentages for categorical variables and as means ± standard deviations (SDs) for continuous variables. Group comparisons were performed using one-way analysis of variance for continuous variables and the chi-squared test for categorical variables. Paired t-tests were used to compare coagulation indicators measured before and after HIFU treatment. To minimize the risk of type I errors and false-positive findings resulting from multiple comparisons of coagulation parameters, a false discovery rate (FDR) correction was applied. Multiple logistic regression models were constructed to assess the association between each HIFU treatment parameter and the risk of elevated D-dimer or FDP levels after treatment. Covariate selection was guided by a comprehensive approach integrating clinical relevance, evidence from the literature, and univariable screening results. The final models included nine covariates: age, BMI, PLT, hemoglobin, aspartate aminotransferase (AST), albumin, triglycerides, serum creatinine, and pretreatment D-dimer. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were reported. As a sensitivity analysis, HIFU parameters were modeled as continuous variables, rescaled into clinically meaningful units such as per 100 kJ of exposure energy or per 1 min of sonication time. All continuous predictors in the models were evaluated for linearity with the logit of the outcome using the Box–Tidwell test and by inspecting component-plus-residual plots. No violations of the linearity assumption were detected. All statistical analyses were performed using R (version 4.0.3), and statistical significance was defined as p < 0.05 (two-tailed).

Baseline characteristics of patients undergoing HIFU treatment Between August 2015 and November 2020, 1,189 patients (mean age, 39.3 ± 6.0 years) who underwent HIFU treatment at the Shanghai First Maternal and Infant Hospital were included in the study. After rigorous data review, 41 patients were excluded due to incomplete records: missing treatment time, or treatment volume in surgical records (n = 19), missing coagulation indicator results before or after HIFU treatment (n = 17), and incomplete baseline information such as height or weight (n = 5). A total of 1,148 patients were eligible for the final analysis (). Among them, 674 patients were diagnosed with uterine fibroids and 474 with adenomyosis. The mean age was 39.3 ± 6.0 years, and the mean BMI was 22.48 ± 2.96 kg/m2. The mean values for exposure energy, sonication time, treatment volume, treatment time, and average power were 293,444.34 ± 184,106.62 J, 745.94 ± 458.75 s, 3.36 ± 1.82 cm3, 86.26 ± 44.68 min, and 390.86 ± 18.83 W, respectively. The average therapeutic intensity was 523.06 ± 195.65 s/h. Overall, most baseline characteristics were comparable between the two groups. However, the uterine fibroid group was younger and had a lower BMI than the adenomyosis group (38.74 ± 6.44 vs 40.13 ± 5.22 years; 22.19 ± 2.80 vs 22.88 ± 3.14 kg/m2, respectively). No significant differences were observed in HIFU treatment parameters between the two groups (). Assessment of missing data pattern indicated that the occurrence of missing values was not associated with individual baseline characteristics, consistent with a missing-at-random mechanism. Hypercoagulable state after HIFU treatment All patients had coagulation indicators within the normal range before HIFU treatment (), including APTT, PT, TT, fibrinogen, FDP, D-dimer, INR, and PLT. One day after treatment, significant changes were observed in all these indicators. PT and TT were prolonged, APTT was shortened, fibrinogen and PLT levels decreased, and D-dimer and FDP levels increased (p < 0.05; ). Similar patterns were observed when the study population was stratified into uterine fibroid and adenomyosis groups (Figures S1 and S2). Furthermore, an FDR adjustment was applied to account for multiple comparisons, and all previously significant findings remained statistically significant after correction. Following HIFU treatment, the majority of patients maintained PT, TT, and APTT values within the normal range; 61.8% (710 of 1,148) exhibited elevated D-dimer levels (>1 mg/L), and 55.7% (639 of 1,148) showed elevated FDP levels (>5 μg/mL), with mean values of 1.87 ± 1.90 mg/L and 7.03 ± 6.36 μg/mL, respectively. Notably, 54.6% (627 of 1,148) of patients demonstrated simultaneous elevation of both D-dimer and FDP levels. During follow-up, none of the patients with D-dimer levels five times higher than the normal value (>2.75 mg/L) exhibited any signs of thromboembolism based on lower extremity venous ultrasonography and CTPA. Notably, D-dimer and FDP levels peaked on the first day after HIFU treatment, followed by a progressive decline, with most patients achieving normalization of these indicators by postoperative day 7. All remaining patients had returned to baseline levels by day 14 after treatment. Similarly, other key coagulation parameters, including PT, APTT, TT, and PLT, demonstrated consistent recovery trends throughout the 14-day observation period, gradually returning to their pretreatment ranges. HIFU treatment parameters related to the post-HIFU hypercoagulable state To better clarify the relationship between coagulation indicators and HIFU treatment parameters, we examined the association of D-dimer and/or FDP levels with various HIFU parameters. Higher tertiles of exposure energy, sonication time, treatment volume, treatment time, average power, and therapeutic intensity were associated with a greater risk of both simultaneous and separate elevations in D-dimer (>1 mg/L) and FDP (>5 μg/mL) levels (). Exposure energy, which represents the most integrative parameter of HIFU treatment, showed the strongest association. Compared with the lowest tertile, the highest tertile group had a significantly greater risk of simultaneous elevation of both D-dimer and FDP levels (aOR [95% CI]: 4.58 [3.17, 6.66]), after adjustment for age, BMI, PLT, hemoglobin, AST, albumin, triglycerides, serum creatinine, and pretreatment D-dimer. These associations remained consistent in both the uterine fibroid and adenomyosis subgroups (Table S1). For treatment volume, sonication time, treatment time, and average power, compared with the lowest tertile, the highest tertile group was associated with a significantly higher risk of simultaneous elevation of both D-dimer and FDP levels (adjusted OR [95% CI]: 2.95 [2.07, 4.23], 4.29 [2.99, 6.21], 2.32 [1.61, 3.34], and 2.62 [1.77, 3.89], respectively), after adjusting for the same covariates. Additionally, for therapeutic intensity, compared with the lowest tertile, the highest tertile group demonstrated a greater risk of simultaneous elevation of both D-dimer and FDP levels (aOR [95% CI]: 4.30 [2.98, 6.24]; p < 0.05), after adjusting for the same covariates. Consistent with these results, similar associations were observed between the individual elevations of D-dimer or FDP levels and HIFU treatment parameters (). These associations remained stable within both the uterine fibroid and adenomyosis groups (Tables S2 and S3). We also performed logistic regression analyses treating the HIFU parameters as continuous variables. These analyses demonstrated clear dose–response relationships that were fully consistent with the tertile-based findings, confirming that the observed associations were not artifacts of categorization. Although the six HIFU parameters were highly correlated with one another, they were not included in the same logistic regression model. Each model incorporated only one HIFU parameter at a time to avoid potential multicollinearity among these variables. To ensure robustness, variance inflation factors were calculated for all covariates in each model, and no evidence of problematic multicollinearity was detected.

In this large retrospective cohort of patients treated with HIFU, we report for the first time changes in multiple coagulation indicators observed on the first day after treatment. These changes included significant elevations in D-dimer and FDP, accompanied by corresponding alterations in PLT, PT, APTT, and TT. Furthermore, we identified significant associations between these changes and HIFU ablation parameters, particularly higher exposure energy and therapeutic intensity. These findings suggest that increased exposure energy during HIFU may induce alterations in coagulation function, leading to a transient post-treatment hypercoagulable state. As a sensitive marker of thrombotic activity, we observed a simultaneous elevation of D-dimer and FDP in 54.6% of patients. D-dimer is a well-established and widely accepted biomarker for the diagnosis of acute VTE, including deep vein thrombosis and pulmonary embolism [Citation19,Citation24]. Although D-dimer elevation can result from various physiological or pathological processes, it generally serves as a reliable indicator of hypercoagulability and fibrinolysis [Citation23,Citation25]. The concurrent elevation of D-dimer and FDP specifically reflects activation of the coagulation and fibrinolytic systems, indicating a hypercoagulable state [Citation26]. In addition, we observed alterations in other coagulation indicators, including decreased PLT counts, prolonged PT and TT, and shortened APTT on the first postoperative day. Unlike the isolated increase in D-dimer, these combined changes strongly suggest activation of both intrinsic and extrinsic coagulation pathways following HIFU ablation, indicating a transient hypercoagulable state [Citation27]. The systemic impact of HIFU ablation on coagulation function has been scarcely documented, and the mechanisms underlying the transient hypercoagulable state remain incompletely understood. By integrating our clinical findings with the known biological effects of HIFU therapy, we considered that four interrelated pathways may act synergistically to induce the hypercoagulable state observed following HIFU treatment. First, microvascular disruption within the target region is a direct consequence of HIFU’s thermal and mechanical effects [Citation17]. Focused ultrasound energy induces rapid temperature elevation (>60 °C) and acoustic cavitation, resulting in microvessel rupture and loss of vascular integrity [Citation28]. Endothelial injury represents a significant risk factor for thrombosis due to its role in activating the intrinsic coagulation pathway. This dysfunction promotes the upregulation of endothelial adhesion molecules, and structural damage exposes subendothelial collagen, which acts as a binding site for platelet adhesion and thereby contributes to thrombus formation [Citation29]. Second, coagulative necrosis of the target tissue and vascular injury induced by HIFU treatment lead to the exposure of tissue factor (TF) to blood flow. Subsequently, TF acts as a trigger for coagulation, initiating the extrinsic coagulation cascade [Citation30]. Third, HIFU treatment can induce platelet activation, highlighting its potential to promote thrombotic complications [Citation31]. Platelets contribute to thrombus formation by directly activating the coagulation cascade [Citation32]. They are a well-established component of venous thrombi and have been identified as key players in the pathophysiology of deep vein thrombosis [Citation33]. Fourth, during HIFU treatment, patients are placed in a prone position and immobilized, while sedative and analgesic agents are administered to achieve baseline anesthesia. These physiological conditions result in reduced blood flow, leading to endothelial activation and promoting the adhesion of platelets and leukocytes. This cellular adhesion, through TF expression and the formation of neutrophil extracellular traps (NETs), contributes to the activation of coagulation [Citation34]. Unlike chronic hypercoagulable states—typically characterized by sustained elevations in fibrinogen and PLT levels—our findings indicate an acute HIFU-induced hypercoagulable response accompanied by decreased fibrinogen and PLT levels. This pattern reflects an acute consumptive coagulopathy triggered by HIFU. During HIFU ablation, thermal and mechanical energy induce immediate microvascular disruption and coagulative necrosis of the target tissue [Citation17,Citation28], leading to rapid activation of both the intrinsic and extrinsic coagulation pathways. This acute activation results in substantial consumption of fibrinogen and PLT, causing their transient reduction post-treatment. Collectively, these mechanisms contribute to the development of a transient, HIFU-induced hypercoagulable state. Our analysis of the relationship between the post-HIFU hypercoagulable state and ablation parameters revealed significant associations between elevated D-dimer and FDP levels and higher exposure energy, larger treatment volume, greater power output, and longer sonication and treatment times. Among all HIFU parameters, exposure energy serves as an integrative and controllable metric that directly determines the extent of tissue damage [Citation35]. During HIFU treatment, ultrasound beams are precisely focused on a small region within the body, and the ablation effect depends on localized energy deposition [Citation36]. Effective energy concentration and focal precision form the physical basis for the therapeutic use of HIFU as a medical energy source [Citation37]. However, excessive energy deposition results in more extensive vascular endothelial injury, greater tissue necrosis, and stronger stimulation of the coagulation system [Citation28]. In our study, the odds ratio for the highest versus the lowest tertile of exposure energy was 4.58 (95% CI, 3.17–6.66). These associations remained consistent across both the uterine fibroid and adenomyosis subgroups, even after adjustment for potential confounders. Excessive exposure energy may therefore exacerbate tissue injury and increase the risk of thrombosis. Previous studies have reported that intratumoral ethanol injection or the use of oxytocin combined with sulfur hexafluoride microbubbles during HIFU ablation for uterine fibroids or adenomyosis can reduce exposure energy and shorten treatment time compared with conventional HIFU alone [Citation38,Citation39]. Such approaches may be considered to optimize HIFU protocols for uterine fibroids and adenomyosis and to minimize the risk of the thrombotic events. It is well recognized that arbitrary categorization of continuous variables can reduce statistical power and obscure potential dose–response relationships. To address this limitation, we extended our analyses by implementing logistic regression models treating each HIFU parameter as a continuous variable. Notably, these analyses revealed clear dose–response patterns that were fully consistent with the tertile-stratified findings, thereby confirming that the observed associations between HIFU parameters and hypercoagulable outcomes were not artifacts of variable categorization. By providing a more intuitive visualization of risk gradients, the tertile-based models enhance the interpretability of clinical risk and support the practical application of our findings in routine clinical practice. Although significant coagulation activation was observed after HIFU treatment, whether this response is transient or can progress to thrombosis warrants further investigation. In our study, coagulation parameters were routinely monitored on the first day after HIFU treatment, when hypercoagulable changes were most apparent. Follow-up testing was then conducted on postoperative days 3, 7, and 14 to detect any signs of thromboembolic events, particularly in patients who initially exhibited markedly elevated D-dimer and FDP levels. However, no cases of thrombosis were identified during follow-up. In fact, most patients with elevated D-dimer levels returned to normal values by postoperative day 3 and were discharged from further monitoring. A large-scale study conducted by Liu et al. [Citation10] reported two cases of VTE following HIFU treatment; however, the absence of detailed baseline information, especially coagulation-related indicators, precluded determining whether these thrombotic events were directly attributable to HIFU exposure. VTE often presents without specific clinical symptoms, yet it represents a severe and potentially life-threatening postsurgical complication. Delayed diagnosis and inadequate treatment of VTE can lead to debilitating chronic sequelae, including post-thrombotic syndrome, chronic venous insufficiency, and pulmonary hypertension. Therefore, early identification of high-risk individuals, coupled with effective thromboprophylaxis, is essential to reduce the incidence of this common but largely preventable cause of morbidity and mortality [Citation11]. A hypercoagulable state represents the central pathophysiological mechanism underlying VTE. Although transient hypercoagulability following HIFU therapy is primarily a physiological stress response, it may progress to pathological “overactivation” of the coagulation system, thereby posing a significant thrombotic risk—particularly in vulnerable patient populations. Based on our findings, we recommend a comprehensive, individualized clinical management framework for patients undergoing HIFU therapy, integrating pretreatment assessment, intra-procedural optimization, and post-treatment monitoring and intervention, thereby establishing a systematic approach of risk stratification, precise monitoring, and stepwise intervention. Before HIFU therapy, a thorough risk stratification assessment for hypercoagulability should be conducted. In addition to routine coagulation testing, validated thrombotic risk assessment tools—such as the Caprini score—are recommended to evaluate individual risk profiles. For high-risk patients with comorbidities such as obesity, diabetes, or hypertension, or those with a personal or family history of thrombosis, lower extremity venous ultrasonography should be considered to exclude occult thrombosis and mitigate the potential synergistic risk between treatment-induced hypercoagulability and underlying predisposition. During HIFU ablation, exposure energy should be carefully modulated to maintain therapeutic efficacy while preventing excessive energy deposition, thereby achieving precise control of energy delivery. After treatment, dynamic monitoring of coagulation parameters is essential. For patients exhibiting markedly elevated D-dimer levels or identifiable high-risk factors, combined lower extremity venous ultrasonography and CTPA are recommended to exclude deep vein thrombosis and pulmonary embolism. When clinically indicated, prophylactic anticoagulation with low-molecular-weight heparin should be initiated. Early mobilization should also be encouraged to enhance venous return and reduce the risk of thrombus formation. This structured approach enables systematic risk stratification, precise monitoring, and stepwise intervention, ultimately maintaining an optimal and dynamic equilibrium between treatment efficacy and risk mitigation. With the growing adoption of HIFU therapy, careful attention must be paid to its potential risks. Future studies incorporating dynamic monitoring of D-dimer levels after HIFU treatment are warranted to improve understanding of coagulation changes and to facilitate the early identification and management of treatment-related thrombotic complications. This study has two primary limitations. First, although coagulation indicators were routinely assessed on the first postoperative day, predefined standardized follow-up intervals were lacking. Consequently, the exact timing of peak hypercoagulability after HIFU treatment and the period of greatest risk for postoperative thrombotic events could not be determined. Second, despite the large sample size, this was a single-center retrospective study. As with other studies in this field, potential retrospective bias and limited generalizability to external populations remain important considerations.

Using detailed data from a large retrospective cohort, we demonstrated for the first time that HIFU treatment induces multiple alterations in coagulation function, leading to a transient hypercoagulable state on the first postoperative day. Importantly, the development of this hypercoagulable response was significantly associated with several ablation parameters, particularly exposure energy. Given that HIFU therapy is increasingly applied in the management of bone, breast, pancreatic, and hepatocellular carcinomas, as well as benign gynecological disorders, careful control of exposure energy during ablation and individualized assessment and management of thrombotic risk are essential to ensure treatment safety. Supplemental material Supplemental Material Download PDF (578.3 KB)Supplemental MaterialAcknowledgments We thank Yanan Li and Zhengyu Guo for their help with data collecting. Disclosure statement No potential conflict of interest was reported by the authors. Data availability statement The data that support the findings of this study are available from the corresponding author, upon reasonable request. A preprint version of this work has been made available on Authorea [Citation40]. Additional information Funding

- Sanchez M, Barrere V, Treilleux I, et al. Development of a noninvasive HIFU treatment for breast adenocarcinomas using a toroidal transducer based on preliminary attenuation measurements. Ultrasonics. 2021;115:106459. doi: 10.1016/j.ultras.2021.106459. - Benaim EH, Nieri C, Mamidala M, et al. High-intensity focused ultrasound for benign thyroid nodules: systemic review and meta-analysis. Am J Otolaryngol. 2023;44(6):103999. doi: 10.1016/j.amjoto.2023.103999. - Reddy D, Peters M, Shah TT, et al. Cancer control outcomes following focal therapy using high-intensity focused ultrasound in 1379 men with nonmetastatic prostate cancer: a multi-institute 15-year experience. Eur Urol. 2022;81(4):407–413. doi: 10.1016/j.eururo.2022.01.005. - Zhou K, Strunk H, Dimitrov D, et al. US-guided high-intensity focused ultrasound in pancreatic cancer treatment: a consensus initiative between Chinese and European HIFU centers. Int J Hyperthermia. 2024;41(1):2295812. doi: 10.1080/02656736.2023.2295812. - Napoli A, Bazzocchi A, Scipione R, et al. Noninvasive therapy for osteoid osteoma: a prospective developmental study with mr imaging-guided high-intensity focused ultrasound. Radiology. 2017;285(1):186–196. doi: 10.1148/radiol.2017162680. - Martínez-Fernández R, Paschen S, del Álamo M, et al. Focused ultrasound therapy for movement disorders. Lancet Neurol. 2025;24(8):698–712. doi: 10.1016/S1474-4422(25)00210-8. - Chen D, Guo XJ, Luo SK, et al. Efficacy and safety of high-intensity focused ultrasound cyclo-plasty in glaucoma. BMC Ophthalmol. 2022;22(1):401. doi: 10.1186/s12886-022-02622-5. - de Smit NS, de Lange ME, Boomsma MF, et al. Current treatment for symptomatic uterine fibroids: available evidence and therapeutic dilemmas. Lancet. 2025;406(10498):91–102. doi: 10.1016/S0140-6736(25)00728-7. - Bahutair SN, Alhubaishi LY. High-intensity focused ultrasound in adenomyosis treatment: insights on safety, efficacy, and reproductive prospects. Womens Health (Lond). 2024;20:17455057241295593. doi: 10.1177/17455057241295593. - Liu Y, Zhang WW, He M, et al. Adverse effect analysis of high-intensity focused ultrasound in the treatment of benign uterine diseases. Int J Hyperthermia. 2018;35(1):56–61. doi: 10.1080/02656736.2018.1473894. - American College of O. Gynecologists’ Committee on Practice B-G Prevention of venous thromboembolism in gynecologic surgery: ACOG Practice Bulletin, Number 232. Obstet Gynecol. 2021;138(1):e1–e15. - Lewis GK, Spaulding AC, Brennan E, et al. Caprini assessment utilization and impact on patient safety in gynecologic surgery. Arch Gynecol Obstet. 2023;308(3):901–912. doi: 10.1007/s00404-023-07038-0. - Ji Y, Hu K, Zhang Y, et al. High-intensity focused ultrasound (HIFU) treatment for uterine fibroids: a meta-analysis. Arch Gynecol Obstet. 2017;296(6):1181–1188. doi: 10.1007/s00404-017-4548-9. - Li X, Zhu X, He S, et al. High-intensity focused ultrasound in the management of adenomyosis: long-term results from a single center. Int J Hyperthermia. 2021;38(1):241–247. doi: 10.1080/02656736.2021.1886347. - Hou R, Wang L, Li S, et al. Pilot study: safety and effectiveness of simple ultrasound-guided high-intensity focused ultrasound ablating uterine leiomyoma with a diameter greater than 10 cm. Br J Radiol. 2018;91(1082):20160950. doi: 10.1259/bjr.20160950. - Wang Z, Bai J, Li F, et al. Study of a “biological focal region” of high-intensity focused ultrasound. Ultrasound Med Biol. 2003;29(5):749–754. doi: 10.1016/s0301-5629(02)00785-8. - Elhelf IAS, Albahar H, Shah U, et al. High intensity focused ultrasound: the fundamentals, clinical applications and research trends. Diagn Interv Imaging. 2018;99(6):349–359. doi: 10.1016/j.diii.2018.03.001. - von Elm E, Altman DG, Egger M, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: guidelines for reporting observational studies. Int J Surg. 2014;12(12):1495–1499. doi: 10.1016/j.ijsu.2014.07.013. - Kline JA, Hogg MM, Courtney DM, et al. D-dimer threshold increase with pretest probability unlikely for pulmonary embolism to decrease unnecessary computerized tomographic pulmonary angiography. J Thromb Haemost. 2012;10(4):572–581. doi: 10.1111/j.1538-7836.2012.04647.x. - van der Hulle T, Tan M, Den Exter PL, et al. Selective D-dimer testing for the diagnosis of acute deep vein thrombosis: a validation study. J Thromb Haemost. 2013;11(12):2184–2186. doi: 10.1111/jth.12419. - Zhang X, Tian T, Zhu J, et al. High intensity focused ultrasound treatment for diffuse uterine leiomyomatosis: a feasibility study. Int J Hyperthermia. 2020;37(1):1060–1065. doi: 10.1080/02656736.2020.1815871. - Dai H, Chen F, Yan S, et al. In vitro and in vivo investigation of high-intensity focused ultrasound (HIFU) hat-type ablation mode. Med Sci Monit. 2017;23:3373–3382. doi: 10.12659/msm.902528. - Halaby R, Popma CJ, Cohen A, et al. D-Dimer elevation and adverse outcomes. J Thromb Thrombolysis. 2015;39(1):55–59. doi: 10.1007/s11239-014-1101-6. - Singer AJ, Zheng H, Francis S, et al. D-dimer levels in VTE patients with distal and proximal clots. Am J Emerg Med. 2019;37(1):33–37. doi: 10.1016/j.ajem.2018.04.040. - Liu DM, Zhou BB, Li Z, et al. Effectiveness of benzbromarone versus febuxostat in gouty patients: a retrospective study. Clin Rheumatol. 2022;41(7):2121–2128. doi: 10.1007/s10067-022-06110-5. - Moresco RN, Júnior RH, Cláudio Rosa Vargas L, et al. Association between plasma levels of D-dimer and fibrinogen/fibrin degradation products (FDP) for exclusion of thromboembolic disorders. J Thromb Thrombolysis. 2006;21(2):199–202. doi: 10.1007/s11239-006-4837-9. - Winter WE, Flax SD, Harris NS. Coagulation testing in the core laboratory. Lab Med. 2017;48(4):295–313. doi: 10.1093/labmed/lmx050. - van den Bijgaart RJ, Eikelenboom DC, Hoogenboom M, et al. Thermal and mechanical high-intensity focused ultrasound: perspectives on tumor ablation, immune effects and combination strategies. Cancer Immunol Immunother. 2017;66(2):247–258. doi: 10.1007/s00262-016-1891-9. - Poredos P, Jezovnik MK. Endothelial dysfunction and venous thrombosis. Angiology. 2018;69(7):564–567. doi: 10.1177/0003319717732238. - Park S, Park JK. Back to basics: the coagulation pathway. Blood Res. 2024;59(1):35. doi: 10.1007/s44313-024-00040-8. - Brahmandam A, Chan SM, Dardik A, et al. A narrative review on the application of high-intensity focused ultrasound for the treatment of occlusive and thrombotic arterial disease. JVS Vasc Sci. 2022;3:292–305. doi: 10.1016/j.jvssci.2022.08.001. - Müller F, Mutch NJ, Schenk WA, et al. Platelet polyphosphates are proinflammatory and procoagulant mediators in vivo. Cell. 2009;139(6):1143–1156. doi: 10.1016/j.cell.2009.11.001. - von Brühl M-L, Stark K, Steinhart A, et al. Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo. J Exp Med. 2012;209(4):819–835. doi: 10.1084/jem.20112322. - Navarrete S, Solar C, Tapia R, et al. Pathophysiology of deep vein thrombosis. Clin Exp Med. 2023;23(3):645–654. doi: 10.1007/s10238-022-00829-w. - Zhou Y. Generation of uniform lesions in high intensity focused ultrasound ablation. Ultrasonics. 2013;53(2):495–505. doi: 10.1016/j.ultras.2012.09.001. - Fry F. Intense focused ultrasound in medicine - some practical guiding physical principles from sound source to focal site in tissue. Eur Urol. 1993;23(1):2–7. doi: 10.1159/000474671. - Ter Haar G. HIFU tissue ablation: concept and devices. Adv Exp Med Biol. 2016;880:3–20. doi: 10.1007/978-3-319-22536-4_1. - Yang Z, Zhang Y, Zhang R, et al. A case-control study of high-intensity focused ultrasound combined with sonographically guided intratumoral ethanol injection in the treatment of uterine fibroids. J Ultrasound Med. 2014;33(4):657–665. doi: 10.7863/ultra.33.4.657. - Yao R, Zhao W, Gao B, et al. Microbubble contrast agent SonoVue combined with oxytocin improves the efficiency of high-intensity focused ultrasound ablation for adenomyosis. Int J Hyperthermia. 2021;38(1):1601–1608. doi: 10.1080/02656736.2021.1993357. - Zhang X, Ni J, Xu W, et al. Coagulation function changes after High-intensity focused ultrasound treatment for uterine fibroids and adenomyosis: a large retrospective cohort study. New York (NY): Authorea Inc.; 2024. doi: 10.22541/au.172596255.53967203/v1.