A systematic review and meta-analysis for the association between duration of anticoagulation therapy and the risk of venous thromboembolism in patients with lower limb superficial venous thrombosis.

OBJECTIVE: The aim of this study was to determine the association between the duration of systemic anticoagulation therapy (ACT) and the risk of further venous thromboembolism (VTE) in patients with superficial venous thrombosis (SVT). METHODS: A systematic review and meta-analysis were performed using searches of Medline and Cochrane Library databases in September 2023. Papers that provided VTE incidence within mid-term follow-up of ≥45 days in patients who received any ACT were included. Patients were categorized into subgroups according to the course of treatment: (1) no ACT (0 days); (2) ACT of ≤14 days; (3) ACT of 15 to 30 days; (4) ACT of 31 to 45 days; and (5) ACT of >45 days. Reported events were transformed to events per 100 patient-years, and a random-effects model was used to calculate pooled rates for proportions. The primary outcome (VTE) was a combination of SVT progression or recurrence with the occurrence of deep vein thrombosis (DVT) and pulmonary embolism (PE). Secondary outcomes included major and clinically relevant non-major or minor bleeding. RESULTS: Twenty-four studies (10 randomized controlled trials and 14 cohort studies) combining outcomes in 12,341 patients were included in the quantitative synthesis. Minimum VTE and SVT recurrence or progression rates were observed with the ACT duration of 31 to 45 days of 16.2 (95% confidence interval [CI], 10.4-23.3) and 8.2 (95% CI, 3.1-15.8) events per 100 patient-years, respectively. Minimum DVT and PE rates observed with the treatment duration of 15 to 30 days were 5.5 (95% CI, 2.8-9.1) and 0.9 (95% CI, 0.5-1.3) events per 100 patient-years, respectively. Short-term treatment of ≤14 days was associated with the highest rates of VTE of 59.7 (95% CI, 37.7-86.4), DVT of 13.7 (95% CI, 9.6-18.4), and PE of 3.1 (95% CI, 1.4-5.6) events per 100 patient-years. Major bleeding rates were unrelated to the duration of ACT and did not exceed 0.5 events per 100 patient-years. The highest rate of clinically relevant non-major or minor bleeding was observed with ACT duration of 31 to 45 days of 14.2 (95% CI, 5.5-26.8) events per 100 patient-years. The most common risk factors for VTE included male sex, cancer, personal history of DVT, PE, or SVT, and thrombosis of non-varicose veins. CONCLUSIONS: Prolonged systemic anticoagulation is associated with the tendency to decrease VTE rates in patients with lower limb SVT.

The trends in venous thromboembolism occurrence and prevention after minimally invasive varicose vein surgery.

OBJECTIVES: To assess the trends of VTE occurrence and prevention in varicose vein surgery. METHOD: The registry-based CAPSIVS trial (NCT03041805) analysis includes results in 1878 lower limbs. The primary outcome is a 28-day symptomatic or asymptomatic DVT revealed with duplex ultrasound. RESULTS: Any DVT, including EHIT, was observed in 3.4%, while symptomatic in 0.5%. Prophylactic anticoagulation was administrated in 20.4% with LMWH (13.2%) or DOAC (7.1%) for patients with higher VTE risk but did not reduce the events rate. With propensity score matching DOACs were superior to LMWHs (1.5% vs 9.8%). Duration of anticoagulation was essential: the lowest incidence (4.2%) was associated with prophylaxis for up to 7 days, while a single LMWH injection resulted in a DVT rate of 8.8%. With individual VTE history, any anticoagulation duration appeared insufficient. CONCLUSIONS: Prophylactic anticoagulation after varicose vein surgery should be based on the individual VTE risk and provided for ≥7-30 days.

The correlation between Caprini score and the risk of venous thromboembolism after varicose vein surgery.

BACKGROUND: The study aims to identify the incidence of symptomatic and asymptomatic venous thromboembolism (VTE) after minimally invasive varicose vein surgery and to assess the predictability of the Caprini risk score (CRS). METHODS: CAPrini Score In Venous Surgery (NCT03041805) is a registry-based prospective study that enrolls patients undergoing minimally invasive open (high ligation, stripping, miniphlebectomy) and endovascular (thermal and non-thermal ablation) surgery on varicose veins. The main inclusion criteria are CRS assessment before intervention and a duplex ultrasound scan performance within 2-4 weeks after surgery. The primary outcome is a combination of asymptomatic or symptomatic DVT, including EHIT of class 2-4 and PE. RESULTS: Totally 1878 records with defined outcomes were analyzed. The mean age of patients was 46.9±13.3 years; 66% were female. Endovenous laser ablation was performed in 88%. Varicose tributaries were treated in 40%, perforating veins in 3.9% of cases. CRS ranged from 1 to 12 (mean of 4.0±1.5). Prophylactic anticoagulation was prescribed in 20%. The primary outcome was reported in 63 cases (3.4%; 95% CI, 2.7-4.3%), comprising asymptomatic (N.=29, 1.5%) or symptomatic (N.=10, 0.5%) DVT or EHIT (n=28, 1.6%). No PE was reported. A significant correlation was found between CRS and VTE incidence (P=0.001). Under logistic regression CRS (OR, 1.3; 95% CI, 1.1-1.6) along with treatment of tributaries (OR, 6.3; 95% CI, 3.0-13.0) and perforating veins (OR, 10.7; 95% CI, 3.8-30.2) were associated with VTE in the absence of prophylactic anticoagulation. CONCLUSIONS: The incidence of VTE after ablation of superficial veins is 3.4%, predominantly due to asymptomatic EHIT and DVT, and significantly correlates with CRS.

Diagnostic criteria for Buerger's disease: International Consensus of VAS - European Independent Foundation in Angiology/Vascular Medicine.

Buerger's disease (BD) remains a debilitating condition and early diagnosis is paramount for its effective management. Despite many published diagnostic criteria for BD, selective criteria have been utilized in different vascular centers to manage patients with BD worldwide. A recent international Delphi Consensus Study on the diagnostic criteria of BD showed that none of these published diagnostic criteria have been universally accepted as a gold standard. Apart from the presence of smoking, these published diagnostic criteria have distinct differences between them, rendering the direct comparison of patient outcomes difficult. Hence, the expert committees from the Working Group of the VAS-European Independent Foundation in Angiology/Vascular Medicine critically reviewed the findings from the Delphi study and provided practical recommendations on the diagnostic criteria for BD, facilitating its universal use. We recommend that the 'definitive' diagnosis of BD must require the presence of three features (history of smoking, typical angiographic features and typical histopathological features) and the use of a combination of major and minor criteria for the 'suspected' diagnosis of BD. The major criterion is the history of active tobacco smoking. The five minor criteria are disease onset at age less than 45 years, ischemic involvement of the lower limbs, ischemic involvement of one or both of the upper limbs, thrombophlebitis migrans and red-blue shade of purple discoloration on edematous toes or fingers. We recommend that a 'suspected' diagnosis of BD is confirmed in the presence of a major criterion plus four or more minor criteria. In the absence of the major criterion or in cases of fewer than four minor criteria, imaging and laboratory data could facilitate the diagnosis. Validation studies on the use of these major and minor criteria are underway.

A randomized clinical trial to assess the impact of laser power with constant linear endovenous energy density on outcomes of endovenous laser ablation (SLEDGE trial).

OBJECTIVE: To date, conflicting evidence has been reported regarding the energy settings to use during endovenous laser ablation (EVLA). In the present study, we evaluated the outcomes of EVLA of the great saphenous veins (GSVs) using different power settings with the same linear endovenous energy density (LEED) of ∼70 J/cm. METHODS: We performed a single-center, randomized, controlled noninferiority trial with a blinded outcome assessment of patients with varicose veins of the GSV who underwent EVLA with a wavelength of 1470 nm and a radial fiber. The patients were randomly assigned to three groups according to the energy setting: group 1, 5 W power and an automatic fiber traction speed of 0.7 mm/s (LEED, 71.4 J/cm); group 2, 7 W and 1.0 mm/s (LEED, 70 J/cm); and group 3, 10 W and 1.5 mm/s (LEED, 66.7 J/cm). The primary outcome was the rate of GSV occlusion at 6 months. The secondary outcomes were pain intensity along the target vein the next day and at 1 week and 2 months after EVLA, the necessity for analgesics, and the occurrence of significant complications. RESULTS: From February 2017 to June 2020, 245 lower extremities of 203 patients were enrolled. Groups 1, 2, and 3 included 83, 79, and 83 limbs, respectively. At 6 months of follow-up, 214 lower extremities were examined with duplex ultrasound. GSV occlusion was observed in 72 of 72 limbs (100%; 95% confidence interval [CI], 100%-100%) in group 1 and 70 of 71 limbs (98.6%; 95% CI, 97%-100%) in groups 2 and 3 (P < .05 for noninferiority). No difference was found in the pain level, necessity for analgesics, or rate of any other complications. CONCLUSIONS: The technical results, pain level, and complications of EVLA were not associated with the combination of energy power (5-10 W) and the speed of automatic fiber traction when a similar LEED of ∼70 J/cm was reached.

The Thresholds of Caprini Score Associated With Increased Risk of Venous Thromboembolism Across Different Specialties: A Systematic Review.

OBJECTIVE: Estimation of the specific thresholds of the Caprini risk score (CRS) that are associated with the increased incidence of venous thromboembolism (VTE) across different specialties, including identifying the highest level of risk. BACKGROUND: Accurate risk assessment remains an important but often challenging aspect of VTE prophylaxis. One well-established risk assessment model is CRS, which has been validated in thousands of patients from many different medical and surgical specialties. METHODS: A search of MEDLINE and the Cochrane Library was performed in March 2022. Manuscripts that reported on (1) patients admitted to medical or surgical departments and (2) had their VTE risk assessed by CRS and (3) reported on the correlation between the score and VTE incidence, were included in the analysis. RESULTS: A total of 4562 references were identified, and the full text of 202 papers was assessed for eligibility. The correlation between CRS and VTE incidence was reported in 68 studies that enrolled 4,207,895 patients. In all specialties, a significant increase in VTE incidence was observed in patients with a CRS of ≥5. In most specialties thresholds of ≥7, ≥9, and ≥11 to 12 were associated with dramatically increased incidences of VTE. In COVID-19, cancer, trauma, vascular, general, head and neck, and thoracic surgery patients with ≥9 and ≥11 to 12 scores the VTE incidence was extremely high (ranging from 13% to 47%). CONCLUSION: The Caprini score is being used increasingly to predict VTE in many medical and surgical specialties. In most cases, the VTE risk for individual patients increases dramatically at a threshold CRS of 7 to 11.

Fake-news-free evidence-based communication for proper vein-lymphatic disease management.

Published scientific evidence demonstrate the current spread of healthcare misinformation in the most popular social networks and unofficial communication channels. Up to 40% of the medical websites were identified reporting inappropriate information, moreover being shared more than 450,000 times in a 5-year-time frame. The phenomenon is particularly spread in infective diseases medicine, oncology and cardiovascular medicine. The present document is the result of a scientific and educational endeavor by a worldwide group of top experts who selected and analyzed the major issues and related evidence-based facts on vein and lymphatic management. A section of this work is entirely dedicated to the patients and therefore written in layman terms, with the aim of improving public vein-lymphatic awareness. The part dedicated to the medical professionals includes a revision of the current literature, summing up the statements that are fully evidence-based in venous and lymphatic disease management, and suggesting future lines of research to fulfill the still unmet needs. The document has been written following an intense digital interaction among dedicated working groups, leading to an institutional project presentation during the Universal Expo in Dubai, in the occasion of the v-WINter 2022 meeting.

Pharmacological treatment for chronic venous disease: an umbrella review of systematic reviews.

INTRODUCTION: Chronic venous disease is a persistent venous drainage alteration caused by valvular incompetence and/or outflow obstruction. Disease management includes a variety of treatments, whose evidence and clinical performance in the mid-long term are variable. The objective of this umbrella review was to summarize efficacy data for pharmacological treatments including venoactive drugs from previously published reviews that included a meta-analytic component. EVIDENCE ACQUISITION: Systematic database searches were conducted via Ovid SP on 13 August 2019, covering MEDLINE, Embase, and the Cochrane Database of Systematic Reviews. Reviews that included a meta-analytic component of four or more clinical trials or observational studies reporting on the efficacy of systemic or topical pharmacological treatments for adults with chronic venous disease published since 2010 were eligible for inclusion. EVIDENCE SYNTHESIS: Eleven publications were included in this umbrella review. Change in ankle circumference was the most commonly reported outcome. Overall, several systemic treatments had significant effects compared with placebo on multiple efficacy outcomes, including measures of edema and pain. Out of them, Micronized Purified Flavonoid Fraction had the most comprehensive evidence of effectiveness on main symptoms and signs and on improving quality of life throughout chronic venous disease stages. CONCLUSIONS: Systemic pharmacotherapies represent a valuable therapeutic option in CVD management. As a result of this umbrella review, several gaps were identified with respect to research topics that warrant further investigation, particularly in the category of topical medications.

Rivaroxaban for the prevention of venous thromboembolism after radiofrequency ablation of saphenous veins concomitant with miniphlebectomy, sclerotherapy, or no treatment of varicose tributaries.

OBJECTIVE: To assess the efficacy and safety of once-daily 10 mg rivaroxaban for venous thromboembolism prophylaxis after ClosureFast radiofrequency ablation (RFA) of saphenous veins. METHOD: The medical records of patients, who had a Caprini score of ≥3, underwent RFA, received prophylactic rivaroxaban for five days, and completed follow up at one month were reviewed for efficacy (a combination of endovenous heat-induced thrombosis [EHIT] grade of 2-4, any symptomatic or asymptomatic deep vein thrombosis [DVT], and symptomatic pulmonary embolism [PE]) and safety (a combination of major and clinically relevant non-major [CRNM] bleeding) outcomes. RESULTS: The results of RFA for 248 great saphenous and 24 small saphenous veins with the concomitant miniphlebectomy (63.8%) and sclerotherapy (16.5%) were analyzed. The primary efficacy outcome occurred in 5 of 218 (2.3%; 95%CI, 1.0-5.3%) patients: three EHITs and two symptomatic DVTs. The CRNM bleeding was reported in two patients (0.9%; 95% CI, 0.2-3.3%). No difference was observed in comparison with 79 similar patients who received 40 mg of subcutaneous enoxaparin during the same time period. CONCLUSION: Once-daily 10 mg rivaroxaban is suitable for VTE prophylaxis after RFA of saphenous veins.

The original and modified Caprini score equally predicts venous thromboembolism in COVID-19 patients.

OBJECTIVE: The study aimed to validate the original Caprini score and its modifications considering coronavirus disease (COVID-19) as a severe prothrombotic condition in patients admitted to the hospital. METHODS: The relevant data were extracted from the electronic medical records with an implemented Caprini score and were retrospectively evaluated. The score was calculated twice: by the physician on admission and by the investigator at discharge (death). The final assessment considered additional risk factors that occurred during inpatient treatment. Besides the original Caprini score (a version of 2005), the modified version added the elevation of D-dimer and specific scores for COVID-19 as follows: two points for asymptomatic, three points for symptomatic, and five points for symptomatic infection with positive D-dimer. Cases were evaluated retrospectively. The primary end point was symptomatic venous thromboembolism (VTE) detected during inpatient treatment and confirmed by appropriate imaging testing or autopsy. The secondary end points included those observed during hospitalization (admission to the intensive care unit, a requirement for invasive mechanical ventilation, death, bleeding), and those assessed at 6-month follow-up (symptomatic VTE, bleeding, death). The association of eight different versions of the Caprini score with VTE events was evaluated. RESULTS: A total of 168 patients (83 males and 85 females at the age of 58.3 ± 12.7 years) were admitted to the hospital between April 30 and May 29, 2020, and were discharged or died to the time of data analysis. The original Caprini score varied between 2 and 12 (5.4 ± 1.8) at the admission and between 2 and 15 (5.9 ± 2.5) at discharge or death. The maximal score was observed with modification including specific COVID-19 points of 5 to 20 (10.0 ± 3.0). Patients received prophylactic (enoxaparin 40 mg once daily: 2.4%), intermediate (enoxaparin 80 mg once daily: 76.8%), or therapeutic (enoxaparin 1 mg/kg twice daily: 20.8%) anticoagulation. Despite this, symptomatic VTE was detected in 11 (6.5%) inpatients. Of the 168 individuals, 28 (16.7%) admitted to the intensive care unit, 8 (4.8%) required invasive mechanical ventilation, and 8 (4.8%) died. Clinically relevant nonmajor bleeding was detected in two (1.2%) cases. The Caprini score of all eight versions demonstrated a significant association with inpatient VTE frequency. The highest predictability was observed for the original scale when assessed at discharge (death). Only symptomatic VTE was reported after discharge with a cumulative incidence of 7.1%. This did not affect the predictability of the Caprini score. Extended antithrombotic treatment was prescribed to 49 (29%) patients with a cumulative incidence of bleeding of 1.8% at 6 months. CONCLUSIONS: The study identified a significant correlation between the Caprini score and the risk of VTE in patients with COVID-19. All models including specific COVID-19 scores showed equally high predictability, and use of the original Caprini score is appropriate for patients with COVID-19.

Intermittent Pneumatic Compression in Addition to Standard Prophylaxis of Postoperative Venous Thromboembolism in Extremely High-risk Patients (IPC SUPER): A Randomized Controlled Trial.

OBJECTIVE: To assess the efficacy of adjunctive IPC to standard prophylaxis of postoperative VTE in patients at extremely high-risk. SUMMARY OF BACKGROUND DATA: The standard prophylaxis for postoperative VTE is insufficient in extremely high-risk patients. It is unclear whether an adjunctive use of IPC would result in a lower incidence of postoperative venous thrombosis. METHODS: We randomly assigned patients who underwent major surgery and had a Caprini score of ≥11 to receive either IPC in addition to standard prophylaxis with anti-embolic stockings (pressure of 18-21 mm Hg at the ankle) and low-molecular-weight heparin (IPC group) or standard prophylaxis alone (control group). The primary outcome was an asymptomatic venous thrombosis of the lower limbs, as detected by duplex ultrasound scan performed before inclusion and every 3-5 days after surgery. RESULTS: A total of 407 patients underwent randomization, of which 204 were assigned to the IPC group and 203 to the control group. The primary outcome occurred in 1 (0.5%) patient in the IPC group and 34 (16.7%) patients in the control group [relative risk, 0.03, 95% confidential interval (CI): 0.01-0.21]. Pulmonary embolism occurred in none of the 204 patients in the IPC group and in 5 (2.5%) patients in the control group (relative risk, 0.09; 95% CI, 0.01-1.63), and postoperative death occurred in 6 (2.9%) patients in the IPC group and 10 (4.9%) in the control group (relative risk, 0.50; 95% CI, 0.50-1.60). CONCLUSIONS: Among patients with a Caprini score of ≥11 who received standard prophylaxis for VTE, adjunctive IPC resulted in a significantly lower incidence of asymptomatic venous thrombosis.

Pulmonary Artery Thrombosis: A Diagnosis That Strives for Its Independence.

According to a widespread theory, thrombotic masses are not formed in the pulmonary artery (PA) but result from migration of blood clots from the venous system. This concept has prevailed in clinical practice for more than a century. However, a new technologic era has brought forth more diagnostic possibilities, and it has been shown that thrombotic masses in the PA could, in many cases, be found without any obvious source of emboli. Chronic obstructive pulmonary disease, asthma, sickle cell anemia, emergency and elective surgery, viral pneumonia, and other conditions could be complicated by PA thrombosis development without concomitant deep vein thrombosis (DVT). Different pathologies have different causes for local PA thrombotic process. As evidenced by experimental results and clinical observations, endothelial and platelet activation are the crucial mechanisms of this process. Endothelial dysfunction can impair antithrombotic function of the arterial wall through downregulation of endothelial nitric oxide synthase (eNOS) or via stimulation of adhesion receptor expression. Hypoxia, proinflammatory cytokines, or genetic mutations may underlie the procoagulant phenotype of the PA endothelium. Both endotheliocytes and platelets could be activated by protease mediated receptor (PAR)- and receptors for advanced glycation end (RAGE)-dependent mechanisms. Hypoxia, in particular induced by high altitudes, could play a role in thrombotic complications as a trigger of platelet activity. In this review, we discuss potential mechanisms of PA thrombosis in situ.

Diosmin 600 in adjunction to rivaroxaban reduces the risk of post-thrombotic syndrome after femoropopliteal deep vein thrombosis: results of the RIDILOTT DVT study.

BACKGROUND: To assess the efficacy and safety of long-term diosmin 600 therapy added to rivaroxaban and elastic compression stockings (ECS) in patients with femoropopliteal deep vein thrombosis (DVT). METHODS: This single-center, open-label randomized clinical trial RIDILOTT DVT enrolled patients with their first femoropopliteal DVT confirmed by duplex ultrasound scan (DUS). Participants were randomly allocated to the control group (standard treatment with rivaroxaban for six months and ECS for 12 months) or the experimental group (standard treatment with the additional use of diosmin 600 mg once daily for 12 months). Patients were followed for 12 months. The primary outcome was post-thrombotic syndrome (PTS), according to the Villalta Score (≥5). The secondary outcomes were deep vein recanalization, chronic venous disease (CVD) progression, the severity of PTS (Villalta), and CVD (VCSS), quality of life (CIVIQ-20), venous thromboembolism recurrence, and adverse event (AE). RESULTS: Ninety patients were randomized (45 per group). There were 56 men and 34 women with a mean age of 57.8±13.4 years, and 69% had clinically unprovoked DVT. PTS frequency at 12 months was significantly lower (8.9% vs. 48.9%) in the experimental group compared with control one (relative risk, 0.14; 95% confidential interval, 0.04-0.43, P<0.001). Adding diosmin 600 was associated with quicker and complete vein recanalization, lower CVD progression rate, and lower Villalta, VCSS, and CIVIQ-20 scores. There was no difference in recurrent DVT or AE. CONCLUSIONS: Adjunctive use of diosmin 600 to rivaroxaban and ECS in patients with femoropopliteal DVT can improve the clinical and ultrasound outcomes after 12 months of treatment.

The frequency and clinical significance of nontarget superficial and deep vein occlusion after physician compounded foam sclerotherapy of varicose tributaries.

OBJECTIVE: To evaluate the incidence and clinical relevance of silent nontarget occlusion (NTO) of superficial and deep veins occurring after ultrasound-guided foam sclerotherapy (UGFS) that can be detected by serial duplex ultrasound scan (DUS). METHODS: This retrospective analysis evaluated the medical records of patients treated with UGFS at a private clinic in Moscow, Russia from 2015 to 2017. All patients underwent serial DUS at 1 to 2 weeks and 1, 3, 6, and 12 months after UGFS. RESULTS: During the observation period, 268 patients were treated with UGFS, using physician compounded polidocanol foam 257 lower limbs of 196 patients (73%) with varicose veins who underwent DUS at 1 to 2 weeks after the last session of UGFS (inclusion time-point): 139 women and 57 men (mean age: 44.2 ± 12.2 years) with the following CEAP clinical class distribution: C2, 74.0%; C3, 20.0%; C4, 4.5%; and C5, 1.5%. NTO at the inclusion time-point occurred in 60 limbs (23.3%) of 57 patients (28.5%) and was symptomatic only in three limbs (1.2%). Most occlusions were localized in the untreated great saphenous vein trunk (n = 28) and the calf muscle veins (n = 23). Overall, 72%, 44%, 29%, and 10% of all limbs and 77%, 45%, 28%, and 12% of limbs with NTO were followed up by DUS at 1, 3, 6, and 12 months, respectively. There were no cases of thrombus progression or symptomatic venous thromboembolism (VTE). At six months, no deep vein occlusions persisted. CONCLUSIONS: The frequency of nontarget vein occlusion after UGFS revealed by serial DUS may be as high as 23.3%. These occlusions tend to resolve within six months and are not associated with symptomatic VTE.

Utilization of the Caprini score in conjunction with thrombodynamic testing reduces the number of unpredicted postoperative venous thromboembolism events in patients with colorectal cancer.

BACKGROUND: The thrombodynamic test (TD) is a novel global test of hemostasis that allows to study the spatial-temporal characteristics of a clot formation in real time under conditions close to natural ones and demonstrates high sensitivity to detect the state of hypercoagulation. The main paraments of the test are the velocity of clot growth, clot's size, and clot density. The objective of this study was to compare the classic Caprini 2005 score and its modified version in association with the results of TD. The goal is to predict postoperative venous thromboembolism (VTE) in surgical patients undergoing surgery for colorectal cancer. METHODS: This was a prospective observational clinical study involving 80 patients (33 men and 47 women; mean age, 73.9 ± 7.2 years) who underwent major (79 cases) or minor (1 case) surgery for colorectal cancer. Patients were at high risk for postoperative VTE (ie, a mean Caprini score of 9.9 ± 2.0) and received combined prophylaxis (ie, antiembolic compression stockings and enoxaparin 40 mg once daily) until discharge. Enoxaparin was administered at a fixed time of blood sampling for the TD test. Duplex ultrasound scan was performed to detect postoperative vein thrombosis before and 5 to 7 days after surgery. RESULTS: Postoperative vein thrombosis was found in 21 of 80 patients (26.3%; 95% confidence interval, 17.9%-36.8%). Regression analysis and receiver operating characteristic (ROC) curve showed that Caprini scores significantly predicted VTE (P < .0001; area under the curve [AUC] = 0.839 ± 0.045). Analysis of ROC curve coordinates showed that a cutoff point of 11 scores had a sensitivity of 76.2% and a specificity of 74.6%. The results of the TD test showed significant hypercoagulation despite enoxaparin administration in patients with VTE. Regression analysis and ROC curves demonstrated that the following TD parameters had the greatest predictability for postoperative DVT: initial velocity of clot growth (Vin) and clot size (CS) measured at 12 hours after enoxaparin administration (AUC, 0.697 ± 0.063 and AUC, 0.790 ± 0.059, respectively), as well as Vin and CS measured 24 hours after the enoxaparin injection (S = 0.847 ± 0.059 and S = 0.803 ± 0.069, respectively). The cutoff points for VTE prediction at 12 and 24 hours seemed to be a Vin of greater than 62.5 and greater than 64.5 µm/minute (normal range, 35-56 µm/minute) as well as a CS of greater than 1351.5 and greater than 1333.5 µm (normal range, 800-1200 µm), respectively. Identified thresholds for TD parameters have been integrated into Caprini scores under the item "other congenital or acquired thrombophilia." The total Caprini scores were recalculated in patients where one or all TD parameters had exceeded the cutoff followed by reanalysis of the ROC curves. The best predictability was found for Caprini scores considering the elevation of all four TD parameters (AUC, 0.924 ± 0.029) with increased cutoff to a score of 12 with a sensitivity of 85.7% and a specificity of 81.4%. The use of cutoffs for the original and modified scores could be used to calculate the number of patients that were under cutoff but developed with VTE: 10.2% and 5.9%, respectively. CONCLUSIONS: Integrating TD parameters into the Caprini score increases the ability to predict postoperative VTE.

Rivaroxaban in the treatment of upper extremity deep vein thrombosis: A single-center experience and review of the literature.

INTRODUCTION: Direct oral anticoagulants (DOACs) have become widely used to treat patients with venous thromboembolism (VTE), but evidence about their use in the treatment of upper extremity deep vein thrombosis (UEDVT) is lacking. OBJECTIVES: To assess rivaroxaban's efficacy and safety in the treatment of UEDVT. PATIENTS/METHODS: This was a single-center prospective observational study involving patients with their first UEDVT episode confirmed by duplex ultrasound scan. All patients initially received low-molecular-weight heparin for 1 to 2 days and then were switched to rivaroxaban for 3-6 months. The primary endpoint was any symptomatic episode of recurrent VTE. RESULTS: Thirty patients were included in the study, and all patients were followed for 6 months. There were no episodes of recurrent symptomatic venous thromboembolism or asymptomatic UEDVT. No episode of major bleeding was observed. Clinically relevant non-major bleeding occurred in two patients (6.7%, 95% confidence interval [CI]: 1.9-21.4%) with uterine bleeding and large skin hemorrhage. Minor bleeding was observed in two patients (6.7%, 95% CI: 1.9-21.4%) presenting with nasal and gingival bleeding. Recanalization of the upper extremity deep veins was observed in all affected limbs at three months, and it persisted up to 6 months. The signs of upper limb post-thrombotic syndrome (PTS) were found in four patients (13.4%; 95% CI: 5.4-29.8%), and the mean modified Villalta score was 2.1 ±â€¯1.9. CONCLUSION: Treatment of UEDVT with rivaroxaban, preceded by one to two days of LMWH, seems to be safe and effective.

Use of Micronized Purified Flavonoid Fraction Together with Rivaroxaban Improves Clinical and Ultrasound Outcomes in Femoropopliteal Venous Thrombosis: Results of a Pilot Clinical Trial.

INTRODUCTION: The aim of this study was to assess the impact of adding long-term micronized purified flavonoid fraction (MPFF) to standard treatment of femoropopliteal deep vein thrombosis (DVT). METHODS: This pilot, comparative, open-label study with blinded outcome assessor enrolled patients with a first episode of femoropopliteal DVT confirmed by duplex ultrasound scanning (DUS). All participants were randomly allocated to one of two treatment groups: (1) control that received a standard treatment with oral rivaroxaban, and (2) experimental that involved additional treatment with MPFF 1000 mg/day. Both drugs were used for 6 months. Patients were followed for the whole treatment period and underwent DUS every 2 months to determine the degree of recanalization by popliteal (PV), femoral vein (FV), and common femoral vein (CFV) compressibility. Thrombi extension were assessed by the modified Marder score. At the end of the follow-up period, patients were assessed with Villalta and venous clinical severity scales (VCSS). Patients with a Villalta score ≥ 5 were diagnosed with post-thrombotic syndrome (PTS). RESULTS: Sixty patients were randomized to the control or MPFF groups (n = 30 in each group). There were 40 men and 20 women with a mean age ± SD of 56.3 ± 13.4 years. Clinically unprovoked DVT was recognized in 65% of cases and left side localization in 45%. The mean baseline Marder score was 15.0 ± 4.8 and 11.1 ± 4.3 in the experimental and control groups, respectively (p = 0.002). At 6 months, the mean Villalta score in the MPFF group was significantly lower compared with control (2.9 ± 2.7 versus 5.8 ± 3.0; p < 0.0001). PTS was diagnosed in six patients (20%) and 17 patients (57%) in the experimental and control groups respectively (p = 0.007). A significant difference between the groups was also observed for the VCSS value (2.3 ± 1.9 versus 4.9 ± 1.9; p < 0001). After 6 months of treatment the Marder score decreased to 0.8 ± 1.6 and 2.8 ± 3.5 in the experimental and control groups, respectively (p = 0.006). In the MPFF group, there was a greater reduction in the Marder score (p < 0.0001) and more rapid rate of recanalization for the FV (p < 0.0001), with a non-significant trend for the CFV (p = 0.130) and PV (p = 0.204) compared with the control group. Full recanalization of the PV at 6 months was observed in 24 patients (80%) who had received MPFF, and only 17 patients (57%) in the control group (p = 0.095). CONCLUSION: The addition of MPFF to standard therapy for DVT in the form of oral rivaroxaban can reduce the incidence of PTS at 6 months in patients with proximal DVT and increase the speed of deep vein recanalization. FUNDING: Les Laboratoires Servier funded the article processing fees, editorial assistance, and open access fee for this manuscript.

Electrical calf muscle stimulation in patients with post-thrombotic syndrome and residual venous obstruction after anticoagulation therapy.

BACKGROUND: The aim of this study was to assess the impact of electrical calf muscle stimulation (EMS) on clinical and ultrasound outcomes in patients with post-thrombotic syndrome (PTS) and residual venous obstruction (RVO). METHODS: This was a prospective, comparative, non-randomized clinical trial involving patients who had completed a standard 6-month course of anticoagulation therapy for a first episode of unprovoked femoro-popliteal DVT and had signs of RVO in the affected veins and PTS as shown by a Villalta Score of >5. A blinded outcome assessor performed the ultrasound evaluations. A total of 60 patients in the age range from 40 to 86 years (mean 58.5±11.4) consisting of 38 men and 22 women were enrolled. They were divided into two groups of 30 participants each. Both groups (experimental and control) were treated by active walking, below-knee graduated compression stockings, and micronized purified flavonoid fraction. In the experimental group, EMS with «Veinoplus VI¼ device (three applications for 30 min every day) was also used. The patients were followed for 12 months with monthly DUS to reveal recurrent DVT and changes in RVO. The clinical criteria for treatment efficacy included changes in Villalta, VCSS and CIVIQ-20 scores. RESULTS: Recurrent DVT was found in seven of 30 patients in the control group and in zero of 30 patients in the experimental group (23.3% versus 0%, P=0.01). Through the follow-up period the degree of RVO decreased in all affected veins in both groups (P<0.01). The most significant changes were found in the popliteal vein; 60.8% decreased to 28.8% in the experimental group and 50.9% to 27.3% in the control group (P<0.01) with significant differences between the groups (P<0.01). VCSS, Villalta and CIVIQ-20 scores also significantly decreased in both groups (P<0.01). In the group with EMS, changes in the current parameters were more intensive (P<0.01). CONCLUSIONS: There is an ongoing process of deep vein recanalization during the 12 months after anticoagulant therapy cessation. Use of EMS in PTS treatment allows for reduction of recurrent DVT rates, increase the speed of deep vein recanalization and leads to additional improvement in the clinical PTS outcomes.

Thrombodynamics-A new global hemostasis assay for heparin monitoring in patients under the anticoagulant treatment.

BACKGROUND: Heparin therapy and prophylaxis may be accompanied by bleeding and thrombotic complications due to individual responses to treatment. Dosage control based on standard laboratory assays poorly reflects the effect of the therapy. The aim of our work was to compare the heparin sensitivity of new thrombodynamics (TD) assay with sensitivity of other standard and global coagulation tests available to date. STUDY POPULATION AND METHODS: A total of 296 patients with high risk of venous thromboembolism (deep vein thrombosis (DVT), early postoperative period, hemoblastosis) were enrolled in the study. We used a case-crossover design to evaluate the sensitivity of new thrombodynamics assay (TD) to the hemostatic state before and after unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) therapy/prophylaxis and to compare it with the activated partial thromboplastin time (APTT), anti-Xa activity test, thrombin generation test (TGT) and thromboelastography (TEG). A receiver operating characteristic (ROC) curve analysis was used to evaluate changes before and after heparin prophylaxis and therapy. Blood was sampled before heparin injection, at the time of maximal blood heparin concentration and before the next injection. RESULTS: Hypercoagulation before the start of heparin treatment was detected by TD, TGT and TEG but not by APTT. The area under the ROC curve (AUC) was maximal for TD and anti-Xa, intermediate for TGT and TEG and minimal for APTT. CONCLUSIONS: These results indicate that TD has a high sensitivity to the effects of UFH and LMWH after both prophylactic and therapeutic regimes and may be used for heparin monitoring.