Treatment Of Superficial Vein Thrombosis Research Articles

Management of lower-extremity venous thromboembolism: An updated review.

According to the 2021 updated guidelines of the American College of Chest Physicians, the location of venous thromboembolism, the severity of symptoms, the risk of thrombus extension vs that of bleeding, and comorbidities all affect the decision to treat, the choice of anti-thrombotic agent, and the duration of therapy. In patients with isolated distal deep vein thrombosis without high-risk features, monitoring progression is recommended over initiating anticoagulation. However, treatment of proximal deep vein thrombosis with anticoagulation is strongly recommended by the guidelines. More evidence now supports the treatment of superficial vein thrombosis with anticoagulation in high-risk patients.

Common Practice in the Treatment of Superficial Vein Thrombosis Involving the Sapheno-Femoral Junction: Results from a National Survey of the Italian Society of Angiology and Vascular Medicine (SIAPAV).

Background and Objectives: Prophylactic doses of low-molecular-weight heparins or fondaparinux showed their efficacy and safety for treatment of all superficial vein thrombosis (SVT) of the lower limbs, yet not for those extended to the last 3 cm of the great saphenous vein, close to the sapheno-femoral junction, or considered as a deep-vein thrombosis. Some experts suggest that these patients should be managed with full anticoagulant doses but evidence to support this recommendation is lacking, suggesting the need for a properly designed trial. Materials and Methods: Before starting a new trial, the Italian Society of Angiology and Vascular Medicine (SIAPAV) decided to verify the common therapeutic approaches for patients with an SVT in Italian vascular centers based on a hypothetical significant variation in each daily clinical practice. A standardized questionnaire of 10 questions was administered to all SIAPAV affiliates by means of the official Society website. Results: From 1 December 2022 to 20 January 2023 a total of 191 members (31.8%) answered the questionnaire, showing a detailed and a substantial heterogeneity in the therapeutic approach to SVT patients among experienced vascular physicians and angiologists. Detailed results are reported in the relative section. Conclusions: The therapeutic approach of SVT extended to the iuxta-femoral segment of the great saphenous vein is still a matter of debate, and data to support therapeutic strategies are lacking. The wide heterogeneity in the management of SVT patients, including those with more extended thrombosis, confirmed that a randomized controlled clinical trial investigating the efficacy and the safety of a tailored therapeutic regimen in this particular subgroup of patients is strongly warranted.

Comparison of endovenous laser ablation and conservative treatment in acute thrombophlebitis of the varicose great saphenous vein: rationale, design and first results of clinical trial

Thrombophlebitis of the superficial lower limb veins is one of the most common complications of chronic vein disease. Nowadays a long-term (at least 45 days) subcutaneous injection of fondaparinux sodium or heparin in combination with elastic compression of the limb is recommended for treatment of superficial vein thrombosis with a moderate risk of thrombus propagation to deep venous system. However, long-term use of anticoagulants is not always possible and sometimes contraindicated. Endovenous laser ablation (EVLA) around thrombus-free junction of great or small saphenous veins without subsequent long-term use of anticoagulants seems to be a promising intervention for treatment of acute thrombophlebitis of varicose superficial veins.The prospective single-center randomized open-label clinical trial was dedicated for comparison the efficacy and safety of three following treatments options for patients with acute thrombosis of the varicose great saphenous vein and location of thrombi in the trunk and/ or its large inflows: EVLA close to saphenous vein junction without anticoagulation, EVLA and 7 days of anticoagulation and noninvasive treatment with anticoagulation for 45 days (subcutaneous injections of the fondaparinux 2,5 mg). Class 2 compression stockings are used in all patients. Adverse outcomes are recorded at 7, 45 and 90 days after randomization. These include the progression of superficial vein thrombosis, recurrent superficial vein thrombosis, thrombosis involvement of the superficial segment of the perforating vein up to the fascia, deep vein thrombosis according to compression ultrasound, and pulmonary embolism with symptoms. Bleedings according to the World Society of Thrombosis and Hemostasis and the Academic Research Consortium classification as well other complications are also recorded. The first 30 patients included in the study have a low incidence of venous thrombosis risk factors and localization of the thrombus relatively far from the saphenofemoral junction. EVLA resulted in persistent cessation of venous blood flow at the intervention site. New episodes of venous thrombosis were noted only in the group of medical treatment — deep vein thrombosis of the contralateral tibia 5 days after stopping of 45-day treatment with fondaparinux and thrombus in the recanalized inflow of the great saphenous vein without involving its trunk at the 21st day after stopping of 45-day injection of fondaparinux. There were no complications in the area of intervention and bleedings.

Risk of recurrent thromboembolic events according to treatment duration in patients with superficial vein thrombosis treated with intermediate dose of tinzaparin.

To evaluate the risk of symptomatic venous thromboembolism (VTE) recurrence at 3months in relation to treatment duration, according to baseline risk factor profiles, in patients with superficial vein thrombosis (SVT) treated with intermediate dose of tinzaparin. We performed a pooled analysis on individual data from two prospective studies designed to assess the efficacy and safety of tinzaparin in intermediate dose (131IU/kg) in patients with SVT. Treatment duration was at the treating physician's discretion. All patients were followed up for at least 3months. A total of 956 patients (65% female, mean age 58.7 ± 13.7years) were included. The median treatment duration was 30days (range, 3-200days). History of deep vein thrombosis (DVT), location of SVT above the knee, and palpable induration were the only independent factors associated with prolonged treatment duration. During follow-up, 95.9% of patients were event free. Outcomes-related adverse events occurred in 39 (4.1%) patients and their median duration of treatment was 33days (range, 7-200days). Recurrent VTE events occurred in 33 patients, including 22 cases of SVT recurrence, 8 cases of DVT, and 1 case of pulmonary embolism. The median time to the event was 29 (6-113) days. Recurrent thromboembolic events were not related to treatment duration as occurred in 17 patients (51.5%) treated up to 30days and in 16 patients (48.8%) received prolong treatment (p = .46). Length of thrombus at the index event was significantly associated with higher risk for VTE recurrence. Intermediate dose of tinzaparin for 30days is an effective and safe treatment for SVT. The risk of recurrent VTE events may be higher in patients with greater amount of thrombus at index event.

Urgent surgery versus anticoagulation for treatment of superficial vein thrombosis in patients with varicose veins.

Background: We performed a prospective observational study to compare the results of surgery and anticoagulation in patients with superficial vein thrombosis (SVT). Patients and methods: A total of 190 patients (195 limbs) with varicose veins and SVT were included and treated by anticoagulation or by surgery. Patients were followed-up during 6 months. The primary outcome for treatment efficacy was the composite rate of SVT extension/recurrence; deep vein thrombosis (DVT) or symptomatic pulmonary embolism (PE). The primary outcome for safety was the rate of wound complications and rate of bleedings. Results: Surgery was performed in 85 (44.7%) patients and 105 patients (5 with bilateral SVT) were treated conservatively. In the whole study cohort the primary outcome for treatment efficacy was registered in 15 (7.6%) cases: 9/85 (10.5%) in surgical group and 6/110 (5.4%) in anticoagulation group. Nine patients treated with surgery were diagnosed with postoperative DVT. In anticoagulation group SVT extension occurred in 3 limbs; SVT recurrence in 2 and DVT in one. There were no cases of PE or death during the follow-up. Time-to-event analysis demonstrated no significant difference between groups (HR 0.48; 95% CI 0.17-1.34). The total length of the thrombus was associated with primary efficacy outcome in surgical group (HR 1.07; 95% CI 1.02-1.11); and duration of anticoagulation (HR 0.91 per day; 95% CI 0.83-0.99) and value of Caprini score (HR 1.86; 95% CI 1.1-3.14) in anticoagulation group. Six (7%) wound complications were registered after surgery and 6 (5.71%) bleedings during anticoagulation. Conclusions: Urgent surgery is not associated with reduction of venous thromboembolism compared to anticoagulation in treatment of patients with SVT and varicose veins during 6-months follow-up. However, in patients with isolated thrombosis of varicose tributaries or with limited involvement of the saphenous trunk surgery is relatively safe.

Anticoagulants in the treatment of superficial vein thrombosis of lower limbs: possibilities and limitations

This article presents a critical analysis of the results of three prospective randomized controlled trials of anticoagulant use in patients with superficial vein thrombosis of lower limbs CALISTO using fondaparinux sodium, STEFLUX using different doses of parnaparin sodium, and SURPRISE comparing the effectiveness and safety of fondaparinux sodium and the preventive dose of the oral anticoagulant rivaroxaban.Evidence from these clinical trials suggests that low-dose anticoagulants should be used for at least 1.5 months in superficial vein thrombosis of lower limbs with thrombus localization beyond 3 cm from the saphenofemoral and/or saphenopopliteal junction. However, anticoagulant treatment does not appear to prevent the progression of venous thrombosis after withdrawal, so in patients with persisting risk factors, it is reasonable to consider extended treatment. This seems to apply primarily to patients with superficial thrombophlebitis a history of superficial or deep venous thrombosis in the lower extremities, a family history of venous thromboembolic complications, and possibly a broader contingent of high-risk patients, not represented in the CALISTO and STEFLUX studies (with active malignancy, ongoing anticancer therapy, severe chronic heart or respiratory failure, inability to withdraw hormone replacement therapy, autoimmune disease). According to the accumulated evidence, subcutaneous injections of fondaparinux sodium, intermediate doses of low molecular weight heparin, and direct oral anticoagulant rivaroxaban in the dose of 10 mg once a day are effective and sufficiently safe in the treatment of superficial vein thrombosis of lower limbs with localization beyond 3 cm from the saphenofemoral and/or saphenopopliteal junction. Questions about the feasibility of increasing the doses of anticoagulants to further reduce the rate of superficial thrombophlebitis - progression during treatment and the optimal duration of their use remain open.

Acute Surgery versus Anticoagulation for the Treatment of Superficial Vein Thrombosis in Patients with Varicose Veins: A Prospective Study

Acute Surgery versus Anticoagulation for the Treatment of Superficial Vein Thrombosis in Patients with Varicose Veins: A Prospective Study

Treatment of superficial vein thrombosis with intermediate dose of tinzaparin: A real word cohort study - The SeVEN EXTension study.

To assess the treatment of superficial vein thrombosis (SVT) with intermediate dose of tinzaparin in a setting of real world practice. Prospective observational study of consecutive patients treated by vascular physicians in the private sector with tinzaparin (131 IU/Kg) once daily. Treatment duration was at the treating physician's discretion. The outcomes of the study were symptomatic venous thromboembolism, extension of thrombus and bleeding complications. 660 patients were included and followed up for at least 3 months. Median duration of treatment was 30 days (14-120). History of prior deep vein thrombosis (HR 2.77; 95% CI= 1.18-6.49; p = 0.018) and current SVT above the knee (HR1.84; 95% CI = 1.33-3.53; p = 0.0002) were associated with prolonged treatment duration. Primary efficacy outcomes occurred in 20 (3%) patients. The median time to the event was 24 (6-92) days and was not related to treatment duration. Tinzaparin at intermediate dose is an effective and safe treatment for SVT.

The effect of graduated elastic compression stockings on clinical findings, complications and inflammatory and thrombotic markers in patients with superficial vein thrombophlebitis

Introduction/Objective. The objective of the paper is an assessment of the effect of graduated elastic compression stockings on clinical findings, complications, and inflammatory and thrombotic markers in patients with superficial vein thrombophlebitis. Methods. This prospective study was conducted between January and July of 2017, at the Clinic for Vascular and Endovascular Surgery of the Clinical Centre of Serbia. All the patients were clinically examined, and color duplex ultrasonography of the superficial and deep venous systems was performed. In all cases, we follow clinical finding, inflammatory and thrombotic markers, and superficial vein thrombosis (SVT) complication. Results. SVT was detected in 60 patients (36 women, aged 23?75 years and 24 men, aged 18?76 years. Most patients were with unilateral, subacute, above-knee located SVT. Regarding the typical clinical symptoms of SVT, patients were divided into four groups. The majority of our patients (group D) had all the symptoms associated. Regarding the severity of SVT and risk factors, the patients were divided into a greater risk group (Group I) and a lesser risk group (Group II), and treated with low-molecular-weight heparin, aspirin and two classes of graduated elastic compression stockings regarding the level of SVT. Laboratory testing of inflammatory and thrombotic markers in patients with SVT was performed at the beginning and at the end of therapy. Conclusions. In treatment of SVT, higher class of graduated compression therapy has stronger influence in decrement of inflammatory and thrombotic factors and prompt and adequately chosen therapy of SVT allows stoppage and regression of the thrombotic process.

Management of Superficial Vein Thrombosis in Patients with Varicose Veins: A Survey among Members of National Surgical Society from Republic of Moldova.

PurposeManagement of superficial vein thrombosis (SVT) in patients with varicose veins (VV) is not currently standardized. We performed a survey aimed to demonstrate patterns in the management of SVT in the Republic of Moldova.Materials and MethodsThis was a descriptive study whereby members of the National Surgical Society were asked to complete an online questionnaire. In the questionnaire, multiple-choice questions were supplemented with four clinical vignettes of real patients with SVT.ResultsThe questionnaire was completed by 102 participants (31.1% response rate). In the treatment of SVT, duplex ultrasound was routinely used by 74.5% of respondents, and anticoagulants were used by 70.5%. The full therapeutic dose of anticoagulants was recommended by 63.3% of surgeons, intermediate dose by 21.1%, and prophylactic dose by 15.6%. Only 50% of respondents were prescribed anticoagulants for 1 month or more. In case of surgical intervention for SVT, crossectomy and stripping were performed by 84.0% of surgeons, while isolated crossectomy by 10.7%. In all clinical vignettes, the majority of respondents opted for urgent surgical treatment. The rate of proponents of surgery varied from 43% in cases of isolated thrombosis of tributaries, and up to 72.5% in cases of thrombosis up to the sapheno-femoral junction.ConclusionManagement of patients with SVT and VV in the Republic of Moldova is far from standardized. Prescribed doses of anticoagulants, as well as the duration of anticoagulation are highly variable and often contradict the recommendations of current guidelines. Urgent crossectomy and stripping dominate the pattern of current therapeutic approaches.

Effectiveness of treatment of patients with superficial vein thrombosis associated with varicose veins in real clinical practice

Introduction. Approaches to the treatment of superficial vein thrombosis associated with varicose veins (V-SVT) has undergone significant changes in the last decade as a result of randomized clinical studies on the effectiveness of anticoagulant therapy in V-SVT. At the same time, there is still not enough specific clinical data covering the results of treatment of patients with V-SVT and reflecting the willingness of doctors to abandon active surgical tactics in this variant of thrombophlebitis.Aim – study the effectiveness of treatment of patients with superficial vein thrombosis associated with varicose veins (V-SVT) in real clinical practice.Materials and methods. A retrospective non-comparative study of the results of treatment of 82 patients with V-SVT (w/m – 49/33, mean age – 55.5 years) who underwent of treatment in two departments of vascular surgery in 2019. A retrospective analysis of outpatient records of 81 patients with V-SVT discharged from the hospital was performed. Clinical and ultrasound parameters were highlighted to summarize the results. The methods of standard statistics applied using the program MS Excel 2016.Results. The localization of thrombus in the system of the great saphenous vein (GSV) in 68 cases (82.9%), in system of the small saphenous vein (SSV) in 8 cases (9.8%), in both systems – 6 cases (7.3%). Localization of the top of the thrombus 20–80 mm from the sapheno-femoral (SFJ)/sapheno-popliteal junctions (SPJ) – 60 (67.5%), passage into deep veins – 12 (13.4%), localization of the top of the thrombus to the level of the middle third of the thigh – 8 (9.0%), in the tributaries and trunk of the GSV/SSV on the leg below knee – 9 (10.1%). The type of the thrombus proximal part: occlusal – 61 (68.5%), non-occlusal – 6 (6.7%), floating – 22 (24.7%). Surgical interventions: high ligation of SFJ – 49 (55.1%), dissection of the SPJ – 8 (9.0%), high ligation + thrombectomy – 12 (13.4%). Conservative treatment at vascular surgery department – 20 (22.5%). Recovery – 81 (98.7%). Death – 1 (massive pulmonary embolism upon admission). After 1 month in the outpatient period, a complete relief of the inflammatory process was registered in 76 patients (93.8%), partial in 5 patients (6.2%). Regression of the thrombotic process: complete in 7 patients (8.7%), partial in 74 patients (91.3%). A case of successful treatment of a patient with V-SVT using parnaparin sodium given in this article.Conclusion. It is necessary to revise the drug therapy of V-SVT with increasing dose of anticoagulants and prolongation of anticoagulant therapy to achieve effective results in regression of thrombotic process in superficial veins of the lower extremities.

Treatment of Superficial Vein Thrombosis: A Systematic Review and Meta-Analysis.

The optimal first line treatment for patients with isolated superficial venous thrombosis (SVT) of the lower extremity is unknown. This article reports estimates of the rate of venous thromboembolic complications among patients with SVT according to treatment. A systematic review and meta-analysis was performed using unrestricted searches of electronic databases. Reported events were transformed to event per 100 patient-years of follow-up and a random effects model was used to calculate pooled rates according to pre-specified treatment categories. The primary outcome was the occurrence of deep vein thrombosis (DVT) or pulmonary embolism (PE) during the study follow-up period. Seventeen articles, including 6,862 patients, were included in the meta-analysis. Fondaparinux had the lowest event rate with 1.4 events per 100 patient-years of follow-up (95% confidence interval [CI], 0.5-2.8, I 2 = 18%). Pooled event rates for DVT or PE ranged from 9.3 to 16.6 events per 100 patient-years across other treatment categories, and the pooled event rate for no treatment/placebo was 10.5 events per 100 patient-years (95% CI, 3.0-22.0). Major bleeding was low and similar across all treatment categories. Heterogeneity was moderate to high for most pooled estimates. While pooled event rates suggest that fondaparinux achieves the lowest rate of DVT or PE, low-quality evidence for other treatments prevents firm conclusions about the optimal treatment for SVT.

Extended-Duration Treatment of Superficial Vein Thrombosis of the Lower Limbs with Tinzaparin.

PurposeTo identify risk factors for recurrent thromboembolic events (RTEs) and define the optimum duration of treatment with tinzaparin in patients with superficial vein thrombosis (SVT) of the lower limbs.Materials and MethodsA total of 147 consecutive patients with significant SVT were treated with subcutaneously administered tinzaparin. The composite primary endpoint of the study was RTE, deep-vein thrombosis (DVT) and/or pulmonary embolism (PE) at 120 days. Patients were stratified into group A, where patients received a variable dose of tinzaparin for up to 60 days (n=98), and a subsequent group B-ext, where patients received a standardized intermediate dose of tinzaparin (n=49) for 90 days.ResultsRTEs occurred in 15/147 patients (10.2%), including recurrent SVT (n=10), DVT (n=4) and fatal PE (n=1). RTEs were less frequent in group B-ext (0% vs. 15.3% for group A, P=0.004), a difference that remained significant at the one-year follow-up. Clinically extensive SVT was an independent predictor for RTEs (hazard ratio, 5.94; 95% confidence interval, 2.05–17.23; P=0.001, Cox regression). Predictors or DVT or PE in group A included clinically extensive SVT (P=0.004), absence of local pain (P=0.023) and the ultrasound findings of superficial axial vein thrombosis (any, P=0.006 or isolated, P=0.036) and multiple thrombosed superficial venous sites (P<0.001).ConclusionAn extended three-month regimen of tinzaparin in patients with SVT of the lower limbs is more effective than a shorter course and may be desirable in patients with risk factors.

Use of Rivaroxaban for Prophylaxis of Superficial Venous Thrombosis in Klippel-Trenaunay-Weber Syndrome

Klippel-Trenaunay-Weber syndrome (KTWS) is a congenital malformation syndrome involving blood and lymph vessels and disturbed bone and soft tissue growth. Complications of KTWS include deep-vein thrombosis, pulmonary embolism, gastrointestinal bleeding, and vascular (usually lymphatic) blebs within capillary malformations. We present a case of a young male patient with KTWS who presented with superficial venous thrombosis and microangiopathic hemolytic anemia in a presentation similar to disseminated intravascular coagulation. He was ultimately maintained on prophylactic rivaroxaban to prevent recurrent thrombotic events. We performed a literature search to identify similar cases and to summarize common presenting features and treatment modalities that were offered.&#x0D; Résumé&#x0D; Le syndrome de Klippel-Trenaunay-Weber (KTWS) est un syndrome de malformation congénitale impliquant le sang et les vaisseaux lymphatiques et les os perturbés et la croissance des tissus mous. Les complications de la KTWS comprennent la thrombose veineuse profonde, l'embolie pulmonaire, les saignements gastro-intestinaux et les bulles vasculaires (habituellement lymphatiques) dans les malformations capillaires. Nous présentons un cas d'un jeune patient mâle avec KTWS qui a présenté une thrombose veineuse superficielle et une anémie hémolytique microangiopathique dans une présentation semblable à la coagulation intravasculaire disséminée. Il a finalement été maintenu sur des rivaroxaban prophylactiques pour prévenir les épisodes récurrents de purpura. Nous avons effectué une recherche documentaire pour identifier des cas similaires et pour résumer les caractéristiques communes de présentation et les modalités de traitement qui ont été offerts.&#x0D; &#x0D; &#x0D;

Tinzaparin in intermediate dose for the treatment of superficial vein thrombosis: Results from an observational multicenter study-SeVEN study.

Objectives Low-molecular-weight heparins are recommended in the treatment of superficial vein thrombosis but with low grade of evidence. This study was conducted to assess the treatment outcomes of acute superficial vein thrombosis with intermediate dose of Tinzaparin. Methods Retrospective analysis of records from outpatients over a period of 16 months treated in seven centers with Tinzaparin 0.5 ml (10,000 anti-Xa IU) once daily for a period that was at the treating physician's discretion. All the patients were followed up for at least 12 weeks. Results A total of 296 patients (189 females, mean age 57.4 years) were included. Two thirds of the patients (191/296, 64.5%) received treatment for approximately five weeks (mean 36.9 days) and the remaining (105/296, 35.5%) for a shorter period (mean 16.2 days). There was no difference in patients' characteristics between the two treatment duration groups. The presence of thrombus above the knee and restricted daily activity were associated with longer period of treatment. Only one case with minor bleeding was observed. Recurrence of thrombosis over a 12-week follow-up period occurred in 6% (superficial vein thrombosis in 14 (4.7%), deep vein thrombosis in 3 (1%) and thrombus extension in the superficial veins in 1 (0.3%)). Recurrence was not related to the duration of treatment. Conclusions Intermediate dose of Tinzaparin was an effective and safe treatment for superficial vein thrombosis in the setting of real world practice. Location of thrombus and status of patients' mobilization were associated with longer duration of treatment. Future prospective randomized studies are needed to corroborate these findings.

Medical management of acute superficial vein thrombosis of the saphenous vein.

Acute superficial vein thrombosis (SVT) of the axial veins, such as the great saphenous vein (GSV), is a common clinical condition that carries with it significant risk of propagation of thrombus, recurrence, and, most concerning, subsequent venous thromboembolism (VTE). Conservative therapy with nonsteroidal anti-inflammatory medication and heat does not prevent extension of thrombus or protect against recurrent or future VTE in patients with extensive SVT (thrombotic segment of at least 5cm in length). To prevent future thromboembolic events, anticoagulation has become the treatment of choice for extensive acute SVT in the GSV. In spite of this, the dose and duration of anticoagulation in the treatment of SVT vary widely. This review summarizes the evidence from large prospective, randomized clinical trials on the treatment of SVT with anticoagulation (vs placebo or different doses and durations of anticoagulation) with respect to the outcome measures of thrombus extension, SVT recurrence, and future VTE. A systematic search was performed using the MEDLINE database to identify all prospective, randomized controlled trials of treatment with anticoagulation in patients with SVT in the GSV. Six prospective, randomized trials were identified that met the inclusion criteria and were reviewed in detail. Treatment of acute SVT was most commonly managed in an outpatient setting using either low-molecular-weight heparin (LMWH) in four studies or, alternatively, a factor Xa inhibitor in one large multicenter trial. LMWH was associated with a lower rate of thrombus extension and subsequent recurrence, especially when an intermediate dose (defined as a dose between prophylactic and therapeutic doses) was used for a period of 30days. The full effect of treatment with LMWH on the risk of subsequent VTE remains unclear, as do the optimal dose and duration of this drug. Prophylactic doses of fondaparinux, a factor Xa inhibitor, were found to be beneficial in reducing the rate of thrombus extension and recurrence as well as in reducing the risk of subsequent VTE both during treatment and after cessation of anticoagulation in the short term. These data suggest that treatment of acute SVT of the GSV with anticoagulation, at doses below therapeutic levels, does offer the benefit of decreased risk of thrombus propagation, recurrence, and, at least in one largerandomized clinical trial, subsequent VTE. Future studies to refine optimal dose and duration of anticoagulation tolower the rate of subsequent thromboembolic events and SVT recurrence are needed.

Rationale, design, and methodology of the observational INSIGHTS-SVT study on the current state of care and outcomes of patients with superficial vein thrombosis.

Superficial vein thrombosis (SVT) is a common disease in clinical practice. In terms of pathophysiology and outcomes, the condition is related to venous thromboembolism, bearing a potential for severe thromboembolic complications if it is not treated adequately. A wide range of treatment approaches (including oral and injectable anticoagulants, pain medication, nondrug therapy including compression therapy, and no treatment at all) are applied in clinical practice, but there is sparse information about selection of patients for therapies, current treatment pathways, and drug use as well as outcomes. The INvestigating SIGnificant Health TrendS in the management of Superficial Vein Thrombosis (INSIGHTS-SVT) study aims to close this gap by collecting representative data on the current treatmentof SVT. The observational prospective study of about 1200 patients is carried out by up to 120 clinical and office-based physicians who regularly treat patients with SVT and are capable of conducting appropriate compression ultrasound diagnostics, such as vascular physicians, phlebologists, internists, vascular surgeons, and general practitioners. Patients are eligible for inclusion if they have ultrasound-confirmed acute, isolated SVT of the lower extremities. Documentation about the characteristics of the patients, diagnostics, comorbidities, and medical and nonmedical treatment is collected at baseline, at 10± 3days or at approximately 45days (depending on treatment), at approximately 3months, and at approximately 12months. Patients are requested to fill in quality of life questionnaires (on pain, Venous Insufficiency Epidemiological and Economic Study on Quality of Life/Symptoms [VEINES-QOL/Sym], EuroQol-5 Dimension 5-Level [EQ-5D-5L]) at baseline and at approximately 3months. Interventions are not stipulated by the trial protocol. The primary efficacy outcome is the incidence of venous thromboembolism at 3months; the primary safety outcome is the combined incidence of major and clinically relevant bleeding events at 3months. As quality measures, plausibility checks at data entry, queries based on statistical analyses that focus on outliers and distribution of values, monitoring visits, and adjudication procedures will be applied. This large study is expected to provide a comprehensive picture of patients with SVT under clinical practice conditions in Germany.

ASH Meeting 2016: developments in hemostaseology.

SummaryDuring the annual meeting of the American Society of Hematology (ASH) in San Diego/California, novel developments in the field of hemostaseology were presented. Alternative treatment strategies besides factor replacement were discussed for patients with hemophilia. One of the highlights of the meeting in this year’s plenary session was the presentation of successful adeno-associated virus mediated gene transfer in patients with hemophilia B leading to sustained elevation of factor IX:C (FIX:c). Other alternative treatment approaches in patients with hemophilia A may include bispecific antibodies mimicking factor VIIIa (FVIIIa) activity or disrupting anticoagulant proteins. Focusing on anticoagulation, data on the use of direct oral anticoagulants (DOACs) in cancer patients with atrial fibrillation as well as treatment of superficial vein thrombosis with rivaroxaban were presented. In this short review, we try to highlight the most important presentations during the ASH meeting 2016.

Rivaroxaban Versus Fondaparinux in the Treatment of Superficial Vein Thrombosis - the Surprise Trial

▪BackgroundThe current standard of therapy in superficial vein thrombosis (SVT) comprises subcutaneous injections of the indirect factorXainhibitorfondaparinuxfor up to 45 days, which was highlyeffectivecompared to placebo in the CALISTO trial. However,fondaparinuxis expensive, requires daily injections and cost-effectiveness in SVT therapy has been questioned. Rivaroxaban is a direct oral factorXainhibitor which has been shown to be effective in the prevention and treatment of venous thromboembolism (VTE). We hypothesizedthat SVT patientsat high risk for VTE complications may be treated as efficacious and safe with rivaroxaban as withfondaparinux.MethodsThe SURPRISE trial, a randomized, open-label blinded outcome event adjudication trial, compared rivaroxaban 10 mg once daily withfondaparinux2.5 mg once daily in patients with SVT at high risk of VTE complications (defined assupragenualSVT + age > 65 years, male sex, previous VTE, cancer, autoimmune disease or SVT of non-varicose veins). Treatment duration for both treatments was 45+5 days with an observational period until day 90+10. The primary efficacy outcome was a composite endpoint of deep vein thrombosis, pulmonary embolism, SVT progression towards thesaphenofemoraljunction, SVT recurrence or all cause death in the per-protocol analysis at day 45. A predefined sensitivity analysis was performed in all randomized patients (full analysis set). The primary safety outcome was the rate of ISTH major bleeding during treatment. Further outcome measures included the composite efficacy outcome up to day 90, each component of the primary efficacy outcome, rates of surgical treatment of SVT and rates of major VTE (composite of symptomatic PE or symptomatic proximal DVT or VTE-related death) at days 45 and 90. The trial was designed to test for non-inferiority of rivaroxaban compared tofondaparinuxwith respect to the primary efficacy outcome and to the rates of ISTH major bleeding.ResultsA total of 472 patients were randomized (mean age 60.3 years; 60.4% female) and treated with rivaroxaban (n=236) orfondaparinux(n=236). Mean treatment duration was 44.0 days for rivaroxaban and 44.8 days forfondaparinux. Until day 45+5, the primary efficacy outcome (n=435 in per-protocol analysis set) occurred in 3.3% (95%-CI 0.90; 5.73) of patients treated with rivaroxaban and 1.8% (95%-CI 0.05; 3.52) of patients receivingfondaparinux(absolute difference between rivaroxaban andfondaparinuxwas 1.53%; one-sided upper CI limit 4.03%; p-value for non-inferiority 0.025; table 1 and figure 1). Until day 90+10, the respective rates were 7.1% for rivaroxaban and 6.7% forfondaparinux(absolute difference 0.41;one-sided upper CI limit 4.41%;p-value for non-inferiority 0.047). Non-inferiority of rivaroxaban vs.fondaparinuxwas preserved in the full analysis set.No major bleeding occurred and rates of non-major, clinically relevant bleeding were 2.5 vs. 0.4% for day 45+5 and 2.5 vs. 0.9% for day 90+10 in safety set for rivaroxaban andfondaparinux, respectively (table 1).Mean±SDadherence (pill/syringe count at day 45) was 98.9±13.4% for rivaroxaban and 99.3±6.2% forfondaparinux(full analysis set).ConclusionsIn high-risk SVT patients, rivaroxaban was non-inferior tofondaparinuxin preventing thromboembolic complications with comparable safety. VTE events were predominantly SVT recurrence. Few cases of DVT and PE occurred, which indicates that a 45 days course of rivaroxaban 10 mg orfondaparinux2.5 mg is sufficient to prevent serious complications in this specific subset of SVT patients. As to whether oral rivaroxaban offers a better quality of life compared to 45 days of injections, this has to be investigated in future studies.We found higher SVT complications rates in both treatment arms compared to thefondaparinuxarm in the CALISTO trial. Therefore, patients at higher VTE risk can be identified by use of a simple risk factor assessment, which may help to improve cost-effectiveness of SVT therapy. However, the concept of SVT risk stratification needs to be further investigated, since patients without additional risk factors may not need anticoagulant therapy at all.(Funded by Bayer Vital GmbH, Germany, ClinicalTrials.gov NCT01499953)In response to a pre-submission enquiry, the New England Journal of Medicine indicated potential interest in the study results and a simultaneous publication/presentation is targeted. [Display omitted] [Display omitted] DisclosuresBeyer-Westendorf:Daichii Sankyo: Consultancy, Honoraria, Research Funding; Boehringer Ingelheim: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria, Research Funding; LEO: Consultancy, Honoraria, Research Funding. Schellong:Bayer: Honoraria; Pfizer: Honoraria; Boehringer-Ingelheim: Honoraria; Daichii Sankyo: Honoraria; LeoPharma: Honoraria. Gerlach:ASPEN: Honoraria; Bayer: Honoraria; Boehringer-Ingelheim: Honoraria; LeoPharma.: Honoraria. Rabe:Bayer: Honoraria; Boehringer Ingelheim: Honoraria; Daichii-Sankyo: Honoraria; LeoPharma: Honoraria; Pfizer: Honoraria. Bauersachs:Bayer: Honoraria, Research Funding; Boehringer Ingelheim: Honoraria, Research Funding; BristolMyers Squibb: Honoraria, Research Funding; Daiichi Sankyo: Honoraria, Research Funding; ASPEN: Honoraria, Research Funding.

The safety of fondaparinux sodium for the treatment of venous thromboembolism

ABSTRACTIntroduction: Venous thromboembolism (VTE) is a common and potentially fatal disease. Fondaparinux is a synthetic agent able to act on single factors involved in the coagulation network, which could be administered at fixed doses and with a more predictable response.Areas covered: This review will focus on the efficacy and safety of fondaparinux in the treatment of major VTE (deep vein thrombosis and pulmonary embolism) and in the treatment of superficial vein thrombosis (SVT).Expert opinion: Results of high quality randomized controlled trials have clearly shown the efficacy and safety of fondaparinux in comparison to conventional treatment in patients with a major VTE. There are limited evidences on the safety and efficacy of different options in patients presenting with SVT. Fondaparinux has been evaluated in a large population of patients presenting with a SVT. Results of this high quality RCT provided the evidence on the efficacy and safety of fondaparinux 2.5 mg s.c./day for 45 days in this setting. Thus, considering the evidence of the literature and thanks to its pharmacokinetic and pharmacodynamic characteristics, fondaparinux represent a valid treatment option for both the acute management of patients with major VTE, and for the treatment of SVT.