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Introduction The epidemiology of isolated distal deep venous thrombosis (iDDVT) among cancer patients is not well described, particularly the incidence of recurrent venous thromboembolism (rVTE) and effect on mortality by cancer type.Methods The cumulative incidence (CI) of iDDVT was determined for patients with 13 common cancers between 2005 and 2017 using the California Cancer Registry linked to the California Patient Discharge and Emergency Department Utilization datasets. The CI of rVTE was calculated and association of incident cancer-associated thrombosis (CT) location with rVTE was determined using Cox proportional hazards regression models. The association of incident CT location with overall and cancer-specific mortality was determined using Cox models, stratified by cancer site, and adjusted for individual characteristics.Results Among 942,109 cancer patients, CT occurred in 62,003 (6.6%): of these, 6,841 (11.0%) were iDDVT. Compared with more proximal sites of CT, iDDVT was associated with similar risk for rVTE. IDDVT was associated with increased mortality across all cancer types when compared with patients without CT (hazard ratio: 1.56-4.60). The effect of iDDVT on mortality was similar to that of proximal DVT (pDVT) for most cancers except lung, colorectal, bladder, uterine, brain, and myeloma, where iDDVT was associated with a lesser association with mortality.Conclusion iDDVT represented 11% of CT. The risk of rVTE after iDDVT was similar to other sites of CT and rVTE occurred in more proximal locations after an incident iDDVT. IDDVT was associated with increased mortality and this effect was similar to that of pulmonary embolism or pDVT for most cancer types.

Isolated distal deep vein thrombosis (IDDVT) is a common clinical presentation of DVT. The efficacy and safety of anticoagulant therapy for the management of IDDVT in patients with cancer are unclear. We sought to assess the incidence of recurrent venous thromboembolism (VTE) and major bleeding in this patient population. A systematic search of MEDLINE, EMBASE and PubMed, from inception to June 2, 2022 was performed. The primary efficacy outcome was recurrent VTE and the primary safety outcome was major bleeding. The secondary outcomes were clinically relevant non-major bleeding (CRNMB) and mortality. The incidence rates of thrombotic, bleeding, and mortality outcomes were pooled using random effects model and expressed as events per 100 patient-months with associated 95 % confidence intervals (CI). Out of a total of 5234 articles, 10 observational studies including 8160 patients with cancer and IDDVT were included in the analysis. The incidence rate of recurrent VTE was 5.65 (95 % CI: 2.09–15.30) per 100 patient-years regardless of type and duration of anticoagulant therapy. The incidence rate of major bleeding was 4.08 (95 % CI: 2.52–6.61) per 100 patient-years. The incidence rates for CRNMB and mortality per 100 patient-years were 8.11 (95 % CI: 5.56–11.83) and 30.22 (95 % CI: 22.60–40.42.89), respectively. Patients with cancer and IDDVT are at high risk of developing recurrent VTE and bleeding complications (both major bleeding and CRNMB). More studies are needed to define the optimal management for this high-risk population. • Patients with cancer and isolated distal deep vein thrombosis (IDDVT) are at high risk of recurrent events and bleeding. • The risk of recurrent events in patients with cancer and IDDVT is higher than in patients without cancer. • In the setting of cancer, the risk of recurrent events is similar between patients with IDDVT and proximal DVT after anticoagulation discontinuation. • These risks need to be considered when deciding on the use of anticoagulant therapy. [ABSTRACT FROM AUTHOR]

Isolated distal deep vein thrombosis (IDDVT) is presumed to be more benign than proximal DVT (PDVT) or pulmonary embolism (PE), suggesting a need for different management approaches. This subgroup analysis of the RE-COVERY DVT/PE global, observational study investigated patient characteristics, hospitalization details, and anticoagulant therapy in patients with IDDVT in real-world settings in 34 countries enrolled from January 2016 to May 2017. Data were analyzed descriptively according to the type and location of the index venous thromboembolism (VTE): IDDVT, PDVT ± distal DVT (DDVT), and PE ± DVT. Of the 6,095 eligible patients, 323 with DVT located outside the lower limb and no PE were excluded. Of the remaining 5,772 patients, 17.6% had IDDVT, 39.9% had PDVT ± DDVT, and 42.5% had PE ± DVT. IDDVT patients were younger and had fewer risk factors for VTE than the other groups. Other comorbidities were less frequent in the IDDVT group, except for varicose veins, superficial thrombophlebitis, and venous insufficiency. IDDVT patients were less likely to be diagnosed in an emergency department (22.3 vs. 29.7% for PDVT ± DDVT and 45.4% for PE ± DVT) or hospitalized for VTE (29.2 vs. 48.5% for PDVT ± DDVT and 75.0% for PE ± DVT). At hospital discharge or 14 days after diagnosis (whichever was later), non–vitamin K antagonist oral anticoagulants were the most commonly used anticoagulants (55.6% for IDDVT, 54.7% for PDVT ± DDVT, and 52.8% for PE ± DVT). Although differences in patient characteristics, risk factors, and clinical management were identified, anticoagulant treatment of IDDVT was almost equal to that of PDVT or PE. Prospective studies should investigate whether, in a global perspective, this is an appropriate use of anticoagulants. [ABSTRACT FROM AUTHOR]

Treatment of low-risk patients with isolated symptomatic distal deep vein thrombi (IDDVT) is uncertain. Objective: assess whether two weeks of therapeutic anticoagulation is efficacious/safe for IDDVT. Primary outcome: symptomatic three-month venous thromboembolism (VTE) incidence in the two-week anticoagulation group. Secondary outcomes included post-thrombotic syndrome (PTS) and bleeding. Prospective multicentre cohort study. Consecutive low-risk IDDVT patients enrolled within 72 h of diagnosis and treated with therapeutic dose enoxaparin or rivaroxaban. At two weeks, patients had repeat complete whole leg compression ultrasound (CUS)/clinical review. If resolution of leg symptoms AND no radiological evidence of thrombus extension, anticoagulation was stopped. If ongoing symptoms and/or radiographic extension within distal veins, anticoagulation was continued for four more weeks. Patients with extension into the popliteal vein on two-week ultrasound were treated off-study. Patients were reviewed at three and six months. 241 eligible patients received ≥2 weeks anticoagulation. 167/241 (69%) were assigned to the 2-week anticoagulation group; 71/241 (30%) to the six-week anticoagulation group; 3/241 patients (1%) had extension into the popliteal vein on two-week CUS. Two patients in the two-week anticoagulation group had symptomatic IDDVT recurrence in ≤3 months; VTE recurrence 2/156; 1.3%(95% CI 0.05–4.85%). 69% of patients had complete resolution of symptoms within two weeks. Six-month PTS rates were 8/184, 4.4%(95% CI 2.1–8.5%). No major bleeding was reported. Our findings suggest it's safe/efficacious to stop therapeutic anticoagulation at two weeks in low-risk IDDVT patients with resolution of symptoms/no extension on ultrasound. This could replace 6–12 weeks of anticoagulation for ambulatory, low-risk IDDVT patients. ClinicalTrials.gov NCT01252420 • The optimal treatment for isolated distal deep vein deep vein thrombosis (IDDVT) is uncertain. • This was a multicentre prospective cohort study enrolling consecutive patients with IDDVT. • Two weeks of anticoagulation achieved symptomatic relief in the majority of patients with low-risk IDDVT (69%). • Two weeks of anticoagulation was associated with a low risk of recurrent venous thromboembolism (VTE); 1.3%. [ABSTRACT FROM AUTHOR]

Distal or calf deep vein thrombosis (DVT) are said to have low rates of propagation, embolization, and recurrence. The objective of this study was to determine outcomes among cancer patients with calf DVT compared to those without cancer. Consecutive patients with ultrasound confirmed acute calf DVT (3/1/2013–8/10/2019) were assessed for venous thromboembolism (VTE) recurrence and bleeding outcomes compared by cancer status. There were 830 patients with isolated calf DVT; 243 with cancer and 587 without cancer. Cancer patients were older (65.9 ± 11.4 vs. 62.0 ± 15.9 years; p = 0.006), with less frequent recent hospitalization (31.7% vs. 48.0%; p < 0.001), surgery (30.0% vs. 38.0%; p = 0.03), or trauma (3.7% vs. 19.9%; p < 0.001). The four most common cancers included hematologic malignancies (20.6%), lung (11.5%), gastrointestinal (10.3%), and ovarian/GYN (9.1%). Nearly half of patients had metastatic disease (43.8%) and 57% were receiving chemotherapy. VTE recurrence rates were similar for patients with (7.1%) and without cancer (4.0%; p = 0.105). Major bleeding (6.3% vs. 2.3%; p = 0.007) were greater for cancer patients while clinical relevant non major bleeding rates did not differ (7.1% vs. 4.6%; p = 0.159). In this retrospective analysis, cancer patients with calf DVT have similar rates of VTE recurrence but higher major bleeding outcomes compared to patients without cancer. [ABSTRACT FROM AUTHOR]

Isolated distal deep vein thrombosis (DVT) represents up to 50% of all lower limb DVT in ultrasound series and is a frequent medical condition, which management is not well established. Data arising from registries and non-randomized studies suggest that most distal DVTs do not extend to the proximal veins and have an uneventful follow-up when left untreated. This data had some impact on international recommendations like the American College of Chest Physicians (ACCP), whose last version stated that ultrasound surveillance might be an option for selected low-risk patients. However, robust data arising from randomized studies are scarce. Indeed, only seven randomized trials assessing the need for anticoagulation for calf DVT have been published. Many of these trials had an open-label design and were affected by methodological limitations. When considering randomized placebo-controlled trials, one included low-risk patients and was hampered by a limited statistical power (CACTUS study). Nevertheless, data from this trial tend to confirm that the use of therapeutic anticoagulation in low-risk patients with symptomatic calf DVT is not superior to placebo in reducing VTE but is associated with a higher risk of bleeding. A second randomized placebo-controlled trial did not assess the necessity of anticoagulant treatment but rather the long-term risk of recurrence and compared 6 weeks versus 12 weeks of treatment with rivaroxaban (RIDTS study). Finally, the last available randomized trial compared a 3-month versus a 12-month edoxaban treatment in patients with cancer and mainly asymptomatic distal DVT, detected by systematic compression ultrasonography. Overall, available data suggest that the use of therapeutic anticoagulation in low-risk patients with symptomatic calf DVT is not superior to placebo in reducing VTE. High risk patients (previous VTE, active cancer, inpatients) might benefit from a course of anticoagulant treatment. However, the optimal anticoagulant intensity and duration are uncertain and further studies are needed.

Objective: Thrombi in the axial calf veins have quite different anatomical and physiological characteristics from that in the muscular calf veins, but their treatment was usually addressed in the same manner. We performed a meta-analysis of randomized and cohort studies to compare clinical outcomes among patients with isolated axial vs muscular calf deep vein thrombosis (DVT)., Methods: Recurrent venous thromboembolism (VTE) was selected as the primary outcome. Resolution, proximal propagation of calf DVT, pulmonary embolism (PE), major bleeds, and clinically relevant non-major bleeds were separately analyzed as secondary outcomes. Data were pooled and compared with risk ratio (RR) and 95% confidence interval (CI)., Results: Thirteen studies, consisting of 4889 patients, met the inclusion criteria and were included for analysis. A greater rate of recurrent VTE (FE model: RR, 1.23; 95% CI, 1.00-1.53; I 2  = 29%), resolution (FE model: RR, 1.32; 95% CI, 1.01-1.72; I 2  = 31%), proximal propagation (FE model: RR, 1.63; 95% CI, 1.10-2.41; I 2  = 40%), and PE (FE model: RR, 2.79; 95% CI, 1.31-5.95; I 2  = 0%) in the axial group compared with the muscular group. There was no difference in the pooled estimates for major bleeds (FE model: RR, 1.09; 95% CI, 0.61-1.95; I 2  = 0%), and clinically relevant non-major bleeds (FE model: RR, 1.80; 95% CI, 0.93-3.48) in the axial and muscular arms., Conclusions: Patients with calf DVT limited to muscular veins might have a lower rate of recurrent VTE, resolution, proximal propagation, and PE vs those with axial calf vein involvement and exhibited similar safety outcomes., Competing Interests: Disclosures None., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Recent years have witnessed an onslaught of large, multicenter, randomized controlled trials evaluating the prevention and management of thrombotic vascular diseases. While these trials have applied rigorous methodology to pragmatic and clinically relevant questions, several important gaps in knowledge remain. In this review, we critically appraise landmark studies in thrombosis published between 2016 and 2017 that address several ongoing areas of clinical uncertainty. Specifically, we review the role of endovascular therapy in the prevention of post-thrombotic syndrome following acute lower limb deep vein thrombosis (DVT) (ATTRACT trial), the efficacy of edoxaban as the first direct oral anticoagulant used for the treatment of cancer-associated thrombosis (HOKUSAI VTE-Cancer study), whether aspirin can be considered for thromboprophylaxis post-major orthopedic surgery (EPCAT-2 trial), and the need for anticoagulant therapy for treatment of isolated distal DVT (CACTUS trial). Using illustrative cases, we highlight the applicability of these trials to current practice and emphasize the unanswered questions that remain. [ABSTRACT FROM AUTHOR]

Abstract Background and aims Women present with pulmonary embolism (PE) more often than men, while the opposite is true for proximal deep vein thrombosis (DVT). We investigated whether sex-specific differences exist in the presenting location of acute symptomatic DVT among patients without concomitant PE. Methods We tested our hypothesis in a meta-analysis of studies selected by systematically reviewing PubMed, Embase, and the grey literature. Thereafter, we analysed data of a single-center cohort including patients with first isolated acute DVT to assess the additional impact of age and provoking risk factors on the presenting location of DVT. Results We identified 7 studies for a total of 20,534 patients. The weighed pooled absolute difference in the proportion of distal DVT between women and men was +5.4% (95%CI: +0.7%; +9.5%), which corresponds to a pooled odds ratio (OR) of 1.30 (95%CI: 1.07–1.58). This difference was +6.5% (95%CI: +2.1%; +10.9%) for first distal DVT (OR 1.38; 95%CI: 1.11–1.72) and +5.3% (95%CI: +0.5%; +10.0%) for either first or recurrent distal DVT (OR 1.29; 95%CI: 1.03–1.61). In the cohort study, the larger difference in the proportion of distal DVT between women and men was observed among patients aged 51–70 (+9.5%; 95CI: +2.8%; +16.0% compared to those aged 18–50) or with unprovoked events (+8.5%; 95CI: −0.9%; +17.9%). Conclusions Among patients with first symptomatic isolated acute DVT, women presented with distal DVT more often than men, whereas men had a higher proportion of proximal DVT events. This pattern appeared to depend on age and the absence of provoking risk factors for VTE. Highlights • The proportions of pulmonary embolism versus proximal deep vein thrombosis (DVT) events differ between sexes. • We investigated whether the distal versus proximal presenting location of isolated DVT is influenced by sex. • Women presented with distal DVT more often than men, whereas men had more often proximal DVT. • This pattern appeared to depend on age and the absence of provoking risk factors, but further studies are warranted. [ABSTRACT FROM AUTHOR]

After acute proximal deep vein thrombosis (DVT) the thrombotic mass decreases, especially during the first months of anticoagulation. The persistence of residual vein obstruction (RVO) may predict future recurrence in patients with cancer-associated DVT. We aimed to evaluate the proportion of patients with RVO after an episode of cancer associated isolated distal DVT (IDDVT), to identify variables associated with RVO, and to provide initial evidence of its association with recurrent VTE. We performed a post-hoc analysis of a multicenter cohort study of patients with isolated cancer-associated acute IDDVT. We included patients who underwent a control ultrasonography at the end of the anticoagulant treatment between day 30 and day 365 after index IDDVT, given that no recurrent VTE had already occurred on anticoagulant treatment. A total of 153 patients had ultrasonographic follow-up after a median of 92 days from index IDDVT: 45.8% had RVO and 54.2% exhibited complete recanalization. Female sex, Body Mass Index > 30 Kg/m2 and involvement of axial calf veins showed the strongest association with RVO. The risk of recurrence was twofold higher in patients with (versus without) RVO. RVO persisted in approximately half of patients with an episode of cancer-associated IDDVT at anticoagulant discontinuation. Patients with RVO appeared to be at a higher risk for recurrent events. [ABSTRACT FROM AUTHOR]

Isolated distal deep vein thrombosis (DVT), also known as calf DVT, represents up to 50% of all lower limb DVT in ultrasound series and is therefore a frequent medical condition. Unlike proximal DVT and pulmonary embolism (PE), which have been extensively studied and for which management is well standardized, much less is known on the optimal management of isolated calf DVT. Recent data arising from registries and non-randomized studies suggest that most distal DVTs do not extend to the proximal veins and have an uneventful follow-up when left untreated. This data had some impact on the international recommendations which recently stated that ultrasound surveillance instead of systematic therapeutic anticoagulation might be an option for selected low-risk patients. However, robust data arising from randomized studies are scarce. Indeed, only five randomized trials assessing the need for anticoagulation for calf DVT have been published. Many of these trials had an open-label design and were affected by methodological limitations. The only randomized placebo-controlled trial included low-risk patients (outpatients without cancer or previous venous thromboembolic events (VTE)) and was hampered by a limited statistical power. Nevertheless, data from this trial tend to confirm that the use of therapeutic anticoagulation in low-risk patients with symptomatic calf DVT is not superior to placebo in reducing VTE, but is associated with a significantly higher risk of bleeding. Further randomized studies are needed to define the best therapy for high-risk patients (inpatients, patients with active cancer or previous VTE), and the optimal dose and duration of treatment. [ABSTRACT FROM AUTHOR]

Background It is standard of care to treat proximal vein deep vein thrombosis ( DVT) for a minimum of 3 months. Conversely, management of isolated distal DVT ( IDDVT) is controversial, with options including observation and repeat ultrasound scan within 1 week to detect and anticoagulate those with proximal propagation, or anticoagulation for periods of up to 3 months. Aim The aim was to assess the rates of proximal propagation and venous thromboembolism ( VTE) recurrence within 3 months of diagnosis of IDDVT, and to examine how the duration of treatment might influence this. Methods Study patients were identified by retrospective audit of data from the North Shore Hospital VTE database. All patients presenting with established axial vein distal DVT from July 2007 to June 2012 were included. A 6-week treatment duration cut-off was used to separate the treatment arms (<6 weeks vs 6 weeks vs >6 weeks), and Fisher's exact or Pearson's Chi-squared tests were used to assess between-group comparisons. Results Five hundred and seven patients were included in the study, mean age 59.7 years; 53% female. There were three cases of proximal propagation, all occurring in those receiving <6 weeks treatment. There were six VTE recurrences, three in the <6 week and three in the ≥6 week treatment groups respectively. Malignancy was the only significant predictor of VTE recurrence ( P = 0.001). Conclusion A 6-week duration of anticoagulation appears to be an effective and safe treatment for isolated axial distal DVT, with low rates of VTE recurrence and proximal propagation. [ABSTRACT FROM AUTHOR]

Abstract: Isolated distal deep-vein thromboses (DVT) are infra-popliteal DVT without involvement of proximal veins or pulmonary embolism (PE). They can affect deep calf (tibial anterior, tibial posterior, or peroneal) or muscular (gastrocnemius or soleal) veins. They represent half of all lower limbs DVT. Proximal and distal DVTs differ in terms of risk factor profile, proximal DVT being more frequently associated with chronic risk factors and distal DVT with transient ones. Their natural history (rate of spontaneous proximal extension) is debated leading to uncertainties on the need to diagnose and treat them with anticoagulant drugs. In the long term, the risk of venous thromboembolic recurrence is lower than that of proximal DVT and their absolute risk of post-thrombotic syndrome is unknown. French national guidelines suggest treating with anticoagulants for 6 weeks a first episode of isolated distal DVT provoked by a transient risk factor and treating for at least 3 months unprovoked or recurrent or active cancer-related distal DVT. The use of compression stockings use is suggested in case of deep calf vein thrombosis. Ongoing therapeutic trials should provide important data necessary to establish an evidence-based mode of care, especially about the need to treat distal DVT at low risk of extension with anticoagulants. [Copyright &y& Elsevier]

The authors consider isolated distal deep-vein thrombosis (DVT) to be significant and recommend treating isolated symptomatic distal DVT in the same way as proximal lower-limb DVT. There is no guidance for the treatment of asymptomatic isolated distal DVT; however, certain triggers could be used to guide therapy. Our policy is as follows: all patients with distal DVT (asymptomatic and symptomatic) are given graduated compression stockings and early ambulation. We use anticoagulant therapy to treat asymptomatic distal DVT greater than 10 cm in length, or more proximal ones that are near the confluence of the venous trifurcation that forms the popliteal vein. Those patients with asymptomatic thrombi of 5-10 cm and with ongoing risk factors for propagation, for example immobilization or malignancy, generally receive treatment. We generally do not anticoagulate asymptomatic soleal vein and other small isolated distal DVT. We empirically watch untreated patients more closely, with repeat compression ultrasound scanning, and even continue anticoagulant thromboprophylaxis for varying lengths of time. [ABSTRACT FROM AUTHOR]

In the general population, serial imaging is recommended over anticoagulant therapy for below-knee deep vein thrombosis (BKDVT). However, no clinical trial in Asian patients with spinal cord injury and BKDVT has been performed. Therefore, we evaluated the natural course of BKDVT in patients with acute spinal cord injury. We retrospectively analyzed inpatients with spinal cord injury with BKDVT between 2016 and 2020. All patients underwent inpatient rehabilitation treatment and duplex ultrasonographic examination of both the lower extremities at follow-up. After screening 172 patients with acute spinal cord injury for deep vein thrombosis using duplex ultrasound, 27 patients with below-the-knee deep vein thrombosis were included in this study. The mean lower-extremity motor score (median, interquartile range) was 66.0, 54.0–74.5. Sixteen patients received a non-vitamin K antagonist oral anticoagulant (NOAC) for anticoagulation. None of the patients had proximal propagation according to the follow-up duplex ultrasonography. BKDVT disappearance was not significantly different between the NOAC treatment and non-treatment groups. Asian patients with spinal cord injury have a low incidence of venous thromboembolism and favorable natural history of BKDVT. We recommend serial imaging over anticoagulant therapy for BKDVT in these patients. [ABSTRACT FROM AUTHOR]

Objective: Although distal deep vein thrombosis (DDVT) has been more frequently diagnosed with the availability of better ultrasound imaging quality, the data on the best method to manage DDVT have been conflicting. The aim of the present review was to summarize the current and evidence-based recommendations for the diagnosis and management of DDVT and to provide a summary of the most recent societal guideline recommendations., Methods: A literature review of DDVT was performed. The PubMed databases were queried for articles on the epidemiology, risk factors, diagnosis, and management of DDVT., Results: The prevalence of isolated DDVT has been reported in a broad range. The reported risk factors include older age, active malignancy, a low degree of mobility, acute infection, and atrial fibrillation. With more evidence, anticoagulation therapy was found to be associated with a reduced risk of recurrent venous thromboembolism (VTE) and/or thrombus propagation compared with conservative management. However, anticoagulation was associated with an increased risk of bleeding in a number of studies. The rate of VTE recurrence ranged from 7% to 23% during a follow-up period ranging from 3 months to 8 years. The significant risk factors for VTE recurrence included cancer, older age, an unprovoked event, and inpatient status., Conclusions: Few studies have addressed the diagnosis and management of DDVT. Further research is needed to standardize the best approach to diagnose and treat DDVT., (Copyright © 2021 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: There is insufficient evidence regarding the optimal treatment method for distal deep vein thrombosis (DVT), including indications for anticoagulation therapy. Treatment results of patients with distal DVT were evaluated to clarify the risk factors that result in extension of distal DVT to the proximal vein and indications for anticoagulation therapy., Methods and results: Among 430 patients with DVT between January 2018 and December 2019, 253 were diagnosed with distal DVT; 41 patients who had already started anticoagulation therapy were excluded, and the remaining 212 were included as study subjects. Anticoagulation therapy was not started immediately; conservative treatment with compression stockings was performed. Ultrasonography after 2 weeks revealed thrombus disappearance in 39 patients (21%), and thrombus reduction in 38 patients (20%). In contrast, extension of thrombus to the proximal vein was noted in 12 patients (6.3%) and anticoagulation therapy was commenced. After 3 months, the thrombus had disappeared in 75 patients (52%). No patient developed pulmonary thromboembolism during follow-up. With respect to the risk factors for extension to proximal vein during conservative treatment, active cancer (P=0.03), prolonged bed rest (P<0.01), and D-dimer level >8µg/mL (P=0.01) were identified., Conclusions: It is reasonable to consider anticoagulation therapy in distal DVT patients with active cancer, prolonged bed rest or high D-dimer level.

Essentials Management of patients with calf deep vein thrombosis remains controversial. We conducted a post-hoc analysis of a placebo controlled LMWH randomized clinical trial. Pain was assessed using visual analogue scale at inclusion, one and six weeks. There was no difference in pain control between the two arms. SUMMARY: Background The optimal management of distal deep vein thrombosis (DVT) is highly debated. The only available placebo-controlled trial suggested the absence of clear benefit of anticoagulation. Many physicians feel that, beyond preventing thromboembolic complications, anticoagulation with low-molecular-weight heparin (LMWH) has the potential to improve pain control. Objectives To analyze whether LMWHs decrease pain in patients with distal deep vein thrombosis. Patients and methods Two-hundred and fifty-two patients included in a multicenter, placebo-controlled, randomized clinical trial of LMWH in patients with acute distal DVT and who were asked to rate their pain at inclusion and at each medical visit, using a visual analogue pain scale (VAS). Results One hundred and thirty patients were randomized in the therapeutic nadroparin arm and 122 patients were randomized in the placebo arm. Mean VAS values were 4.6 (standard deviation [SD] 2.5) at inclusion, 2.1 (SD 2.0) at 1 week and 0.4 (SD 1.2) at 6 weeks. We calculated the individual variation in VAS between inclusion and 1 week in patients in whom VAS was available at the two study time-points. There was no difference in the mean VAS reduction between patients treated with therapeutic nadroparin (n = 106) and with placebo (n = 109): -2.6 (SD 2.4) vs. -2.3 (SD 2.0) after 1 week and -4.4 (SD 2.8) vs. -4.0 (SD 2.4) after 6 weeks, respectively. The use of compression stockings was associated with a reduction in pain. Conclusion These data suggests that LMWH use does not improve pain control as compared with placebo in patients with acute distal DVT., (© 2019 International Society on Thrombosis and Haemostasis.)

Essentials Isolated distal deep vein thrombosis (IDDVT) is frequently associated with cancer. No study has specifically evaluated the long-term clinical course of cancer-associated IDDVT. Patients with cancer-associated IDDVT are at very high risk of symptomatic recurrence and death. We observed low rates of major bleeding during anticoagulation., Summary: Background Although isolated distal deep vein thrombosis (IDDVT) is frequently associated with cancer, no study has specifically evaluated the long-term clinical course of IDDVT in this setting. Aim To provide data on the rate of recurrent venous thromboembolism (VTE), major bleeding events and death in IDDVT patients with active cancer. Patients and Methods Consecutive patients with active cancer and an objective IDDVT diagnosis (January 2011 to September 2014) were included from our files. We collected information on baseline characteristics, IDDVT location and extension, VTE risk factors, and type and duration of anticoagulant treatment. Results A total of 308 patients (mean age 66.2 [standard deviation (SD), 13.2 years]; 57.1% female) with symptomatic IDDVT and a solid (n = 261) or hematologic (n = 47) cancer were included at 13 centers. Cancer was metastatic in 148 (48.1%) patients. All but three (99.0%) patients received anticoagulant therapy, which consisted of low-molecular-weight heparin in 288 (93.5%) patients. Vitamin K antagonists were used for the long-term treatment in 46 (14.9%) patients, whereas all others continued the initial parenteral agent for a mean treatment duration of 4.2 months (SD, 4.6 months). During a total follow-up of 355.8 patient-years (mean, 13.9 months), there were 47 recurrent objectively diagnosed VTEs for an incidence rate of 13.2 events per 100 patient-years. During anticoagulant treatment, the annual incidence of major bleeding was 2.0 per 100 patient-years. Conclusions Cancer patients with IDDVT have a high risk of VTE recurrence. Additional studies are warranted to investigate the optimal intensity and duration of anticoagulant treatment for these patients., (© 2017 International Society on Thrombosis and Haemostasis.)

Essentials The long-term risk of recurrence and death after distal deep vein thrombosis (DVT) is uncertain. We included subjects with first proximal or isolated distal DVT (IDDVT) and no pulmonary embolism. The risk of symptomatic and asymptomatic recurrence is lower after IDDVT (vs. proximal). IDDVT may be associated with a lower long-term risk of death, especially after unprovoked DVT., Summary: Background A few studies have focused on the risk of recurrence after first acute isolated distal deep vein thrombosis (IDDVT) compared with proximal DVT (PDVT), whereas the incremental risk of death has never been explored beyond the first 3 years after acute event. Methods Our single-center cohort study included patients with first symptomatic acute PDVT or IDDVT. Patients were excluded if they had concomitant pulmonary embolism (PE) or prior venous thromboembolism. The primary outcomes were symptomatic objectively diagnosed recurrent PDVT or PE and all-cause death. Results In total, 4759 records were screened and 831 subjects included: 202 had symptomatic IDDVT and 629 had PDVT. The median age was 66 years and 50.5% were women. A total of 125 patients had recurrent PDVT or PE during 3175 patient-years of follow-up: 109 events occurred after PDVT (17.3%) and 16 after IDDVT (7.9%). Annual recurrence rates were 4.5% (95% confidence interval [CI], 3.7-5.4%) and 2.0% (95% CI, 1.1-3.2%), respectively, for an adjusted hazard ratio (aHR) for IDDVT patients of 0.32 (95% CI, 0.19-0.55). Death occurred in 263 patients (31.6% [95% CI, 28.6-34.9%]) during 5469 patient-years of follow-up for an overall annual incidence rate of 4.8% (95% CI, 4.2-5.4%). The mortality rate was 33.5% (n = 211) in PDVT patients and 25.7% (n = 52) in IDDVT patients. The long-term hazard of death appeared lower for IDDVT patients (aHR, 0.75 [95% CI, 0.55-1.02]), especially after unprovoked events (aHR, 0.58 [95% CI, 0.26-1.31]). Conclusions Compared with PDVT, IDDVT patients were at a lower risk of recurrent VTE. The risk of death appeared lower after IDDVT during a median follow-up of 7.6 years., (© 2017 International Society on Thrombosis and Haemostasis.)

Essentials The optimal management of isolated distal deep vein thrombosis (IDDVT) is undefined. This meta-analysis aimed to assess the clinical benefit of anticoagulation for IDDVT. Anticoagulation reduced the rate of pulmonary embolism without increasing major bleeding risk. Recurrent thromboembolism was less common with more than 6 weeks vs. 6 weeks of anticoagulation., Summary: Background The optimal management of patients with isolated distal deep vein thrombosis (IDDVT), concerning both the need for anticoagulation and its duration, is undefined. Objectives We performed a meta-analysis of randomized and cohort studies in patients with IDDVT to assess the clinical benefit of: (i) anticoagulation versus no anticoagulation; and (ii) anticoagulant treatment for 6 weeks versus for > 6 weeks. Methods The primary outcome of this analysis was recurrent venous thromboembolism (proximal propagation, recurrence of deep vein thrombosis, and pulmonary embolism). Data were pooled and compared by the use of odds ratio (OR) and 95% confidence interval (CI). Results A reduction in the rate of recurrent venous thromboembolism was observed in patients who received anticoagulation relative to those who did not receive anticoagulation (either therapeutic or prophylactic) (20 studies, 2936 patients; OR 0.50, 95% CI 0.31-0.79), without an increase in the risk of major bleeding (OR 0.64, 95% CI 0.15-2.73). The rate of pulmonary embolism was lower in anticoagulant-treated patients than in controls (15 studies, 1997 patients; OR 0.48, 95% CI 0.25-0.91). A lower rate of recurrent venous thromboembolism was observed in patients who received > 6 weeks of anticoagulant therapy than in those who received 6 weeks of anticoagulant therapy (four studies, 1136 patients; OR 0.39, 95% CI 0.17-0.90). Conclusions In patients with IDDVT, anticoagulation (both therapeutic and prophylactic) reduces the rate of recurrent venous thromboembolism and the incidence of pulmonary embolism as compared with no anticoagulation, without an increased risk of major bleeding. Anticoagulation for > 6 weeks should be preferred over shorter durations., (© 2017 International Society on Thrombosis and Haemostasis.)