Effect of exercise after a deep venous thrombosis: A systematic review.

Post-thrombotic syndrome (PTS) is a common complication after deep vein thrombosis (DVT) and has a major impact on physical symptoms, quality of life (QoL) and economic costs. Relatively simple lifestyle interventions as physical exercise might reduce PTS severity and increase QoL. To evaluate the direct and long-term effects of physical activity in patients with an acute or previous DVT. We conducted a systematic review through an additional search from 2007 up to March 2022, to complement the comprehensive systematic review of Kahn et al. Articles evaluating the effect of exercise after a DVT including symptoms, QoL and the incidence and severity of PTS, were included. Quality of the studies was assessed using a GRADE-like checklist and results were reported according to the PRISMA Statement. Ten studies were included, seven randomized controlled trials and three cohort studies. We identified three types of physical activity based on timing and duration; (1) early mobilisation in the acute phase of the DVT; (2) short duration exercise 1 year after DVT and (3) prolonged exercise during follow-up after a previous DVT. Early mobilisation showed improvement in QoL and pain reduction and after 2 years it resulted in a significant reduction of PTS severity. Prolonged supervised exercise resulted in improvement of QoL. In addition, positive effects on symptoms of venous insufficiency and muscle functions were observed. None of the included studies reported an increased risk of PTS or worsening of symptoms due to physical activity. Physical exercise after a DVT is safe, improves QoL, reduces pain and decreases PTS severity. Lifestyle intervention such as guided individualized training programs can be a useful supplementary therapy for patients after a DVT or for PTS patients. Optimal training programs may be identified by further studies that improve patient-oriented outcomes for both adults and children after a DVT.

Postthrombotic Syndrome and Chronic Pulmonary Embolism after Obstetric Venous Thromboembolism.

OBJECTIVE: While the majority of venous thromboembolism (VTE) during pregnancy events resolve with anticoagulation, long-term complications may occur including (1) postthrombotic syndrome and (2) chronic pulmonary embolism. The objective of this study was to determine risk of these two complications. STUDY DESIGN: A retrospective cohort study using the MarketScan databases was performed on deliveries from 2008 to 2014. We identified women aged 15 to 54 years diagnosed with acute VTE during pregnancy, the delivery hospitalization, or ≤60 days postpartum who received at least one prescription postpartum for anticoagulants. Risks of (1) chronic PE and (2) postthrombotic syndrome were evaluated for women at 6, 12, 24, and 60 months after delivery hospitalization through 2017 via the International Classification of Diseases, 9th/10th Revision, Clinical Modification codes. RESULTS: Of 4,267 of 4,128,900 pregnancies complicated by VTE, the majority had DVT alone (61.8%, n = 2,637), while 25.8% had PE alone (n = 1,103) and 12.4% (n = 527) had both DVT and PE. Of the entire cohort, 3,328 retained insurance coverage at 6 months, 2,823 at 12 months, 2,161 at 24 months, and 831 at 60 months. Restricted to DVT, risk of postthrombotic syndrome was 0.7% at 6 months (n = 17), 1.1% at 12 months (n = 22), 1.7% at 24 months (n = 26), and 2.7% at 60 months (n = 16). Among women with PE diagnoses, the risk of chronic PE was 2.4% at 6 months (n = 30), 3.3% at 12 months (n = 36), 4.2% at 24 months (n = 36), and 7.2% at 60 months (n = 24). CONCLUSION: In comparison to the general population, the risk of postthrombotic syndrome was lower. In comparison, the risk of chronic PE was similar to the estimates in the general population at comparable time points after PE events. For women with obstetric PE, it may be appropriate to be vigilant for findings and symptoms associated with chronic PE. KEY POINTS: · Risk of postthrombotic syndrome after obstetric deep vein thrombosis is low.. · Risk of chronic pulmonary embolism may approximate that in the general population.. · Overall risk of chronic complications after obstetric VTE was relatively low..

Venous stasis-induced fibrinolysis prevents thrombosis in mice: role of α2-antiplasmin.

Stasis of venous blood triggers deep vein thrombosis by activating coagulation, yet its effects on the fibrinolytic system are not fully understood. We examined the relationship between stasis, fibrinolysis, and the development of experimental venous thrombosis. Effects of stasis-induced deep vein thrombosis and fibrinolysis on thrombosis were examined by inferior vena cava ligation in congenic mice with and without α2-antiplasmin (α2AP), the primary inhibitor of plasmin. Venous thrombus weights were measured and thrombus composition was determined by Martius scarlet blue and immunofluorescence staining. Venous thrombi from α2AP+/+ mice contained plasminogen activators, plasminogen activator inhibitor-1, plasminogen, and α2AP, which changed with thrombus age. Normal, α2AP+/+ mice developed large, occlusive thrombi within 5 hours after ligation; thrombi were even larger in plasminogen-deficient mice (P < .001). No significant thrombus formation was seen in α2AP-/- mice (P < .0001) or in α2AP+/+ mice treated with an α2AP-inactivating antibody (P < .001). Venous stasis activated fibrinolysis, measured by D-dimer levels, in α2AP-/- mice vs α2AP+/+ mice (P < .05). Inhibition of fibrinolysis by the indirect plasmin inhibitor ε-aminocaproic acid or by α2AP restored thrombosis in α2AP-/- mice. In addition to its effects on acute thrombosis, thrombus formation was also markedly suppressed in α2AP-/- mice vs α2AP+/+ mice (P < .0001) 1, 7, and 14 days after ligation. We conclude that experimental venous stasis activates the fibrinolytic system to block the development of venous thrombosis. Suppression of fibrinolysis by α2AP appears essential for stasis-induced thrombus development, which suggests that targeting α2AP may prove useful for preventing venous thrombosis.

[Stenting of calcified iliofemoral venous segment in post-thrombotic syndrome]. / Stentirovanie kal'tsinirovannogo iliofemoral'nogo venoznogo segmenta pri posttromboticheskom sindrome.

Stenting of the iliac veins in patients with post-thrombotic syndrome is an intervention associated with a low risk of complications, high primary and secondary patency rates, low incidence of restenosis, leading to a significant decrease in the severity of symptoms of chronic venous disease and a high rate of trophic ulcer healing, as compared with conservative therapy. Unlike subcutaneous veins, the formation of calcinates in deep veins after endured thrombosis is of considerably less frequent occurrence. Described in the article is a clinical case report concerning successful stenting of the iliofemoral venous segment in a female patient presenting with post-thrombotic syndrome, a trophic ulcer of the crus, and the presence of linear calcinosis in the lumen of the iliac veins and common femoral vein. This case report demonstrates the possibilities of contemporary endovenous techniques in treatment of this cohort of patients. Despite calcified segments, stenting was performed without technical obstacles and with a favourable clinical outcome. Such interventions may be regarded as justified and safe provided the operating surgeon has appropriate skill and experience.

Symptoms Associated With Chronic Venous Disease in Response to a Cooling Treatment Compared to Placebo: A Randomized Clinical Trial.

PURPOSE: The purpose of this study was to examine the efficacy of a self-administered cooling treatment on clinically meaningful differences (CMDs) in symptom changes in patients with chronic venous disease. DESIGN: Blinded, prospective, randomized controlled trial. SUBJECTS AND SETTING: Two hundred seventy-six community-dwelling adults 21 years and older with skin changes and/or a healed venous leg ulcer (Clinical-Etiologic-Anatomic-Pathologic [CEAP] 4 and 5 classification) completed the 6-month active treatment period. METHODS: Participants were recruited from wound and medicine clinics and from the general population through referrals or advertisements. Participants were randomly allocated to a sham control cuff or interventional cooling cuff group. Demographic and symptom-specific data were collected at baseline and at months 1, 3, and 6 with the 11-item symptom Venous Insufficiency Epidemiological and Economic Study Quality of Life/Symptom (VEINES QOL/Sym) questionnaire subscale for heavy legs, aching legs, swelling, night cramps, heating or burning sensation, restless legs, throbbing, itching, tingling sensation (pins and needles), pain, and irritability. Participants in the intervention group received a cooling gel cuff and those in the control group received a cotton-filled cuff to be place around the most affected lower leg during leg elevation. Both groups received standard of care for their chronic venous disease with compression wraps and skin hygiene. Dosing consisted of daily 30-minute treatment for 1 month, twice weekly for 2 months, and then thrice weekly for 3 months. To analyze and compare data, a mixed percentage clinically meaningful percentage change was used to assess CMDs in symptoms between groups for treatment modality, sex, and age group. RESULTS: All symptoms showed improvement, with throbbing, aching, itching, and pain demonstrating the greatest CMD in response to the cooling treatment. For throbbing and aching, similar improvements were noted in response to cooling; 50% in the cooling group showed improvement, whereas 60% in both groups responded favorably to pain. More than 50% of females and males reported improvements in throbbing; both males and females reported 60% improvements in pain in response to cooling. In contrast, far fewer females reported worsening of aching in the treatment group as compared to male participants (8% vs 20%). Age differences were noted for throbbing in the younger group (<65 years of age); older individuals 65 years or older saw CMDs in aching in response to cooling. CONCLUSIONS: Of the 11 symptoms, aching, throbbing, itching, and pain had greater clinically meaningful improvements in response to a cooling cuff applied to lower leg skin affected by chronic venous disease. These CMDs inform evidence-based practice by enhancing clinician understanding of which symptoms, physical, physiological, and behavioral outcomes, respond to treatment change in a meaningful way for the patient.

Case 4: using octenilin Solution with the schülke WoundPad.

This case study demonstrates the use of a debridement pad with octenilin.

Impact of optimal anticoagulation therapy on chronic venous ulcer healing in thrombophilic patients with post-thrombotic syndrome.

OBJECTIVE: Post-thrombotic syndrome (PTS) is the long-term sequelae of deep venous thrombosis (DVT). PTS clinical manifestations include chronic leg pain, oedema, lipodermatosclerosis and ulcers. The objective of this study is to determine in patients with documented history of thrombophilias and DVT whether the number of previous thrombotic events and optimal anticoagulation therapy are associated with the time to venous ulcer healing following the start of compression therapy. METHOD: Retrospective analysis performed in thrombophilic patients under the age of 50 years old with chronic venous ulcers secondary to DVT at the wound clinic in the National Institute of Medical Sciences and Nutrition 'Salvador Zubirán ' in Mexico City. Variables such as the number or episodes of thrombotic events, type of hypercoagulable disorder, optimal anticoagulation therapy with Warfarin monitored by therapeutic International Normalised Ratio (INR) (2-3) and compliance to compression therapy were examined. Patients that underwent superficial or perforator vein interruption or endovascular recanalisation of deep veins were excluded from the study. RESULTS: From a database of 29 patients with chronic venous ulcers followed in our clinic from January 1992 to September 2012, only 13 patients (61% female) met the inclusion criteria. Mean age±standard deviation (SD) was 32±12 years old. Of these, seven (54%) patients with suboptimal INR presented with an average of two previous thrombotic events and the remaining six (46%) patients with optimal INR only one event (p=0.28), the mean time to the clinical manifestation of a venous ulcer after the first episode of DVT was 39 months (range: 12-72) for patients with suboptimal INR and 82 months (range: 12-216) for those with optimal anticoagulation therapy (p=0.11). During the mean follow-up period of 52 months, all patients in optimal anticoagulation healed their ulcer; their mean time for wound healing was 44 months (range: 4-102). In the suboptimal INR group, only four healed the ulcers with an mean of 72 months (range: 2-204) (p=0.94). CONCLUSION: There seems to be an association between an optimal anticoagulation therapy with Warfarin monitored by INR and wound healing rates in thrombophilic patients with chronic venous ulcers. Further research is warranted. DECLARATION OF INTEREST: The authors have no conflict of interest.

[Thrombosis and post-thrombotic syndrome as a consequence of an accident]. / Thrombose und postthrombotisches Syndrom als Unfallfolge.

Phlebothromboses represent alarming complications in accident victims since they can cause fatal pulmonary embolisms. More than half of those affected also develop post-thrombotic syndrome in the course of the illness. In addition to making clinical assessments, the traumatologist should also have fundamental knowledge about diagnostic methods and be familiar with interpreting internal findings. Colour-coded duplex sonography plays a central role in diagnosing thrombosis and in assessing functional limitations. Further information can be gathered from various phlebological procedures. The expert evaluation of the immediate, as well as the long-term consequences of an accident frequently require leg swelling to be classified. It is not uncommon for post-thrombotic syndrome to be diagnosed for the first time during this process. An additional vascular appraisal is often required. An appreciation of social-medical and insurance-related aspects means a high degree of responsibility is placed on the expert.

Catheter-Directed Thrombolysis Protocols for Deep Venous Thrombosis of the Lower Extremities-A Systematic Review and Meta-analysis.

OBJECTIVE: To summarize characteristics, complications, and success rates of different catheter-directed thrombolysis (CDT) protocols for the treatment of lower extremity deep venous thrombosis (LE-DVT). METHODS: A systematic review using electronic databases (MEDLINE, Scopus, and Web of Science) was performed to identify randomized controlled trials and observational studies related to LE-DVT treated with CDT. A random-effects model meta-analysis was performed to obtain the pooled proportions of early complications, postthrombotic syndrome (PTS), and venous patency. RESULTS: Forty-six studies met the inclusion criteria reporting 49 protocols (n = 3,028 participants). In studies that addressed the thrombus location (n = 37), LE-DVT had iliofemoral involvement in 90 ± 23% of the cases. Only four series described CDT as the sole intervention for LE-DVT, while 47% received additional thrombectomy (manual, surgical, aspiration, or pharmacomechanical), and 89% used stenting.Definition of venogram success was highly variable, being the Venous Registry Index the most used method (n = 19). Among those, the minimal thrombolysis rate (<50% lysed thrombus) was 0 to 53%, partial thrombolysis (50-90% lysis) was 10 to 71%, and complete thrombolysis (90-100%) was 0 to 88%. Pooled outcomes were 8.7% (95% confidence interval [CI]: 6.6-10.7) for minor bleeding, 1.2% (95% CI: 0.8-1.7%) for major bleeding, 1.1% (95% CI: 0.6-1.6) for pulmonary embolism, and 0.6% (95% CI: 0.3-0.9) for death. Pooled incidences of PTS and of venous patency at up to 1 year of follow-up were 17.6% (95% CI: 11.8-23.4) and 77.5% (95% CI: 68.1-86.9), respectively. CONCLUSION: Assessment of the evidence is hampered by the heterogeneity of protocols, which may be reflected in the variation of PTS rates. Despite this, CDT is a low-risk treatment for LE-DVT.

A systematic review and meta-analysis of the incidence of post-thrombotic syndrome, recurrent thromboembolism, and bleeding after upper extremity vein thrombosis.

BACKGROUND: Data on complications after upper extremity vein thrombosis (UEVT) are limited and heterogeneous. METHODS: The aim of the present study was to evaluate the pooled proportions of venous thromboembolism (VTE) recurrence, bleeding, and post-thrombotic syndrome (PTS) in patients with UEVT. A systematic literature review was conducted of PubMed, Embase, and the Cochrane Library databases from January 2000 to April 2023 in accordance with the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines. All studies included patients with UEVT and were published in English. Meta-analyses of VTE recurrence, bleeding, and of PTS after UEVT were performed to compute pooled estimates and associated 95% confidence intervals (CIs). Subgroup analyses of cancer-associated UEVT and catheter-associated venous thrombosis were conducted. Patients with Paget-Schroetter syndrome or effort thrombosis were excluded. RESULTS: A total of 55 studies with 15,694 patients were included. The pooled proportions for VTE recurrence, major bleeding, and PTS were 4.8% (95% CI, 3.8%-6.2%), 3.0% (95% CI, 2.2%-4.0%), and 23.8% (95% CI, 17.0%-32.3%), respectively. The pooled proportion of VTE recurrence was 2.7% (95% CI, 1.6%-4.6%) for patients treated with direct oral anticoagulants (DOACs), 1.7% (95% CI, 0.8%-3.7%) for patients treated with low-molecular-weight heparin (LMWH), and 4.4% (95% CI, 1.5%-11.8%) for vitamin K antagonists (VKAs; P = .36). The pooled proportion was 6.3% (95% CI, 4.3%-9.1%) for cancer patients compared with 3.1% (95% CI, 2.1%-4.6%) for patients without cancer (P = .01). The pooled proportion of major bleeding for patients treated with DOACs, LMWH, and VKAs, was 2.1% (95% CI, 0.9%-5.1%), 3.2% (95% CI, 1.4%-7.2%), and 3.4% (95% CI, 1.4%-8.4%), respectively (P = .72). The pooled proportion of PTS for patients treated with DOACs, LMWH, and VKAs was 11.8% (95% CI, 6.5%-20.6%), 27.9% (95% CI, 20.9%-36.2%), and 24.5% (95% CI, 17.6%-33.1%), respectively (P = .02). CONCLUSIONS: The results from this study suggest that UEVT is associated with significant rates of PTS and VTE recurrence. Treatment with DOACs might be associated with lower PTS rates than treatment with other anticoagulants.

Marjolin's ulcer in a patient with chronic venous stasis.

Marjolin's ulcer is an aggressive form of squamous cell carcinoma that develops over time from chronic wounds and scars, including burns and chronic venous stasis ulcers. The incidence of malignant transformation is low, resulting in a delay in diagnosis and increased morbidity and mortality in these patients. We report a case of Marjolin's ulcer that was incidentally found after limb amputation for chronic venous stasis ulcer along with a comprehensive literature review on the etiology, diagnosis, and treatment of this disease.

Foam sclerotherapy with enoxaparin prophylaxis in high-risk patients with postthrombotic syndrome.

BACKGROUND: According to the current guidelines for sclerotherapy hypercoagulability and thrombophilia with or without deep venous thrombosis are seen as relative contraindication for this treatment. But often such patients have an indication for a sclerotherapy. Recommendations for additional anticoagulation for sclerotherapy are missing. PATIENTS AND METHODS: In this retrospective analysis (2009 - 2010), 54 patients with deep venous thrombosis and/or pulmonal embolism in their medical history that had had foam-sclerotherapy of truncal or tributary veins with polidocanol 0.5 - 3 % without prior anticoagulation therapy were included. In addition to compression treatment (23 - 32 mmHg) for 3 weeks patients were treated with enoxaparin 40 mg once a day for 3 days after sclerotherapy. Clinical and duplex controls were conducted before every treatment and 2 - 3 weeks after the last injection. RESULTS: Sclerotherapy was done on one (30/54) or on both (24/54) legs. In 2/54 legs a truncal vein and in all patients tributaries were treated. The volume per treatment session averaged 3.3 ml foam (2 - 6 ml). The patients had undergone an average of 4.9 treatments (1 - 11); altogether 262 sessions. There were no cases of deep venous thrombosis or symptomatic pulmonary embolism. In 7/262 treatments (2.7 %) symptomatic localized phlebitis occurred and in 2/262 (0.8 %) patients an ascending phlebitis beyond the sclerotherapy region was observed. CONCLUSIONS: Based on current data, foam sclerotherapy can be regarded as safe in patients with anamnestic thromboembolism when co-treated with compression therapy (23 - 32 mmHg) and enoxaparin 40 mg once per day for 3 days post sclerotherapy. The current study is the first with a standardized regime. In view of the limitations of this study there should be further randomized controlled trials.

Unraveling the pathophysiology of lower-limb postthrombotic syndrome in adolescents: a proof-of-concept study.

A better understanding of the pathophysiology of pediatric postthrombotic syndrome (PTS) is needed to develop strategies to treat this condition. We investigated calf pump function, exercise capacity, balance in power output, and changes in limb muscle oxygen saturation (SmO2) and fluid content during exercise in 10 pediatric patients with unilateral lower-limb PTS, and in age- and sex-matched controls (1:1-1:2 ratio). Outcomes were investigated using bioimpedance spectroscopy, torque-sensing pedals, and near-infrared spectroscopy during incremental- and constant-load cycling tests. The median age at participation was 17 years (25th-75th percentile, 15-18 years); 68% of participants were females. The median CAPTSure score in the affected leg of affected participants was 35 points (25th-75th percentile, 24-46 points), indicating moderate/severe PTS; 20% of patients had a history of central venous catheter-related thrombosis. Increasing PTS severity was associated with higher calf pump venous volume and higher ejection volume, leading to compensated calf pump performance. We found no evidence of PTS impact on exercise capacity. Leg contribution to power output was similar in affected and unaffected legs. However, the PTS-affected legs showed lower SmO2 during active cycling and recovery with increasing PTS severity, indicating impaired microvascular function in the muscle. These findings suggest that PTS severity is associated with impaired blood flow, presumably from elevated venous pressure during and after exercise. The fact that microvascular function is impaired in young patients with PTS underscores the relevance of developing strategies to mitigate the effects of this chronic vascular disease to minimize its deleterious effects as children grow older.

Biomarkers in pediatric venous thromboembolism: a systematic review of the literature.

BACKGROUND: Accurate prediction of the individual risk of venous thromboembolism (VTE) remains suboptimal in children, and biomarkers are currently not used to stratify the risk of VTE in children. OBJECTIVES: This study aimed to assess which biological or radiological biomarkers may predict VTE or VTE complications in children. PATIENTS/METHODS: A literature search was performed for peer-reviewed publications (1990-2022). We included studies addressing the use of biomarkers for patients aged 29 days to 18 years to predict VTE or its complications, including but not limited to TE-related death, VTE recurrence, or postthrombotic syndrome. Given the heterogeneity of the study designs, populations, and outcomes, no quantitative data synthesis was performed. RESULTS: Forty studies were included, totaling 10,987 participants (median age: 4.7 years). Reports were often lacking critical methodological data, including blood collection method (68% of studies) and timepoints, laboratory testing technique (41%), or primary outcome definition (20%). Forty-six individual biomarkers were assessed for VTE prediction (32 studies, 9525 participants), including d-dimers, fibrinogen, platelet count, white blood cell count, and factor VIII. Albumin, C-reactive protein, d-dimers, factor VIII, and thrombin-antithrombin levels showed promising results for VTE prediction. In 9 studies (1606 participants), no biomarker was consistently predictive of postthrombotic syndrome, VTE persistence, or VTE recurrence in children. CONCLUSIONS: Several candidate biomarkers were promising in the prediction of VTE in children. Still, discrepancies between different studies and the high risk of bias from the current literature prevent their widespread use in the clinical setting. Further prospective research in various pediatric subpopulations is required.

Venous thromboembolic screening in pediatric trauma: A prospective cohort study of risk-stratified ultrasonography.

BACKGROUND: This prospective observational cohort study evaluates risk-stratified venous thromboembolism (VTE) screening in injured children. While the reported incidence of VTE is 6% to 10% among critically injured children, there is no standard for screening. Venous thromboembolism may have long-term sequelae in children, including postthrombotic syndrome. METHODS: Patients admitted to a level 1 pediatric trauma center were risk stratified for VTE using a validated prediction algorithm. Children at high risk (risk scores ≥523; i.e., ≥1% risk) received screening duplex ultrasonography. Children at moderate risk (risk scores 410-522; i.e., 0.3-0.99% risk) were screened as a comparison/control. RESULTS: Three-hundred fifty-five children were consecutively risk stratified from October 2019 to May 2021. Forty-seven children received screening duplex ultrasounds: 21 from a high-risk cohort and 26 from a moderate-risk cohort. Four children were diagnosed with VTE in the high-risk cohort compared with seven in the moderate-risk cohort ( p = 0.53). Total incidence of VTE among screened children was 23.4% (11 of 47). Asymptomatic VTE accounted for 81.8% of all events (9 of 11). Fifty-four percent (6 of 11) of VTE were central venous catheter associated. Venous thromboembolism in surviving children resolved by 3 to 6 months with no symptoms of postthrombotic syndrome after 1 year. No cases of VTE were identified in unscreened children, yielding an institutional VTE incidence of 3.1% (11 of 355). DISCUSSION: Risk-stratified screening demonstrates a significant incidence of asymptomatic VTE in injured children. These results may guide reevaluation of prediction algorithms developed from symptomatic VTE risk and longitudinal study of the sequelae of asymptomatic VTE. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

Developing and optimizing a machine learning predictive model for post-thrombotic syndrome in a longitudinal cohort of patients with proximal deep venous thrombosis.

BACKGROUND: Post-thrombotic syndrome (PTS) is the most common chronic complication of deep venous thrombosis (DVT). Risk measurement and stratification of PTS are crucial for patients with DVT. This study aimed to develop predictive models of PTS using machine learning for patients with proximal DVT. METHODS: Herein, hospital inpatients from a DVT registry electronic health record database were randomly divided into a derivation and a validation set, and four predictive models were constructed using logistic regression, simple decision tree, eXtreme Gradient Boosting (XGBoost), and random forest (RF) algorithms. The presence of PTS was defined according to the Villalta scale. The areas under the receiver operating characteristic curves, decision-curve analysis, and calibration curves were applied to evaluate the performance of these models. The Shapley Additive exPlanations analysis was performed to explain the predictive models. RESULTS: Among the 300 patients, 126 developed a PTS at 6 months after DVT. The RF model exhibited the best performance among the four models, with an area under the receiver operating characteristic curves of 0.891. The RF model demonstrated that Villalta score at admission, age, body mass index, and pain on calf compression were significant predictors for PTS, with accurate prediction at the individual level. The Shapley Additive exPlanations analysis suggested a nonlinear correlation between age and PTS, with two peak ages of onset at 50 and 70 years. CONCLUSIONS: The current predictive model identified significant predictors and accurately predicted PTS for patients with proximal DVT. Moreover, the model demonstrated a nonlinear correlation between age and PTS, which might be valuable in risk measurement and stratification of PTS in patients with proximal DVT.

Functional impact of pediatric postthrombotic syndrome.

BACKGROUND: Postthrombotic syndrome (PTS) is the most common complication of deep vein thrombosis (DVT) in children. OBJECTIVES: We aimed to assess the impact of pediatric PTS on functioning as assessed by movement ability, mobility, functional disability, and physical activity levels in children after diagnosis of limb DVT. METHODS: Patients aged 8-21 years in follow-up care after objectively documented limb DVT were prospectively recruited in this cross-sectional study. Measures of functioning (outcomes) included self-reported questionnaires that assessed: 1) movement ability, measured with the Movement Ability Measure-Computer Adaptive Test version; 2) mobility, evaluated with the Computer Adaptive Test version of the Patient-Reported Outcomes Measurement Information System Pediatric Physical Functioning, Mobility domain; 3) functional disability, evaluated with the Functional Disability Inventory; and 4) physical activity levels, evaluated with the Godin Leisure-Time Exercise Questionnaire. The main predictor was PTS severity, which was assessed using the index for the Clinical Assessment of PTS in children. The association between PTS and outcomes was analyzed using linear models. RESULTS: Eighty-seven patients (median age, 16 years; 25th-75th percentile, 15-18 years; 56% boys) were enrolled. Adjusted for age, sex, and underlying condition, increasing PTS severity was associated with lower current movement ability, a wider gap between current vs preferred movement ability, lower mobility, and slightly higher functional disability scores. There was a nonsignificant effect of PTS severity on moderate-strenuous physical activity. CONCLUSION: In children, increased PTS severity is associated with lower movement ability and impaired mobility. Reducing the gap between the patients' current vs preferred movement ability is a relevant aspect of PTS management in children.

Residual Venous Obstruction as an Indicator of Clinical Outcomes following Deep Vein Thrombosis: A Management Study.

BACKGROUND: Residual venous obstruction (RVO) is considered a risk factor of recurrence and possibly other clinical outcomes following deep vein thrombosis (DVT). Current guidelines do not support an RVO-tailored duration of anticoagulant therapy; contemporary data of such management strategies are scarce. We aimed to evaluate an RVO-based management strategy and to assess associations of RVO with recurrence, post-thrombotic syndrome (PTS), arterial events and cancer. To gain further insight, D-dimer levels were measured 1 month after stopping anticoagulant therapy. METHODS: Consecutive patients with symptomatic, proximal DVT were treated in a 2-year clinical care pathway (CCP) at Maastricht University Medical Center and were followed up to 5 years. RVO was assessed at the end of regular duration of anticoagulant therapy, which was extended once if RVO was detected. The study was approved by the medical ethics committee. RESULT: From a total of 825 patients, 804 patients (97.5%) completed the CCP and 755 (93.9%) were available for extended follow-up. Most patients (76.5%) stopped anticoagulant therapy. Incidence rates of recurrence, PTS, arterial events, and cancer were 4.4, 11.9, 1.7, and 1.8 per 100 patient-years, respectively. RVO was independently associated with PTS (hazard ratio [HR]: 1.66 [1.19-2.32]) and arterial events (HR: 2.07 [1.18-3.65]), but not with recurrence or cancer. High D-dimer was associated with recurrence (HR: 3.51 [2.24-5.48]). CONCLUSION: Our RVO-based management strategy might have attenuated the association of RVO with recurrence. In addition, RVO identified patients at increased risk of PTS and arterial events, which might be used to identify patients in need of alternative treatment strategies.

Exploring phenotypes of deep vein thrombosis in relation to clinical outcomes beyond recurrence.

BACKGROUND: Deep vein thrombosis (DVT) is a multifactorial disease with several outcomes, but current classifications solely stratify it based on recurrence risk. OBJECTIVES: We aimed to identify DVT phenotypes and assess their relation to recurrent venous thromboembolism (VTE), postthrombotic syndrome, arterial events, and cancer. PATIENTS/METHODS: Hierarchical clustering was performed on a DVT cohort with a follow-up of up to 5 years using 23 baseline characteristics. Phenotypes were summarized by discriminative characteristics. Hazard ratios (HRs) were calculated using Cox regression; the recurrence risk was adjusted for the anticoagulant therapy duration. The study was carried out in accordance with the Declaration of Helsinki and approved by the medical ethics committee. RESULTS: In total, 825 patients were clustered into 4 phenotypes: 1. women using estrogen therapy (n = 112); 2. patients with a cardiovascular risk profile (n = 268); 3. patients with previous VTE (n = 128); and 4. patients without discriminant characteristics (n = 317). Overall, the risks of recurrence, postthrombotic syndrome, arterial events, and cancer were low in phenotype 1 (reference), intermediate in phenotype 4 (HR: 4.6, 1.2, 2.2, 1.8), and high in phenotypes 2 (HR: 6.1, 1.6, 4.5, 2.9) and 3 (HR: 5.7, 2.5, 2.3, 3.7). CONCLUSIONS: This study identified 4 distinct phenotypes among patients with DVT that are not only associated with the increasing recurrence risk but also with outcomes beyond recurrence. Our results thereby highlight the limitations of current risk stratifications that stratify based on the predictors of the recurrence risk only. Overall, risks were lowest in women using estrogen therapy and highest in patients with a cardiovascular risk profile. These findings might inform a more personalized approach to clinical management.

Postthrombotic syndrome: feasibility of a strategy of imaging-guided endovascular intervention.

PURPOSE: To describe the short-term efficacy of a strategy of imaging-guided endovascular intervention for the treatment of patients with established postthrombotic syndrome (PTS). MATERIALS AND METHODS: The medical records of 183 patients with venous disease who were seen in a single interventional radiology clinic were retrospectively reviewed. Study inclusion criteria were (i) endovascular intervention performed to treat established PTS from January 1, 2000, to March 10, 2009; (ii) patient age greater than 18 years; and (iii) availability of follow-up records. A total of 44 patients (20 men, 24 women; mean age, 42.2 y ± 14.1) with PTS who had received 72 interventions (iliac vein stent placement [n = 52] and endovenous laser ablation [EVLA; n = 20]) were identified. A reviewer who did not participate in their care evaluated the follow-up records; recorded the presence or absence of pain, swelling, and active ulceration; and categorized the degree of symptom improvement. RESULTS: Of 45 treated limbs in 40 patients with available follow-up, complete, partial, or no improvement of overall symptoms was observed in 46.7%, 33.3%, and 20.0%, respectively. The proportions of limbs with pain (35.0% after treatment vs 82.5% before; McNemar test, P < .01) and swelling (50.0% after treatment vs 90.0% before; P < .01) were significantly reduced after treatment with iliac vein stent placement and/or EVLA. Six of seven ulcerated limbs showed significant healing. CONCLUSIONS: The use of an endovascular strategy to treat patients with established PTS was associated with complete or partial symptom relief in 80% of patients at short-term follow-up.