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BACKGROUND: Deep vein thrombosis (DVT) is a multifactorial disease with several outcomes, but current classifications solely stratify based on recurrence risk.OBJECTIVES: We aimed to identify DVT phenotypes and assess their relation to recurrent venous thromboembolism (VTE), post-thrombotic syndrome, arterial events, and cancer.PATIENTS/METHODS: Hierarchical clustering was performed on a DVT cohort with up to five years follow-up using 23 baseline characteristics. Phenotypes were summarized by discriminative characteristics. Hazard ratios (HR) were calculated using Cox regression; recurrence risk was adjusted for 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 four phenotypes: 1.women using estrogen therapy (n=112); 2.patients with a cardiovascular risk profile (n=268); 3.patients with previous VTE (n=128); 4.patients without discriminant characteristics (n=317). Overall, risks of recurrence, post-thrombotic 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 four distinct phenotypes among DVT patients that are not only associated with increasing recurrence risk, but also with outcomes beyond recurrence. Our results thereby highlight the limitations of current risk stratifications that stratify based on predictors of 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.

European Society for Vascular Surgery (ESVS) 2021 Clinical Practice Guidelines on the Management of Venous Thrombosis

Objective Animal models suggest that toll-like receptor 9 (TLR9) promotes thrombus resolution after acute deep venous thrombosis (DVT). We hypothesized that TLR9 expression is lower in patients with post-thrombotic syndrome (PTS) and investigated the role of TLR9 in residual thrombosis (RT) and recurrence. Methods Patients with a history of DVT with PTS (cases, n = 30) and without PTS after minimal 24 months follow-up (controls, n = 30) were selected. Healthy individuals (HI, n = 29) without DVT were included as reference. TLR9 mRNA expression in leukocytes was determined by qPCR and normalized to the housekeeping succinate dehydrogenase subunit A gene using the ΔCt method. Sub analyses were performed to explore the TLR9 expression in patients with and without RT and multiple DVT episodes. Results The median TLR9 expression was 0.45 (interquartile range 0.31 to 0.93), 0.39 (0.25 to 0.69) and 0.62 (0.32 to 0.75) in cases, controls and HI respectively (p = 0.61). The median TLR9 expression was 0.39 (0.26 to 0.51) in patients with RT compared to 0.55 (0.30 to 0.86, p = 0.13) in those without. The median TLR9 expression was significantly lower in patients who had one DVT compared to patients with recurrent DVT, 0.37 (0.23 to 0.63) versus 0.55 (0.43 to 0.96) respectively (p Conclusion No significant difference in TLR9 expression was found between cases, controls and HI. However TLR9 expression seems lower in individuals with DVT and RT, albeit not significant. Interestingly, TLR9 might play a role in recurrent DVT, as the TLR9 expression was significantly higher in patients with recurrent DVT.

Post thrombotic syndrome (PTS) is a very common chronic complication of deep venous thrombosis (DVT), as three out of ten patients with lower extremity DVT will develop PTS. The possibility to identify patients at risk is limited. Diagnosis is challenging, because there is no gold standard diagnostic method. Progress in diagnostic options may therefore change future diagnostic strategies. The better understanding of pathophysiologic processes that underlie PTS may stimulate the development of treatment modalities and improve and diversify management options. The quest for adequate preventive strategies and treatment is important because PTS has a detrimental effect on patients' quality of life and is associated with increased healthcare as well as societal costs. [1,2]The problem of PTS prevention is therefore clearly relevant to patients, doctors as well as policy makers.

Introduction Over the last years venous stent placement after deep venous thrombosis (DVT) in the iliofemoral veins has gained more attention. The majority of studies evaluating the safety and efficacy of this intervention are of poor methodological quality and the association with antithrombotic therapy has not been studied explicitly. We performed a systematic review to summarize the available literature on antithrombotic management in relation to the safety and efficacy of venous stenting. Methods We performed a Medline search to identify studies that addressed anticoagulation and/or antiplatelet treatment options after venous stenting in patients with a prior DVT in the iliofemoral area. We identified 192 articles and finally selected 14 articles for use in this review. Results In 86% (12/14) of the included studies anticoagulation was administered to all patients who underwent iliac venous stenting. In 33% of the studies patients received antiplatelet therapy consisting of aspirin and/or clopidogrel (4/12). The duration of antithrombotic treatment was not guided by the stenting procedure in 93% (13/14) of studies. The incidence of re-thrombosis in (sub) groups of only stented patients, ranged from 5% to 25%. Primary, assisted primary, and secondary patency rates 12 months after stent placement ranged from 54%, 72%, 83% respectively to 78%, 83%, 95% in (sub)groups of only stented patients. Rates of major bleedings during long term follow-up ranged from 0% to11%. Conclusion Antithrombotic therapy does not seem to influence any of the outcomes in patients with venous stenting after DVT: recurrent DVT, patency, post-thrombotic syndrome or restenosis and bleeding.

Management and prevention of venous thromboembolism (VTE) in cancer patients is challenging. Not only is the risk of VTE in cancer patients elevated compared to patients without malignancies, but also is standard treatment based on Vitamin K antagonists (VKAs) less effective and associated with an increased frequency of major bleeding. Therapy with Low Molecular Weight Heparin (LMWH) is less sensitive to drug interactions, not hindered by a narrow therapeutic window and needs no monitoring. LMWH therapy therefore seems more practical and may also be more effective in cancer patients. Moreover a possible survival benefit has been suggested, the underlying mechanism of which is not yet unraveled. A combination of cancer and thrombosis is a predictor of poor long-term survival. Anticoagulant drugs, especially LMWH, may be of influence on tumor progression. Hypercoagulability in cancer patients may indicate an aggressive change in the tumor and is associated with tumor progression. Hypercoagulability could on the other hand also be a risk factor for developing cancer. To assist clinicians in defining the role of LMWH in cancer patients, we categorized, summarized and critically weighed all available evidence on the subject. Based on available data derived from clinical trials recommendations on the application of heparin in oncological patients are made. However, many uncertainties remain regarding the subject of cancer related thrombosis in view of treatment and the possible effects on tumor biology by heparins.