Post-thrombotic syndrome (PTS) is a chronic venous insufficiency manifestation following an episode of deep-vein thrombosis (DVT). It is an important and frequent long-term adverse event of proximal DVT affecting 20-50% of patients. This position paper integrates data guiding clinicians in deciding PTS diagnosis, treatment and follow-up.

Post-thrombotic syndrome – a position paper from European Society of Vascular Medicine

Post-thrombotic syndrome in patients with venous thromboembolism treated with dabigatran or warfarin: A long-term cross-sectional follow-up of RE-COVER study patients.

The incidence of post-thrombotic syndrome (PTS) in patients with deep vein thrombosis (DVT) treated with direct oral anticoagulants (DOACs) remains a matter of debate. Hence, our endeavor to investigate a large cohort of patients with a first episode of proximal DVT treated with DOACs to ascertain the incidence and predisposing risk factors for PTS. All consecutive patients referred to the Thrombotic and Haemorrhagic Diseases Unit of Padova University Hospital (Italy) between January 2014 and January 2018 for a first episode of proximal DVT were considered for enrollment. Participants received DOACs for a minimum period of 3 months. PTS was assessed using the Villalta score up to 36 months after DVT diagnosis. Among 769 enrolled patients (M/F 353/416, age range 26–87 years), 152 (19.8%) developed PTS and 30 (3.9%) developed severe PTS. The adjusted hazard ratio was significant for obesity (1.64, 95% CI 1.28–2.39) and DVT site (femoral and/or iliac veins vs popliteal vein) (1.23, 95% CI 1.15–3.00). The incidence of PTS is not negligible in patients with proximal DVT despite the use of DOACs. We identified obesity and iliofemoral DVT as possible risk factors for PTS. Larger prospective studies are needed to confirm our findings and optimize therapeutic strategies.

Risk Factors for Post-Thrombotic Syndrome in Patients With a First Proximal Deep Venous Thrombosis Treated With Direct Oral Anticoagulants

Post-thrombotic syndrome (PTS) is the most frequent complication of deep vein thrombosis, and it can be detrimental to the quality of life of affected patients. Once affected by this chronic condition, treatment options are very limited, so preventive therapies are paramount. Currently, the prevention of PTS is hampered by the lack of unequivocally effective therapies. However, increased pathogenic insight acquired in recent years, including the central role of residual venous obstruction, could lead to better application of existing therapies and identification of novel therapeutic targets. Plausible therapeutic agents include flavonoids and statins, while promising future agents include those that target leukocyte-endothelial interaction. Moreover, differences in PTS risk were found to be partly explained by a tendency of patients to form clots which are less susceptible to lysis. Finally, identifying patients that are expected to benefit most from certain therapies is equally valuable for the success of future preventive strategies. This requires exploration of better risk stratification through machine learning techniques.

How to optimize the prevention of post-thrombotic syndrome: recent advances.

Postthrombotic syndrome (PTS) remains one of the major late complications of deep vein thrombosis (DVT) with a reported prevalence from 10 to 50%. Many factors were found to be related with the development and severity of PTS such as ipsilateral recurrent DVT, advanced age, obesity, ilio-femoral DVT and primary chronic venous disease presence. Some PTS prediction models have been proposed based on risk factor weight. However, it is still difficult to predict which patient with DVT will develop PTS and thus, the clinical application of these models remains limited. Among the identified problems the heterogeneity of the DVT patient population together with the variety of PTS clinical presentations and difficulties concerning PTS severity assessment should be mentioned. Difficulties on the implementation of the specific and objective PTS identification method have also the significant influence on the research focusing on PTS prevention modalities including risk factor modification, compression treatment, anticoagulation and invasive DVT treatment. In this review, the current approach and knowledge on PTS prediction and prevention are presented, including the conservative and invasive DVT treatment possibilities.

Can we predict and prevent the postthrombotic syndrome

Background. Vascular adventitia contains progenitor cells and is shown to participate in vascular remolding. Progenitor cells are recruited into the venous thrombi in mice to promote neovascularization. We hypothesized that the adventitial progenitor cells of human great saphenous vein (HGSV-AdPC) enhance the resolution of venous thrombosis via neovascularization. Methods. Human great saphenous vein (HGSV) was harvested from the patients with great saphenous vein varicose and sectioned for immunohistochemistry, or minced for progenitor cell primary culture, or placed in sodium dodecyl sulfate solution for decellularization. Human venous thrombi were collected from patients with great saphenous vein varicose and superficial thrombophlebitis. Infrarenal abdominal aorta of New Zealand white rabbits was replaced with interposing decellularized vessel, and the patency of the grafts was confirmed by ultrasonic examination. Animal venous thrombi in the left infrarenal vena cava of mice were produced with Prolene suture ligation and ophthalmic force clipping of this portion. After HGSVs were digested by collagenase, the CD34+CD117+ HGSV-AdPC were isolated on FACS system, labelled with CM-Dil, and transplanted into the adventitia of infrarenal vena cava of nude mice. The percentage of thrombus organization area to the thrombus area was calculated as the organization rate. The thrombus cell, endothelial cells, and macrophages in the thrombi were counted in sections. Cell smears and frozen sections of human saphenous veins and venous thrombi were labeled with Sca1, CD34, CD117, Flk1, CD31, and F4/80 antibodies. The CD34+CD117+ HGSV-AdPC were cultured in endothelial growth medium with vascular endothelial growth factor (VEGF) to induce endothelial cell differentiation and analyzed with real time-PCR, Western blotting, and tube formation assays. Results. Immunohistochemical staining showed that the CD34+CD117+ cells were located within the adventitia of HGSVs, and many CD34+ and CD117+ cells have emerged in the human venous thrombi. The number of progenitor cells within the marginal area of 7 days mice thrombi was shown to be Sca1+ ≈21%, CD34+ ≈12%, CD117+ ≈9%, and Flk1+ ≈5%. Many CD34+adventitial progenitor cells have migrated into the decellularized vessels. FACS showed that the number of CD34+CD117+ HGSV-AdPC in primary cultured cells as . After CD34+CD117+HGSV-AdPC were transplanted into the adventitia of nude mice vena cava with venous thrombi, the organization rate, nucleate cell count, endothelial cells, and macrophage cells of thrombi were shown to be significantly increased. The transplanted CD34+CD117+ HGSV-AdPC at the adventitia have crossed the vein wall, entered the venous thrombi, and differentiated into endothelial cells. The CD34+CD117+ HGSV-AdPC in the culture medium in the presence of VEGF-promoted gene and protein expression of endothelial cell markers in vitro and induced tube formation. Conclusions. HGSV-AdPC could cross the vein wall and migrate from the adventitia into the venous thrombi. Increased HGSV-AdPC in the adventitia has enhanced the resolution of venous thrombi via differentiating into endothelial cells of neovascularization.

/pdf/adventitial-progenitor-cells-of-human-great-saphenous-vein-30c0vpr8uj.pdf

Adventitial Progenitor Cells of Human Great Saphenous Vein Enhance the Resolution of Venous Thrombosis via Neovascularization.

Risk of post-thrombotic syndrome after deep vein thrombosis treated with rivaroxaban versus vitamin-K antagonists: A systematic review and meta-analysis.

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Adventitial Progenitor Cells of Human Great Saphenous Vein Enhance the Resolution of Venous Thrombosis via Neovascularization.

Risk of post-thrombotic syndrome after deep vein thrombosis treated with rivaroxaban versus vitamin-K antagonists: A systematic review and meta-analysis.