Blood coagulation and beyond: Position paper from the Fourth Maastricht Consensus Conference on Thrombosis

The 4th Maastricht Consensus Conference on Thrombosis (MCCT), included the following themes: Theme 1: The coagulome as a critical driver of cardiovascular disease Blood coagulation proteins also play divergent roles in biology and pathophysiology, related to specific organs, including brain, heart, bone marrow and kidney. Four investigators shared their views on these organ-specific topics. Theme 2: Novel mechanisms of thrombosis Mechanisms linking factor XII to fibrin, including their structural and physical properties, contribute to thrombosis, which is also affected by variation in microbiome status. Virus infections associated-coagulopathies perturb the hemostatic balance resulting in thrombosis and/or bleeding. Theme 3: How to limit bleeding risks: insights from translational studies This theme included state of the art methodology for exploring the contribution of genetic determinants of a bleeding diathesis; determination of polymorphisms in genes that control the rate of metabolism by the liver of P2Y12 inhibitors, to improve safety of antithrombotic therapy. Novel reversal agents for direct oral anticoagulants are discussed. Theme 4: Hemostasis in extracorporeal systems: how to utilize ex vivo models? Perfusion flow chamber and nanotechnology developments are developed for studying bleeding and thrombosis tendencies. Vascularised organoids are utilized for disease modeling and drug development studies. Strategies for tackling extracorporeal membrane oxygenation (ECMO) associated coagulopathy are discussed. Theme 5: Clinical dilemmas in thrombosis and antithrombotic management Plenary presentations addressed controversial areas, ie thrombophilia testing, thrombosis risk assessment in hemophilia, novel antiplatelet strategies and clinically tested factor XI(a) inhibitors,both possibly with reduced bleeding risk. Finally, Covid-19 associated coagulopathy is revisited

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

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 one month after stopping anticoagulant therapy. Consecutive patients with symptomatic, proximal DVT were treated in a two-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. 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 (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]). 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 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.</p