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 sum-marized by discriminative characteristics. Hazard ratios (HRs) were calculated using Cox regression; the recurrence risk was adjusted for the anticoagulant therapy dura-tion. 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 es-trogen therapy (n = 112); 2. patients with a cardiovascular risk profile (n = 268); 3. pa-tients 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 strat-ifications 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 cardio-vascular risk profile. These findings might inform a more personalized approach to clinical management.

Automated summary

This study identified 4 distinct phenotypes among patients with DVT, and assessed their relation to various outcomes. Risks were lowest in women using estrogen therapy and highest in patients with a cardiovascular risk profile. These findings have important implications for personalized clinical management.