Systematic review and meta-analysis of the pooled rate of post-thrombotic syndrome after isolated distal deep venous thrombosis

Objective: To identify the rate of post-thrombotic syndrome (PTS) after isolated distal deep venous thrombosis (IDDVT) by performing a meta-analysis of the rate of PTS across randomised and observational studies.  Data sources: MEDLINE, Embase, the Cochrane Controlled Trials Register, Clinicaltrials.gov, European Union Clinical Trials, International Standard Randomised Controlled Trial Number, and the Australian and New-Zealand Trials Registries.  Review methods: This review followed PRISMA guidelines using a registered protocol (CRD42021282136). Databases were searched up to December 2021 and prospective studies reporting the development of post-thrombotic syndrome were included; these were pooled with the meta-analysis.  Results: The results showed a post-thrombotic rate of 17% (95% CI 11 – 26%) (seven studies, 217 cases, 1 105 participants). Heterogeneity was high (I2 = 89%). On meta-regression, the rate of post-thrombotic syndrome was not correlated with the length of follow up (p =.71). Three studies (302 participants) reported the severity of post-thrombotic syndrome: 78% were mild (Villalta score 5 – 9); 11% were moderate (Villalta score 10 – 14), and 11% were severe (Villalta score ≥ 15).  Conclusion: The risk of post-thrombotic syndrome after IDDVT was one in five and the risk of severe clinical manifestations, including ulceration, was one in 50. There was significant clinical, methodological, and statistical heterogeneity between studies and a substantial risk of bias from pooled studies. Randomised trials to support interventions for prevention of post-thrombotic syndrome are urgently needed.</p