Post-Thrombotic Syndrome and Recurrent Thromboembolism in Patients with Upper Extremity Deep Vein Thrombosis: A Systematic Review and Meta-Analysis of Proportions

Background: Upper extremity deep vein thrombosis (UEDVT) is known to be less common than lower extremity DVT (LEDVT). In comparison to LEDVT, there is limited data on the occurrence of complications in patients with UEDVT. As a result, it remains uncertain as to how aggressively these patients should be treated. In this systematic review, we aimed to determine the rate of complications, including post-thrombotic syndrome and recurrent thromboembolism, in patients with UEDVT.

Methods: We conducted a systematic literature search of MEDLINE and EMBASE databases for relevant studies from 1970 onwards. Our search included conference publications from major international meetings. Studies were eligible for inclusion if they were observational studies (case-control, cohort), randomized trials, or cases series including more than 20 patients. Studies must have included only patients age 18 or older and have objectively diagnosed UEDVT by means of venography or ultrasound. The primary outcome measures were the recurrence rate of UEDVT in patients with previously documented UEDVT and the rate of PTS. The secondary outcome measure was the rate of major bleeding, as defined by the International Society on Thrombosis and Haemostasis (ISTH), following the initiation of treatment for UEDVT. For each outcome, we calculated a pooled proportion using a fixed effects model and its 95% confidence interval (CI) using the Wilson score method. We also determined the mean proportions of outcomes and the interquartile ranges (IQR) of single proportions from individual studies.

Results: A total of 61 studies were included in the meta-analysis (58 full text articles and 3 conference publications). The studies included a total of 5500 patients diagnosed with UEDVT. Of the 61 included studies, 39 reported data on recurrence, 21 on PTS, and 28 on major bleeding. PTS was defined either by the Villalta scale explicitly (a score of 5 or more) or by similar clinical descriptors posed by the investigators.

The results are summarized in Table 1. When evaluating all studies, the pooled proportions of outcomes were: 2.4% (95% CI: 2.0-2.9%) for recurrence, 15.0% (95% CI: 12.8-17.5%) for PTS, and 2.9% (95% CI: 2.5-3.5%) for major bleeding. The mean proportions were: 8.4% (IQR: 0.0-10.1%), 18.4% (IQR: 0.0-26.7%), and 4.3% (IQR: 0.0-5.7%), respectively.

When evaluating studies specific to primary UEDVT in the setting of venous thoracic outlet syndrome, the pooled proportions were: 5.5% (95% CI: 4.3-7.1%) for recurrence, 16.0% (95% CI: 13.4-19.0) for PTS, and 3.3% (95% CI: 2.0-5.3%) for major bleeding. The mean proportions were: 6.8% (IQR: 0.0-9.5%), 19.6% (IQR: 0.0-30.5%), and 3.2% (IQR: 0.0-4.8%), respectively.

When evaluating studies specific to secondary UEDVT (catheter-associated and/or malignancy-associated), the pooled proportions were: 2.0% (95% CI: 1.5-2.6%) for recurrence, 8.0% (95% CI: 4.9-12.8) for PTS, and 3.9% (95% CI: 3.2-4.8%) for major bleeding. The mean proportions were: 18.1% (IQR: 1.5-18.4%), 17.1% (IQR: 9.8-26.5%), and 3.8% (IQR: 0.0-5.2%), respectively.

Conclusions: This review included a large number of patients diagnosed with UEDVT and found that both primary and secondary UEDVT are associated with high rates of PTS. The pooled proportions of PTS and recurrent thromboembolism were higher in patients with primary UEDVT than in patients with secondary UEDVT. The rates of major bleeding were similar in both groups. Further analysis is needed on the association of these complications with different treatment modalities for UEDVT to better guide the management of patients. Our next step is to calculate pooled proportions using a random effects model and present this data at the 59^th American Society of Hematology (ASH) Annual Meeting.

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