Novel tissue biomarker candidates to predict both deep venous thrombosis and healing outcome after Achilles tendon rupture

Deep venous thrombosis (DVT) and poor long-term patient outcomes frequently occur in patients with Achilles tendon rupture (ATR). Biomarkers for DVT and their possible relationship to long-term healing outcomes remain unexplored. To identify DVT biomarkers from proteomic profiles during the inflammatory and proliferative healing stages and assess their associations with one-year healing outcomes after surgical repair of ATR. A cohort of 53 patients undergoing standardized ATR repair from previous clinical trials was investigated. Intraoperative inflammatory-stage tendon biopsies were obtained from 40 patients, and tendon microdialysates from 28 patients were collected two weeks later during the proliferative stage. Liquid chromatography-tandem mass spectrometry proteomic profiles were linked to DVT status at two weeks post-surgery using ultrasonography screening and to patient-reported outcomes at one-year post-surgery. Six candidate DVT biomarkers were identified from tendon biopsies, whereof four (ABI3BP, IGKV2-40/IGKV2D-40, PCYOX1, STIP1) were associated with one-year healing outcomes. In tendon microdialysates, 43 candidate DVT biomarkers were identified, but none were associated with healing outcomes. Bioinformatic analysis revealed pathways related to heat shock response, platelet signaling, collagen and extracellular matrix metabolism, and immunoglobulins. The results support shared inflammatory-stage protein pathways in regulating venous thrombosis and reported healing outcomes, where elements of individual hypoxic tolerance and platelet signaling emerge as potential key links.