TY - JOUR T1 - Splenectomy delays thrombus resolution JF - European Respiratory Journal JO - Eur Respir J VL - 42 IS - Suppl 57 SP - P2603 AU - Maria Frey AU - Sherin Alias AU - Max-Paul Winter AU - Bassam Redwan AU - Gerald Stuebiger AU - Adelheid Panzenboeck AU - Johannes Jakowitsch AU - Helga Bergmeister AU - Klaus T. Preissner AU - Irene Lang Y1 - 2013/09/01 UR - http://erj.ersjournals.com/content/42/Suppl_57/P2603.abstract N2 - Purpose: Splenectomy is a clinical risk factor for chronic thromboembolic pulmonary hypertension (CTEPH). Recent data suggest that CTEPH is a complication of venous thromboembolism. Therefore, we investigated the effects of splenectomy on venous thrombus resolution.Methods: We analyzed phospholipid profiles in thrombotic material from splenectomized and non-splenectomized CTEPH patients using mass spectrometry. To study the role of these phospholipids in thrombus resolution, we employed a mouse model of stagnant flow venous thrombosis and performed splenectomy in the study group. We examined murine thrombi using immunohistochemistry and mass spectrometry and murine blood using FACS. To analyze angiogenesis, cell proliferation and sprouting assays were performed.Results: We observed a different phospholipid profile in splenectomized CTEPH patients compared with non-splenectomized CTEPH patients. In the mouse model, prior splenectomy was associated with larger and more persistent thrombi. FACS revealed higher counts of procoagulant platelet microparticles and increased leukocyte–platelet aggregates compared with controls. Mass spectrometry disclosed a relative enrichment of anionic phospholipids like phosphatidylserine (PS) in murine thrombi proximal to the caval ligation after splenectomy. Thrombus histologies demonstrated fewer vessels. Compared with neutral phospholipids, PS enriched phospholipids inhibited angiogenesis in a cell proliferation assay and in a sprouting assay.Conclusions: The data confirm that an increase in circulating negatively charged phospholipids as a consequence of splenectomy enhances thrombus growth by amplifying platelet activation, and delays thrombus resolution by inhibition of thrombus angiogenesis. ER -