Levels of tissue inhibitor of metalloproteinases-1 in blood transfusion components

Abstract

Blood transfusion during surgery for solid tumors may reduce patient survival because of various bioactive substances present in blood preparations. The antiproteolytic protein tissue inhibitor of metalloproteinases-1 (TIMP-1) present in large quantities in platelets has been shown to stimulate cell growth and to inhibit apoptosis and may therefore be considered to influence tumor progression. We measured TIMP-1 levels in blood transfusion preparations, especially in plateletcontaining preparations, before and after leucofiltration and at different timepoints during storage. The mean TIMP-1 levels in whole blood (WB) and plateletrich plasma (PRP) were slightly reduced by leucofiltration; WB: 41.6 mug/L versus 34.9 mug/L, PRP: 139.8 mug/L versus 127.2 mug/L. However, with prestorage leucofiltration, TIMP-1 levels in buffy-coat-derived platelet (BCP) pools were significantly reduced from 134.2 mug/L to 102.2 mug/L (p=0.0013). In saline-adenineglucose-mannitol (SAG-M) blood preparations in which the platelet content is reduced by more than 99%, TIMP-1 could not be detected. Extracellular TIMP-1 accumulated significantly in non-filtered WB and in aferesis platelet concentrates (APC), but TIMP-1 was at no time detectable in SAG-M blood during storage. In conclusion, TIMP-1 is present in various platelet-containing blood preparations, but not in platelet-free preparations such as SAG-M, indicating that most of the TIMP-1 measured in blood preparations originates from platelets. Furthermore, TIMP-1 levels increased during storage in preparations containing platelets, which suggests a continuous disintegration of platelets. These data imply that information on preoperative blood transfusions should be taken into account when evaluating plasma TIMP-1 levels in patients.