Development of Novel, Reversible, Non-Toxic Anticoagulants for Greatly Extended Platelet Storage

摘要

The project to develop a novel anticoagulant for preservation of blood platelets was carried through the in vitro testing stages before termination due to Congressional budget restrictions. The next phase would have begun the toxicity and efficacy studies in animals necessary for application of our findings to practical use in blood banking. We were able to demonstrate, in vitro, preservation of platelet function and integrity for 15 days at 22 C through the addition of protease inhibitors and inhibitors of platelet activation to the citrate anticoagulant. Many formulations were devised and tested; the best was composed of the additions of PGE-1 and theophylline to increase cyclic AMP plus a thrombin inhibitor (Thromstop) and a plasmin-kallikrein inhibitor (aprotinin). A lowering of the surface area-to-PC volume ratio was necessary to achieve full benefit of the inhibitors. Our results demonstrate that storage of platelets can in principle be remarkably improved by developing means to inhibit platelet activation. Keywords: Human blood donors; Anticoagulants; Platelet concentrates (PC); Protease inhibitors; Platelet activation inhibitors; Plasmin; Thrombin; Complement; Surfact-to-volume ratio; Storage lesion. (KT)