Effect of Recombinant Lubricin on Coagulation Parameters in Human Blood

Abstract

Lubricin (proteoglycan 4; PRG4) is a proteoglycan which acts as a joint lubricant. Lubricin is present in synovial fluid and plays a major role in synovial homeostasis. A recombinant form of lubricin, rhPRG‐4 is developed to treat a variety of inflammatory diseases. (Lubris Pharmaceutical). The purpose of this study is to determine the effect of rhPRG‐4 on blood coagulation utilizing various experimental studies.rhPRG‐4 was supplemented with citrated whole blood from normal human donors (n = 10) to obtain concenration range of 0 ‐ 200 mg/mL. Activated clotting time (ACT), thrombelastographic analysis (TEG), and whole blood prothrombin time (PT), partial thromboplastin time (aPTT), and thrombin times (TT) were measured. Similarly, citrated plasma was supplemented with rhPRG‐4 at 0‐200 mg/ML to determine PT, aPTT and TT. The effect of this agent was also studied on the generation of proteases. In addition, rhPRG‐4 was also studied for its effect on platelet aggregation.rhPRG‐4 did not produce any effect on the whole blood clotting assays, such as the PT, aPTT and TT. Similarly, in the citrated plasma, none of the clotting assays were altered. rhPRG‐4 did not produce any inhibition of thrombin generation in plasma. Furthermore, it did not produce any inhibition or augmentation of agonist‐induced platelet aggregation. These studies suggest that rhPRG‐4 does not modify whole blood and plasma coagulation profile and produce and more relation of platelet function.These studies suggest that because of no potential alteration of the coagulation system, lubricin is not expected to modulate bleeding or thrombotic processes in clinical indications.