Effects of Aprosulate, a Novel Synthetic Glycosaminoglycan, on Coagulation and Platelet Function Parameters: A Prospective, Randomized Phase I Study

Abstract

In a phase I clinical trial the effect of the highly sulfated polyanion "Aprosulate" was studied in healthy volun teers using different coagulation and platelet function param eters. Eighteen healthy volunteers aged 21 to 30 years received two single subcutaneous doses of aprosulate (0.5 mg/kg body weight; 1.0 mg/kg body weight), or unfractionated heparin (Calciparin® 7,500 IU). The washout period between the dif ferent drugs/doses was at least 7 days. Coagulation and platelet function parameters (activated partial thromboplastin time, Heptest, fibrinogen, von Willebrand factor, ristocetin cofactor, platelet adhesion to siliconized glass, and platelet-induced thrombin generation time [a new method for measuring throm bin generation in platelet-rich plasma in the presence of plate lets]) were assessed during 24 hours after each injection. Aprosulate led to a significant and dose-dependent prolonga tion of activated partial thromboplastin time and Heptest. This effect lasted for 4 hours (activated partial thromboplastin time) to 8 hours (Heptest). Activated partial thromboplastin time was not prolonged after the injection of unfractionated heparin (7,500 IU). Fibrinogen, von Willebrand factor, and ristocetin cofactor remained unchanged with both drugs. Platelet induced thrombin generation time was slightly prolonged and platelet adhesion was slightly diminished up to 2 hours using 0.5 mg/kg aprosulate, and up to 4 hours using 1.0 mg/kg aprosulate while the platelet induced thrombin generation time system was not influenced by the subcutaneous injection (7,500 IU) of unfrac tionated heparin. Both drugs and doses were well tolerated. Plasma transaminase concentrations alanin aminotransferase and aspartate aminotransferase serum values were slightly in creased in some volunteers but returned to normal during or after the study (<4 weeks). Further clinical trials will have to establish whether aprosulate is an effective drug for the pro phylaxis of deep venous thrombosis.