Effects of aprosulate, a novel synthetic glycosaminoglycan, on coagulation and platelet function parameters: a prospective, randomized phase I study.
In a phase I clinical trial the effect of the highly sulfated polyanion "Aprosulate" was studied in healthy volunteers using different coagulation and platelet function parameters. 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 different 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 thrombin generation in platelet-rich plasma in the presence of platelets]) were assessed during 24 hours after each injection. Aprosulate led to a significant and dose-dependent prolongation 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 unfractionated heparin. Both drugs and doses were well tolerated. Plasma transaminase concentrations alanin aminotransferase and aspartate aminotransferase serum values were slightly increased 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 prophylaxis of deep venous thrombosis.
Schenk
J F
JF
Department of Clinical Hemostaseology and Transfusion Medicine, University of Homburg, Germany.
Radziwon
P
P
Mörsdorf
S
S
Eckenberger
P
P
Breddin
H K
HK
D000293:Adolescent; D000328:Adult; D001777:Blood Coagulation / Q000187:drug effects*; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D004187:Disaccharides / Q000008:administration & dosage*; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D015539:Platelet Activation / Q000187:drug effects; D011446:Prospective Studies
D004187:Disaccharides; D005343:Fibrinolytic Agents; C069690:aprosulate