Effects of a supersulfated low molecular weight heparin (IK-SSH) on different hemostatic parameters

In a phase I trial effects of a new supersulfated low molecular weight hepa rin (IK-SSH) on different hemostatic parameters were investigated in health y volunteers. Parameters studied were activated partial thromboplastin time (aPTT), thrombin time, Heptest, anti-activated factor II (anti-FIIa) and a nti-activated factor X (anti-FXa) activity, platelet adhesion, platelet cou nt, platelet-induced thrombin generation time (PITT), bleeding time, antith rombin III, fibrinogen and several safety parameters. After single intraven ous (i.v.) injections of IK-SSH (0.14, 0.33 and 0.66 mg/kg) aPTT, Heptest a nd PITT were strongly and dose-dependently prolonged. After ascending subcu taneous (s.c.) doses of IK-SSH (0.33, 0.66 and 1 mg/kg) aPTT, Heptest and P ITT were prolonged in a dose-dependent manner. Repeat s.c. injections of 1 mg/kg IK-SSH for 5 days markedly prolonged aPTT, Heptest and PITT. No cumul ative effects were observed. Anti-FIIa and anti-FXa activity were not or on ly slightly increased. Bleeding time, thrombin time and platelet adhesion w ere not significantly changed after i.v. and s.c. injections of IK-SSH. How ever, tissue factor pathway inhibitor (TFPI) concentration was markedly inc reased after each injection of IK-SSH and returned to the preinjection valu e 24 h later. IK-SSH prolongs aPTT, Heptest and PITT in a similar manner as other low molecular weight heparins but without significantly affecting th rombin time, FIIa and FXa activity. The release of TFPI may well be respons ible for the prolongation of aPTT, Heptest and PITT. IK-SSH may be further developed as an antithrombotic agent.