Low molecular weight (LMW) heparin derivatives in experimental extra-corporeal circulation (ECC)

Low molecular weight (LMW) heparin has been shown to prevent experimental venous thrombosis. In order to investigate its biological action and its potential use in open heart surgery, we have conducted an experimental study using extracorporeal circulation (ECC) in sheep as an experimental model. 18 sheep were randomly selected to receive either LMW heparin (2 mg/kg), high dose heparin (HD; 160 U/kg), or low dose heparin (LD; 60 U/kg). The HD heparin yielded the same circulating anti-activated factor X (anti-Xa) activities as the LMW heparin and the LD heparin yielded the same anti-thrombin activity. LMW heparin and HD heparin were both effective in preventing blood clotting in the ECC circuit, demonstrating the antithrombotic activity of the LMW heparin. Clotting in the circuit was observed following LD heparin administration showing that the efficacy of LMW heparin does not only rely upon its weak anti-activated partial thromboplastin time (APTT) and anti-thrombin activity. Fibrinogen, fibrinogen degradation products (FDP), factor V (FV), platelet count, antithrombin III (AT III), fast acting antiplasmin (AP) were evaluated during and after ECC. The defects in hemostasis were similar in the three groups. Conclusions were: (1) heparin chain depolymerization diminishes the anti-APTT activity without altering the anti-thrombotic property; (2) LMW heparin is an effective alternative to heparin in cardiac surgery; (3) the absence of postoperative circulating anti-APTT activity might be associated with a reduced incidence of hemorrhagic complication, but we were not able to demonstrate it.