Low Molecular Weight (LMW) Heparin Derivatives in Experimental Extra-Corporeal Circulation (ECC)

Abstract

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 antithrombin activity. Fibrinogen, fibrinogen degradation products (FDP), factor V (F V), 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 antithrombotic 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.

Anticoagulant therapy during cardiopulmonary bypass

“…Aiach et al [35], reporting on the use of LMWHs in a sheep model of extracorporeal circulation, found that they effectively prevented thrombus formation within the circuit. Hemostatic activation and consumption of fibrinogen, factor V, antithrombin III and platelets were similar in experiments with LMWH and either low-or high-dose UFH.…”

Low Molecular Weight Heparin: A Better Drug?

“…The relation ship between LMW heparin and reduced bleeding may therefore be more related to a diminished effect on platelets than on blood clotting. For example, 2 groups failed to demonstrate a correlation between anti-Xa blood levels or APTT and bleeding compli cations, either in rabbits or in man [15,17], Aiach et al [18] reported their experience with an LMW heparin in sheep during extra corporeal circulation. While LMW heparin was an effective alternative to heparin in car diac surgery, with no post-operative circulat ing activity prolonging the APTT, they were unable to demonstrate a reduced incidence of haemorrhagic complications in their animals.…”

Practical Considerations on the Measurement of Low Molecular Weight Heparin Anti-Xa Activity

“…1,2,5,11,17,19,20 LMW heparins have been shown to prevent thrombus formation or to reduce thrombus extension in numerous experimental models. 3,6,19 Clinical efficacy in postoperative venous thrombosis prophylaxis has also been demonstrated. 10 The use of LMW heparins in clinical trials needed the development of biologic assays aimed at assessing the in vitro biologic potency of the commercial preparation and monitoring the in vivo biologic effects.…”