A randomized blind study comparing standard heparin and a new low molecular weight heparinoid in cardiopulmonary bypass surgery in dogs.
Postoperative hemorrhage remains a serious complication in cardiopulmonary bypass (CPB) surgery. In our study, alternative anticoagulation with a new low molecular weight (LMW) heparinoid (Org 10172) was compared with a standardized heparin regimen. A preliminary dose-finding study indicated the minimal effective heparinoid dose to be 260 anti-Xa U/kg body weight, which was comparable to the standardized heparin regime, as revealed by similar plasma anti-Xa values. The following randomized open pilot study in 12 mongrel dogs undergoing CPB showed the heparinoid to be as effective as heparin, with an additional advantageous decrease in postoperative blood loss in the Org 10172 group. Our randomized blind study in 16 mongrel dogs undergoing CPB was performed to confirm previous results. Both antithrombotic agents were effective in the prevention of clot formation within the extracorporeal circuit. Hematocrit values and erythrocyte and platelet counts showed no significant intergroup differences. Post-CPB leukocyte counts revealed a significantly more rapid increase in the group given heparinoid (P less than 0.05). In the group given heparin, the expected prolongations of both the thrombin time (TT) and activated partial thromboplastin time (APTT) were noted, whereas in the group given heparinoid, only a transient peak prolongation of the TT after dose administration was revealed, and no significant prolongation of the APTT. Mean anti-Xa plasma levels were similar during CPB, showing a rapid decrease in the group given heparin on protamine administration, as did the APTT. Assessment of the operating field indicated an elevated intraoperative blood loss in the group given heparin. Postoperative blood loss measured over a period of 2.5 hours after closure of the thorax was significantly lower in the group given heparinoid than in the heparinized animals (625 +/- 100.0 ml, mean +/- SD, and 806 +/- 178.2 ml, respectively; P less than 0.05). Our observations suggest that the LMW heparinoid Org 10172 has an increased benefit/risk ratio over standard heparin and is effective in CPB in dogs. Additional investigations in humans should verify the possibility of use of this substance as an alternative means of anticoagulation during CPB in patients in whom heparin is relatively contraindicated.
D000818:Animals; D000991:Antithrombins / Q000032:analysis; D001780:Blood Coagulation Tests; D001810:Blood Volume / Q000187:drug effects; D002315:Cardiopulmonary Bypass; D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D005343:Fibrinolytic Agents / Q000633:toxicity; D006025:Glycosaminoglycans / Q000494:pharmacology* / Q000633:toxicity; D006400:Hematocrit; D006470:Hemorrhage / Q000139:chemically induced*; D006493:Heparin / Q000494:pharmacology* / Q000633:toxicity; D006497:Heparan Sulfate; D007958:Leukocyte Count; D008970:Molecular Weight; D010976:Platelet Count; D011183:Postoperative Complications; D011897:Random Allocation
D000991:Antithrombins; D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D005343:Fibrinolytic Agents; D006025:Glycosaminoglycans; D006493:Heparin; D006497:Heparan Sulfate; C035838:danaparoid