r-Hirudin inhibits platelet-dependent thrombosis during cardiopulmonary bypass in baboons.
BACKGROUND
Systemic anticoagulation is required during cardiopulmonary bypass (CPB) to inhibit the activation of platelets, the coagulation system and ultimately thrombus formation. Unfractionated heparin is most commonly used, but it is neither entirely safe nor completely effective. The use of protamine sulphate to reverse the anticoagulant effect further complicates the use of heparin. The clinical need for a heparin substitute is therefore obvious. We evaluated the efficacy of r-Hirudin, a potent and specific inhibitor of thrombin, as anticoagulant in a baboon model of cardiopulmonary bypass.


METHODS
Ten baboons, divided into two groups of five each, were used. The one group received 0.7 mg/kg r-Hirudin as a bolus before CPB was started, followed by a constant infusion of 1.4 mg/kg/hr for the 90 min of CPB. The other group received a bolus of 2.5 mg/kg heparin before the start of CPB, followed by maintenance dosages to maintain the activated clotting time (ACT) >400 sec.


RESULTS
Adequate anticoagulation was obtained with both anticoagulants. Haemodilution due to priming the extracorporeal system with Ringer's lactate and appropriately anticoagulated donor blood, was equivalent in both groups. During CPB with heparin, but not with hirudin, there was a significant increase in the number of circulating platelet aggregates, thrombin-antithrombin (TAT) complexes and 111In-labelled platelet accumulation in the oxygenator. After the initial decrease in platelet count due to haemodilution, it further decreased significantly during CPB with heparin but remained relatively constant when r-Hirudin was used.


CONCLUSIONS
Our results strongly suggest that r-Hirudin is superior to heparin especially with respect to its inhibitory effect on platelet dependent thrombogenesis caused by the biomembranes of the oxygenator.
van Wyk
V
V
Department of Haematology, Faculty of Medicine, University of the Free State, Bloemfontein, South Africa.
Neethling
W M
WM
Badenhorst
P N
PN
Kotzé
H F
HF
D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage; D000990:Antithrombin III / Q000378:metabolism; D000991:Antithrombins / Q000008:administration & dosage / Q000627:therapeutic use*; D002315:Cardiopulmonary Bypass / Q000379:methods*; D004195:Disease Models, Animal; D006438:Hemodilution / Q000379:methods; D006493:Heparin / Q000008:administration & dosage; D024764:Hirudin Therapy; D006629:Hirudins / Q000008:administration & dosage; D007262:Infusions, Intravenous; D010215:Papio; D010447:Peptide Hydrolases / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects*; D010976:Platelet Count; D011994:Recombinant Proteins; D012449:Safety; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy*; D016896:Treatment Outcome
D000925:Anticoagulants; D000991:Antithrombins; D006629:Hirudins; D011994:Recombinant Proteins; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D006493:Heparin; D010447:Peptide Hydrolases