Potential use of recombinant hirudin as an anticoagulant in a cardiopulmonary bypass model.
Recombinant (r) hirudin is a potent thrombin-specific inhibitor derived from the natural hirudin of the leech (Hirudo medicinalis). We have studied the efficacy of r-hirudin compared with heparin in a canine model of cardiopulmonary bypass operations. Two administration regimens were used for r-hirudin: group 1, 1.0 mg/kg intracardiac bolus then intravenous bolus at 30 minutes (n = 10); and group 2, 1.0 mg/kg intracardiac bolus with 1.25 +/- 0.04 mg.kg-1.h-1 intravenous infusion (n = 8). Group 3 was given an intracardiac bolus of heparin, 1.66 mg/kg (n = 9). Aspiration of blood from the chest cavity revealed no significant difference between the three groups. Measurement of fibrin deposits in the pump line filter revealed higher amounts in the r-hirudin groups (p = 0.02). Decreases in platelets, fibrinogen, and hematocrit due primarily to hemodilution were the same in each group. The bleeding time assay showed less prolongation for r-hirudin than for heparin (p less than 0.001). No antagonist for r-hirudin was used; however, due to its short half-life all coagulation variables returned to baseline within 30 minutes after cardiopulmonary bypass. Because r-hirudin lacks effect on platelets, is a poor immunogen, does not require a plasma cofactor, and may not require an antagonist, it may provide an alternative anticoagulant to heparin in cardiopulmonary bypass. Additional studies are, however, needed to optimize the dose and to evaluate other clinical aspects of r-hirudin.
Walenga
J M
JM
Department of Thoracic and Cardiovascular Surgery, Loyola University Medical Center, Maywood, Illinois.
Bakhos
M
M
Messmore
H L
HL
Fareed
J
J
Pifarre
R
R
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D002315:Cardiopulmonary Bypass / Q000379:methods*; D004285:Dogs; D004334:Drug Administration Schedule; D006400:Hematocrit; D006629:Hirudins / Q000008:administration & dosage*; D008297:Male; D010976:Platelet Count / Q000187:drug effects; D011994:Recombinant Proteins / Q000008:administration & dosage
D006629:Hirudins; D011994:Recombinant Proteins