Future alternatives to heparin: low-molecular-weight heparin and hirudin.
The antithrombotic effects of standard heparin were compared with those of low-molecular-weight heparin (LMWH) and hirudin by use of an in vitro perfusion system. Fresh blood collected from human volunteers was treated with varying doses of these three agents and perfused in a recirculating system over everted porcine vein segments. A low shear rate (100/sec) was selected to simulate conditions in large arteries and veins. Platelet and fibrinogen deposition were evaluated with indium 111 and iodine 125 radiolabels, respectively. Anticoagulant activity was assessed by measuring the activated clotting time (ACT). Anti-Xa activity was assayed to determine the degree to which these agents used antithrombin III pathways. Low-molecular-weight heparin was the weakest anticoagulant, requiring 32 micrograms/ml blood to double the ACT. By contrast, the ACT doubled with only 0.75 and 1.10 micrograms/ml blood of heparin and hirudin, respectively. Heparin and hirudin inhibited platelet and fibrin deposition at equivalent doses. Low-molecular-weight heparin was a less potent inhibitor of fibrin than heparin or hirudin. Hirudin, a direct thrombin inhibitor, exhibited minimal anti-Xa activity, contrasted with 0.14 anti-Xa units/micrograms for LMWH and 0.13 anti-Xa units/mg for heparin. These data suggest that heparin and hirudin are more potent anticoagulants and antiplatelet agents than LMWH.
Donayre, CE; Ouriel, K; Rhee, RY; Shortell, CK
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