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DOI: 10.1055/s-0028-1086088
In Vitro Effects of Argatroban, Lepirudin, Bivalirudin, and Danaparoid on Fibrin Gel Permeability
Publikationsverlauf
Publikationsdatum:
28. Oktober 2008 (online)


ABSTRACT
In the fibrin gel permeability assay, fibrin formation depends on thrombin generated endogenously, giving greater physiological relevance. The present study evaluated the effects of three direct thrombin inhibitors (argatroban, bivalirudin, and lepirudin) and one indirect factor Xa inhibitor (danaparoid) on fibrin gel permeability. Fibrin gels were prepared by adding tissue factor, phospholipids, and CaCl2 to normal plasma mixed with one of the inhibitors. The permeability constant (Ks) was determined through flow measurements. At concentrations corresponding to plasma levels during antithrombotic therapy, argatroban, bivalirudin, and danaparoid led to similar increases in Ks, by 320 to 370% of the control; in contrast, almost no effect on Ks could be detected for lepirudin. At concentrations above the “plasma-like” levels, the dose–response curve for lepirudin was noticeably steep, whereas those for the other drugs were shallow. This study suggests that argatroban, bivalirudin, and danaparoid have comparable potential to inhibit thrombin or Xa and the consequent coagulation, rendering the fibrin network permeable. The lack of influence on fibrin gel permeability by lepirudin at the “plasma-like” levels may contradict the antithrombotic effect observed in therapy, but the sharp dose–response curve shown at higher drug concentrations corresponds with reports of bleeding complications from lepirudin with overdosages.
KEYWORDS
Thrombin inhibitor - factor Xa inhibitor - fibrin gel permeability - in vitro