title: Lepirudin: a review of its potential place in the management of thrombotic disorders.
abstract: Lepirudin is a recombinant hirudin derived from transfected yeast cells. The hirudins are direct thrombin inhibitors which render the thrombin molecule incapable of promoting fibrin formation and catalysing other haemostatic reactions. In initial studies, parenteral lepirudin has shown promising efficacy as an antithrombotic agent. Lepirudin increased or maintained platelet counts at normal baseline values while maintaining adequate anticoagulation in patients with heparin-induced thrombocytopenia (HIT), and has not been associated with the development of immune-mediated thrombocytopenia. Preliminary studies in patients with deep vein thrombosis (DVT) suggest that lepirudin may be more effective than unfractionated heparin (UFH) at preventing pulmonary perfusion defects. In patients with unstable angina pectoris, preliminary data also showed lepirudin to be significantly more effective than UFH according to the combined incidence of cardiovascular mortality, new acute myocardial infarction (AMI) or refractory angina. However, additional studies involving larger patient numbers are necessary before firm conclusions can be made regarding the relative efficacy of lepirudin in these indications. Similarly, promising but limited data on the use of lepirudin during haemodialysis or heart surgery and in patients with disseminated intravascular coagulation (DIC) require further confirmation. Bleeding complications and the possible induction of allergic or anaphylactic reactions are the most serious adverse events associated with lepirudin therapy. Major bleeding complication rates appear to be similar with lepirudin and UFH monotherapy; however, lepirudin may be associated with an increased incidence of minor bleeding including bruising. Initial encouraging results showing an improvement in coronary artery patency with high-dose lepirudin versus UFH as an adjunct to thrombolytic therapy in patients with AMI were subsequently overshadowed by reports of a high incidence of major bleeding events including cerebral haemorrhage among lepirudin recipients. Moreover, at lower doses which did not produce an unacceptably high incidence of haemorrhagic complications, lepirudin appeared to have only a small efficacy advantage over UFH.
  
  
  CONCLUSIONS
  Lepirudin has shown promising activity as an antithrombotic agent and may be a suitable substitute anticoagulant for heparin in patients with HIT. The narrow therapeutic window of lepirudin makes it difficult to assess the role of this agent when used as an adjunct to thrombolytic therapy in patients with AMI. However, initial data suggest that lepirudin may be a potentially useful agent in the management of patients with unstable angina, DVT or DIC and in preventing thrombus formation in extracorporeal circuits. Further studies should more fully elucidate the efficacy of lepirudin in these indications.
authors.affiliation: Adis International Limited, Auckland, New Zealand. demail@adis.co.nz
authors.forename: J C
authors.initials: JC
authors.lastname: Adkins
authors.forename: M I
authors.initials: MI
authors.lastname: Wilde