after 1 year. The risk of recurrence is 3% per year in patients with transient masitinib AB1010 risk factors . Following an episode of DVT, there is an approximate 24% risk of postthrombotic syndrome after 3 years. Of all untreated initial calf vein thrombi, 20% extend proximally.Moreover, thrombus resolution is slower and postthrombotic syndrome is more severe after proximal than distal DVT. The clinical challenges that orthopaedic surgeons, internists, and clinicians face are that current anticoagulants are administered subcutaneously or require monitoring and dose titration to provide effective anticoagulation without increasing bleeding risk. More effective and convenient alternative anticoagulants, which can be given at fixed doses without routine coagulation monitoring, could improve current clinical practice.
New oral anticoagulant drugs are being developed that address these issues, while having similar or better efficacy and safety profiles when compared with current agents. This paper will review the unmet clinical needs with current agents, discuss the new classes of oral agents, Cyclopamine present data on the new oral agents currently available in the European Union and other countries, and discuss how these agents might meet the needs of orthopaedic surgeons and internists in VTE prophylaxis. 2. Current Anticoagulant Regimens 2.1. Parenteral Anticoagulants. Although unfractionated heparins have been available since the early 1930s, studies in the 1970s demonstrated that they prevented VTE and fatal PE in patients undergoing surgery. UFHs act at several points of the coagulation cascade.
Parenteral LMWHs, which emerged in the early 1980s, also act at several levels of the coagulation cascade . During the 1990s, a comprehensive series of studies demonstrated the clinical value of LMWHs in reducing the risk of VTE . Compared with UFHs, LMWHs offered a convenient solution they were available as fixed doses, did not require routine coagulation monitoring or dose adjustment, and led to clinically significant reductions in the number of venous thromboembolic events. The different LMWHs are created chemically or by depolymerization of UFH. LMWHs target both Factor Xa and Factor IIa . The ratio of Factor Xa : Factor IIa inhibition differs between the different available LMWHs and these ratios are considered to be related to safety and efficacy.
The ratio of Factor Xa : Factor IIa inhibition ranges from 2 : 1 to 4 : 1 for the different LMWHs in current use, compared with 1 : 1 for UFH, indicating that antithrombotic activity may be higher when using LMWHs, without the increased risk of bleeding. Fondaparinux, a subcutaneously administered, indirect Factor Xa inhibitor, was more effective than enoxaparin in reducing the risk of VTE. The timing of fondaparinux administration affected the efficacy and incidence of bleeding events after THA/TKA: major bleeding was significantly higher in patients who received their first dose 6 hours after skin closure than in those where the first dose was delayed to 6 hours. This effect was more evident in patients who weighed 50 kg, those 75 years of age, and those with moderate renal impairment. It is important to note that bleeding events are always likely after surgery affecting approximately 2.4% of patients even when no anticoagulants are used and anticoagulants do not increase bleeding risk when administered correctly with regards to dosage, timing and concomitant use of other agents that affect bleeding. LMWHs offer a goo