Comparative efficacy of different low-molecular-weight heparins (LMWHs) and drug interactions with LMWH: Implications for management of vascular disorders

The low-molecular-weight heparins (LMWHs) are more efficacious and safer th an unfractionated heparin (UFH) in the prevention and treatment of venous t hrombosis and to a certain extent in the treatment of acute ischemic syndro mes. Because of their predictable pharmacokinetics and bioavailability afte r subcutaneous administration, LMWHs can be more convenient for outpatient use than UFH. Differences in the manufacturing process of LMWHs result in s ignificant structural and molecular weight differences; thus, LMWHs have in dividual biochemical and pharmacological profiles and are not interchangeab le on the basis of either mass or anti-Xa activity. Using thromboelastograp h (TEG) and platelet aggregometry, this investigation compared the in vitro efficacy among various LMWHs and examined the interactions between LMWHs a nd platelet glycoprotein (GP) IIb/IIIa antagonists. TEG was used to determi ne the ability of platelet and fibrin interactions to augment blood clots, an effect measured under conditions of maximal platelet activation during c lot formation accelerated by recombinant human tissue factor (TF). The comp arative efficacy of LMWHs on different mediator-induced clot retraction in human blood was assessed by TEG, which demonstrated the potency of differen t LMWHs to inhibit various mediator-induced clot formations under shear. Ti nzaparin was relatively more effective in inhibiting TF-, lipopolysaccharid e-, factor (f) Xa-, and thrombin-induced clot formation under shear. Under these conditions, platelets significantly enhance clot strength (eightfold vs. platelet-free fibrin clots). LMWHs appear to have broader efficacy than other anticoagulants. Abciximab and roxifiban further inhibited clot stren gth by affecting the transmission of platelet contractile force to fibrin b y platelet GPIIb/IIIa receptors. Subtherapeutic doses of tinzaparin combine d with abciximab or roxifiban resulted in a distinct synergy that improved anticoagulant and antiplatelet efficacy mediated by TF, fXa, or thrombin. A s these data suggest, the combination of low-dose tinzaparin with low-dose GPIIb/IIIa antagonists (abciximab, roxifiban) may be efficacious in the pre vention and treatment of various thromboembolic disorders.