ABSTRACT

Mechanism of action The pentasaccharide sequence binds to the endogenous anticoagulant protein antithrombin (AT), greatly increasing the ability of AT to inhibit thrombin and factor Xa. However, AT is unable to inhibit thrombin that is bound to fibrin and platelet-bound factor X. It can increase circulating levels of tissue plasminogen activator and TF pathway inhibitor (TFPI) by releasing them from their binding sites on the surface of endothelial cells. TFPI is a tridomain protein that binds to the TF-FVIIa-FX complex that suppresses the generation of factor Xa by TF.29 As TF plays a major role in the coagulation process in cancer patients, this may account for the activity of UFH in these patients. Used intravenously, UFH has the advantage of being easily and rapidly reversed by stopping the infusion and using protamine sulfate if necessary.30 But it does require intravenous administration and costly laboratory monitoring of activated partial thromboplastin time (APTT) to site-specific controls; moreover, it may give rise to heparin resistance and can be complicated by heparininduced thrombocytopenia with thrombosis (HITT).31-33

Mechanism of action LMWH is similar in action to UFH, but with diminished inhibition of thrombin. Prepared by chemical or enzymatic degradation of UFH, LMWH has an average molecular mass of 5000 Da that allows it to be effectively absorbed from the subcutaneous tissue. Its affinity for plasma proteins, platelets, macrophages, and endothelium is reduced, rendering it more predictable thanks to a longer plasma half-life (3.5-4.5 hours) and increased bioavailability (>85%). APTT is not affected, rendering any requirement for dose monitoring superfluous, increasing cost-effectiveness, and allowing simple subcutaneous administration, which is ideal even in outpatient settings. In addition, LMWH has a reduced incidence of HITT,31,34 and a lower risk of bleeding,35-39 and has not been associated with osteoporosis.40-43

Thromboprophylaxis is essential as a means of achieving reduced rates of mortality and morbidity and to maintain the quality of life in those patients whose life expectancy may be short. An effective prevention program needs to target underlying factors predisposing to VTE, minimize any secondary effects, be well tolerated by the patient, and be feasible from both a logistical and an economical point of view.44