Heparins are used in “therapeutic doses” for systemic anticoagulation to treat patients who have confirmed venous thromboembolism, or in “prophylactic doses ”for the prevention of venous thromboembolism : they are generally lower doses and are employed once a day. Structure-function relationships are strongly influenced by the chain length of the molecules. In fact, unfractionated heparin (UFH) binds to ATIII lysine site leading to a conformational change of the ATIII arginine reactive centre able to create a covalent binding to the active centre serine of thrombin in a ternary complex formation composed by heparin, ATIII and thrombin. On the other side, low molecular weight heparins (LMWHs) are too short to be able to form this ternary complex, and mainly exert their anticoagulant effect by binding the factor Xa, always via ATIII. Lastly, the short unique pentasaccharidic sequence which is crucial for heparins activity and has been recently synthesized as Fondaparinux, only acts via the formation of the high affinity ternary complex with ATIII-factor Xa. Due to their structure-function relationships, LMWHs cannot be monitored by conventional coagulation test used for monitoring UFH and need more specific anti-factor Xa activity determinations, but monitoring has been considered unnecessary in the general population due to a predictable dose/effect ratio. However, a disturbing rise of bleeding complications in patients with renal failure treated with LMWH has been published in the last years, that is explained by the accumulation of LMWHs in this setting, due the consequences of structuremetabolisms relationships of the small members of the heparins family. In this context, physicians are often left to a “best guess” method of empiric dose adjustment, which is at risk of achieving inappropriate targets, with a percentage of values above and below target of 51% and 34%, respectively, depending on LMWHs dosage, body mass index and renal function. Without anti-Xa activity monitoring, the quality of care delivered in the setting of renal failure is poor, as over-prophylaxis can result in potentially dangerous anticoagulation, while underprophylaxis can result in life-threatening thrombosis.