In nature,<unk>  is a polymer of varying chain size. Unfractionated<unk>  (UFH) as a pharmaceutical is<unk>  that<unk> as not been fractionated to sequester the fraction of molecules with low molecular weight. In contrast, low-molecular-weight<unk>  (LMWH)<unk> as undergone fractionation for the purpose of making its pharmacodynamics more predictable. Often either UFH or LMWH can be used; in some situations one or the other is preferable. Mechanism of action<unk>  binds to the enzyme inhibitor antithrombin III (AT), causing a conformational change that results in its activation through an increase in the flexibility of its reactive site loop. The activated AT then inactivates thrombin, factor Xa and other proteases. The rate of inactivation of these proteases by AT can increase by up to 1000-fold due to the binding of<unk> .<unk>  binds to AT via a specific pentasaccharide sulfation sequence contained within the<unk>  polymer: : GlcNAc/NS(6S)-GlcA-GlcNS(3S,6S)-IdoA(2S)-GlcNS(6S) The conformational change in AT on<unk> -binding mediates its inhibition of factor Xa. For thrombin inhibition,<unk> owever, thrombin must also bind to the<unk>  polymer at a site proximal to the pentasaccharide. The<unk> ighly negative charge density of<unk>  contributes to its very strong electrostatic interaction with thrombin. The formation of a ternary complex between AT, thrombin, and<unk>  results in the inactivation of thrombin. For this reason,<unk> 's activity against thrombin is size-dependent, with the ternary complex requiring at least 18 saccharide units for efficient formation. In contrast, antifactor Xa activity via AT requires only the pentasaccharide-binding site. This size difference<unk> as led to the development of low-molecular-weight<unk> s (LMWHs) and fondaparinux as anticoagulants. Fondaparinux targets anti-factor Xa activity rather than inhibiting thrombin activity, with the aim of facilitating a more subtle regulation of coagulation and an improved therapeutic index. It is a synthetic pentasaccharide, whose chemical structure is almost identical to the AT binding pentasaccharide sequence that can be found within polymeric<unk>  and<unk>  sulfate. With LMWH and fondaparinux, the risk of osteoporosis and<unk> -induced thrombocytopenia <unk> IT) is reduced. Monitoring of the activated partial thromboplastin time is also not required and does not reflect the anticoagulant effect, as APTT is insensitive to alterations in factor Xa. Danaparoid, a mixture of<unk>  sulfate, dermatan sulfate, and chondroitin sulfate can be used as an anticoagulant in patients<unk> aving developed<unk> IT. Because danaparoid does not contain<unk>  or<unk>  fragments, cross-reactivity of danaparoid with<unk> -induced antibodies is reported as less than 10%. The effects of<unk>  are measured in the lab by the partial thromboplastin time (aPTT), one of the measures of the time it takes the blood plasma to clot. Partial thromboplastin time should not be confused with prothrombin time, or PT, which measures blood clotting time through a different pathway of the coagulation cascade. Administration<unk>  vial for subcutaneous injection<unk>  is given parenterally because it is not absorbed from the gut, due to its<unk> igh negative charge and large size. It can be injected intravenously or subcutaneously (under the skin); intramuscular injections (into muscle) are avoided because of the potential for forming<unk> ematomas. Because of its short biologic<unk> alf-life of about one<unk> our,<unk>  must be given frequently or as a continuous infusion. Unfractionated<unk> <unk> as a<unk> alf-life of about one to two<unk> ours after infusion, whereas LMWH<unk> as a<unk> alf-life of four to five<unk> ours. The use of LMWH<unk> as allowed once-daily dosing, thus not requiring a continuous infusion of the drug. If long-term anticoagulation is required,<unk>  is often used only to commence anticoagulation therapy until an oral anticoagulant e.g. warfarin takes effect. The American College of Chest Physicians publishes clinical guidelines on<unk>  dosing. Natural degradation or clearance Unfractionated<unk> <unk> as a<unk> alf-life of about one to two<unk> ours after infusion, whereas low-molecular-weight<unk> 's<unk> alf-life is about four times longer. Lower doses of<unk> <unk> ave a much shorter<unk> alf-life than larger ones.<unk>  binding to macrophage cells is internalized and depolymerized by the macrophages. It also rapidly binds to endothelial cells, which precludes the binding to antithrombin that results in anticoagulant action. For<unk> igher doses of<unk> , endothelial cell binding will be saturated, such that clearance of<unk>  from the bloodstream by the kidneys will be a slower process.
Heparin
Prokarin
Ticlopidine
Palladin
Argatroban
Lepirudin
Hirudin
Tissue plasminogen activator