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Low molecular weight heparin : ウィキペディア英語版
Low molecular weight heparin
In medicine, low-molecular-weight heparin (LMWH) is a class of anticoagulant medications. They are used in the prevention and treatment of venous thromboembolism (deep vein thrombosis and pulmonary embolism) and in the treatment of myocardial infarction.
Heparin is a naturally occurring polysaccharide that inhibits coagulation, the process that leads to thrombosis. Natural heparin consists of molecular chains of varying lengths, or molecular weights. Chains of varying molecular weights, from 5000 to over 40,000 Daltons, make up polydisperse pharmaceutical-grade heparin. LMWHs, in contrast, consist of only short chains of polysaccharide. LMWHs are defined as heparin salts having an average molecular weight of less than 8000 Da and for which at least 60% of all chains have a molecular weight less than 8000 Da. These are obtained by various methods of fractionation or depolymerisation of polymeric heparin.
Heparin derived from natural sources, mainly porcine intestine or bovine lung, can be administered therapeutically to prevent thrombosis. However, the effects of natural, or unfractionated heparin are more unpredictable than LMWH.
==Anti-factor Xa activity==

Coagulation cascade is a normal physiological process which aims at preventing significant blood loss or hemorrhage following vascular injury. Unfortunately, there are times when a blood clot (thrombus) will form when it is not needed. For instance, some high risk conditions such as prolonged immobilization, surgery, or cancer can increase the risk of developing a blood clot which can potentially lead to significant consequences.
The coagulation cascade consists of a series of steps in which a protease cleaves and subsequently activates the next protease in the sequence.〔 Since each protease can activate several molecules of the next protease in the series, this biological cascade is amplified. The final result of these reactions is to convert fibrinogen, a soluble protein, to insoluble threads of fibrin. Together with platelets, the fibrin threads form a stable blood clot.
Antithrombin (AT), a serine protease inhibitor, is the major plasma inhibitor of coagulation proteases.〔Jeske W, Walenga J, Fareed J. Differentiating between the Low-Molecular-Weight-Heparin used for VTE treatment and prophylaxis. Thromb Clin. 2008;2(3)〕 LMWHs inhibit the coagulation process through binding to AT via a pentasaccharide sequence (see also heparin: mechanism of action). This binding leads to a conformational change of AT which accelerates its inhibition of activated factor X (factor Xa). Once dissociated, the LMWH is free to bind to another antithrombin molecule and subsequently inhibit more activated factor X. Unlike AT activated by Heparin, AT activated by LMWH cannot inhibit thrombin, but can only inhibit clotting factor Xa.
The effects of LMWHs cannot be acceptably measured using the partial thromboplastin time (PTT) or activated clotting time (ACT) tests.〔(enotes.com > Encyclopedia of Nursing & Allied Health > Coagulation Tests ) Retrieved on April 5, 2010〕 Rather, LMWH therapy is monitored by the ''anti-factor Xa'' assay, measuring ''anti-factor Xa activity''. The methodology of an anti-factor Xa assay is that patient plasma is added to a known amount of excess factor Xa and excess antithrombin. If heparin or LMWH is present in the patient plasma, it will bind to antithrombin and form a complex with factor Xa, inhibiting it.〔 The amount of residual factor Xa is inversely proportional to the amount of
heparin/LMWH in the plasma. The amount of residual factor Xa is detected by adding a chromogenic substrate that mimics the natural substrate of factor Xa, making residual factor Xa cleave it, releasing a colored compound that can be detected by a spectrophotometer.〔 Antithrombin deficiencies in the patient do not affect the assay, because excess amounts of antithrombin is provided in the reaction.〔(massgeneral.org > Heparin Antifactor Xa Assay ) Page Updated: September 18, 2009〕 Results are given in anticoagulant concentration in units/mL of antifactor Xa, such that high values indicate high levels of anticoagulation and low values indicate low levels of anticoagulation.〔
LMWHs have a potency of greater than 70 units/mg of anti-factor Xa activity and a ratio of anti-factor Xa activity to anti-thrombin activity of >1.5. (see table 1)
Table 1 Molecular weight (MW) data and anticoagulant activities of currently available LMWH products. ''Adapted from Gray E et al. 2008''.〔Gray E, Mulloy B, Barrowcliffe TW. Heparin and low-molecular-weight-heparin. Thromb Haemost 2008; 99: 807–818.〕

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