Mechanism of action 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.<unk> s inhibit the coagulation process through binding to AT via a pentasaccharide sequence. This binding leads to a conformational change of AT which accelerates its inhibition of activated factor X (factor Xa). Once dissociated, the<unk>  is free to bind to another antithrombin molecule and subsequently inhibit more activated factor X. Unlike AT activated by heparin, AT activated by<unk>  cannot inhibit thrombin (factor IIa), but can only inhibit clotting factor Xa. The effects of<unk> s cannot be acceptably measured using the partial thromboplastin time (PTT) or activated clotting time (ACT) tests. Rather,<unk>  therapy is monitored by the anti-factor Xa assay, measuring anti-factor Xa activity rather than a clotting time. The methodology of an anti-factor Xa assay is that patient plasma is added to a known amount of excess recombinant factor X and excess antithrombin. If heparin or<unk>  is present in the patient plasma, it will bind to antithrombin and form a complex with factor X, inhibiting it from becoming factor Xa. 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. Results are given in units/mL of antifactor Xa, such that high values indicate high levels of anticoagulation and<unk>  values indicate<unk>  levels of anticoagulation in the plasma sample.<unk> s 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)<unk>  Average<unk><unk>  Ratio anti-Xa/anti-IIa activity Bemiparin 3600 8.0 Nadroparin 4300 3.3 Reviparin 4400 4.2<unk>  4500 3.9 Parnaparin 5000 2.3 Certoparin 5400 2.4<unk>  5000 2.5 Tinzaparin 6500 1.6 Table 1<unk><unk>  (MW) data and anticoagulant activities of currently available<unk>  products. Adapted from Gray E et al. 2008.
Low-molecular-weight heparin
Fibrinolysis
Enoxaparin sodium
Thrombectomy
Palladin
Heparin
Tissue plasminogen activator
Tinzaparin sodium