Antithrombotic factors

The antithrombotic factors produced by endothelial cells are thrombomodulin (TM) and protein S (PS), components of the vitamin K-dependent protein C (PC) anticoagulant pathway, inhibiting F-Va-F-Villa (E15) tissue plasminogen activator (tPA), responsible for fibrinolysis (N2, LI8) and the lipoprotein-associated coagulation inhibitor (LACI), which inhibits F-VIIa-TF complex and F-Xa (B51). 

Stief, T.W. and Fareed, J.,The antithrombotic factor singlet oxygen/light ( Oj/hv), Clin. Appl. Thromb. Hemost., 6,1, 2000. 

Fondaparinux, the factor Xa-binding pentasaccharide (Arixtra, MW 1,728 Da), is prepared synthetically, unlike UFH, LMWH and danaparoid, which are obtained from animal sources. Despite only inactivating free factor Xa, clinical trials indicate that fondaparinux is an effective antithrombotic agent, both for venous thromboembolism prophylaxis and treatment, as well as for acute coronary syndrome and ST elevation myocardial infarction [4]. 

Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Analysis of pooled data from five randomized controlled trials. Arch Intern Med 1994 154 1449-1457. 

Identify factors that place a patient at high risk of bleeding while receiving antithrombotic drugs. 

Given that VTE can be debilitating or fatal, it is important to treat it quickly and aggressively.8 On the other hand, because major bleeding induced by antithrombotic drugs can be equally harmful, it is important to avoid treatment when the diagnosis is not reasonably certain. Assessment of the patient s status should focus on the search for risk factors in the patient s medical history... 

The most commonly used oral anticoagulant drug in the U.S. is warfarin. It acts by altering vitamin K so that it is unavailable to participate in synthesis of vitamin K-dependent coagulation factors in the liver (coagulation factors II, VII, IX, and X). Because of the presence of preformed clotting factors in the blood, the full antithrombotic effect of warfarin therapy may require 36 to 72 h. 

Prophylaxis should be continued throughout the period of risk. For general surgical procedures and medical conditions, prophylaxis can be discontinued once the patient is able to ambulate regularly and other risk factors are no longer present. Most clinical trials support the use of antithrombotic therapy for 21 to 35 days after total hip replacement and hip fracture repair surgeries. 

Activation of endothelial cells leads to changes in endothehal ceU properties such as loss of vascular integrity, expression of adhesion molecules, antithrombotic to prothrombotic phenotype changes, cytokine production and the upregulation of HLA molecules. All these diverse effects can be attributed to the activation of transcription factors [44]. Of the presently known transcription factors, NFkB is believed to be one of the most important in the regulation of endothehal cell activation. After a stimulus at the cell surface which is caused by e.g. 

Pharmacology The antithrombotic activity is the result of antithrombin III (ATIII)-mediated selective inhibition of Factor Xa. Neutralization of Factor Xa interrupts the blood coagulation cascade and thus inhibits thrombin formation and thrombus development. 

Antithrombotic. Preventing or interfering with the formation of thrombi (an aggregation of blood factors). 

A number of 1-substituted 2(l//)-pyrazinone derivatives show antithrombotic activity as selective inhibitors of the tissue Factor Vila complex <2003BML23I9> and were examined as mast cell tryptase inhibitors <2004BML48I9>. As a curious effect, dihydropyrazines proved to show DNA strand-breakage activity <2005CPB1359>. 

Protein C exerts an antithrombotic effect by inhibiting Factors Va and Villa. In vitro data indicate that it has indirect prohbri-nolytic activity through its abhity to inhibit plasminogen activator inhibitor-1 (PAI-1) and to hmit production of activated throm-bin-activatable-hbrinolysis inhibitor. In vitro data also indicate that Activated Protein C may exert an anti-inflammatory effect by inhibiting human tumor necrosis factor production by monocytes, by blocking leukocyte adhesion to selectins, and by hmiting thrombin-induced inflammatory responses within the microvascular endothehum. 

Hauptmann J, Kaiser B, Vowak G, Struzebecher J, Markwardt F. Comparison of the anticoagulant and antithrombotic effects of synthetic thrombin and factor Xa inhibitors. Throm Haemostas 1990 63 220-223. 

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