Prophylaxis and Therapy of Thromboses

Drugs that decrease the coagulability of blood, such as coumarins and heparin (A) are employed for the prophylaxis of thromboses. In addition, attempts are directed, by means of acetylsalicylic acid, at inhibiting the aggregation of blood platelets, which are prominently involved in intra-arterial thrombogenesis (p.152). For the therapy of thrombosis, drugs are used that dissolve the fibrin meshwork-fibrinolytics (P-150). 

An overview of the coagulation cascade and sites of action for coumarins and heparin is shown in (A). There are two ways to initiate the cascade (B) (1) conversion of factor XII into its active form (XIIa, intrinsic system) at intravascular sites denuded of endothelium (2) conversion of factor VII into VIIa (extrinsic system) under the influence of a tissue-derived lipoprotein (tissue thromboplastin). Both mechanisms converge via factor X into a common final pathway. 

Ca2 -chelators (B) prevent the enzymatic activity of Ca2+-dependent factors they contain COO groups that bind Ca2+ ions (C) citrate and EDTA (ethylenediaminetetraace-tic acid) form soluble complexes with Ca2+ oxalate precipitates Ca2+ as insoluble calcium oxalate. Chelation of Ca2+ cannot be used in vivo for therapeutic purposes because Ca2 concentrations would have to be lowered to a level incompatible with life (hypo-calcemic tetany). These compounds (sodium salts) are, therefore, used only for rendering blood incoagulable outside the body. This effect can be reversed at any time by addition of Ca2 ions. 

In vivo, the progression of the coagulation cascade can be inhibited as follows (C)  

Coumarin derivatives decrease the blood concentrations of inactive factors II, VII, IX and X, by inhibiting their synthesis in the liver. 

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