Amino acids, antifibrinolytic

The plasminogen molecule contains several sites that specifically bind a number of antifibrinolytic amino acids, such as lysine [56-87-1] and S-aminocaproic acid [60-32-2] (EACA). These sites are known as lysine binding sites (LBS), and are localized mainly to the A or heavy chain of the molecule. One is located in K4 and at least one more is in K1 through K3. One LBS, which is beheved to reside in Kl, has a stronger affinity for EACA, whereas the others have a weaker affinity. The LBS are important for the interaction of plasminogen with several components of the endogenous fibrinolytic system. 

Tranexamic acid (Cyklokapron, Transamin) is a synthetic derivative of the amino acid lysine. It exerts its antifibrinolytic effect through the reversible blockade of lysine binding sites on plasminogen molecules. 

Various other compounds are used clinically as antifibrinolytics. As mentioned above, aprotinin, a small polypeptide that inhibits plasmin, trypsin and kallikrein, is often used in coagulation tlierapy and in fibrin sealant formulations (Trautschold et al, 1967). In the latter applications, the aprotinin serves to delay the fibrinolytic action of plasmin until the fibrin has fiilfilled its function. A monoamino carboxylic acid, e-amino caproic acid, is similar in structure to lysine and interacts with the active kringles or lysine-binding sites of plasminogen and plasminogen activators to inhibit their binding to fibrin and thus their fibrinolytic actions (Thorsen, 1992). This compound is also used in some clinical applications. 

S. Sherry, A. P. Fletcher, N. Alkjaersig and W.D. Sawyer, Epsilon-amino-caproic Acid A Potent Antifibrinolytic Agent, Trans. Ass. Am. Physns 72, 62—70 (1959). 

Metaxas, J., and Campbell, R L. Gas Chromatographic Determination of an Antifibrinolytic Drug, e-Amino-caproic Acid... 

As fibrin is formed during the clotting cascade the fribri-nolytic enzyme plasmin is formed in tandem and breaks down fibrin. Thus, if dot formation is defective, it is necessary to inhibit the action of plasmin. The amino add lysine (Fig. 19.1) was observed to have antifibrinolytic activity and e-aminocaproic add (Fig. 19.1) was found to have even greater activity. Screening of analogues of e-aminocaproic add resulted in the discovery of tranexamic acid (Fig. 19.1), which is a potent inhibitor of the conversion of plasminogen into plasmin. 

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