Preface Thrombin – Applied Clinical Biochemistry of the Main Factor of Coagulation

Thrombin, the factor 2a (F2a) of blood coagulation, physiologically transforms soluble fibrinogen (F1) into insoluble glue-like fibrin at local areas of injured vessels. Thrombin is a 36000 Dalton-sized arginine-specific serine protease, i.e. a trypsin-like protease with an active catalytic Ser....His...Asp centre (ACC) in its B-chain (Fig. 1) [1]. The B-chain contains also the two major binding regions, called exosite-1 to bind lysine-rich fibrinogen and the positively charged exosite-2 to bind negatively charged sulphated glycosaminoglycans (such as heparin). Close to the pocket with the negatively charged catalytic centre and an apolar region [2] there is a switch region near Asp189 that binds cations, preferably Na; the bound cation upregulates thrombin ́s activity possibly via changing the molecular position of Glu192 [3], an amino acid close to Ser195 of the ACC: in normal human plasma the intrinsic thrombin generation is increased twofold by addition of about 4 mM Na, 3 mM K, or 6 mM Li [4,5]. Cations also activate other serine proteases via a similar mechanism as in thrombin [6].