[The evolution of the coagulation system from primitive defense mechanisms]

Sequence analysis shoes that the probability of amino acid substitution in a particular protein is a constant function of time. The appearance of specific marker proteins within the phylogenetic system serves as "molecular clock", indicating the time of divergence of any species from a common ancestor. The circulatory system represents an adaption of coelom liquid from animals such as primitive metazoans, poriferes, coralles and coelenterates to the more effectiv transport system in higher animals. Amoebocytes are the predecessor of macrophages and leucocytes. During the development of higher organized animals, thrombocytes or platelets arise from such a common ancestor, the haemocytes. Fibrinogen, as a clottable protein, develops from a structurally related coagulogen of primitive arthropods. In comparison to cytochrom C or collagen, it is a phylogenetically young protein. In early evolution haemostatic problems were solved in primitive animals by the tryptic activation of coagulogen, inducing a slow polymerisation process or by the direct formation of a covalently linked protein network by the activity of ligases. Both enzymes are preserved during phylogenesis and are comparable with thrombin and factor XIII in higher developed vertebrates. The two-domain evolution of serine proteases, comprising binding site and the reactive serine, leads finally to the complete cascade of clotting enzymes to adapt the circulatory system to the increased demands for haemostatic protection.