Breakdown products of fibrin and fibrinogen: molecular mechanisms and clinical implications.

The major terminal enzymatic expression of the fibrinolytic cascade system in vivo is plasmin. This enzyme is piesumed to interact with fibrinogen and fibrin in vivo and is arguably man's major defence against the deposition of fibrin, an important component in the general hazard of thrombosis. Our understanding of the molecular details of plasmin interactions with fibrinogen and fibrin has been established over the past 10 years. As a part of the overall strategy to elaborate the primary sequence of human fibrinogen the precise locations of the peptide bonds ruptured by plasmin at various stages in the degradation process have been reported. Such precise data are not available as yet for fibrinplasmin interactions. I shall discuss the major aspects of fibrinogen-plasmin interactions only briefly since these have been recently reviewed by, among others, Mosesson and Finlayson1 and Gaffney.2 I shall deal with the current knowledge of fibrin-plasmin interactions in more detail since new and exciting data concerning fibrin fragmentation, which may have significance in vivo, have recently emerged. In this review I am supposing that the major breakdown products of fibrinogen and fibrin (FDPs) are mediated by plasmin in vivo. Thus the in-vitro experiments conducted in many laboratories over the years have concentrated on plasmin-mediated interactions. It is, however, well to point out that the interactions between fibrinogen and a number of other proteolytic enzymes have also been studied in vitro (for review see Latallo et al.3). Indeed, Moroz and Gilmore4 thought that a variety of proteolytic enzymes of cellular origin may play a far more important part in the lysis of established thrombin in vivo than does plasmin. Nevertheless, there is little doubt that plasmin interacts with forming fibrin, attempting to prevent its deposition on the vessel wall. I shall expand this last opinion when discussing plasmin-fibrin interactions and their significance in vivo. Fibrin-plasmin breakdown products