Introduction

Before the early 1960s interaction between platelets and plasmatic thrombin or ‘thromboplastin’ generation was the subject of intensive study. Since the introduction of the aggregation and adhesion methods, most studies on platelets are done under conditions where clotting is prevented, whereas blood coagulation is usually studied in the absence of platelets. In this way only indirect information (e.g. recognition of thrombin-receptors) is obtained on the interaction between platelet and plasma. Direct information on the platelet-clotting system reinforcement loops has been reappearing only recently.

In the body, platelet activation and thrombin generation are two intimately linked processes. Thrombin is a potent platelet activator and adequate thrombin formation is impossible without activated platelets. Because thrombin generation and platelet activation are mutually interdependent, each process requiring the product of the other for its full activity, the two are interlocked in positive feedback. Unlike the better known negative feedback that has regulatory properties, a positive feedback loop amplifies product formation explosively. Hemostasis is an intricate complex of positive and negative feedback loops. Here, we will focus on the amplification mechanism constituted by the platelet–clotting system interaction. The thrombin induced positive feedback loop has been known for over half a century (see fig. 26.1 from ref.1) but only recently has it again become a focus of wider interest.