Rethinking events in the haemostatic process: role of factor V and TFPI.

Regulatory mechanisms responsible for limiting blood clot formation are critical for maintaining normal haemostasis. Dysregulation can lead to bleeding (e.g. haemophilia) or thrombosis. New findings showing that tissue factor pathway inhibitor-alpha (TFPIα) binds coagulation factor V(a) and inhibits prothrombinase assembly highlights that our understanding of the initiation of coagulation is evolving. Work over the past decade on the biochemistry of FV activation has laid the groundwork for deciphering the mechanistic bases that may underpin how TFPIα mediates these anticoagulant effects. Collectively, these new findings are re-shaping our thinking about how coagulation is initiated at the site of injury. These ideas could have important clinical implications and help identify new ways to bias the coagulation response for the treatment of haemophilia and other disorders of the haemostatic process.