How has our understanding of the hemostatic orchestra evolved and where is it taking us? Dr. David Lillicrap begins with an overview of the molecular evolution of the hemostatic orchestra from the horseshoe crab and the Japanese puffer fish to modern day humans.
The hemostatic mechanism has remained mostly stable over the past 450 million years, but it was not until just 40 years ago that a “coagulation cascade” was first proposed by both MacFarlane (an “Enzyme Cascade” in Nature, May,1964) and Davie & Ratnoff (a “Waterfall Sequence” in Science, September, 1964). Now, 40 years later, we are still asking how it is that this cascade gets turned on.
Dr. Lillicrap makes the argument for the extrinsic pathway as the initiator of the hemostatic orchestra, citing the work of Ken Mann’s group on the three phases of thrombin generation. Moreover, Dr. Lillicrap proposes that measuring thrombin generation may become more useful in clinical practice than measuring of individual factor levels.
Dr. Lillicrap concludes his presentation with a discussion of the future of hemostasis research and therapeutics in which he introduces his own work on gene therapy for hemophilia A and addresses the obstacles to gene therapy in humans.
The potential roles of desmopressin and low-titer inhibitors in hemophilia management are also discussed.