LAUSR

DOI:10.1097/MOH.0000000000000370 As an introduction to my inaugural issue as associate editor for hemostasis and thrombosis of Current Opinion in Hematology, I want to present the themes that comprise this year’s edition. The field of hemostasis and thrombosis has robust research activities in several of the topics covered in this issue: contact activation, vascular biology, blood coagulation, and platelet and neutrophil activities. In the article by Dr Gailani et al. (pp. 411–418), the authors address the issue of how the first molecule of factor XIIa may arise. This question is an old one that could only have been addressed in the modern era with the creation of recombinant proteins. Dr Gailani et al. (pp. 411–418) created mutant zymogen factor XII that has its three arginine in its catalytic domain (the light chain) changed to alanine. It was observed that this mutant zymogen factor XII still has intrinsic factor XIIa activity, allbe-it 4200-fold less than normal factor XIIa. True zymogen factor XII may have low-intrinsic enzymatic activity to create the first molecules of factor XIIa and initiate contact activation. This situation is analogous to single-chain tissue and urokinase plasminogen activator, proteins that are most similar in structure to factor XII. Dr Renné et al. (pp. 419–426) reviewed some of the newer, potential antithrombotic agents that are in clinical development. In particular, targeting factor XII/factor XIIa may provide well tolerated antithrombosis without bleeding risk. One agent, a humanized Fab 3F7 selectively neutralizes factor XIIa. In a rabbit extracorporeal membrane oxygenation model, it was as effective as heparin with less fibrin deposition on the membrane oxygenator. Other antifactor XIIa agents such as rHA-Infestin-4 and antisense oligonucleotides reduce risk in several murine models for thrombosis and inflammation. The contact activation field also has had a revival in interest as several new biologic substances such as polyphosphates, DNA, collagen, and denatured protein has been recognized to support activation of factor XII. It has been appreciated for some time now that denatured amyloid b-protein support contact and platelet activation. Dr Strickland et al. (pp. 427–431) present a summary of their work showing the amyloid b-protein of Alzheimer’s disease supports in-vivo contact activation in murine