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Personalized Approaches to the Treatment of Hemostatic Disorders.

The last 20 years has seen dramatic improvements in the clinical management of hemostatic and thrombotic disorders. We have witnessed the introduction of novel therapeutic agents into the clinic, including direct oral anticoagulants (DOACs), and the rapid evolution of personalized therapy for patients with the development of high-throughput genetic analysis and gene therapy. Moreover, growing awareness of nonlineargenotype-phenotypecorrelations indiseasepresentation, includingbleedingor thrombosis risk, has catalyzed the concept of tailored individualized therapies. Many of these clinical milestones have been made possible by improved understanding of the fundamental biology and thus pathophysiology underpinning hemostatic disorders, as well as development of novel technologies and diagnostic tools. This review series aims to provide an overview of some of these advancements, with a particular focus on novel and personalizedapproaches to themanagementofdisordersofhemostasis and thrombosis. The nature of the circulatory systemmeans that regulation of vascular integrity and associated disorders is both complex and dynamic. Hemostatic responses typically occur under conditions of varying shear stress across the vasculature, with platelets flowing across the endothelium and with concentration gradients of specific procoagulant and anticoagulant factors. Studying and understanding the crosstalk between all these processes in in vitro or ex vivo settings presents particular challenges. Nevertheless, the first part of this review series describes the significant advances that have been made in preclinical and diagnostic technologies, including three-dimensional cellularizedmicrofluidic devices, which provide a platform to examinemany of these biological components in unison. Caruso and Lam detail the current state-of-the-art technologies underpinning their application in point-of-care diagnostic devices that assess hemostasis parameters in the clinical setting.1 Another unique approach to the challenge of understanding the complex biological interplay regulating hemostasis is computational modeling. In the second contribution of this series, Leiderman et al provide a comprehensive overview of the key inputs in designing robust integrated mathematical models of thrombus formation and how these unique systems can be used to interrogate the complex nature of thrombosis and hemostasis and provide insight into novel disease mechanisms.2 In addition to diagnostic and technological advances in this field, theadventofDOACs,first approved forclinicaluse in2010, has significantly shifted the therapeutic landscape for venous thromboembolic disease. DOACs have emerged as effective, safe, and convenient therapeutic options for thromboprophylaxis. This is exemplified in amendments to many of the published guidelines, with inclusion of DOACs as therapeutic alternatives for thromboprophylaxis in high-risk cancer patients. In the third part of this issue, Dhami et al summarizes the advances in the management of cancer-associated thrombosis, including insights into the pathophysiology, refinement of risk prediction models, and novel therapies.3 This is timely given the recently published data from the much-anticipated CARAVAGGIO trial evaluating the DOAC apixaban in the oncology setting.4 The predictable clinical and pharmacokinetic profile of DOACs also favors them as agents of choice over vitamin K antagonists and low molecular weight heparins for reducing the risk of stroke and for treatment of venous thromboembolism. Revision of international guidelines in the field now places emphasis on a personalized “best-fit” strategy for use of DOACs for thromboprophylaxis.5 With the expanding role of DOACs, clinicians are now faced with increasingly complex decisions including duration of treatment and monitoring parameters. The clinical monitoring of plasma DOAC activity in these cohorts can be challenging, given that many routine coagulation assays are not sensitive to DOACs in the samemanner as other anticoagulants.6Despite thewidespread