The practice of thromboprophylaxis in hospitalized children is evolving. Emerging research in pediatric hospital-acquired venous thromboembolism (HA-VTE) prevention continues to grow, yet clinical gaps and barriers persist. In this review, we conceptualize the future of thromboprophylaxis in children with an aim to address current challenges related to the prediction of HA-VTE and assessment of bleeding risk, the safe application of effective pharmacological agents, and implementation of pediatric HA-VTE preventive practices. With the rapid rate of advancement of artificial intelligence, biotechnology, and multi-omics technology, we consider the major role that these technologies can play in the field of thromboprophylaxis. Using a precision medicine framework, we give emphasis towards an individualized risk prediction approach by the application of pediatric risk assessment models as clinical decision support tools and the development of personalized antithrombotic regimens. In addition, we review some current state-of-the-art experimental pharmacological agents that can be developed in the future. Lastly, we discuss the importance of both individual and collaborative stewardship to be able to guide and successfully implement sound practice of thromboprophylaxis in children. Overall, we envision the future of pediatric thromboprophylaxis to support the development of pediatric research related to HA-VTE prevention that fosters safe, evidence-based practice and ultimately, improved outcomes.

Factor XI and XIa inhibitors - which include antisense oligonucleotides, monoclonal antibodies, and small peptidomimetic molecules - represent a new class of anticoagulants that inhibit the intrinsic pathway and attenuate thrombosis without disruption of hemostasis, thus making them potentially ideal anticoagulants to use in perioperative settings. Surgical data in patients with Factor XI deficiency (including severe Factor XI deficiency) reveal a phenotype that suggests uncomplicated hemostasis, especially in surgical areas of low fibrinolytic activity. Periprocedural data from completed Phase 2 clinical trials demonstrate two observations: 1) for primary venous thromboprophylaxis of patients undergoing major orthopedic surgery who are at risk of major bleeding, strategies to inhibit FXI result in a lower risk of venous thromboembolism and lower clinically relevant bleeding compared to current recommended therapy such as enoxaparin; 2) for patients on long-term FXI inhibitors undergoing elective procedures, there is potential for simpler and potentially safer periprocedural paradigms without interruption of FXI inhibitors compared to the simplified and standardized approach with direct oral anticoagulants, at least for low and (some) moderate bleed risk procedures. Further work, including tailored perioperative prospective management studies, targeted FXI inhibitor reversal strategies, and assays to assess the anticoagulant effects of FXI inhibitors in perioperative settings are needed.

Platelet membrane protrusions (PMPTs) are a remarkably diverse set of dynamic structures formed by platelets in response to shear stress. They are actively generated and play an integral role in hemostasis, potentially bridging the crosstalk between platelets and leukocytes. Unlike filopodia and lamellipodia, known for driving active cellular motility, PMPTs exhibit distinct characteristics. Some PMPTs, such as glycoprotein Ib-rich tethers and FLIPRs (FLow-Induced PRotrusions), possess pro-coagulant functions, either directly via phosphatidylserine exposure or by fragmenting into microparticles that provide a surface for coagulation activation. With the exception of tractopods, all PMPTs - including PITTs (Platelet-derived Integrin- and Tetraspanin-enriched Tethers) and FLIPRs- support leukocyte adhesion, thereby influencing immune cell recruitment and activation. This strongly indicates a role of PMPTs in the crosstalk between hemostasis and inflammation. Further evidence supporting this connection comes from observations of increased PMPT frequency in infection and certain autoimmune disorders. This review summarizes current knowledge on how PMPTs are formed, summarizes their structural characteristics, and the sparse information available regarding their biological roles and clinical significance.

Subsegmental pulmonary embolism (SSPE) accounts for 5-10% of PE diagnoses, but the optimal diagnostic and management strategies, as well as the long-term outcomes remain debatable. Recent studies have provided more insights into outcomes in this population, and a randomized controlled trial is ongoing to evaluate the role of anticoagulation in patients with isolated SSPE. In this article, we use cases to illustrate the challenges in diagnosis and to discuss management approaches. We aim to provide evidence-based recommendations whenever possible and point out potential areas for future research.