Reversal agents are used in patients taking direct oral anticoagulants (DOACs) to manage bleeding, but evidence for their effectiveness remains limited.

From the beginning of the millennium and the development of genome-wide analyses, the technical advances and remarkable increase in research sample sizes have led to an escalating number of discoveries revealing genetic determinants of levels of the main factors regulating hemostasis and thrombosis, and demonstrating a clear polygenic complex regulation of most coagulation factors. These discoveries have been useful to understand the biology underlying hemostasis regulation, and to understand risk of associated thrombotic disease, such as venous thromboembolism, coronary artery disease, and ischemic stroke. In this historical review, we outline the main discoveries in genetic studies of coagulation factors (fibrinogen and its alternatively spliced γ' isoform, D-dimer, factor V, factor VII, factor VIII, von Willebrand factor, and factor XI), the main natural anticoagulants (protein C, protein S, antithrombin), components of fibrinolysis (tissue plasminogen activator [tPA, plasminogen activator inhibitor-1 [PAI-1]), and global coagulation tests (prothrombin time [PT], activated partial thromboplastin time [aPTT]). We explore the clinical implications of these discoveries and suggest new avenues for future investigation.

Epigenetic regulation with histone deacetylase (HDAC) inhibition by valproic acid (VPA) has been used to regulate a number of pathological conditions to date. Recently, VPA was shown to alter production and local release of tPA and PAI-1 in the blood, and to have utility in the regulation of clot formation, resolution, and stability. However, VPA is known to be associated with a rare risk of hepatotoxicity.

Endothelial injury is the core factor of venous thrombosis. m6A plays a critical role in metabolism and cellular processes. Moreover, the balance of mitochondrial dynamics is essential in regulating cellular growth, apoptosis, and mobility. Now, The roles of m6A modification and mitochondrial dynamics in regulating venous endothelial cells remains elusive.

Acute pulmonary embolism (PE) includes clinical presentations with a wide spectrum of severities, making risk stratification essential to guide the decision-making process in daily practice. However, international guidelines differ in definition of risk classes and consequent treatment recommendations.

Failure rates of clinical decision rules (CDRs) combined with D-dimer to exclude pulmonary embolism (PE) are higher in patients with cancer compared to non-cancer patients, raising concerns about their use in this patient group.

The care of menstruating individuals on anticoagulation is complex and often overlooked in current clinical guidelines. Although existing recommendations address anticoagulant use broadly, they provide little guidance on managing menstrual bleeding, contraception, or reproductive transitions in this population. To address these gaps, we developed a practical clinical toolkit focused on anticoagulation stewardship for individuals who menstruate-from adolescence through menopause. This expert-driven resource outlines best practices for identifying and managing heavy menstrual bleeding (HMB), optimizing contraceptive counseling, and coordinating care during high-risk periods such as pregnancy, surgery, and perimenopause. It also offers guidance for special populations, including adolescents, transgender and gender-diverse individuals, and those with limited access to care. Key topics include medication selection, dose adjustment, screening for anemia, and referral to gynecology when appropriate. The toolkit emphasizes the role of multidisciplinary teams-including hematology, gynecology, primary care, and anticoagulation services-in delivering patient-centered, equitable care. It also highlights practical strategies for integrating menstrual health into routine anticoagulation management, promoting shared decision-making, and improving quality of life for affected individuals.

Reperfusion by mechanical thrombectomy (MT) is an alternative for reperfusion in acute pulmonary embolism (PE) when systemic thrombolysis (ST) is contraindicated or has failed.

One-third of patients undergoing transcatheter aortic valve implantation (TAVI) have a concomitant indication for oral anticoagulation (OAC). Previous studies suggested that periprocedural continuation of OAC could reduce transient hypercoagulation after TAVI.

Thrombotic microangiopathy (TMA) is a common and potentially fatal complication following allogeneic haematopoietic stem cell transplantation (allo-HSCT). Thrombotic thrombocytopenic purpura (TTP), a distinct form of TMA caused by severe deficiency of plasma ADAMTS13 activity, has been reported to be rare in the posttransplant population.

Activated protein C (APC) is a serine protease known for its anticoagulant, anti-inflammatory, and cytoprotective properties. Although clinical evidence links protein C (PC) deficiency to various retinal pathologies, the physiological role of APC in the retina remains unexplored.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare and life-threatening thrombotic microangiopathy. More and more studies have clearly shown a high prevalence of several adverse long-term health issues following recovery in these patients. Therefore, nowadays, the paradigm of iTTP as an acute episodical disease is quickly changing, and it should be considered a chronic disorder. The present review focuses on the two main long-term complications occurring during clinical remission in these patients (i.e. cardiovascular and neurological complications). Our goal is to provide an updated overview on this topic, explaining the main related pathogenic mechanisms and highlighting how iTTP is emerging as a model not only of acute but also of chronic systemic microvascular dysfunction. The most accredited hypothesis supporting the chronicity of the disease is that after recovery from an acute iTTP episode a state of cumulative microvascular damage could persist and progress over time. However, the trajectory remains rather unpredictable and there is still a poor evidence on preclinical biomarkers able to identify those patients at higher risk of long-term cardiovascular and neurological complications, as well as drugs able to prevent chronic cardiac or brain organ damages. To date, there are no clear guidelines in this field and the clinical practice is quite heterogeneous between reference centers. A task force within the scientific community would be important for the standardization of the most appropriate monitoring tools as well as preventive approaches for long-term complications in iTTP patients.