Multidetector CT pulmonary angiography has increased detection of pulmonary embolism at the subsegmental level without a corresponding fall in overall PE mortality, placing isolated subsegmental pulmonary embolism (iSSPE) at the center of a management conflict: the 2021 CHEST guideline permits structured surveillance in selected patients, whereas the 2026 multisociety guideline recommends anticoagulation for all acute pulmonary embolism. We review iSSPE definition, diagnostic reliability, natural history, treatment-versus-surveillance outcomes, and guideline divergence. Across mixed cohorts, anticoagulation has not clearly reduced recurrence or mortality but increases bleeding; cancer-associated thrombosis is the clearest exception however. We propose a four-gate framework to guide surveillance versus anticoagulation.

Thrombin is a central mediator of haemostasis, immune responses, and inflammation. It arises from prothrombin upon prothrombinase cleavage at R[320]-I[321], which triggers the allosteric maturation typical of chymotrypsin-like serine peptidases. Further processing yields the physiologically dominant α-thrombin (αT), whose competent active site centres on catalytic S[525]. Despite widespread biomedical and biotechnological use, plasma-derived αT is heterogeneous and risks pathogen or prion transmission, motivating recombinant alternatives. These have largely relied on suboptimal bacterial or non-human eukaryotic systems, with human-cell efforts focused mainly on prothrombin or engineered variants. Here, we report the recombinant production in Expi293F cells of prethrombin-2 (PE2), a zymogen retaining 13 residues upstream of αT, alongside its catalytically-impaired S[525]A counterpart (PE2-S[525]A). Controlled in vitro maturation was achieved with a matched recombinant system for ecarin, a snake-venom metallopeptidase cleaving R[320]-I[321], which yielded active PE2a and inactive PE2a-S[525]A. PE2a exhibited thermal stability, cleavage activity against the chromogenic substrate S-2238, and performance in thrombin-time assays comparable to those of commercial human αT. By contrast, it cleaved the physiological substrate fibrinogen, including its fluorescein-labelled form, more efficiently. Fresh PE2a slowly underwent autolysis at R[284]-T[285], yielding αT after one week. The direct thrombin inhibitors argatroban and dabigatran further enhanced thermal stability while efficiently blocking substrate cleavage. This fully recombinant workflow provides a practical platform for basic haematological research, structural biology, and inhibitor screening in vitro.

Pulmonary embolism (PE) remains a major cause of cardiovascular morbidity and mortality, but the central management question clinicians increasingly face is not whether to anticoagulate, but how to anticoagulate well. Rapid expansion of the evidence base has transformed anticoagulation management from a largely protocol-driven approach into a more individualised and dynamic model of care. Contemporary treatment decisions extend beyond initial drug selection and increasingly require consideration of dose intensity, treatment duration, bleeding phenotype, cancer status, renal function, drug interactions, and evolving thrombotic risk. Direct oral anticoagulants (DOACs) are now established as first-line therapy for most haemodynamically stable patients, while recent studies have refined selection within the DOAC class and challenged traditional assumptions regarding extended therapy. Emerging evidence suggests that some patients with apparently strongly provoked venous thromboembolism may nevertheless benefit from prolonged anticoagulation when enduring prothrombotic risk factors persist. Other studies support selective dose reduction during long-term therapy, while highlighting important limitations of this strategy in obesity. In cancer-associated thrombosis, contemporary trials increasingly support dynamic and phenotype-driven approaches to prolonged anticoagulation rather than fixed-duration treatment paradigms. This review synthesises evolving evidence on anticoagulation management in PE into a practical framework for clinicians involved in longitudinal venous thromboembolism care. Throughout this review, we distinguish established practice supported by contemporary international guidelines from emerging evidence that may refine future management but has not yet been incorporated into guideline recommendations.