"Unpatients" in haemostasis and thrombosis. A yardstick of current paths in healthy carriers of a genetic susceptibility.

Abstract

"Unpatients" are health-conscious individuals -carrying a genetic susceptibility whose impact is unclear with respect to the risk of a clinical event- who may shape their lives around periodic check-ups and preventive measures. Here, information from likely pathogenic single nucleotide polymorphisms (SNPs) and variants of uncertain significance in haemostasis are used to highlight current issues and directions for "unpatients". Despite their individually low relative risks (RR ≤ 2.0) for a first episode of venous thromboembolism (VTE), weak SNPs and variants of uncertain significance collectively confer RRs that are quantitatively comparable to those of established VTE risk factors. However, a high polygenic risk score (PRS) does not represent a definitive disease risk, and a low PRS does not imply a zero chance of clinical events. Advanced techniques to explore molecular variants may help to refine management and medical decision-making for "unpatients." Artificial intelligence (AI)-based tools are needed to expand disease-specific insights and prevent inappropriate conclusions when handling advanced analyses and large datasets. Yet AI-driven approaches involve the management of sensitive personal health data by non-medical experts and the use of computational methods that may be opaque even to specialists, raising ethical and legal concerns. While new strategies are being explored to generate clinically relevant genomic prediction tools, targeted education for physicians, patients, and families is essential. In domains affecting diagnostic and therapeutic progress, protection against discrimination -and attention to the evolving dimensions of the patient-physician relationship-should be ensured for carriers of genetic susceptibility and members of "genetically bound tribes."