Unraveling Protein S Deficiency: Insights from a Population-Based Multiomic Study

PROS1 sequencing should be considered in select patients with recurrent/unprovoked VTE, as identifying rare high-risk variants can justify lifelong anticoagulation and prevent subsequent thrombosis.

Protein S deficiency challenges venous thromboembolism (VTE) management. Guidelines discourage routine protein S testing in patients requiring lifelong anticoagulation or with unprovoked/recurrent VTE. Questions persist about the role of genetics in these patients. This large-scale (>600,000 individuals), population-based multiomic study from U.K and U.S. datasets clarifies the prevalence of PROS1 variants and their relationship to circulating protein S levels and thrombosis risk. The researchers used the functional impact score (FIS; range 0–1), which categorizes gene variants based on their evolutionary conservation; higher scores predict more-severe disruption of the protein's function.

The results were as follows:

High-risk PROS1 variants…

Reviewing Author

Anjali A. Sharathkumar, MBBS, MD, MS

Disclosures

Consultant/Advisory BoardGenentech

Grant/Research SupportX4 Pharma; Pfizer; Health Resources and Services Administration; American Thrombosis and Hemostasis Network/CDC; Carver College of Medicine

Leadership Positions in Professional SocietiesInternational Society on Thrombosis and Haemostasis (Finance Committee Member); American Society of Hematology Clinical Research Translational Institute

Anjali A. Sharathkumar, MBBS, MD, MS

Disclosures

Consultant/Advisory BoardGenentech

Grant/Research SupportX4 Pharma; Pfizer; Health Resources and Services Administration; American Thrombosis and Hemostasis Network/CDC; Carver College of Medicine

Leadership Positions in Professional SocietiesInternational Society on Thrombosis and Haemostasis (Finance Committee Member); American Society of Hematology Clinical Research Translational Institute

Unraveling Protein S Deficiency: Insights from a Population-Based Multiomic Study

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Reviewing Author