Implementation and clinical utility of multigene panels for bleeding, platelet, and thrombotic disorders.

High-throughput sequencing, with its capacity to simultaneously sequence large volumes of genomic data, has evolved from a research-focused technology to a clinical tool.

This review outlines key steps in the development of a clinical haemostasis and thrombosis genetics service leveraging a multigene panel.

We discuss its value across inherited bleeding, platelet, and thrombotic disorders (BPTDs) in the context of published studies utilizing multigene panels in these conditions.

Benefits of sequencing include establishing a diagnosis through the simultaneous assessment of multiple candidate genes, exclusion of genocopies and predictions of phenotype to deliver targeted therapy.

The presence of concomitant variants may modify phenotype; however, predictions on disease course from oligogenic modifiers are not yet used to guide patient care or counselling. Limitations in the widespread roll out of multigene panels for clinical diagnostics of BPTDs exist.

These challenges relate to detection of structural variants, variable diagnostic hit rates and management of incidental findings. Variants of uncertain significance (VUS) also frustrate diagnostic yield.

Family segregation studies, in vitro characterisation, and protein modelling aid interpretation of variant pathogenicity.

While multigene panels offer substantial opportunities to improve BTPDs diagnostics, their implementation should be guided by appropriate expertise and in conjunction with clinical research to ensure safe and ethical care.