Survey on current practice in thrombophilia testing: from phenotype to genotype. Communication from the SSC of the ISTH

Diagnosing inherited thrombophilia as cause of venous thromboembolism is important for patient management. Deficiencies in antithrombin, protein C, and protein S, are usually diagnosed by plasma-based assays. Genetic testing can confirm the congenital nature of these deficiencies. Factor V Leiden can be detected using activated protein C resistance assays, followed by or replaced by molecular confirmation, while prothrombin G20210A can only be detected genetically. During the last decade, molecular techniques have evolved from single-gene sequencing to multi-gene sequencing panels.
To understand current thrombophilia testing practices, a questionnaire was designed focussing on thrombophilia testing in coagulation laboratories and how they place genetic testing in their diagnostic workflow. All ISTH members and participants in external quality control schemes on thrombophilia testing were invited to complete the survey. Eighty-two unique responses were received.
This international survey showed that laboratories perform plasma-based thrombophilia testing, but 42% restrict it to requests from thrombosis/haemostasis specialists, patients without anticoagulant treatment or those with a strong personal of familial history of venous thrombosis. Phenotypic testing is however not always performed according to published guidelines. More specifically, the transference of reference intervals from manufacturers or literature is often suboptimal. For result interpretation, anticoagulant use and acquired causes were considered the most.
Genetic testing is not systematically included in the diagnostic work-up algorithms and is mostly restricted to single-variant testing. Multi-gene panel testing is performed only by a minority of laboratories. Our results highlight the necessity for recommendations on how and when to perform this kind of testing.