Appendix A — Patient information
Incidental findings and patient consent
When referring a patient for genetic screening there is always a risk of incidental findings. These could be any of:
A variant which is not involved in the direct cause of the phenotype under investigation (bleeding or thrombocytopenia), but might have other clinical consequences for that person or their relatives. Ex: Finding that a woman with increased bleeding is carrier of hemophilia A, but having normal FVIII levels.
A finding which contradicts stated biological relationships between family members. Ex: The finding of a trait that is inherited X-linked is present in the father, but not in his presumed daughter.
The HTS panel recommended by the ISTH-SCC includes 3 genes related to inherited thrombocytopenia (RUNX1, ANKRD26 and ETV6) where pathogenic variants have been shown to convey an increased risk of myelodysplastic syndrome and acute leukemia.
Recommendation
Patients should be asked before testing whether they want to receive information on incidental findings (IF) and should be able to opt-out. The informed consent process should explain the likelihood of IF and the reporting approach taken.
Consent should be taken prior to genetic testing for IPD and should cover: information on breadth of testing, implications of results for patient and extended family, variants of unknown significance and incidental findings, data sharing and non‐hemostatic effects of some variants.
Genetic screening of IPD involves the potential detection of pathogenic variants in genes associated with leukemic risk (RUNX1, ETV6 and ANKRD26). Such variants typically present in families with autosomal dominant thrombocytopenia and a history of blood cancer but may also be an accidental finding in a healthy blood donor. We recommend that patients should be well informed about this possibility prior to performing the test.