Testing for Non-Severe Heritable Platelet Function Disorders

Heritable platelet function disorders (HPFD) are a diverse group of bleeding disorders characterised by a primary qualitative defect in platelet function rather than platelet number. HPFD may be broadly categorised according to the severity of bleeding, with Glanzmann thrombasthenia and Bernard Soulier syndrome classically considered severe HPFD, with well-described clinical and laboratory phenotypes. The remaining non-severe HPFD are less completely characterised and provide additional challenges in diagnosis despite advances in standardising diagnostic approaches for HPFD. Distinguishing patients with non-severe HPFD from patients who do not have a bleeding disorder may be aided by employing bleeding assessment tools early in patient assessment, although there may be limitations according to patient factors. Distinguishing patients with non-severe HPFD from those with acquired platelet function disorders and from those with other heritable disorders of haemostasis (including bleeding disorder of unknown cause) requires more sophisticated clinical and laboratory tools, including platelet light transmission aggregometry, secretion and flow cytometry assays, which can categorise many HPFD to the level of the defective platelet pathway and some to the level of an individual protein. The increasing availability of high-throughput genetic sequencing has made genetic diagnosis possible for some patients with non-severe HPFD; however, this is limited by difficulties with standardisation of laboratory phenotyping and the challenges of distinguishing pathogenic from benign genetic variation. This review will focus on updates in diagnostic approaches for patients with non-severe HPFD since the last IJLH education article on this topic in 2014.