When it's not Glanzmann thrombasthenia or Bernard-Soulier syndrome: diagnosing other qualitative platelet disorders.

Abstract

Inherited and acquired disorders that qualitatively impair platelet function represent important and commonly encountered conditions. While some rare, well-characterized conditions (eg, Glanzmann thrombasthenia and Bernard-Soulier syndrome) have pathognomonic findings and glycoprotein deficiencies, the more commonly encountered platelet function disorders are much more heterogeneous and challenging to diagnose. Qualitative platelet disorders typically present with mild to moderate, mucocutaneous, and challenge-related bleeding, particularly for hemostatic challenges prior to diagnosis. Diagnostic tests should assess platelet counts and size; platelet morphology by light microscopy; platelet function in aggregation assays (a "gold standard" test for qualitative platelet disorders); platelet-dense granule numbers, granule contents, and/or release; and, less commonly, platelet glycoproteins, procoagulant function, α-granule release, or ultrastructure. Genetic tests can be helpful, but the chances of finding a diagnostic, disease-causing, pathogenic mutation with a platelet disorder genetic test panel is much lower if there is not an a priori suspected cause and/or inherited thrombocytopenia. Commonly, the diagnosis of a qualitative platelet disorder is made after confirming impaired platelet aggregation responses to multiple agonists, with a pattern that excludes rare disorders (eg, Glanzmann thrombasthenia and Bernard-Soulier syndrome), and/or platelet-dense granule deficiency; both findings are highly predictive of a bleeding disorder. To communicate and discuss diagnostic test findings with patients and optimize care, it is also important to have knowledge of the bleeding risks for qualitative platelet disorders and their typical responses to therapies.