ReviewInternational journal of laboratory hematology2026
Investigator-Led Research to Improve the Diagnostic Assessment of Platelet Function Disorders: Reflections on the Challenges and Rewards.
Review in International journal of laboratory hematology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
introductionInvestigator-led research and quality improvement initiatives have led to important improvements in the diagnostic assessment of platelet function disorders (PFD).
methodsPersonal reflections were used to summarize our contributions to knowledge on PFD diagnostic assessment, pathogenesis, and bleeding risks.
resultsLight transmittance platelet aggregometry (LTA) and whole mount electron microscopy assessment for platelet dense granule deficiency (DGD) both detect abnormalities that are highly predictive of a bleeding disorder. Observations on LTA findings that are predictive of a bleeding disorder (including those specific to certain conditions) have been incorporated into guidelines to reduce LTA interpretation errors. Efforts to improve LTA assessment of PFD with thrombocytopenia (e.g., Bernard Soulier syndrome) have led to validated, trustworthy diagnostic procedures. Commonly encountered PFD that manifest with abnormal aggregation responses to multiple agonists and/or DGD are now established to have significantly increased bleeding risks, emphasizing the need for diagnosis and treatment. Unraveling of the molecular pathogenesis of some specific PFD has provided important insights and simplified diagnosis. In the case of Quebec platelet disorder (QPD), the pathogenesis is a unique gain-of-function defect in fibrinolysis from a mutation that repositions a megakaryocyte-specific enhancer that normally upregulates VCL expression during megakaryopoiesis and "rewires" PLAU, increasing its expression > 100-fold in megakaryocytes only. Presently, the molecular causes of many "commonly encountered" PFD await elucidation.
conclusionsResearch has meaningfully improved diagnostic laboratory testing for PFD. Unraveling the causes of "commonly encountered" PFD will be important to understanding their pathogenesis and increasing the yield of diagnosis by genetic investigations.
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