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Updated: Oct 31, 2025

Comprehensive Analysis of Procoagulant Platelets Exhibiting Features of Necrosis, Apoptosis and Platelet Activation
Published on: May 23, 2025
Thrombin generation abnormalities in commonly encountered platelet function disorders
Tanmya Sharma1, Justin G Brunet1, Subia Tasneem1
1Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
Introduction:
Studies of thrombin generation (TG) with platelet-rich plasma (PRP) and platelet-poor plasma (PPP) have provided insights on bleeding disorders. We studied TG for a cohort with commonly encountered platelet function disorders (PFD).
Methods:
Participants included 40 controls and 31 with PFD due to: nonsyndromic dense granule (DG) deficiency (PFD-DGD, n = 9), RUNX1 haploinsufficiency (n = 6) and aggregation defects from other, uncharacterized causes (n = 16). TG was tested with PRP and PPP samples. As DG store ADP and polyphosphate that enhance platelet-dependent TG, PFD-DGD PRP TG was tested for correction with ADP, polyphosphate and combined additives. Tissue factor pathway inhibitor (TFPI), platelet factor V (FV), and platelet TFPI and ANO6 transcript levels were also evaluated. Findings were tested for associations with TG endpoints and bleeding.
Results:
PFD samples had impaired PRP TG, but also impaired PPP TG, with strong associations between their PRP and PPP TG endpoints (P ≤ .005). PFD-DGD PRP TG endpoints showed associations to PPP TG endpoints but not to DG counts, and were improved, but not fully corrected, by adding polyphosphate and agonists. PFD participants had increased plasma TFPI and reduced platelet TFPI (P ≤ .02) but normal levels of platelet FV, and platelet TFPI and ANO6 transcripts levels. PFD plasma TFPI levels showed significant association to several PPP TG endpoints (P ≤ .04). Several PFD PRP TG endpoints showed significant associations to bleeding symptoms, including wound healing problems and prolonged bleeding from minor cuts (P ≤ .04).
Conclusion:
TG is impaired in commonly encountered PFD, with their PRP TG findings showing interesting associations to symptoms.
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