Abstract | BACKGROUND: The bleeding risks for nonsyndromic platelet function disorders (PFDs) that impair aggregation responses and/or cause dense granule deficiency (DGD) are uncertain. OBJECTIVES: Our goal was to quantify bleeding risks for a cohort of consecutive cases with uncharacterized PFD. METHODS: Sequential cases with uncharacterized PFDs that had reduced maximal aggregation (MA) with multiple agonists and/or nonsyndromic DGD were invited to participate along with additional family members to reduce bias. Index cases were further evaluated by exome sequencing, with analysis of RUNX1-dependent genes for cases with RUNX1 sequence variants. Bleeding assessment tools were used to estimate bleeding scores, with bleeding risks estimated as odds ratios ( ORs) relative to general population controls. Relationships between symptoms and laboratory findings were also explored. RESULTS: Participants with uncharacterized PFD (n = 37; 23 index cases) had impaired aggregation function (70%), nonsyndromic DGD (19%) or both (11%), unlike unaffected relatives. Probable pathogenic RUNX1 variants were found in 2 (9%) index cases/families, whereas others had PFD of unknown cause. Participants with PFD had increased bleeding scores compared to unaffected family members and general population controls, and increased risks for mucocutaneous (OR, 4-207) and challenge-related bleeding (OR, 12-43), and for receiving transfusions for bleeding (OR, 100). Reduced MA with collagen was associated with wound healing problems and bruising, and more severe DGD was associated with surgical bleeding (P < .04). CONCLUSIONS: PFDs that impair MA and/or cause nonsyndromic DGD have significantly increased bleeding risks, and some symptoms are more common in those with more severe DGD or impaired collagen aggregation.
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Authors | Justin Brunet, Matthew Badin, Michael Chong, Janaki Iyer, Subia Tasneem, Lucas Graf, Georges E Rivard, Andrew D Paterson, Guillaume Pare, Catherine P M Hayward |
Journal | Research and practice in thrombosis and haemostasis
(Res Pract Thromb Haemost)
Vol. 4
Issue 5
Pg. 799-806
(Jul 2020)
ISSN: 2475-0379 [Electronic] United States |
PMID | 32685888
(Publication Type: Journal Article)
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Copyright | © 2020 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis. |