Uncharacterized platelet function disorders significantly increased the risk of mucocutaneous bleeding (OR 4-207), challenge-related bleeding (OR 12-43), and receiving transfusions (OR 100).
Observational (n=37)
What are the bleeding risks associated with uncharacterized platelet function disorders compared to unaffected controls?
Uncharacterized platelet function disorders that impair maximal aggregation or cause nonsyndromic dense granule deficiency are associated with significantly increased risks of mucocutaneous and challenge-related bleeding.
Effect estimate: OR 4-207 (mucocutaneous), OR 12-43 (challenge-related), OR 100 (transfusions)
p-value: p=<.04
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.
Brunet et al. (Sat,) conducted a observational in Uncharacterized platelet function disorders (n=37). Uncharacterized platelet function disorders vs. Unaffected family members and general population controls was evaluated on Bleeding risks estimated as odds ratios relative to general population controls (OR 4-207 (mucocutaneous), OR 12-43 (challenge-related), OR 100 (transfusions), p=<.04). Uncharacterized platelet function disorders significantly increased the risk of mucocutaneous bleeding (OR 4-207), challenge-related bleeding (OR 12-43), and receiving transfusions (OR 100).