Bleeding Risks Associated with Confirmed Platelet Dense Granule Deficiency and/or Impaired Aggregation Responses
Bibliographic record
Abstract
Abstract Platelet function disorders represent a heterogeneous group of bleeding disorders with diverse molecular causes that are frequently associated with platelet dense granule deficiency and/or impaired aggregation responses. With the exception of Quebec platelet disorder (QPD), bleeding risks for common platelet disorders have not been estimated. This led us to study a Canadian cohort with uncharacterized platelet function disorders and confirmed abnormalities in validated assays for platelet dense granule deficiency and/or light transmission aggregometry (reduced aggregation with ≥2 agonists). Subjects were assessed using: (i) the International Society for Thrombosis and Haemostasis bleeding assessment tool (ISTH-BAT) to determine scores and categorize symptom severity, and (ii) CHAT-P, a clinical history assessment tool for assessment of platelet disorders that included questions about general health and bleeding symptoms/problems and questions previously used to assess bleeding risks for QPD. CHAT-P was completed by subjects (or parent in the case of young children) before review by a hematologist. Participants included: 29 individuals with confirmed platelet function disorders of unknown cause (from 7 families, 10 "sporadic" cases), 12 unaffected relatives and 60 general population controls. A one-way ANOVA was used to compare the overall ISTH-BAT scores between the affected individuals, unaffected relatives and healthy controls. Bleeding risks were estimated as odds ratio (OR) with 95% confidence intervals (CI) using CHAT-P data for general population controls as the comparison group. The total number of affected subjects reporting a bleeding problem/symptom from the group of affected individuals was added up and compared with the corresponding numbers of responses for general population controls and unaffected relatives using ANOVA. Summative bleeding scores for CHAT-P items with OR>1 were used to compare the number and range of abnormal bleeding symptoms experienced by subjects. Individuals with confirmed platelet abnormalities had higher ISTH-BAT scores (median: 9, range: 0-18) than unaffected family members (median: 0, range: 0-1) and general population controls (median: 0, range: 0-6) (p < 0.01), and their most severe symptom scores were for: epistaxis, cutaneous bleeding, menorrhagia, bleeding from dental extractions, surgery and a subdural hematoma at birth. Affected individuals had higher risks for bleeding (OR, 95% CI, p value) including: bleeding from minor cuts/wounds lasting >1 hour (56, 3.1-1000, p<0.01); abnormal bruising (15-65, 1.8-140 to 3.7-1200, p<0.01); prolonged nosebleeds (23, 5.9-92, p<0.01) and nosebleeds requiring medical attention (40, 1.5-520, p<0.01), packing (33, 1.8-620, p<0.01) or cautery (27, 1.5-510, p<0.01); wound healing problems (13, 3.4-53, p<0.01); excessive bleeding from injuries/trauma (9.5, 1-87, p=0.03), oral/dental challenges (44, 5.3-370, p<0.01) and surgery (17, 4.1-68, p<0.01). Affected females reported: bleeding interfering with their sex life (6.5, 1.1-38, p=0.04); menses >7 days (11, 2.5-49, p<0.01); flooding/gushing accidents (3.8, 1.2-12, p=0.04 ) and/or clots with menses (13, 2.6-63, p<0.01); menses requiring treatment (7.8, 2.1-29, p<0.01); and excessive bleeding during childbirth (17, 2.7-105, p<0.01), sometimes requiring surgical intervention (41, 2-810, p<0.01). Affected individuals reported more of these bleeding symptoms (median: 15, range: 0-24) than unaffected family members (median: 2, range: 0-6; p<0.01) and general population controls (median: 1, range: 0-14, p<0.01), although there was overlap. Our study illustrates that uncharacterized platelet function disorders are associated with significantly increased bleeding risks and mild rather than severe bleeding problems. It will be important to translate our study findings for patients and healthcare providers to promote evidence-based care of individuals with confirmed dense granule deficiency and/or impaired aggregation responses, which are common amongst individuals tested for bleeding problems. Disclosures No relevant conflicts of interest to declare.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".