Bleeding Risks Associated with Confirmed Platelet Dense Granule Deficiency and/or Impaired Aggregation Responses
Notice bibliographique
Résumé
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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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,001 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».