Clinical outcomes associated with serological subsets of heparin-induced thrombocytopenia
Notice bibliographique
Résumé
Abstract Background: Heparin Induced Thrombocytopenia (HIT) is an immune-mediated drug reaction classically characterized by platelet activating anti-platelet factor 4(PF4)/heparin antibodies, leading to reduced platelet count and increased risk of thrombosis. The gold standard diagnostic test is the serotonin release assay (SRA), which is performed by mixing patient serum with pedigree donor platelets labelled with 14C-serotonin with or without heparin. A typical positive SRA result shows heparin-dependent platelet activation. A subset of patients with HIT also demonstrate platelet activation that is independent of heparin (known as an atypical, or autoimmune SRA pattern). Whether serological subsets of HIT are associated with different clinical outcomes is not known. Objective: To assess the clinical outcomes associated with different serological subsets of HIT patients based on the presence or absence of heparin-independent platelet activation in the SRA. Methods: Retrospective cohort study at McMaster University, which is a tertiary care referral center and the reference HIT testing center for Canada. All patients with a positive anti-PF4/heparin enzyme immunoassay and a positive SRA (14C-serotonin release ≥ 20% with therapeutic dose heparin) managed at our centre between January 2006 and May 2025 were included. The subset of patients with heparin-independent platelet activation was defined by 14C-serotonin release ≥ 20% in the absence of heparin. The first available SRA result and corresponding clinical encounter were analyzed for each patient. Baseline demographics, previous thrombosis, admission diagnosis, heparin exposure and baseline laboratory values were extracted from medical records. The primary outcome was a composite of any objectively confirmed and documented arterial or venous thrombosis within 90 days of the positive SRA result. Other outcomes included platelet count, fibrinogen level, and mortality. Data extraction was completed blinded to the results of the SRA. For each clinical outcome, univariate analyses were conducted to compare patients with with and without heparin-independent platelet activation. Logistic regression was used to examine the association between serological subsets and the occurrence of any thrombosis adjusting for patient sex and age, nadir platelet count, nadir fibrinogen, and surgery during admission. Results: Of 194 patients with HIT, 100 (52%) demonstrated heparin-independent platelet activation. Patients with the heparin-independent serology were similar to patients with the heparin-dependent serology with respect to age (69.0±14.0 and 69.3±11.6), sex (53% and 52.1% female), surgical admission (70% and 68.1%), previous thrombosis (55% and 56.4%) and baseline platelet count (248±89 and 259±89 x10^9/L). Patients with heparin-independent serology had higher 4T scores (6.13±1.18 vs 5.33±1.55, p<0.001) and higher optical density of the anti-PF4/heparin enzyme immunoassay (2.53±0.76 vs 2.25±0.68, p=0.005). The heparin-independent serology was associated with worse clinical outcomes including a lower nadir platelet count (54±29 vs 70±47 x10^9/L, p=0.003), thrombosis (60% vs 46.8%, p=0.033), myocardial infarction (6% vs 0%, p=0.008) and cerebral sinus venous thrombosis (3% vs 0%, p=0.042). There was no difference between groups in nadir fibrinogen level, timing of thrombosis following HIT diagnosis, or mortality. After adjusting for patient demographics and clinical characteristics, the heparin-independent serology was associated with a higher risk of thrombosis (OR=2.04,95%CI 1.05-3.98, p=0.036). Conclusion: The subset of HIT patients with heparin-independent platelet activation had a higher risk of thrombosis and lower platelet count nadir compared with HIT patients who had a heparin-dependent serology. Reporting subsets of SRA results may improve HIT outcomes.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
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 | 0,002 |
| 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 | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,001 |
| 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 ».