Non-Pathogenic Anti-Heparin/PF4 Antibodies Generated by Low Molecular Weight Heparins Mediate Procoagulant Effects.
Notice bibliographique
Résumé
Abstract Abstract 1091 Introduction: While the incidence of symptomatic heparin-induced thrombocytopenia (HIT) is relatively low with the use of low molecular weights heparins (LMWHs), these agents do generate anti-heparin/PF4 antibodies in 10–20% of treated patients. Dosage, duration, and the pathologic predisposition of the patient influence the quantitative and qualitative nature of these antibodies. It has been suggested that these non-pathogenic antibodies (NPAs) which do not produce symptomatic HIT may, nevertheless, be biologically active and mediate thrombogenic responses. The overall pathophysiologic role of NPAs is unknown at this time. Hypothesis: NPAs generated by LMWHs cause coagulation activation and compromise the anticoagulant effects of the administered LMWH. Study Design: Blood plasma samples collected at baseline and day 10 from patients enrolled in orthopedic surgery clinical trials of LMWHs for the prophylactic management of deep vein thrombosis (Lovenox enoxaparin, sanofi-aventis, n=352; Clivarin reviparin, Abbott, n=380) were retrospectively screened for the presence of anti-heparin/PF4 antibodies using the GTI ELISA method (Waukesha, WI). Positive samples were tested by the 14C-SRA to determine if the antibodies were capable of functionally activating platelets. Both ELISA positive and negative samples were evaluated in an assay of thrombin generation (Technothrombin TGA kit, diaPharma, West Chester, OH). Result: In the enoxaparin study, the baseline pre-treatment samples only showed one patient in the heparin control group to be positive by ELISA. On day 10, 11 of 175 (6.3%) enoxaparin patients had a positive ELISA response, whereas 22 of 177 (12.4%) heparin patients were ELISA positive. None of the samples were 14C-SRA positive. In the thrombin generation assay, the ELISA positive samples showed a lesser inhibition of thrombin generation for both the enoxaparin and heparin groups (270 ± 27 nM TGA enoxaparin group; 220 ± 21 nM TGA heparin group) compared to the thrombin generation response of the ELISA negative samples (190 ± 18 nM TGA enoxaparin group; 160 ± 20 nM TGA heparin group). In the reviparin study, none of the patients were ELISA positive at baseline. On day 10, in the reviparin group 19 of 200 (9.5%) patients were ELISA positive, whereas 28 of 180 (15.6%) heparin control patients had a positive ELISA titer. None of the samples were 14C-SRA positive. In comparison to the baseline (pre-treatment), both the reviparin and heparin treated patients showed an inhibition of thrombin generation (410 ± 27 nM TGA baseline vs 180–290 nM with treatment). However, consistent with the above study, those samples that were ELISA antibody positive showed a lesser inhibition of thrombin generation (240 ± 21 nM TGA reviparin group; 210 ± 16 nM TGA heparin group) in comparison to the ELISA negative samples (190 ± 12 nM TGA reviparin group; 180 ± 14 nM TGA heparin group). Interestingly, the D-dimer levels were found to be higher in the ELISA positive samples in all groups for both studies (p<0.05). Conclusion: These studies suggest a potential pathologic role of NPAs. The results of the thrombin generation studies strongly suggest that the generation of NPAs may result in a reduction of the antithrombotic potential of both LMWH and heparin in treated patients. While the exact mechanism of this process is not clear, dosage adjustment may be useful in those patients who generate NPAs. Disclosures: No relevant conflicts of interest to declare.
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 | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 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) | 0,003 | 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 ».