Incidence and Risk Factors for IVIG-Mediated Hemolysis
Notice bibliographique
Résumé
Abstract INTRODUCTION Hemolysis is a recognized complication of high-dose IVIG infusion, but as the majority of case reports are retrospective the actual incidence and risk factors for its occurrence are poorly understood. METHODS: Between November 2012 and October 2016, recipients of high-dose IVIG in Toronto (Canada) were prospectively monitored for hemolysis using a panel of investigations performed pre- and post-infusion and then 5-10 days later. Hemolysis was defined and graded as per the Canadian IVIG Hemolysis Pharmacovigilance Group, with both patient and product risk factors analyzed for correlation. RESULTS: After a preliminary analysis revealed a strong association with ABO group and dose, enrollment was restricted to patients with non-O blood group receiving doses ≥ 2 g/kg, adjusted for lean body mass. Within this cohort, 99 infusions to 78 patients completed the follow-up protocol, with hemolysis observed in 32 (32%) and 28 (36%) of cases, respectively. Hemolytic anemia of Grades 1, 2, 3 and 4 were observed in 10, 9, 2 and 7 patients, respectively, and an additional 4 patients hemolyzed but maintained a stable hemoglobin via reticulocytosis. Although the initial fall in hemoglobin was slightly larger in hemolytic than non-hemolytic reactions (-14.9 vs -11.1 g/L, p = 0.0091), in 84% of cases laboratory confirmation of hemolysis only manifested 5-10 days after the infusion. In contrast, while 88% of hemolyzers had a positive DAT immediately post-IVIG, this proportion had fallen to 38% by day 5-10. Amongst 49 infusions evaluated by day 5-10 monocyte monolayer assay, there was 69% correlation between the development of hemolysis and the presence of heightened phagocytic activity in patient monocytes, vs 43% correlation when testing was performed with monocytes from healthy controls. Further supporting a state of increased macrophage activation, the proportional increase in serum ferritin was greater in hemolyzers than non-hemolyzers (5.1-fold vs 2.1-fold, p = 0.033). Conversely, all positive DAT test results were for IgG only, with no evidence of complement deposition. In regards to predictors of hemolysis, univariate analysis identified a higher incidence with group AB than with other blood groups (90% vs 26%, p = 0.0001), in first-time compared to repeat recipients (50% vs 20%, p = 0.002), in patients not taking immunosuppressant medications (43% vs 23%, p = 0.0316), and in patients whose post-infusion DAT was 1+ or stronger as compared to weak or by eluate only (57% vs 19%, p = 0.0001). One of three manufacturers had a lower rate of hemolysis (0% vs 35%, p = 0.009) but was also more likely than the other two manufacturers to be given to patients on immunosuppressant medications (83% vs 24%, p=0.0001). No correlation was observed with year of treatment, patient age, sex, BMI, diagnosis, rate of infusion, steroid pre-medication, subjective symptoms or pre-infusion levels of CRP or IL1-RA. CONCLUSION: Amongst non-O blood group recipients of high-dose IVIG, hemolysis is common and appears to occur via delayed-onset phagocytosis by activated patient monocytes. The highest risk appears to be in patients with blood group AB, those who are receiving IVIG for the first time, who are not taking immunosuppressive medications, or who have a 1+ or stronger DAT immediately post-infusion. Whether specific IVIG products carry higher risk requires further study. Disclosures Lin: Pfizer: Other: advisory board; Pfizer: Honoraria; CSL Behring, Grifols: Other: unrestricted education grant; Novartis: Research Funding. Pavenski: Novartis: Honoraria; Ablynx: Other: participation in industry sponsored RCT; CSL Behring: Research Funding; Alexion Pharmaceuticals: Honoraria. Branch: CSL Behring (Bern): Research Funding; CSL Behring (Canada): Research Funding; Canadian Blood Services: Employment, Research Funding; ViroCarb Inc.: Other: Founder and stock holder.
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 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| 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) | 0,002 | 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 ».