Impact du COVID-19 et du confinement sur la transfusion

L'émergence de SARS-CoV-2 a entraîné un afflux massif de patients à l'hôpital et particulièrement en réanimation créant de nombreux problèmes. L'un d'entre eux est la transfusion, tant du côté de l'EFS (sécurité, collecte et stocks) que du transfuseur (soins habituels et demande spécifique inconnue liée au COVID-19). Un des risques était la pénurie avec nécessité de planifier des restrictions transfusionnelles. Nous avons analysé en parallèle l'activité transfusionnelle dans un CHU ainsi que la collecte et la délivrance au niveau de l'EFS entre le 24/02 et le 31/05/2020 et les avons comparées aux données de 2019. L'activité globale a baissé de 33 % sur la période (arrêt des soins réglés hors urgence ou soins ne pouvant être différés et admissions de 2291 patients COVID-19) alors que la transfusion n'a été réduite que de 17 %. Un total de 237 patients COVID-19 (10,3 %) ont nécessité une transfusion, dont 45 pour hémorragie. Parallèlement, la baisse des dons a été contenue à 11 % avec une discrète augmentation des stocks. La diminution de l'activité ne se traduit que par une baisse modérée de l'activité transfusionnelle, celle-ci dépendant principalement de la chirurgie urgente, des syndromes hémorragiques et de la prise en charge des patients en aplasie chimio-induite ou ayant des pathologies hématologiques. Le confinement a entraîné une diminution des dons par suppression des collectes mobiles mais avec un impact limité sur une courte période par mobilisation des donneurs réguliers. Il n'a pas été observé d'inadéquation entre demande et suppléance et il n'a donc pas été nécessaire de mettre en place des restrictions. (French) [ABSTRACT FROM AUTHOR] Copyright of Transfusion Clinique et Biologique is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Impact of COVID-19 and lockdown regarding blood transfusion.

BACKGROUND: The outbreak of a SARS-CoV-2 resulted in a massive afflux of patients in hospital and intensive care units with many challenges. Blood transfusion was one of them regarding both blood banks (safety, collection, and stocks) and consumption (usual care and unknown specific demand of COVID-19 patients). The risk of mismatch was sufficient to plan blood transfusion restrictions if stocks became limited. STUDY DESIGN AND METHODS: Analyses of blood transfusion in a tertiary hospital and blood collection in the referring blood bank between February 24 and May 31, 2020. RESULTS: Withdrawal of elective surgery and non-urgent care and admission of 2291 COVID-19 patients reduced global activity by 33% but transfusion by 17% only. Only 237 (10.3) % of COVID-19 patients required blood transfusion, including 45 (2.0%) with acute bleeding. Lockdown and cancellation of mobile collection resulted in an 11% reduction in blood donation compared to 2019. The ratio of reduction in blood transfusion to blood donation remained positive and stocks were slightly enhanced. DISCUSSION: Reduction of admissions due to SARS-CoV-2 pandemic results only in a moderate decrease of blood transfusion. Incompressible blood transfusions concern urgent surgery, acute bleeding (including some patients with COVID-19, especially under high anticoagulation), or are supportive for chemotherapy-induced aplasia or chronic anemia. Lockdown results in a decrease of blood donation by cancellation of mobile donation but with little impact on a short period by mobilization of usual donors. No mismatch between demand and donation was evidenced and no planned restriction to blood transfusion was necessary.

Liposomal encapsulation of trans-crocetin enhances oxygenation in patients with COVID-19-related ARDS receiving mechanical ventilation.

Current therapeutic treatments improving the impaired transportation of oxygen in acute respiratory distress syndrome (ARDS) have been found to be relevant and beneficial for the therapeutic treatment of COVID-19 patients suffering from severe respiratory complications. Hence, we report the preclinical and the preliminary results of the Phase I/II clinical trial of LEAF-4L6715, a liposomal nanocarrier encapsulating the kosmotropic agent trans-crocetin (TC), which, once injected, enhance the oxygenation of vascular tissue and therefore has the potential to improve the clinical outcomes of ARDS and COVID-19 in severely impacted patients. We demonstrated that the liposomal formulation enabled to increase from 30 min to 48 h the reoxygenation properties of free TCs in vitro in endothelial cells, but also to improve the half-life of TC by 6-fold in healthy mice. Furthermore, we identified 25 mg/kg as the maximum tolerated dose in mice. This determined concentration led to the validation of the therapeutic efficacy of LEAF-4 L6715 in a sepsis mouse model. Finally, we report the preliminary outcomes of an open-label multicenter Phase I/II clinical trial (EudraCT 2020-001393-30; NCT04378920), which was aimed to define the appropriate schedule and dosage of LEAF-4L6715 and to confirm its tolerability profile and preliminary clinical activity in COVID-19 patients treated in intensive care unit.

Population pharmacokinetic and pharmacodynamic modeling of capecitabine and its metabolites in breast cancer patients.

PURPOSE: The present study was performed to examine relationships between systemic exposure of capecitabine metabolites (5-FU, 5'-DFCR and 5'-DFUR) and toxicity or clinical response in patients with metastatic breast cancer. METHODS: A population pharmacokinetic model for capecitabine and its three metabolites was built. Typical parameter values, characteristics of random distributions, associated with parameters, and covariates impact were estimated. Area under the curve (AUC) were computed for 5-FU and compared with grades of toxicity. Pharmacokinetic modeling was based on data collected on the first treatment cycle. Toxicity was assessed on the two first treatment cycles. RESULTS: The study was conducted in 43 patients. The population pharmacokinetic model (a one-compartment model per compound) was able to capture the very complex absorption process of capecitabine. Statistically significant covariates were cytidine deaminase, alkaline phosphatase and dihydrouracilemia (UH2)/uracilemia (U) ratio. UH2/U ratio was the most significant covariate on 5-FU elimination and CDA on the transformation of 5'-DFCR in 5'-DFUR. A trend was observed between 5-FU AUC and thrombopenia toxicity grades, but not with other toxicities. Best clinical response was not linked to systemic exposure of capecitabine metabolites. CONCLUSION: In our study, we propose a model able to describe, meanwhile, and its main metabolites, with a complex absorption process and inclusion of enzyme activity covariates such as CDA and UH2/U ratio. Trial registration Eudract 2008-004136-20, 2008/11/26.