Efficacy and safety of TPO receptor agonists in treatment of ITP associated with predominantly antibody deficiencies.

Predominantly antibody deficiencies have an estimated prevalence of more than 1/25,000. Their classical phenotype entails the association of autoimmune manifestations with increased susceptibility to infections. Up to 8% of these patients ultimately develop immune thrombocytopenic purpura (ITP). Reducing the risk of infections and considering non immunosuppressive treatments, such as thrombopoietin receptor agonists (TPO-RAs), are important needs in these patients. This nationwide retrospective case series assessed outcomes and safety of TPO-RAs as treatment for ITP in adults diagnosed with predominantly antibody deficiencies. Response and complete response to treatment were defined as platelet count reaching 30 x 109/L and 100 x 109/L respectively. We analyzed data from 28 patients. The median follow-up after introduction of the first TPO-RAs was 33 months (range, 2 weeks - 10,6 years). After 6 weeks of follow up, response was achieved for 24 out of 28 patients (85.7%), among which 21 patients (75%) displayed a complete response. At the last available follow-up visit only 7 patients (25%) needed second-line therapies for ITP among which only 5 patients (17.9%) received immunosuppressants. Only 3 patients (10.7%) reported hepatobiliary laboratory adverse events of light or mild severity and 3 patients (10.7%) reported thrombotic events. In conclusion, TPO-RAs appeared as an effective and safe option of treatment in these case series. Our results suggest that Eltrombopag or Romiplostim should be considered as second line therapy of ITP related to predominantly antibody deficiencies.

A High Postoperative Atropinic Burden is Associated with Postoperative Delirium in Elderly Patients with Hip Fracture: Results of the Prospective, Observational, ATROPAGE Trial.

Background: Postoperative delirium frequently occurs in the elderly after hip fracture surgery and is associated with poor outcomes. Our aim was to identify a correlation between the atropinic burden (AB) due to drugs with clinical antimuscarinic effect and the occurrence of postoperative delirium. Methods: We carried out a prospective, monocentric, observational study including 67 patients over 65 years of age who underwent hip fracture surgery. The addition of the anticholinergic weight of each drug was calculated at different time points to distinguish the prehospital, intra- and postoperative part of the AB. A multivariate analysis was carried out to identify the explanatory variables associated with postoperative delirium. Results: Patients were 78 [71-86] years old. The time from admission to surgery was 12 [12-24] hours. The ADL and CIRS scores were 6 [5.5-6] and 6 [4-9], respectively. The total (prehospital plus intraoperative plus postoperative) AB was 5 [3-9]. The incidence of postoperative delirium was 54% (36/67). The demographic characteristics were comparable between delirium and no delirium groups. Univariate analysis showed statistically significant differences between no delirium and delirium groups concerning the number of prehospital atropinic drugs, prehospital AB, the number of postoperative atropinic drugs, postoperative AB, in-hospital AB and the MMSE calculated on postoperative day 5. Using multivariate analysis, postoperative AB, but not pre- and in-hospital ABs, was associated with postoperative delirium with an odds ratio of 1.84 (95% CI: 1.25-2.72; p = 0.002). A postoperative AB > 2 was associated with a postoperative delirium with an area under ROC curve of 0.73 (95% CI: 0.61-0.83; p = 0.0001). Conclusion: Contrary to a prior exposure to atropinic drugs, a postoperative atropinic burden >2 was associated with postoperative delirium in elderly patients with hip fracture. Postoperative administration of (new) antimuscarinic drugs is a precipitating factor of delirium that could be avoided.