DNase analysed by a novel competitive assay in patients with complications after ChAdOx1 nCoV-19 vaccination and in normal unvaccinated blood donors.

Increased levels of neutrophil extracellular traps (NETs) have been detected in individuals with vaccine complications after the ChAdOx1 nCov vaccine with a correlation between the severity of vaccine side effects and the level of NETosis. DNases may disrupt NETs by degrading their content of DNA, and a balance has been reported between NETs and DNases. Because of this and since the inflammatory marker NETs may be used as a confirmatory test in diagnosing VITT, it is of interest to monitor levels of DNase in patients with increased NETs levels. The current novel rapid DNase ELISA was tested in blood samples of patients with known increased levels of NETs with or without VITT after ChAdOx1 nCoV-19 vaccination. DNase levels in VITT patients were significantly increased compared with normal unvaccinated blood donors and compared with patients with post-vaccination symptoms but not VITT. However, since EDTA was found to inhibit DNase, serum and not EDTA-plasma samples should be applied for DNase testing. The novel DNase assay may serve as a supplementary test to the NETs test when analysing samples from patients with suspected increased NETs levels.

Elevated NETs and Calprotectin Levels after ChAdOx1 nCoV-19 Vaccination Correlate with the Severity of Side Effects.

ChAdOx1 nCoV-19 vaccination has been associated with the rare side effect; vaccine-induced immune thrombotic thrombocytopenia (VITT). The mechanism of thrombosis in VITT is associated with high levels of neutrophil extracellular traps (NETs). The present study examines whether key markers for NETosis, such as H3-NETs and calprotectin, as well as syndecan-1 for endotheliopathy, can be used as prognostic factors to predict the severity of complications associated with ChAdOx1 vaccination. Five patients with VITT, 10 with prolonged symptoms and cutaneous hemorrhages but without VITT, and 15 with only brief and mild symptoms after the vaccination were examined. Levels of H3-NETs and calprotectin in the vaccinated individuals were markedly increased in VITT patients compared to vaccinees with milder vaccination-associated symptoms, and a strong correlation (r ≥ 0.745, p < 0.001) was found with severity of vaccination side effects. Syndecan-1 levels were also positively correlated (r = 0.590, p < 0.001) in vaccinees to side effects after ChAdOx1 nCoV-19 vaccination. We hypothesize that the inflammatory markers NETs and calprotectin may be used as confirmatory tests in diagnosing VITT.

Deliberate employment of postoperative hypotension for brain arteriovenous malformation surgery and the incidence of delayed postoperative hemorrhage: a prospective cohort study.

OBJECTIVE The aim of this study was to examine the impact of deliberate employment of postoperative hypotension on delayed postoperative hemorrhage (DPH) for all Spetzler-Ponce Class (SPC) C brain arteriovenous malformations (bAVMs) and SPC B bAVMs ≥ 3.5 cm in diameter (SPC B 3.5+). METHODS A protocol of deliberate employment of postoperative hypotension was introduced in June 1997 for all SPC C and SPC B 3.5+ bAVMs. The aim was to achieve a maximum mean arterial blood pressure (BP) ≤ 70 mm Hg (with cerebral perfusion pressure > 50 mm Hg) for a minimum of 7 days after resection of bAVMs (BP protocol). The authors compared patients who experienced DPH (defined as brain hemorrhage into the resection bed that resulted in a new neurological deficit or that resulted in reoperation during the hospitalization for microsurgical bAVM resection) between 2 periods (prior to adopting the BP protocol and after introduction of the BP protocol) and 4 bAVM categories (SPC A, SPC B 3.5- [that is, SPC B < 3.5 cm maximum diameter], SPC B 3.5+, and SPC C). Patients excluded from treatment by the BP protocol were managed in the intensive care unit to avoid moderate hypertensive episodes. The pooled cases of all bAVM treated by surgery were analyzed to identify characteristics associated with the risk of DPH. These identified characteristics were then examined by multiple logistic regression analysis in both SPC B 3.5+ and SPC C cases. RESULTS From a cohort of 641 bAVMs treated by microsurgery, 32 patients with DPH were identified. Of those, 66% (95% CI 48-80) had a permanent new neurological deficit with a modified Rankin Scale score of 2-6. This included a mortality rate of 13% (95% CI 4.4-29). The BP protocol was used to treat 162 patients with either SPC B 3.5+ or SPC C. For SPC B 3.5+, there was no significant reduction in DPH with the introduction of the BP protocol (p = 0.77). For SPC C, there was a significant (p = 0.035) reduction of DPH from 29% (95% CI 13%-53%) to 8.2% (95% CI 3.2%-18%) associated with the introduction of the BP protocol. Multiple logistic regression analysis found that the absence of the BP protocol (p = 0.011, odds ratio 7.5, 95% CI 1.6-36) remained significant for the development of DPH in patients with SPC C bAVMs. CONCLUSIONS Treating patients with SPC C bAVMs with a protocol that lowers BP immediately after resection seems to reduce the risk of DPH. For SPC A and SPC B 3.5- bAVMs, there is unlikely to be a need to do more than avoid postoperative hypertension. For SPC B 3.5+ bAVMs, a larger number of patients would be required to test the absence of benefit of the BP protocol.