Background Vaccine-induced Immune Thrombotic Thrombocytopenia (VITT) is characterized by thrombocytopenia and thrombosis, mediated by platelet-activating platelet factor 4 (PF4) antibodies following adenoviral COVID-19 vaccination. While initially considered transient, recent VITT cases revealed prolonged anti-PF4 seropositivity (~0.3–3 years, and in one case ~4 years). Key clinical question How long can functional PF4 antibodies persist after VITT, and what are the clinical implications for thrombosis risk and long-term management? Clinical approach We describe a VITT patient who presented with thrombocytopenia and thrombosis following Ad26.COV2·S vaccination, with a follow-up of ~4.5 years post-vaccination, including serial testing at five different timepoints with evaluation of anti-PF4 levels and anti-PF4-induced functional platelet aggregation. Conclusions Platelet-activating anti-PF4 remained present from onset of VITT until follow-up 4.5 years later, with chronic thrombocytopenia but without recurrent thrombosis under anticoagulation therapy. These findings underline the importance of continued monitoring of VITT patients post-vaccination, including assessment of optimal anticoagulation duration and long-term thrombotic risk.
We evaluated 18-month changes in pancreatic iron burden and its relationship with systemic iron balance and glucose metabolism in non-transfusion-dependent thalassemia (NTDT) patients.We retrospectively studied 32 non-transfused (NT) and 57 regularly transfused(RT) NTDT patients enrolled in the Extension-Myocardial Iron Overload in Thalassemia project. Iron overload (IO) was assessed by T2* magnetic resonance imaging and glucose metabolism by oral glucose tolerance test.At baseline, iron chelation therapy was administered in 40.6% of NT-NTDT and 98.2% of RT-NTDT patients. No significant overall changes in pancreatic iron burden were observed in either group. New-onset pancreatic IO occurred in 22.7% of NT and 35.3% of RT patients with normal baseline pancreatic T2* values. Longitudinal changes in pancreatic iron burden were not associated with age, serum ferritin, baseline liver iron concentration(LIC), or changes in LIC, but were inversely related to baseline pancreatic T2* values. In RT patients, pancreatic iron changes were not influenced by baseline glucose metabolism status. After adjustment for baseline pancreatic T2*, NT-NTDT patients showed a greater increase in global pancreatic T2* than RT-NTDT patients. This difference was more pronounced among patients with baseline pancreatic IO.In NTDT patients, pancreatic iron burden showed slow longitudinal changes that were primarily driven by baseline pancreatic iron status rather than systemic iron balance, with a more favorable evolution in non-transfused than in regularly transfused patients.
This case series on managing paroxysmal nocturnal hemoglobinuria (PNH) with iptacopan focuses on scenarios in which the risk of breakthrough hemolysis (BTH) or thrombotic events is heightened. Patient 1 was a 46-yearold woman with PNH and a history of hepatic vein thrombosis. Patient 2 was a 30-year-old woman with PNH and a history of right posterior cerebral artery stroke and cerebral venous sinus thrombosis with extensive right superficial thrombophlebitis. Patient 3 was a 48-year-old woman with PNH who contracted a gastrointestinal infection 3 months after starting iptacopan. Patient 4 was a 39-year-old man with PNH who experienced serous otitis media, a complement-amplifying condition (CAC), concurrent with upper respiratory infection. Patient 5 was a 56-year-old woman with PNH who underwent radiofrequency ablation of the spine while on iptacopan. No patients experienced BTH or hospitalization while on iptacopan. No new thrombotic events were reported after initiating iptacopan. For patients experiencing CACs or surgery, no changes in PNH therapy were required. Notably, BTH did not occur in the patient with gastroenteritis, which can cause drug malabsorption. This case series suggests that iptacopan effectively maintains complement inhibition and prevents PNH-related hemolysis and thrombosis in the setting of past thromboses, gastrointestinal illness, and other CACs.
The need for compatible blood remains a persistent challenge to timely and safe transfusion support. Despite this, the stability and functional behavior of antigen-blocking strategies under storage and physiologically relevant conditions remain poorly understood, particularly regarding their stability during prolonged exposure to changing blood environments. This study evaluates a trispecific triabody designed to simultaneously target A, B, and Rh(D) antigens on red blood cells to block antigen recognition and prevent incompatibility-related hemagglutination. Triabody-coated RBCs were prepared through repeated incubation cycles and assessed for stability in incompatible plasma under storage (4 degrees C) and physiologically relevant temperatures (37 degrees C). Results showed that the triabody bound efficiently and reached saturation across tested blood groups. During storage at 4 degrees C, detachment remained minimal during early storage but increased after prolonged incubation, coinciding with declining pH and increased free hemoglobin. At 37 degrees C, triabody detached progressively, with anti-B dissociation occurring earlier than anti-A and anti-Rh(D), while differential stability was also observed during prolonged storage at 4 degrees C. Detachment showed a closer temporal association with pH decline than with ionic strength or free hemoglobin changes and was followed by hemagglutination in incompatible plasma. Triabody-coated RBCs maintained antigen blocking during early exposure but showed differential stability during prolonged incubation, supporting their potential to improve transfusion compatibility while highlighting the need for further in vitro optimization of triabody binding stability before in vivo validation.
Background The urea breath test (UBT) detects Helicobacter pylori (H. pylori) by measuring 13CO(2) in exhaled air after the ingestion of a 13C-urea metabolized by bacterial urease. However, the influence of CO2 concentrations in exhaled breath on UBT results remains unclear. This study aimed to evaluate the effect of varying exhaled CO2 levels on the outcomes of infrared spectroscopy-based & sup1;& sup3;C-UBT. Methods Six volunteers confirmed to be H. pylori-negative via & sup1;& sup3;C-UBT and stool antigen assay were enrolled. All participants completed overnight fasting and oral rinsing before specimen collection, followed by standardized breath sampling with three breath-holding durations (5 s, 10 s, and 20 s). Baseline samples were collected at 0 min, followed by a 30-min rest without & sup1;& sup3;C-urea administered, then test samples were collected. Following each sampling cycle, participants rested with spontaneous quiet breathing for 20-30 s before performing the next breath-holding procedure. Each participant completed 30 sampling cycles, yielding 30 paired baseline-test samples per individual. CO2 concentrations and delta over baseline (DOB) values were measured using three independent infrared spectrometers under calibration settings of 5.0 and 6.0. A DOB value >= 4 was defined as a positive result. High CO2 was defined as a test-sample CO2 concentration greater than or equal to the corresponding calibration concentration plus 0.2. Results A total of 180 paired baseline-test datasets were included in the analysis. At calibration concentrations of 5.0, positive results were observed in 104 of 118 high CO2 datasets (88.14%; 95% exact CI, 80.90%-93.36%), whereas none of the 62 low CO2 datasets showed positive result (0.00%; 95% exact CI, 0.00%-5.78%). At a calibration concentration of 6.0, positive results occurred in 20 of 26 high-CO2 datasets (76.92%; 95% exact CI, 56.35%-91.03%), whereas all 154 low CO2 datasets tested negative (0.00%; 95% exact CI, 0.00%-2.37%). Sample-level Fisher's exact tests were significant at both settings (both P < 0.001). Conclusion Elevated CO2 concentrations may be associated with false-positive DOB results in infrared spectroscopy-based & sup1;& sup3;C-UBT, particularly when test-bag CO2 exceeds the calibration value by more than 0.2 units. Monitoring of exhaled CO2 during specimen collection is essential to guarantee accurate results.
