Background Direct oral anticoagulants (DOACs) cause false positive lupus anticoagulant (LA) results. We assessed the impact of DOAC-Stop, reversing in vitro effects of DOACs, on LA testing in anticoagulated patients. Methods We assessed 75 venous thromboembolism patients aged 44.5±14.6 years. Blood samples were collected 2–28 h since intake of DOACs, including 50 patients on rivaroxaban, 20 on dabigatran and five on apixaban. LA testing was performed at baseline and after DOAC-Stop treatment. Positive LA was defined as the normalized (patient/standard plasma clotting time) LA screening and screening (LA1)/confirmation (LA2) ratios exceeding 1.2. Results LA diluted Russell’s viper venom time (dRVVT) normalized screening test revealed abnormal results in 73 (97.3%) and activated partial thromboplastin time (APTT)-LA in 49 (65.3%) patients. In six (8%) patients, antiphospholipid syndrome (APS) was diagnosed. dRVVT LA1/LA2 was abnormal in 35 (50.7%) patients taking DOACs. The APTT ratio was normal in all studied subjects. DOAC-Stop completely removed dabigatran and reduced by 98% rivaroxaban and by 92.3% apixaban concentrations (all p<0.05). After DOAC-Stop screening dRVVT remained prolonged in 34 (49.3%) patients (p<0.001), while dRVVT LA1/LA2 was abnormal in six (8.7%) subjects, with no association with DOAC concentrations at baseline and after DOAC-Stop. The APTT-LA screening test remained prolonged in five (7.2%) patients, while the APTT LA1/LA2 ratio was normal in those subjects. DOAC-Stop did not influence LA testing in APS patients. Conclusions Application of DOAC-Stop effectively reduced plasma DOAC concentrations leading to appropriate dRVVT results in up to 97% of VTE patients.

Background: Accumulation of advanced glycation end products (AGEs) leads to chronic glycation of proteins and tissue damage, particularly in patients with diabetes mellitus (DM). We aimed to evaluate whether increased accumulation of AGEs in patients with aortic stenosis (AS) and concomitant type 2 diabetes (DM) is associated with AS severity. Methods: We prospectively enrolled 76 patients with severe AS (47.1% males; nonDM), aged 68 [66-72] years, and 50 age-matched DM patients with a median blood glucose level of 7.5 [5.9-9.1] mM and glycated hemoglobin (HbA1c) of 6.8 [6.3-7.8]%, scheduled for aortic valve replacement. Valvular expression of AGEs, AGEs receptor (RAGE), interleukin-6 (IL-6), and reactive oxygen species (ROS) induction were evaluated ex vivo by immunostaining and calculated as the extent of positive immunoreactive areas/total sample area. Plasma levels of AGEs and soluble RAGE (sRAGE) were assessed by ELISAs. Results: Subjects with DM had increased valvular expression of both AGEs (6.6-fold higher, 15.53 [9.96-23.28]%) and RAGE (1.8-fold higher, 6.8 [4.9-8.45]%) compared to nonDM patients (2.05 [1.21-2.58]% and 2.4 [1.56-3.02]%, respectively; both p < 0.001). Plasma levels of AGEs (12-fold higher) and sRAGE (1.3-fold higher) were elevated in DM patients, compared to nonDM (both p < 0.0001). The percentage of valvular ROS-positive (2.28 [1.6-3.09] vs. 1.15 [0.94-1.4]%, p < 0.0001) but not IL-6-positive areas was higher within DM, compared to nonDM valves. In DM patients, the percentage of valvular AGEs-and RAGE-positive areas correlated with HbA1c (r = 0.77, p < 0.0001 and r = 0.30, p = 0.034). Similarly, plasma AGEs and sRAGE levels were associated with HbA1c in the DM group (r = 0.32, p = 0.024 and r = 0.33, p = 0.014, respectively). In all DM patients, we found an association between the amount of valvular AGEs and the disease severity measured as aortic valve area (AVA; r = 0.68, p < 0.0001). Additionally, in DM patients with HbA1c > 7% (n = 24, 48%) we found that valvular expression of AGEs correlated with mean transvalvular pressure gradient (PG mean ; r = 0.45, p = 0.027). Plasma AGEs levels in the whole DM group correlated with AVA (r = − 0.32, p = 0.02), PG mean (r = 0.31, p = 0.023), and PG max (r = 0.30, p = 0.03). Conclusions: Our study suggests that poorly-controlled diabetes leads to increased AGEs and RAGE valvular accumulation, which at least partially, might result in AS progression in DM patients.