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Background: Antiphospholipid antibodies (aPL), including lupus anticoagulant, antibodies against β 2 glycoprotein I (anti-β2GPI), and anticardiolipin (aCL) antibodies are associated with ischemic stroke (IS). Their prevalence and clinical relevance in atrial fibrillation (AF) remain unclear., Objectives: To assess whether aPL are associated with increased risk of IS in AF patients despite anticoagulation., Methods: We conducted a post hoc analysis of aPL using blood samples from 243 consecutive AF patients enrolled in a cohort study. Markers of a prothrombotic state, including endogenous thrombin potential, fibrin clot permeability, and lysis time, were measured at baseline. During a median follow-up of 52 months, IS/transient ischemic attack and major bleeding were recorded., Results: We observed aPL at a moderate or high titer in 51 (21%) patients, including 17 (7%) with anti-β2GPI, 19 (7.8%) with aCL antibodies, and 37 (15.2%) with lupus anticoagulant. aPL-positive patients were more likely to have prior stroke (P = .01) and be active smokers (P = .03), along with increased endogenous thrombin potential (P = .02), without any changes in fibrin clot properties. Anti-β2GPI (hazard ratio, 4.38; 95% CI, 1.58-12.19) and aCL (hazard ratio, 4.70; 95% CI, 1.80-12.30) at a moderate or high titer were associated with IS during follow-up (n = 20; 1.9% per year). There were 23 major bleedings (2.1% per year) and 20 deaths (1.9% per year), which were not associated with aPLs., Conclusion: Our study showed a relatively high prevalence of aPL positivity in AF patients, which was linked to an increased risk of IS/transient ischemic attack. This suggests that screening for aPL might help optimize anticoagulant therapy in such patients., Competing Interests: Declaration of competing interests All authors have no competing interests to disclose., (Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Context.—: A positive association between antithrombin activity and selenium level was reported. Selenoprotein P, the most important selenium carrier, was identified within human plasma fibrin clots., Objective.—: To investigate the relationship between selenoprotein P and antithrombin and its role in modulation of fibrin clot properties in antithrombin-deficient patients., Design.—: Proteomic analysis of plasma fibrin clots was performed with mass spectrometry. In 108 patients with genetically confirmed type I (57%) or type II (43%) antithrombin deficiency and in healthy controls (n = 50), we assessed plasma selenoprotein P levels and thiobarbituric acid-reactive substances by enzyme-linked immunosorbent assay, along with fibrin clot permeability, clot lysis time, and thrombin generation., Results.—: Clot-bound antithrombin concentration was 0.46 ± 0.32 mg/g protein, while selenoprotein P level was 30-fold lower (0.015 ± 0.012 mg/g). Type I compared to type II antithrombin-deficient patients had higher clot-bound antithrombin and selenoprotein P levels (both P < .001), associated together (ρ = 0.93, P < .001). Individuals with type I compared to type II antithrombin deficiency or controls had about 40% lower plasma selenoprotein P levels (P < .001). In antithrombin-deficient patients, plasma selenoprotein P was associated with antithrombin antigen (ρ = 0.35, P < .001) and thiobarbituric acid-reactive substances (ρ = 0.42, P < .001). Plasma selenoprotein P correlated also with endogenous thrombin potential (r = -0.33, P < .001), fibrin clot permeability (r = 0.43, P < .001), and clot lysis time (r = -0.40, P < .001) in antithrombin-deficient patients but not in controls., Conclusions.—: Patients with type I antithrombin deficiency had higher clot-bound selenoprotein P and reduced plasma selenoprotein P levels. Plasma selenoprotein P was associated with prothrombotic fibrin clot phenotype and enhanced thrombin generation., (© 2024 College of American Pathologists.)

Background: Lipoprotein-associated phospholipase A2 (Lp-PLA2) may play an important role in the development of atherosclerotic cardiovascular disease (ASCVD). Increased plasma levels of Lp-PLA2 may predict future cardiovascular (CV) events in type 2 diabetes (T2D). The potential beneficial effects of polyunsaturated fatty acids (PUFA) on ASCVD have been widely investigated. However, the impact of different PUFA concentrations on Lp-PLA2 remains uncertain., Objectives: We sought to determine the intergender differences in a population of patients with both T2D and ASCVD regarding Lp-PLA2 mass and the association between Lp-PLA2 mass and plasma levels of PUFA., Material and Methods: In this cross-sectional study, we measured the Lp-PLA2 mass, PUFA concentrations and inflammatory markers in 74 patients (49 males and 25 females) with T2D and ASCVD., Results: In this very high-risk population, males had, on average, 33.6% higher levels of Lp-PLA2 than females. The Lp-PLA2 mass was positively associated with interleukin 6 (IL-6) (r = 0.27, p = 0.019), creatinine (r = 0.29, p = 0.03) and triglyceride levels (r = 0.41, p = 0.002). Additionally, male gender and higher levels of triglycerides, leptin, oxidized low-density lipoprotein (oxLDL), and intercellular adhesion molecule 1 (ICAM-1) were independent predictors for an increased Lp-PLA2. Moreover, arachidonic acid (AA) negatively correlated with Lp-PLA2 (r = -0.26, p = 0.024), which was especially apparent in the female subgroup., Conclusions: In the population of patients with ASCVD and T2D, males present with higher plasma levels of Lp-PLA2 than females. Additionally, higher plasma levels of AA were associated with lower Lp-PLA2 levels. Our findings support the utilization of Lp-PLA2 as a novel biomarker in ASCVD risk assessment in a very high CV risk population.

Aims: This prospective, single-center study sought to assess to what extent there is interference between the hybrid technique of single-photon emission tomography-computed tomography with technetium99m-hexamethylpropyleneamine oxime-labeled leukocytes (99mTc-HMPAO-SPECT/CT) and antimicrobial therapy in patients with infective endocarditis (IE)., Methods and Results: During the years 2015-2019, we enrolled 205 consecutive adults with suspected IE, all underwent 99mTc-HMPAO-SPECT/CT. The study population was divided into those who had received antimicrobial therapy up to 30 days prior to 99mTc-HMPAO-SPECT/CT (group 1, n = 96) and those who had not (group 2, n = 109). Patients were prospectively observed for 12 ± 10 months. Group 1 presented higher positive predictive values (91.89% vs. 60.00%, = 0.001), and decreased negative predictive values (77.97% vs. 90.54%, P = 0.04). Patients treated with antimicrobial therapy displayed false-negative 99mTc-HMPAO-SPECT/CT results more often [odds ratio (OR), 4.63; 95% confidence interval (CI), 1.41-15.23, P = .01], particularly when intravenous (OR 5.37; 95% CI 1.73-16.62, P = .004), definite (OR 9.43; 95% CI 2.65-33.51, P = .001), and combination antibiotic regimens (OR 8.1; 95% CI 2.57-25.64, P = .001) had been administered., Conclusion: Prior antibiotic therapy affects 99mTc-HMPAO-SPECT/CT diagnostic properties. Patients treated with antimicrobial therapy display false-negative 99mTc-HMPAO-SPECT/CT results more often, especially if intravenous, definite, or combination regimens are administered., (© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.)

Background:  Atrial fibrillation (AF) is associated with a prothrombotic state. Presence of active tissue factor (TF), activated factor IX (FIXa) and FXIa in circulating blood contributes to thrombosis. We investigated a prognostic value of these factors in AF patients., Methods:  In this cohort study, 284 AF patients (aged 63.3 ± 8.8 years) treated with oral anticoagulants were enrolled. Plasma levels of active coagulation factors were evaluated using thrombin generation assay. Concentrations of fibrinogen, D-dimer, interleukin-6 (IL-6), and endothelial damage markers, including von Willebrand factor (VWF) and soluble (s)E-selectin, were also measured. Ischemic stroke and cardiovascular death, analyzed separately or as a composite endpoint, were recorded during a mean follow-up of 47 months., Results:  Cerebrovascular events were observed in 20 patients (1.8%/year) who had at baseline higher fibrinogen, D-dimer, and VWF levels. Active TF and FXIa at enrollment were detectable in 12 (60%) and 15 (75%) patients who experienced ischemic stroke during follow-up. The composite endpoint observed in 23 patients (2.1%/year) was associated with increased concentrations of the above laboratory variables, along with 26% higher IL-6 levels. sE-selectin did not differ between the studied groups. On multivariable regression analysis, advanced age, anticoagulation discontinuation, and detectable FXIa, but not active TF, independently predicted the composite endpoint. No associations of FIXa with the study endpoints were observed., Conclusion:  FXIa present in circulating blood is associated with increased risk of ischemic stroke and cardiovascular death in anticoagulated AF patients during long-term follow-up. FXIa inhibition could be useful in cardiovascular prevention in AF beyond the current oral anticoagulation., Competing Interests: None declared., (Thieme. All rights reserved.)

Formalin-fixed, paraffin embedded fragments of normal human placenta were subjected to immunoperoxidase technique with the use of Dako Kits appropriate for detection of vimentin, desmin, and cytokeratins (K 660, 530, and 518 respectively). Distribution of the intermediate filament proteins in syncytiotrophoblast, connective tissue of villous stroma, walls of blood vessels as well as in cells of basal plate and placental islets was compared. General pattern of staining and its localization was characteristic for each of the 3 types of antibodies. In spite of that, most structures observed revealed the presence of more than one type of intermediate filament proteins, with the exception of syncytiotrophoblast containing cytokeratins only. Staining of blood serum and of connective tissue matrix with anti-desmin and anti-cytokeratin antibodies was also observed, whereas fibrinoid remained always negative.

The histochemical activity of 4 lysosomal enzymes, acid phosphatase (AP), nonspecific esterase (NE), aryl sulphatase (AS), and beta-glucuronidase (BG), was compared in following structures of the human placenta: syncytiotrophoblast, villous stromal cells, fetal capillaries and larger blood vessels, cells of basal plate, macrophages, and Hofbauer cells. In spite of a general similarity in distribution of the investigated enzymes, differences concerning particular structures were found. Thus positively stained granules in endothelia of capillary vessels were revealed only in the reaction for BG, although contours of capillaries were also outlined by the diffuse reaction product for AS. The muscular layer of larger vessels reacted strongly for AS and weakly for NE with the remaining reactions being negative. In syncytiotrophoblast, BG appeared much less active than the other 3 enzymes. The possible significance of the BG positive granules in endothelial of capillaries and of the occasional divergence in distribution of the classical lysosomal markers (AP and BG) is discussed.