Type 2 diabetes mellitus (T2DM) is associated with a hypercoagulable state and increased neutrophil extracellular traps formation (NETosis). We investigated predictors of NETosis and cell death markers in circulating blood and their association with a prothrombotic state in T2DM. In a cross-sectional study involving 113 T2DM patients aged 63.7 ± 8.2 years, we investigated citrullinated histone H3 (H3Cit), cell-free deoxyribonucleic acid (cfDNA), myeloperoxidase, neutrophil elastase, and inflammation markers, along with thrombin generation (TG), plasma clot lysis time (CLT), clot permeability (Ks) and fibrinolysis inhibitors. On multivariate logistic regression analysis adjusted for age and gender, predictors of high H3Cit (≥ 7.36 ng/mL, upper quartile) were: glycated hemoglobin (HbA1c) ≥ 7.0% and interleukin-6. Interleukin-6 was also found to be a predictor of high cfDNA (≥ 2.84 µg/mL, upper quartile) along with glucose. Citrullinated histone H3 and cfDNA correlated positively with CLT and inversely with Ks, while TG associated solely with cfDNA. These associations were not seen with myeloperoxidase and neutrophil elastase. Patients with previous myocardial infarction (n = 21, 18.6%) had higher H3Cit (+108%, p < 0.001) and cfDNA (+45%, p = 0.022). On multivariable analysis adjusted for potential confounders, H3Cit and cfDNA, along with plasminogen activator inhibitor-1 and concomitant cardiovascular disease, were predictors of CLT. Citrullinated histone H3 alone was a predictor of Ks and only cfDNA was a predictor of peak thrombin generated. In T2DM, NETosis detectable in circulating blood is associated with inflammatory state and a prothrombotic state, especially hypofibrinolysis.

Significance: Aging is a complex process associated with an increased risk of many diseases, including thrombosis. This review summarizes age-related prothrombotic mechanisms in clinical settings of thromboembolism, focusing on the role of fibrin structure and function modified by oxidative stress. Recent Advances: Aging affects blood coagulation and fibrinolysis via multiple mechanisms, including enhanced oxidative stress, with an imbalance in the oxidant/antioxidant mechanisms, leading to loss of function and accumulation of oxidized proteins, including fibrinogen. Age-related prothrombotic alterations are multifactorial involving enhanced platelet activation, endothelial dysfunction, and changes in coagulation factors and inhibitors. Formation of more compact fibrin clot networks displaying impaired susceptibility to fibrinolysis represents a novel mechanism, which might contribute to atherothrombosis and venous thrombosis. Alterations to fibrin clot structure/function are at least in part modulated by post-translational modifications of fibrinogen and other proteins involved in thrombus formation, with a major impact of carbonylation. Fibrin clot properties are also involved in the efficacy and safety of therapy with oral anticoagulants, statins, and/or aspirin. Critical Issues: Since a prothrombotic state is observed in very elderly individuals free of diseases associated with thromboembolism, the actual role of activated blood coagulation in health remains elusive. It is unclear to what extent oxidative modifications of coagulation and fibrinolytic proteins, in particular fibrinogen, contribute to a prothrombotic state in healthy aging. Future Directions: Ongoing studies will show whether novel therapies that may alter oxidative stress and fibrin characteristics are beneficial to prevent atherosclerosis and thromboembolic events associated with aging.

To investigate the effect of low blood glucose on thrombin generation and fibrin clot properties in type 2 diabetes (T2DM). In 165 patients with T2DM and high cardiovascular risk, we measured ex vivo plasma fibrin clot permeation [Ks], turbidity and efficiency of fibrinolysis including clot lysis time [t50%], together with thrombin generation and platelet activation markers in relation to fasting blood glucose. As compared to patients in medium (4.5-6.0 mmol/l, n = 52) and higher (>6.0 mmol/l, n = 75) glucose group, subjects with low glycemia (<4.5 mmol/l, n = 38) had lower Ks by 11% (p < 0.001) and 8% (p = 0.01), respectively, prolonged t50% by 10% (p < 0.001) and 7% (p = 0.016), respectively, and higher peak thrombin generation by 21% and 16%, respectively (p < 0.001 for both). There were no significant differences in Ks and t50% between patients in medium and higher glucose group. In the whole group, a J-shape relationship was observed between glycemia and the following factors: peak thrombin generation, Ks and t50%. Only in patients with HbA1c < 6.0% (42 mmol/mol) (n = 26) fasting glucose positively correlated with Ks (r = 0.53, P = 0.006) and inversely with t50% (r = −0.46, P = 0.02). By multiple regression analysis, after adjustment for age, fibrinogen, HbA1c, insulin treatment and T2DM duration, fasting glycemia was the independent predictor of Ks (F = 6.6, df = 2, P = 0.002), t50% (F = 8.0, df = 2, P < 0.001) and peak thrombin generation (F = 13.5, df = 2, P < 0.0001). In T2DM patients fasting glycemia <4.5 mmol/l is associated with enhanced thrombin formation and formation of denser fibrin clots displaying lower lysability, especially when strict glycemia control was achieved (HbA1c<6.0%).

Background: Non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used for stroke prevention in patients with atrial fibrillation (AF) worldwide. Few articles have compared current understanding of AF patients about the disease and anticoagulant therapy in relation to the medications used. Aim: The aim of this study was to compare the knowledge of AF and anticoagulation between AF patients treated with NOACs and those on vitamin K antagonists (VKA). Methods: We used the Jessa AF Knowledge Questionnaire (JAKQ), developed and validated in Belgium. Patients were recruited at a tertiary center in Krakow, Poland. Results: A total of 479 AF patients completed JAKQ. Patients on NOACs (n=276, 57.6%) compared with those on VKA (n=175, 36.5%), did not differ regarding demographic and clinical variables. The mean score of the JAKQ was very similar in the NOACs and VKA group (60.7±17.0% vs 61.6±17.1%, p=0.4, respectively). The differences in the proportion of correct responses referred to 3 questions. Consequences of AF such as blood clots and cerebral infarction were more obvious for patients on NOACs compared with those on VKAs (81.5% vs. 70.9%; p=0.01). The patients on NOACs (78.7% vs. 67.6%; p=0.009) would consider more frequently consulting physicians before surgery for advice concerning anticoagulant treatment, while less patients on NOAC were aware of the need to take their medication even if they do not feel AF (76.1 vs 89.7%; p=0.0004). Only 25.9% of the VKA patients and 49.3% of the NOACs users knew what to do if they have missed a dose of the anticoagulant. Conclusions: The knowledge of arrhythmia and anticoagulation is better regarding the safety issues among subjects on NOACs compared with VKA. Irrespective of the type of OAC therapy, education of AF patients should be improved. Background: Non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used for stroke prevention in patients with atrial fibrillation (AF) worldwide. Few articles have compared current understanding of AF patients about the disease and anticoagulant therapy in relation to the medications used. Aim: The aim of this study was to compare the knowledge of AF and anticoagulation between AF patients treated with NOACs and those on vitamin K antagonists (VKA). Methods: We used the Jessa AF Knowledge Questionnaire (JAKQ), developed and validated in Belgium. Patients were recruited at a tertiary center in Krakow, Poland. Results: A total of 479 AF patients completed JAKQ. Patients on NOACs (n=276, 57.6%) compared with those on VKA (n=175, 36.5%), did not differ regarding demographic and clinical variables. The mean score of the JAKQ was very similar in the NOACs and VKA group (60.7±17.0% vs 61.6±17.1%, p=0.4, respectively). The differences in the proportion of correct responses referred to 3 questions. Consequences of AF such as blood clots and cerebral infarction were more obvious for patients on NOACs compared with those on VKAs (81.5% vs. 70.9%; p=0.01). The patients on NOACs (78.7% vs. 67.6%; p=0.009) would consider more frequently consulting physicians before surgery for advice concerning anticoagulant treatment, while less patients on NOAC were aware of the need to take their medication even if they do not feel AF (76.1 vs 89.7%; p=0.0004). Only 25.9% of the VKA patients and 49.3% of the NOACs users knew what to do if they have missed a dose of the anticoagulant. Conclusions: The knowledge of arrhythmia and anticoagulation is better regarding the safety issues among subjects on NOACs compared with VKA. Irrespective of the type of OAC therapy, education of AF patients should be improved.

It has been shown that patients’ knowledge about venous thromboembolism (VTE) and its therapy is suboptimal, which might reduce compliance and worsen prognosis. We investigated whether low VTE patients’ knowledge affects their clinical outcomes during long-term follow-up. We evaluated 151 consecutive patients (51.8 ± 15.7 years) after unprovoked VTE, who were recruited from the outpatient clinic (Krakow, Poland). All patients received anticoagulant treatment, mostly with direct oral anticoagulants (n = 113, 74.8%). The modified Jessa Atrial fibrillation Knowledge Questionnaire (JAKQ-VTE; 16 questions) was used to assess the knowledge of VTE and anticoagulant therapy. During a median follow-up of 58.0 months, VTE recurrence, major bleeding, and anticoagulation withdrawal were recorded. The median percentage of correct responses was 62.5% (12.5–100%) and was inversely correlated with age ( P < .01). Diabetic patients and those with positive family history of VTE had lower overall scoring compared to the remainder (both P < .05). Major bleeding (n = 10, 6.6%) and anticoagulation withdrawal (n = 28, 18.5%), but not VTE recurrence (n = 12, 7.9%), were associated with lower overall scoring compared to the remainder (48.8% ± 12.5% vs 63.8% ± 16.3%, P = .003 and 55.3% ± 14.7% vs 64.4% ± 16.3%, P = .040, respectively). Major bleeding was independently associated with the female sex (hazard ratio [HR] 6.18; 95% confidence interval [CI] 1.15–33.19, P = .034), younger age (HR per 10 years 0.55; 95% CI 0.34–0.90, P = .016), OAC therapy discontinuation (HR 6.69; 95% CI 1.62–27.70), and lower overall scoring of JAKQ-VTE (HR 0.60 per 10 percentage points; 95% CI 0.40–0.92, P = .019). Insufficient knowledge about VTE and anticoagulant treatment predisposes to a higher risk of major bleeding and therapy discontinuation, but not VTE recurrence in unprovoked VTE patients during long-term follow-up.

INTRODUCTION The current awareness of venous thromboembolism (VTE) and knowledge of thromboprophylaxis among patients receiving oral anticoagulation therapy (OAC) are insufficient. OBJECTIVES We sought to develop and evaluate the usefulness of the Jessa AF Knowledge Questionnaire (JAKQ), modified for VTE patients. PATIENTS AND METHODS Consecutive patients at least 1 month since the VTE event (n = 273, mean [SD] age, 51 [17] years; 52.7%, women; 55.9%, unprovoked event) were enrolled to the study. RESULTS The median percentage of correct responses was 64.2% (interquartile range, 53%-73%; minimum, 12%; maximum, 100%). Younger patients had better knowledge about VTE in general, including a higher proportion of correct responses to the question about the definition of PE (71.4% vs 57.7%, P = 0.03), about the possible consequence of DVT, including PE (81.1% vs 62%, P = 0.001) and VTE risk related to long travels (78.1% vs 59.2%, P = 0.002). There was no difference in overall scoring between patients taking new oral anticoagulants and those taking vitamin K antagonists (mean [SD], 64.1% [16.3%] vs 63.9% [13.8%], respectively, P = 0.7). Regardless of the type of anticoagulants, 39.3% of patients knew that VTE is not always symptomatic, 33.6% knew what to do when they missed an OAC dose, and 50% did not know which painkillers are the safest in combination with anticoagulants. Education applied in 27 patients resulted in an increase in the median percentage of correct responses from 60% to 80% (P = 0.0001). CONCLUSIONS Knowledge on VTE and anticoagulation is suboptimal among patients on VKA and NOACs. Education of VTE patients should be improved especially in older individuals on NOACs.