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Venous thromboembolism is associated with formation of denser fibrin clots resistant to lysis. We investigated whether prothrombotic plasma clot properties are associated with the severity of acute pulmonary embolism (PE). We enrolled 126 normotensive acute PE patients (aged 58 ± 14 years) and 25 age- and sex-matched healthy controls. Plasma fibrin clot permeability (Ks), clot lysis time (CLT), endogenous thrombin potential (ETP), plasminogen activator inhibitor-1 (PAI-1), and citrullinated histone H3 (citH3) were evaluated on admission. PE patients compared to controls had 370% higher citH3 levels, 41% higher ETP, 16.5% reduced Ks, and 25.6% prolonged CLT. Patients with intermediate-high (n = 29) and intermediate-low (n = 77) PE mortality risk had reduced Ks and prolonged CLT, increased PAI-1 and ETP as compared to low-risk PE (n = 20) patients. Prolonged CLT was predicted by PAI-1 and citH3, while low Ks by C-reactive protein. During a 12-month follow-up 9 (7.1%) patients who had 24% higher ETP, 45% higher citH3 levels, and 18% prolonged CLT at baseline died. High ETP combined with elevated citH3 levels and prolonged CLT was associated with eightfold increased risk of PE-related death. Prothrombotic fibrin clot properties and enhanced neutrophil extracellular traps formation are associated with higher early mortality risk in acute PE patients, which suggests a prognostic role of these biomarkers. [ABSTRACT FROM AUTHOR]

The aim of the presented study was to assess the relationship between air pollution expressed as particulate air matters less than 10 μm (PM10) and acute coronary syndromes (ACSs). In this observational study, we selected regions with low pollution according to PM10 (non-polluted) and with the highest pollution (polluted). The occurrence of percutaneous coronary interventions (PCIs) in patients with ACSs was matched according to the location. The current study included 7678 patients in polluted areas and 4327 patients from non-polluted regions. Analysing the period from January to December 2017, the number of patients undergoing angioplasty in monitored catheterization laboratories and the mean daily concentration of PM10 in all selected cities were calculated for each day. The annual average concentration of PM10 amounts to 50.95 μg/m3 in polluted and 26.62 μg/m3 in non-polluted cities (P < 0.01). The rise in PM10 pollution levels was related with the increased frequency of PCIs in patients with ACSs in polluted (P < 0.01) and non-polluted (P < 0.01) areas. In the non-polluted regions, the increase in PM10 concentration by every 1 μg/m3 causes 0.22 additional ACS angioplasties per week. In polluted regions, the same increase in PM10 concentration causes 0.18 additional ACS angioplasties per week. In non-winter weeks, the mean number of ACS PCIs expressed in promiles was lower than in winter weeks in polluted (P = 0.03) and non-polluted cities (P = 0.02). The study shows that the increase in air pollution expressed as PM10 concentration and winter time influences the frequency of ACS-related PCIs. [ABSTRACT FROM AUTHOR]

Venous ulcers are the most severe manifestation of post-thrombotic syndrome (PTS). We have previously demonstrated that formation of compact fibrin clots resistant to lysis is observed in patients following deep-vein thrombosis (DVT) who developed PTS. The current study investigated whether unfavourable fibrin clot properties can predict post-thrombotic venous ulcers. In a cohort study on 186 consecutive patients following DVT, we determined plasma fibrin clot characteristics, including clot permeability and lysability, inflammatory markers, thrombin generation, fibrinolysis proteins at 3 months since the index event. Occurrence of PTS and venous ulcers was recorded during follow-up (median, 53; range 24 to 76 months). Fifty-seven DVT patients (30.6%) developed PTS, including 12 subjects (6.45%) with a venous ulcer (4 individuals with recurrent ulcers). Patients who developed ulcers compared with the remainder had at enrolment 13.0% lower clot permeability (Ks), 17.4% longer clot lysis time (CLT), 13.1% longer lag phase of clot formation, and 5.0% higher maximum absorbance, with no difference in fibrinogen, C-reactive protein, and thrombin generation. The baseline prothrombotic fibrin clot phenotype (Ks ≤ 6.5 × 10−9 cm2 and CLT > 100 min) was associated with a higher risk of ulcers [hazard ratio (HR), 5.37; 95% confidence interval (CI), 1.3–21.5]. A multivariate model adjusted for age, sex, and fibrinogen showed that independent predictors of the ulcer occurrence were body mass index (HR 1.53; 95% CI 1.30–1.86), CLT (HR 1.43; 95% CI 1.04–2.05), and α2-antiplasmin (HR 0.95; 95% CI 0.90–0.99). This study suggests that formation of denser fibrin clots with impaired fibrinolysis predisposes to post-thrombotic venous ulcers. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) with non-obstructive coronary arteries (MINOCA) is an important clinical problem especially in the era of extensive utilization of coronary angiography in MI patients. Its pathophysiology is poorly understood which makes diagnostics and treatment of MINOCA challenging in everyday clinical practice. The aim of the study was to assess characteristics of MINOCA patients in Poland based on data from the Polish National ORPKI Registry. In 2016, 49,893 patients with non-ST-segment elevation (NSTEMI) or ST-segment elevation (STEMI) myocardial infarction entered the ORPKI registry. MINOCA was defined as a non-obstructive coronary artery disease (CAD) and a lack of previous coronary revascularization. MINOCA was identified in 3924 (7.8%) patients and clinical presentation was more often NSTEMI than STEMI (MINOCA: 78 vs. 22%; obstructive CAD 51.1 vs. 48.9%; p < 0.0001). MINOCA patients were younger and more often females with significantly lower rates of diabetes, smoking, arterial hypertension, kidney disease, previous MI and previous stroke comparing to patients with obstructive CAD. Myocardial bridge was visualized in angiography more often in the MINOCA group (2.2 vs. 0.4%; p < 0.0001). Additional coronary assessment inducing fractional flow reserve, intravascular ultrasound, optical coherence tomography was marginally (< 1%) used in both groups. Periprocedural mortality was lower in MINOCA group (0.13% vs. 0.95%; p < 0.0001). MINOCA patients represent a significant proportion of MI patients in Poland. Due to multiple potential causes, MINOCA should be considered rather as a working diagnosis after coronary angiography and further efforts should be taken to define the cause of MI in each individual patient. [ABSTRACT FROM AUTHOR]

Valvular heart disease is associated with an increased thromboembolic risk. Impaired fibrinolysis was reported in severe aortic stenosis (AS). Little is known about fibrinolysis in mitral stenosis (MS). We sought to compare fibrinolysis impairment in AS and MS. We studied 121 individuals scheduled for elective aortic valve (AV) or mitral valve (MV) surgery for AS (n = 76) or MS (n = 45), in order to compare fibrinolysis impairment. Fibrinolytic capacity was assessed by determination of clot lysis time (t50%) and fibrinolysis inhibitors, including plasma plasminogen activator inhibitor-1 (PAI-1) antigen (PAI-1:Ag) and activity, thrombin-activatable fibrinolysis inhibitor (TAFI) antigen and activity. Prolonged t50% (+ 29%), elevated TAFI activity (+ 12%), TAFI:Ag (+ 21%), and PAI-1:Ag (+ 84%) were observed in patients with MS, compared with those with AS. t50% Correlated with mean and maximal MV gradients (r = 0.43, p < 0.0001 and r = 0.39, p < 0.0001, respectively), but not with AV gradients. Mean and maximal MV gradients correlated with TAFI activity and PAI:Ag. Patients with permanent atrial fibrillation (AF; 35 with MS and 5 with AS) had longer t50% (by 22%, p = 0.0002) and higher PAI-1:Ag (by 74%, p < 0.0001) than the remainder. In the whole group, postoperative drainage volumes correlated inversely with PAI-1:Ag (r = − 0.22, p = 0.02). MS is associated with more pronounced impairment of global fibrinolytic capacity than AS at the stage of surgical intervention, which is in part driven by AF. Our findings suggest that hypofibrinolysis might be implicated in the progression of MS and its thromboembolic complications. [ABSTRACT FROM AUTHOR]

According to guidelines, it is recommended to give P2Y inhibitors (preferably ticagrelor or prasugrel) at the time of first medical contact in patients with STEMI. However, in real life antiplatelet treatment strategies are different among countries. We analyzed data on antiplatelet treatment in STEMI patients included into Polish ORPKI national registry. A total of 23,139 STEMI patients from 153 invasive cardiology centers were reported in ORPKI registry between September 2015 and August 2016. Finally 19,437 patients from 122 centers (immediate PCI in 94%) were included into the analysis (lack of ticagrelor or prasugrel usage reported in 31 centers). The dominant P2Y inhibitor was clopidogrel (69%) with a high rate of precathlab administration (51.3%). Ticagrelor was administered in 10.1% of patients (2.3% during precathlab phase) and prasugrel in 1.1% (0.4% precathlab). The periprocedural switch from clopidogrel to newer generation oral P2Y inhibitors was rare (to ticagrelor: 2%; to prasugrel: 0.15%). Analysis of data from top 10 centers with the highest rate of newer generation P2Y inhibitors usage (1295 patients) revealed ticagrelor administration in 43.1% (prasugrel in 3%). During precathlab phase higher proportion of ticagrelor instead of clopidogrel (ticagrelor 17.9%, clopidogrel 29.8%) and higher rate of periprocedural switch from clopidogrel to ticagrelor (11.9%) was found comparing to all centers data (p < 0.001 for all). The strategy of precathlab administration of P2Y inhibitors applies to about half of STEMI patients in Poland. Generally, ticagrelor or prasugrel use is low, and not equally distributed among centers. In centers with high usage, ticagrelor is main newer generation P2Y inhibitor for precathlab and periprocedural administration. [ABSTRACT FROM AUTHOR]

Denser fibrin networks which are relatively resistant to lysis can predispose to post-thrombotic syndrome (PTS). Histidine-rich glycoprotein (HRG), a blood protein displaying antifibrinolytic properties, is present in fibrin clots. We investigated whether HRG may affect the risk of PTS in relation to alterations to fibrin characteristics. In venous thromboembolism (VTE) patients, we evaluated plasma HRG levels, plasma clot permeability, maximum absorbance, clot lysis time and maximum rate of increase in D-dimer levels released from clots after 3 months of the index event. We excluded patients with cancer and severe comorbidities. After 2 years of follow-up, 48 patients who developed PTS had 18.6% higher HRG at baseline. Baseline HRG positively correlated with clot lysis time, maximum absorbance, and thrombin-activatable fibrinolysis inhibitor (TAFI) activity but was inversely correlated with plasma clot permeability and maximum rate of increase in D-dimer levels released from clots. On multivariate regression model adjusted for age, fibrinogen and glucose, independent predictors of PTS were recurrent VTE, baseline HRG level, and TAFI activity. VTE recurred in 45 patients, including 30 patients with PTS, and this event showed no association with elevated HRG. Our findings suggest that increased HRG levels might contribute to the development of PTS, in part through prothrombotic fibrin clot properties. [ABSTRACT FROM AUTHOR]

Background: Dense fibrin networks resistant to lysis have been reported in patients at high risk of thromboembolism. Little is known about fibrin clot properties in cancer. We investigated fibrin clot properties and their determinants in patients with inoperable lung cancer.Methods: We enrolled 150 patients with advanced lung cancer prior to therapy and 90 control subjects matched by age, sex, cardiovascular disease, and diabetes. Plasma clot permeability (Ks), turbidimetric analysis of clot formation, clot lysis time (CLT), microparticle-associated tissue factor (MP-TF) activity, thrombin generation, and serum cotinine levels were determined.Results: Lung cancer patients, compared with controls, formed at a faster rate (- 8.1% lag phase) denser plasma fibrin networks (- 27.2% Ks) that displayed impaired lysis (+ 26.5% CLT), along with 19.5% higher MP-TF activity and 100% higher peak thrombin generated, also after adjustment for potential confounders. Cotinine levels were associated with fibrin maximum absorbance (r = 0.20, p = 0.016) and Ks (r = - 0.50, p < 0.0001) in cancer patients. On multivariate regression analysis, an increase in cotinine levels was a predictor of low Ks (the lower quartile, < 5.8 × 10-9 cm2; odds ratio = 1.21 per 10 ng/ml, 95% confidence interval 1.02-1.46), but not CLT.Conclusion: Advanced lung cancer is associated with the prothrombotic plasma clot phenotype largely driven by smoking. [ABSTRACT FROM AUTHOR]