COVID-19 is associated with an increased thromboembolic risk. However, the mechanisms triggering clot formation in those patients remain unknown.
In 118 adult Caucasian severe but non-critically ill ...COVID-19 patients (median age 58 years; 73 % men) and 46 controls, we analyzed in vitro plasma thrombin generation profile (calibrated automated thrombogram CAT assay) and investigated thrombophilia-related factors, such as protein C and antithrombin activity, free protein S level, presence of antiphospholipid antibodies and factor V Leiden R506Q and prothrombin G20210A mutations. We also measured circulating von Willebrand factor (vWF) antigen and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) antigen and activity. In patients, blood samples were collected on admission to the hospital before starting any therapy, including heparin. Finally, we examined the relationship between observed alterations and disease follow-up, such as thromboembolic complications.
COVID-19 patients showed 17 % lower protein C activity, 22 % decreased free protein S levels, and a higher prevalence of positive results for IgM anticardiolipin antibodies. They also had 151 % increased vWF, and 27 % decreased ADAMTS13 antigens compared with controls (p < 0.001, all). On the contrary, thrombin generation potential was similar to controls. In the follow-up, pulmonary embolism (PE) occurred in thirteen (11 %) patients. They were characterized by a 55 % elevated D-dimer (p = 0.04) and 2.7-fold higher troponin I (p = 0.002) during hospitalization and 29 % shorter time to thrombin peak in CAT assay (p = 0.009) compared to patients without PE.
In COVID-19, we documented prothrombotic abnormalities of peripheral blood. PE was characterized by more dynamic thrombin generation growth in CAT assay performed on admittance to the hospital.
Venous thromboembolism (VTE) has been considered the dominant major life threatening vascular complication after non-cardiac surgery, but recent studies have shifted the emphasis toward myocardial ...injury after non-cardiac surgery (MINS) as a common adverse event in the peri-operative setting. The aim of the present study was to compare the incidence and influence on mortality of two dominant venous and arterial events in the peri-operative period by prospectively screening a consecutive cohort of patients undergoing vascular surgery.
This was a sub-study of Vascular Events In Non-cardiac Surgery Patients Cohort Evaluation (VISION), the main objective of which was to evaluate major peri-operative complications after non-cardiac surgery. Patients undergoing vascular surgery had their blood collected to measure the Roche fifth generation high sensitivity troponin T (hsTnT) assay before and four times after surgery (6–12 h post-operatively, on the first, second, and third day following the procedure). MINS was defined as an elevated post-operative hsTnT ≥65 ng/L or an hsTnT ≥20 to <65 ng/L with an absolute change of ≥5 ng/L that was judged to be due to ischaemia. All patients underwent ultrasound venous compression testing for deep vein thrombosis (DVT) before, 4, and 7 days after surgery and follow-up was performed by telephone 30 days and 1 year after surgery.
In total, 164 consecutive patients were included in this sub-study. MINS was diagnosed in 39 patients (23.8%) and DVT in four patients (2.4%). The 1 year mortality was higher in MINS (9/39 23.1%) than non-MINS patients (9/125 7.2%; p = .006). None of the patients who developed DVT died in the first year after surgery.
MINS is a common complication after vascular surgery. It occurs more frequently than DVT and is associated with high 1 year mortality.
Mixed connective tissue disease (MCTD) is a chronic immune-mediated disorder defined by the combined presence of serum anti-RNP antibodies and distinct clinical features including progressive lung ...fibrosis. The aim of this study was to evaluate potential associations between lung fibrosis in MCTD and specific clinical and laboratory findings including results of nailfold capillaroscopy (NFC) examination.
Patients with MCTD who were admitted to the Departments of Allergy and Immunology or Dermatology at the University Hospital of Krakow (Poland) in 2015-2018 were identified based on comprehensive individual record review. Diagnosis of MCTD required fulfilment of at least one of the four widely accepted sets of diagnostic criteria. Clinical and laboratory data were collected, and statistical analysis was performed to identify potential predictors of interstitial lung disease (ILD).
Thirty patients (90% females) aged 22-81 years met the study inclusion criteria. The mean duration of symptoms associated with MCTD was 7.3 months. Photosensitivity and Raynaud's phenomenon were the most common clinical manifestations (90% and 70%, respectively). Hand oedema, sclerodactyly and the presence of giant capillaries in NFC correlated significantly with the risk of lung involvement. In multivariate analysis, the presence of enlarged loops in NFC (giant capillaries) was identified as an independent factor for ILD (
= 0.82,
< 0.0000001).
The NFC examination should be considered in all patients with a diagnosis of MCTD. The presence of giant capillaries may be a promising marker for interstitial lung disease in these patients, especially among those with a short duration of disease (i.e. < 1 year).
Bleeding phenotype in patients with congenital factor VII (FVII) deficiency is highly variable. No direct correlation between FVII activity and bleeding tendency is noted. The aim of this study was ...to analyse clinical and laboratory phenotype of patients with FVII deficiency treated in one haemophilia treatment centre in Little Poland. Clinical and laboratory data of 106 patients were collected retrospectively. Bleeding symptoms were evaluated according to the Bleeding Assessment Tool. The mean FVII activity was 19.5% (range: 1.0-49.2) and the mean prothrombin time (PT) was 29.7 seconds (range: 13.2-64.8), comparable in both sexes. Activity was lower than 1% in 6.6% of individuals. The average age at diagnosis (31.2 years; range: 1-76) did not correlate with FVII activity. Half of the patients were diagnosed incidentally, mostly due to routine PT measurement. The most frequently reported symptoms were gum, nose and tooth extraction bleeds. A total of 22.6% of patients remained asymptomatic and 60.4% never required replacement therapy. Thrombotic episodes were diagnosed in five women (4.7%). In conclusion, the clinical picture of the analysed group is similar to the previously described. It should be stressed that a significant risk of bleeds, including joint haemorrhages, can be expected in patients with mildest FVII deficiency (>26%) as well. The rate of thrombosis (4.7%) was similar to other reports, with all affected patients having strong prothrombotic risk factors or being intensively treated with FVII concentrate.
Abstract
Objectives
APS is associated with arterial and venous thrombosis. The unfavourable fibrin clot phenotype, including formation of dense and poorly lysable clots, has been reported in ...thrombotic APS. We investigated whether abnormal plasma clot properties are predictive of recurrent thromboembolism in APS.
Methods
We followed 126 consecutive patients with thrombotic APS and 105 control subjects, without APS, matched for thrombotic events. Plasma fibrin clot permeability (Ks), turbidity measurements and clot lysis time were evaluated ⩾5 months after a thrombotic event. The primary composite end point was symptomatic recurrent venous thromboembolism, ischaemic stroke and/or myocardial infarction.
Results
During follow-up (median, 62 months; range 46-74 months; 1183.2 patient-years), the primary outcome was observed in 33 (26.2%) APS patients and 16 (15.2%) controls, including 25 (19.8%) and 14 (13.3%) subjects with recurrent venous thromboembolism, respectively. Reduced Ks and prolonged clot lysis time predicted recurrent thromboembolic events in APS patients per 1 × 10−9 cm2: hazard ratio (HR) = 0.37; 95% CI: 0.24, 0.56; and per 10 min: HR = 1.20; 95% CI: 1.01, 1.40, respectively and in controls (per 1×10−9 cm2: HR = 0.23; 95% CI: 0.11, 0.42; and per 10 min: HR = 1.51; 95% CI: 1.08, 2.16, respectively). A multivariate analysis showed that positive IgG and IgM anti-β2 glycoprotein I antibodies, withdrawal of anticoagulation, lower platelet count and reduced Ks predicted thromboembolic events in APS patients.
Conclusion
Formation of denser fibrin networks could be a novel risk factor for recurrent thromboembolism in APS, which highlights the importance of fibrin phenotype in thrombotic disorders.
The vibro-acoustic environment generated during a rocket launch induces dynamic loads which may damage critical components of spacecraft and scientific instruments. The research is focused on the ...vibro-acoustic response of the Wide Field Imager (WFI) instrument subjected to an intense diffuse sound field. Noise-induced structural vibrations in low- to mid-frequency can be computed by means of coupled FEM-BEM numerical models. Nevertheless, this approach is unsuited to calculations of cavity-structure interactions of light-weight and thin structures. In this paper the application and assessment of the elasto-acoustic FEM-FEM coupling approach for the cavity - optical blocking thin foil filter interactions is investigated. The diffuse sound field excitation is reconstructed by matching values of the sound pressure level to these obtained from experimental measurements. The viscosity effects on the wave propagation in thin layers are included by using the visco-thermal fluid model. The accuracy and efficiency of this approach are investigated and results obtained are compared to measured data from a reverberant test chamber. The results show that a very good agreement is obtained in terms of the acoustic pressure in the vicinity of the optical blocking filter. The behaviour of mechanical vibrations is correctly reproduced, although some considerable discrepancies in the levels of the vibrations are observed. The case of strong coupling between the cavity acoustic field and the filter membrane is finally discussed.
Leukocytoclastic vasculitis (LCV) is a heterogenous group of disorders that may manifest as a mild disease isolated to the skin or be a part of life-threatening systemic vasculitis. According to the ...2012 Chapel Hill Consensus Conference nomenclature, patients presenting symptoms of LCV confined only to the skin should be defined as suffering from a single-organ cutaneous small vessel vasculitis (SoCSVV). SoCSVV is a benign disease with a good clinical outcome but with a significant risk of relapse and skin ulcer formation.The aim of the current study was to characterize SoCSVV and to identify factors that may be associated with the risk of recurrence and skin ulcers.Medical records of patients with LCV hospitalized at the Department of Dermatology at University Hospital in Cracow in the years 2010 to 2015 were analyzed.A total of 24 patients fulfilled criteria of SoCSVV. Drugs and preceding infections were identified as precipitating factors in 40% and 20% of cases, respectively. Skin lesions other than palpable purpura (i.e., macules, urticarial vasculitis, or ulcers) were identified in almost half of the patients. Interestingly, the presence of macules independently increased the risk of skin ulcer formation (odds ratio = 16; 95% confidence interval: 1.5-176.6; P = 0.0075) in the multivariate logistic regression analysis. One-quarter of patients with SoCSVV experienced relapse during the 6-month follow-up. The greater number of affected skin areas was an independent risk factor of recurrence (odds ratio = 5; 95% confidence interval: 2-45; P = 0.02).SoCSVV was usually associated with drugs and preceding infections. The disease relapses in approximately one-quarter of the patients. The more severe the skin involvement in the course of SoCSVV, the higher is the risk of recurrence.
Esophageal cancer (EC) is a malignant tumor with a typically poor prognosis for patients. It is well known that certain microRNA (miRNA/miR) genes can regulate other genes responsible for ...carcinogenesis. In the present study, a group of these genes (miR-21, miR-134, miR-205 and miR-495) and genes connected with cancer-related pathways (MET, MMP9, PDGFA and SERPINE1) were chosen for analysis in order to find a potential correlation between their expression and the clinicopathological factors of EC. Esophageal tumors and adjacent non-cancerous tissue specimens were collected from a total of 63 patients and embedded in paraffin. Commercial arrays were used on KYSE-30, KYSE-150 and KYSE-270 EC cell lines in order to find genes of different expression profiles compared with those acquired from the control Het-1A cell line. Quantitative polymerase chain reaction was used on formalin-fixed, paraffin-embedded samples in order to analyze the expression of the genes chosen in the earlier step. The results were analyzed by the Kruskal-Wallis and Mann-Whitney U tests, Spearman's rank correlation coefficient, Kaplan-Meier methods and the long-rank test. Only miR-495 was not expressed in the analyzed samples. The expression of MMP9 and SERPINE1 was significantly coefficient with age range (P=0.011 and P=0.044, respectively) according to the Kruskal-Wallis test. The Spearman's rank-order correlation measurement showed that there was a coefficient correlation between age and miR-134 expression. The same measurement demonstrated a correlation between age range and MMP9 expression. The expression of miR-134 and MMP9 were also found to be correlated. In all cases, a value of P<0.049 was recorded. Overall, the present study demonstrated that MMP9, SERPINE1 and miR-134 were the most prognostic genes in Caucasian patients with EC.
Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of vasculitis associated with asthma and eosinophilia. Endothelial dysfunction has been well documented in other types of ...vasculitis but not in EGPA. Thirty patients (10 men and 20 women) diagnosed with EGPA and remaining in a remission, and 58 controls (24 men and 34 women) matched for age, sex, and body mass index, were enrolled in the study. We assessed each participants for typical risk factors of cardiovascular diseases and measured serum levels of vascular cell adhesion molecule-1 (VCAM-1), interleukin 6 (IL-6), and thrombomodulin. We also measured flow-mediated dilatation (FMD) of the brachial artery and intima-media thickness (IMT) of the common carotid artery using ultrasonography. Patients with EGPA had 20% higher serum level of VCAM-1 (
p
< 0.001) and 41.9% of thrombomodulin (
p
< 0.001). They also had 38.8% lower relative increase of FMD (FMD%) (
p
< 0.001), indicating endothelial dysfunction. These differences remained significant also after adjustment for potential confounders. Laboratory and ultrasonographic parameters of endothelial injury were correlated to the markers of inflammation and impaired kidney function. Determinants of lower FMD% in a simple regression model were pack-years of smoking (
β
= − 0.3 95% confidence interval (CI) − 0.5 to − 0.1), serum level of IL-6 (
β
= − 0.36 95% CI − 0.62 to − 0.1), and thrombomodulin (
β
= − 0.34 95% CI − 0.6 to − 0.08). EGPA patients are characterized by inflammatory endothelial injury that is likely related to the pathogenesis of the disease. Proper immunosuppressive treatment is the best method to prevent atherosclerosis and future cardiovascular events, the patients may also benefit from additional preventive interventions.
Acquired hemophilia is a rare bleeding disorder caused by autoantibodies that inhibit coagulation factor VIII. In most cases, it manifests with severe, often life‑threatening bleeds. Acquired ...hemophilia may be idiopathic or secondary to another condition, most commonly other autoimmune disease or cancer. Treatment is directed to stop bleeding and eradicate inhibitory autoantibodies. Like in most life‑threatening conditions, early diagnosis and treatment are essential for good prognosis. Prompt diagnosis and treatment of acquired hemophilia are constantly improving owing to the increasing availability of laboratory diagnostic tests and growing awareness of physicians of various specialties.
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