The role and effect of radiotherapy in the development of VTE has not been extensively explored; Methods: This is a post-hoc analysis from the COMPASS-CAT trial. Patients with breast, lung, colon or ...ovarian cancer, with early, locally advanced or metastatic disease and receiving chemotherapy were included. Primary endpoint was documented symptomatic VTE; Results: A total of 1355 patients were enrolled between November 2013 and November 2015. Of those, 194 patients were excluded because of missing data or the use of anticoagulation. Of the evaluable patients, 361 patients received radiotherapy (33.6%) At a median follow up of 6 months, 9.1% (n = 33) of patients receiving radiotherapy developed a VTE event (excluding those with missing data on follow up). After applying the competing risk model, radiotherapy remained significantly associated with increased risk for VTE (HR 2.47, 95% CI: 1.47-4.12,
= 0.001). Stratification analysis for the cohort that received radiotherapy revealed an increased risk of VTE in women compared to men (10.8% vs. 2.7%;
= 0.03), in those older than 50 (12.2% vs. 3.7%;
= 0.011); for patients receiving anthracycline chemotherapy (14.4% vs. 2.9%;
< 0.001) and hormonal therapy (12.9% vs. 3.9%;
< 0.001); Conclusions: Analysis from the COMPASS-CAT revealed a significant correlation between radiotherapy and VTE in patients with cancer. Further studies are needed to better understand the potential cellular toxicity associated with radiotherapy.
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•The COVID-19 pandemic has challenged the healthcare capacity of many countries.•Strict, horizontal lockdowns have adverse social, economic and health effects that have not been fully ...considered.•Primary and community care have multiple roles in COVID-19 pandemic mitigation.•Greece is a case example of a country which neglected primary and community care, and in November 2020 implemented a second horizontal lockdown.•Primary and community care, represents the only realistic strategy for successful COVID-19 pandemic mitigation in the long-term.
COVID-19 pandemic mitigation strategies are mainly based on social distancing measures and healthcare system reinforcement. However, many countries in Europe and elsewhere implemented strict, horizontal lockdowns because of extensive viral spread in the community which challenges the capacity of the healthcare systems. However, strict lockdowns have various untintended adverse social, economic and health effects, which have yet to be fully elucidated, and have not been considered in models examining the effects of various mitigation measures. Unlike commonly suggested, the dilemma is not about health vs wealth because the economic devastation of long-lasting lockdowns will definitely have adverse health effects in the population. Furthermore, they cannot provide a lasting solution in pandemic containment, potentially resulting in a vicious cycle of consecutive lockdowns with in-between breaks. Hospital preparedness has been the main strategy used by governments. However, a major characteristic of the COVID-19 pandemic is the rapid viral transmission in populations with no immunity. Thus, even the best hospital system could not cope with the demand. Primary, community and home care are the only viable strategies that could achieve the goal of pandemic mitigation. We present the case example of Greece, a country which followed a strategy focused on hospital preparedness but failed to reinforce primary and community care. This, along with strategic mistakes in epidemiological surveillance, resulted in Greece implementing a second strict, horizontal lockdown and having one of the highest COVID-19 death rates in Europe during the second wave. We provide recommendations for measures that will reinstate primary and community care at the forefront in managing the current public health crisis by protecting hospitals from unnecessary admissions, providing primary and secondary prevention services in relation to COVID-19 and maintaining population health through treatment of non−COVID-19 conditions. This, together with more selective social distancing measures (instead of horizontal lockdowns), represents the only viable and realistic long-term strategy for COVID-19 pandemic mitigation.
Introduction
In a prospective cohort of hospitalized COVID-19 patients, an extensive characterization of hemostatic alterations by both global and specific assays was performed to clarify mechanisms ...underlying the coagulopathy and identify predictive factors for thrombotic and hemorrhagic events during hospitalization.
Materials and Methods
Intensive care unit (ICU;
n
= 46) and non-ICU (
n
= 55) patients were enrolled, and the occurrence of thrombotic and hemorrhagic events was prospectively monitored. At study inclusion, thromboelastometry together with the measurement of specific coagulation proteins and hypercoagulation markers was performed.
Results
Patients (median age 67 years) showed significantly shorter clot formation time together with greater maximum clot firmness by thromboelastometry, increased levels of F1 + 2 and D-dimer, as biomarkers of hypercoagulability, and of procoagulant factors V, VIII, IX, XI, and fibrinogen, while FXIII was significantly reduced. The concentration of fibrinolytic proteins, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) were elevated in the overall cohort of patients. Many of these hemostatic alterations were significantly greater in ICU compared to non-ICU subjects and, furthermore, they were associated with inflammatory biomarker elevation i.e., interleukin 6 (IL-6), C-reactive protein (CRP), neutrophil to lymphocyte ratio (NLR), and procalcitonin. After enrollment, 7 thrombosis and 14 major bleedings occurred. Analysis of clinical and biological data identified increased t-PA, PAI-1, and NLR values as independent predictive factors for thrombosis, while lower FXIII levels were associated with bleeding.
Conclusion
This study demonstrates alterations in all different hemostatic compartments analyzed, particularly in severe COVID-19 conditions, that strongly correlated with the inflammatory status. A potential role of fibrinolytic proteins together with NLR and of FXIII as predictors of thrombotic and hemorrhagic complications, respectively, is highlighted.
Identifying adherence to direct oral anticoagulants (DOACs) plays a major role in treatment efficacy and safety. The DOAC Dipstick can detect DOACs in urine samples of acutely diseased patients at ...plasma thresholds of about 30 ng/mL. A prospective observational consecutive cohort study was performed on outpatients taking DOACs. The presence of direct oral factor Xa inhibitors (DXIs) in patient urine samples were independently evaluated by visual interpretation of the DOAC Dipstick pad colors. DOAC plasma concentration was assessed using STA®-Liquid Anti-Xa and STA®-Liquid Anti-IIa chromogenic substrate assays. Positive DOAC Dipstick results were compared with a threshold plasma of DOAC concentration ≥30 ng/mL. Of 120 patients (age 55.4 + 16.1 years, female n = 63), 77 were on rivaroxaban and 43 on apixaban. Plasma concentrations were 129 ± 118 ng/mL for rivaroxaban, and 163 ± 130 ng/mL for apixaban, DOAC Dipstick test has a sensitivity of 97.2% and a positive predictive value of 89.5% at 30 ng/mL. No differences occurred between DXIs. Specificity and negative predictive value could not be determined due to the low number of true negative values. There were no differences in the interpretation of rivaroxaban and apixaban pad colors between observers (Kappa 1.0). Results show that DOAC Dipstick may be a useful tool for identifying DXIs in urine samples in an outpatient setting at a plasma threshold ≥ 30 ng/mL. Further studies should include patients treated with dabigatran, vitamin K antagonists, or other anticoagulants.
Due to the fact that there are scientific discussions about the significance of gene polymorphisms in the risk of developing cardiovascular complications after a percutaneous coronary intervention, ...it is of interest to evaluate the genetic predictors of the development of cardiovascular events. This study is a molecular genetic study. Association with the genes of biomarkers for inflammation and immune response increases the risk of cardiovascular events: rs1234313 (TNFSF4): (A/G, OR-4.57 (2.35-8.87),
≤ 0.0001), (A/G-A/A, OR-3.14 (1.75-5.63),
≤ 0.0001), and (A/G, OR = 4.01 (2.19-7.36),
≤ 0.0001); rs3184504 (SH2D3); ATXN2: (C/T, OR-2.53 (1.28-5.01), T/T, OR-2.99 (1.13-7.92),
= 0.017)), (C/T-T/T, OR-2.61 (1.35-5.07),
= 0.000), and (OR-1.89 (1.15-3.09),
= 0.009)). According to the lipid metabolism biomarker genes, rs2943634: (A/C OR-2.57 (1.18-5.62),
= 0.013); according to the endothelial biomarker genes, rs2713604: (DNAJB8-AS1; GATA2): (C/T, OR-4.27 (2.35-7.76),
≤ 0.0001), (C/T-C/C, OR-4.13 (2.31-7.40),
≤ 0.0001), (OR-4.05 (2.24-7.30),
≤ 0.0001), and (C/T, OR-3.46 (1.99-6.00),
≤ 0.0001). The regression analysis found that in the presence of the rs2943634 gene polymorphism, the risk of late cardiovascular events increases by 4.007 times with 95% CI (1.502:10.692),
= 0.006. The genes of biomarkers for the risk of cardiovascular events are rs1234313(TNFSF4), rs3184504 (SH2D3; ATXN2), rs2943634, and rs2713604 (DNAJB8-AS1; GATA2). The only predictor of the development of new cardiovascular events was rs2943634, which belongs to the group of lipid metabolism biomarkers.
The local immune-inflammatory response elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still poorly described, as well as the extent to which its characteristics ...may be associated with the outcome of critical Coronavirus disease 2019 (COVID-19). In this prospective monocenter study, all consecutive COVID-19 critically ill patients admitted from February to December 2020 and explored by fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) were included. Biological assays, including digital ELISA cytokine profiling and targeted eicosanoid metabolomic analysis, were performed on paired blood and BAL fluid (BALF). Clinical outcome was assessed through the World Health Organization 10-point Clinical Progression Scale (WHO-CPS) at the 28th day (D28) following the admission to intensive care unit. A D28-WHO-CPS value higher than 5 defined a poor outcome. Seventy-six patients were included, 45 (59%) had a poor day-28 outcome. As compared to their counterparts, patients with D28-WHO-CPS > 5 exhibited a neutrophil-predominant bronchoalveolar phenotype, with a higher BALF neutrophil/lymphocyte ratio, a blunted local type I interferon response, a decompartimentalized immune-inflammatory response illustrated by lower BALF/blood ratio of concentrations of IL-6 (1.68 0.30-4.41 vs. 9.53 2.56-19.1; p = 0.001), IL-10, IL-5, IL-22 and IFN-γ, and a biological profile of vascular endothelial injury illustrated by a higher blood concentration of VEGF and higher blood and/or BALF concentrations of several vasoactive eicosanoids. In critically ill COVID-19 patients, we identified bronchoalveolar and blood immune-inflammatory biomarker signature associated with poor 28-day outcome.
Sickle-cell anaemia is a widespread genetic disease prevalent worldwide among African and African-American populations. The pathogenesis is most often revealed by pulmonary conditions, including ...acute thoracic syndrome, which is affecting the life expectancy of these populations. The global spread of CoV2-SARS infection with a respiratory tropism, endothelial damages and procoagulant status endangers the SCD population. However, with only a few case reports, consequences of the Covid-19 pandemic on SCD population remain poorly known.
We report a case of a 33-year-old man with a history of homozygous SS homozygous sickle cell anemia who consulted on March 24, 2020 for febrile dyspnea 11 days after the onset of symptoms. A nasopharyngeal swab was positive for SARS-CoV-2. His respiratory status worsened rapidly in the emergency room and then in ICU leading to severe ARDS requiring intubation, curarization, and venovenous ECMO. Hematologically, severe hemolysis associated with major thrombocytopenia without documented spinal cord injury was noted. Several transfusion exchanges are performed. The evolution was finally slowly favorable and led to discharge from the intensive care unit and then from the hospital.
This case recalls the importance of an increased prevention policy against COVID-19among the SCD population. In addition, from a therapeutic point of view, it advocates (1) a high preventive anticoagulation from the outset according to the level of D-dimers (2) the use of venovenous ECMO in this particular case, whereas this technique has had rather disappointing results in acute chest syndromes. (3) Unexpectedly, our patient did not develop pulmonary arterial hypertension (PAH) and acute cor pulmonale (ACP), whereas this is a common feature of ARDS during SCD. These last two observations suggest a different pathophysiology of pulmonary disorders in SCD patients in the case of SARS COv2. It could be associated with marked hypoxemia secondary to pulmonary vascular vasodilation.
From this retrospective study, we aimed to (1) describe the prevalence and characteristics of non-criteria features in primary antiphospholipid syndrome (p-APS) and (2) determine their prognostic ...value.
This retrospective French multicenter cohort study included all patients diagnosed with p-APS (Sydney criteria) between January 2012 and January 2019. We used Kaplan-Meier and adjusted Cox proportional hazards models to compare the incidence of relapse in p-APS with and without non-criteria manifestations.
One hundred and seventy-nine patients with p-APS were included during the study time, with a median age of 52.50 years 39.0; 65.25 and mainly women (n = 112; 62.6%). Among them, forty-three patients (24.0%) presented at least one non-criteria manifestation during the follow-up: autoimmune cytopenias (n = 17; 39.5%), Libman Sachs endocarditis (n = 5; 11.6%), APS nephropathy (n = 4; 9.3%), livedo reticularis (n = 8; 18.6%), and neurological manifestations (n = 12; 27.9%). In comparison to p-APS without any non-criteria manifestations (n = 136), p-APS with non-criteria features had more arterial thrombosis (n = 24; 55.8% vs n = 48; 35.3%; p = 0.027) and more frequent pre-eclampsia (n = 6; 14.3% vs n = 4; 3.1%; p = 0.02). The prevalence of triple positivity was significantly increased in patients with non-criteria features (n = 20; 47.6% vs n = 25; 19.8%; p = 0.001). Patients with p-APS and non-criteria manifestations (n = 43) received significantly more additional therapies combined with vitamin K antagonists and/or antiaggregants. Catastrophic APS (CAPS) tended to be more frequent in p-APS with non-criteria features (n = 2; 5.1% vs none; p = 0.074). The p-APS with non-criteria manifestations had significantly increased rates of relapse (n = 20; 58.8% vs 33; 33.7%; p = 0.018) in bivariate analysis, but in survival analyses, the hazard ratio (HR) of relapse was not significantly different between the two groups (HR at 1.34 0.67; 2.68; p = 0.40).
The presence of non-criteria features is important to consider, as they are associated with particular clinical and laboratory profiles, increased risk of relapse, and need for additional therapies. Prospective studies are necessary to better stratify the prognosis and the management of p-APS.
In this study, we aimed to analyze the value of annexin-A5 anticoagulant ratio (A5R) and non-criteria antibodies for the diagnosis of APS in patients with clinical seronegative APS. Three groups were ...defined, including 21 seronegative APS patients with unexplained obstetrical adverse events or thrombosis history, 15 confirmed APS patients with triple aPL positivity, and a control group of 20 healthy patients without any history of thrombosis or pregnancy complications. Seronegative APS patients have similar levels of A5R in comparison to healthy controls (202% 171%–238% versus 191% 178%–221%;
p
= 0.65), whereas triple-positive APS patients have significantly more reduced A5R in comparison to both seronegative and healthy patients (149% 138%–158% versus 202% 171%–238% and 191% 178%–221%, respectively,
p
< 0.001). The non-criteria aPL were found in 24% of seronegative APS: anti-PE IgM in 3 cases (14%) and anti-PS/PT IgG and anti-PS/PT IgM in 1 (5%) case each. The frequency of non-criteria APL was significantly more frequent in comparison to healthy controls (
p
= 0.048). All triple-positive APS patients have at least one non-criteria aPL, and the non-criteria aPL were significantly more frequent in these patients compared to seronegative APS and healthy controls (
p
< 0.001). Whereas A5R levels do not allow to discriminate seronegative APS from healthy controls, our results demonstrate that non-criteria aPL can help to APS diagnosis in clinical seronegative APS.
Key points
•
Annexin-A5 resistance testing does not help for the diagnosis of seronegative APS.
•
The non-criteria antiphospholipid antibodies can contribute to APS diagnosis in patients without conventional antibodies.
Biomarkers of hypercoagulability are potential candidates for the evaluation of risk for primary treatment resistance in patients with newly diagnosed multiple myeloma (NDMM). This study aimed to ...identify the most clinically relevant biomarkers for the evaluation of treatment-resistance risk. NDMM patients (n = 144) were enrolled prior to treatment initiation. Response to treatment was assessed at 3 months. STA-Procoag-PPL®, factor VIIa factor V, antithrombin, fibrin monomers, soluble thrombomodulin (TM), free TFPI, D-Dimer, P-selectin, heparanase, and thrombin generation (Calibrated Automated Thrombogram® and PPP-Reagent®) were measured. In total, 23% (n = 33) of the patients showed a poor response/resistance to treatment (defined as stable disease, minor response, progressive disease). Poor response/treatment resistance was associated with longer Procoag-PPL® clotting time, higher Peak of thrombin, and higher D-Dimer levels. These biomarkers were included in a prognostic model derived via multivariate analysis. The model had 84% sensitivity and 59% specificity to identify patients at high risk of treatment resistance. The AUC of the ROC analysis for the model was 0.75. In conclusion, Procoag-PPL®, D-Dimer, and Peak of thrombin generation are clinically relevant for the identification of NDMM patients at risk for poor response to antimyeloma treatment. A prospective multicenter study is necessary for the validation of this new approach.
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