Treatment Resistance Risk in Patients with Newly Diagnosed Multiple Myeloma Is Associated with Blood Hypercoagulability: The ROADMAP-MM Study

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

Comparison of the DOAC Dipstick Test on Urine Samples With Chromogenic Substrate Methods on Plasma Samples in Outpatients Treated With Direct Oral Anticoagulants

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

Genetic Predictors of the Development of Complications after Coronary Stenting

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), p ≤ 0.0001), (A/G-A/A, OR-3.14 (1.75–5.63), p ≤ 0.0001), and (A/G, OR = 4.01 (2.19–7.36), p ≤ 0.0001); rs3184504 (SH2D3); ATXN2: (C/T, OR-2.53 (1.28–5.01), T/T, OR-2.99 (1.13–7.92), p = 0.017)), (C/T-T/T, OR-2.61 (1.35–5.07), p = 0.000), and (OR-1.89 (1.15–3.09), p = 0.009)). According to the lipid metabolism biomarker genes, rs2943634: (A/C OR-2.57 (1.18–5.62), p = 0.013); according to the endothelial biomarker genes, rs2713604: (DNAJB8-AS1; GATA2): (C/T, OR-4.27 (2.35–7.76), p ≤ 0.0001), (C/T-C/C, OR-4.13 (2.31–7.40), p ≤ 0.0001), (OR-4.05 (2.24–7.30), p ≤ 0.0001), and (C/T, OR-3.46 (1.99–6.00), p ≤ 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), p = 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

Persisting Endothelial Cell Activation and Hypercoagulability after COVID-19 Recovery—The Prospective Observational ROADMAP-Post COVID-19 Study

Background. Hypercoagulable state and endothelial cell activation are common alterations in patients with COVID-19. Nevertheless, the hypothesis of persistent hypercoagulability and endothelial cell activation following recovery from COVID-19 remains an unresolved issue. Objectives. To investigate the persistence of endothelial cell activation and hypercoagulability after recovery from COVID-19. Patients/Methods. COVID-19 survivors (n = 208) and 30 healthy individuals were enrolled in this study. The following biomarkers were measured: procoagulant phospholipid-dependent clotting time (PPL-ct), D-Dimer, fibrin monomers (FM), free Tissue factor pathway inhibitor (free-TFP)I, heparinase, and soluble thrombomodulin (sTM). Antibodies against SARS-CoV-2 (IgG and IgA) were also measured. Results. The median interval between symptom onset and screening for SARS-CoV-2 antibodies was 62 days (IQR = 22 days). Survivors showed significantly higher levels of D-Dimers, FM, TFPI, and heparanase as compared to that of the control group. Survivors had significantly shorter PPL-ct. Elevated D-dimer was associated with older age. Elevated FM was associated with female gender. Elevated heparanase was independently associated with male gender. Decreased Procoag-PPL clotting time was associated with female gender. One out of four of COVID-19 survivors showed increase at least one biomarker of endothelial cell activation or hypercoagulability. Conclusions. Two months after onset of COVID-19, a significant activation of endothelial cells and in vivo thrombin generation persists in at least one out of four survivors of COVID-19. The clinical relevance of these biomarkers in the diagnosis and follow-up of patients with long COVID-19 merits to be evaluated in a prospective clinical study

Improved strategies to counter the COVID-19 pandemic:Lockdowns vs. primary and community healthcare

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