Dupontrobertson5082

Overall, 75% of survey respondents answered 10 single-answer knowledge questions correctly, 13% incorrectly, and 12% were unsure of the correct answers. Conclusions This survey highlighted knowledge gaps and educational needs related to gene therapy for hemophilia and, along with other inputs, has informed the development of "Gene Therapy in Hemophilia An ISTH Education Initiative."Introduction We conducted a longitudinal study in patients with pancreatic and colorectal cancer. We determined the effect of chemotherapy on extracellular vesicle tissue factor (EVTF) activity and the association of plasma EVTF activity with venous thromboembolism (VTE) and survival. Material and methods We enrolled 13 patients with pancreatic and 22 patients with colorectal cancer. Plasma samples were collected during the 85-day study period. Patients were followed for 3 months after the study period. BMS-794833 We recorded symptomatic VTE during the study period (3 months) or asymptomatic deep vein thrombosis detected by ultrasound at day 85. We measured EVTF activity before and after chemotherapy. Results and conclusions In the pancreatic cancer group, 2 patients had elevated levels of EVTF activity. One of these patients developed symptomatic VTE and died, and the second patient did not have a VTE but died. Chemotherapy decreased EVTF activity in 2 pancreatic patients with high levels. In the colorectal cancer group, 4 patients developed VTE, but EVTF activity was not elevated in any patient and no patient died. We observed a borderline significant correlation between EVTF activity and D-dimer in the patients with pancreatic but not colorectal cancer. In this small descriptive study, 2 patients with pancreatic cancer had an elevated level of EVTF activity. Both patients died during the study period, and one had a VTE. Chemotherapy decreased EVTF activity in these patients. In contrast, elevated levels of EVTF activity were not observed in patients with colorectal cancer with or without VTE.Background Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia mediated by IgM autoantibodies that trigger hemolysis via classical complement pathway. Increased incidence of thrombotic events (TEs) has been reported in patients with other forms of hemolysis. The incidence of TEs in patients with CAD is unknown. Objective Evaluate TE risk in patients with CAD. Patients/methods This is a matched cohort comparison study evaluating the risk of TEs in patients with CAD and without CAD over a 10-year period. A total of 608 patients with CAD were identified in the Optum Claims-Clinical data set by reviewing clinical notes for CAD terms and matched with up to 10 patients without CAD (N = 5873). TEs were defined as the first medical claim for a TE using International Classification of Diseases, Ninth and Tenth Revision codes. Cox regression models were used to estimate time to first TE. Sensitivity analyses were conducted to estimate TE risk among patients with primary CAD. Results At least 1 TE occurred in 29.6% of patients with CAD and 17.6% of patients without CAD. The proportion of patients experiencing venous, arterial, and cerebral TEs were each higher among CAD patients. The overall risk of having TEs was higher in patients with CAD (adjusted hazard ratio [aHR], 1.94; 95% confidence interval [CI], 1.64-2.30). Patients with presumed primary CAD also demonstrated an increased risk of TEs (aHR, 1.80; 95% CI, 1.46-2.22). Patients with CAD with the fewest comorbidities had 2.44-fold higher risk of having a TE (95% CI, 1.70-3.52). Conclusions Patients with CAD have an increased risk of TEs when compared with a matched non-CAD population.Background Monitoring of anticoagulant activity of direct oral anticoagulants (DOACs) can be necessary in special situations. DOAC plasma levels have a high inter- and intraindividual variation and do not necessarily reflect the coagulation status of the patient. Thrombin generation (TG) is a global hemostatic assay with the capacity to overcome this limitation. The aim of this study was to show correlations between DOAC plasma levels and TG parameters using the fully automated ST Genesia system. Methods A total of 380 blood samples (120 with apixaban, 79 with dabigatran, 79 with edoxaban, and 102 with rivaroxaban) from patients at different time points after DOAC intake were included in the analysis. DOAC plasma levels were analyzed using calibrated anti-Xa or anti-IIa tests. Thrombin generation was measured using the ST Genesia system and STG-DrugScreen reagent. Results There was a significant correlation between the drug levels of all DOACs and the TG parameters' lag time and time to peak. Peak thrombin and velocity index show a negative correlation following an exponential regression curve with all anti-Xa DOACs but not with dabigatran. Apart from a weak correlation with rivaroxaban, there was no correlation between drug levels of all other DOACs and endogenous thrombin potential. Conclusion TG parameters measured with ST Genesia correlate with the drug levels of anti-Xa DOACs. Peak thrombin and velocity index are of special interest for the determination of residual anticoagulant effect at low drug levels. For dabigatran-treated patients, only lag time shows a correlation with the dabigatran plasma levels.Background The residual antithrombotic activity 12 hours after intake of direct oral anticoagulants (DOACs) is of clinical relevance in the setting of bleeding or urgent surgery. Objective To evaluate the effects of DOACs on thrombin generation 12 hours after DOAC intake in comparison to baseline and a healthy control group. Methods Eighty patients were recruited, 20 patients for each approved DOAC apixaban, edoxaban, rivaroxaban, and dabigatran. The patients were either to be put on anticoagulation for the first time or had stopped taking oral anticoagulation for at least 48 hours. Blood plasma was sampled before (baseline) and 12 hours after starting DOAC for quantification of drug levels and thrombin generation assayed using an automated system (ST Genesia). Sixty-one blood donors served as control group. Results The factor Xa inhibitors significantly increased lag time (137%-219%) and reduced thrombin peak (47%-76%) and velocity index (17%-44%) after 12 hours compared to baseline. Dabigatran showed prolongation of lag time to 133% and time to peak to 119%. All patients had residual antithrombotic activity, with reduced thrombin generation parameters 12 hours after DOAC intake compared to baseline and to the healthy control group. This effect remained significant in patients with low residual DOAC plasma levels less then 50 ng/mL. Conclusion Thrombin generation remains reduced 12 hours after DOAC intake. While thrombin peak is particularly modified by factor Xa inhibitors, all DOACs prolong the lag time and time to thrombin peak. In the setting of bleeding or urgent surgery, the automated thrombin generation assay may assist in decision making and antidote administration.Background The benefit of vitamin K antagonists depends on the time within the therapeutic range (TTR). A patient's previous TTR could be a factor in the decision to change the anticoagulation regimen. However, the predictive value of a previous TTR for a future TTR is not well established, nor is it clear which TTR should prompt action. Objectives To investigate the predictive performance of a TTR and identify a threshold below which no recovery of TTR should be expected. Patients/methods From 18 031 patients who used acenocoumarol in a first-line anticoagulation clinic, a TTR was calculated over multiple periods of 90, 180, and 365 days each. We assessed the correlation between baseline and later TTR and the separation between groups by quintile of baseline TTR. We describe the proportion of patients who obtain a TTR≥ 70% conditional on baseline TTR. Results The correlation between baseline and later TTR was 0.25 (95% confidence interval [CI], 0.24-0.26), 0.27 (95% CI, 0.26-0.28) and 0.34 (95% CI, 0.32-0.35) for analyses over 90, 180, and 365 days. Corresponding c statistics for discrimination by baseline group were 0.60, 0.61, and 0.63. The probability to obtain a TTR ≥70% increased with baseline TTR from 42% with a baseline TTR of 50%-65% when TTR was 100% (TTR calculated over 180 days). Conclusions We conclude that a current TTR hardly predicts a future TTR. Physicians and patients should deliberate together which probabilities to accept, take measures to improve TTR, and consider potential alternatives.Background In patients with a venous outflow obstruction following iliofemoral deep vein thrombosis stenting of the venous tract to prevent or alleviate postthrombotic syndrome is applied with increasing frequency. The impact of the quality of anticoagulant therapy with vitamin K antagonists (VKAs) on the development of in-stent thrombosis is currently unknown. Objectives To determine the association between the quality of postinterventional VKA treatment and the occurrence of in-stent thrombosis. Methods Seventy-nine patients with iliofemoral and/or caval venous stent placement for obstruction of the venous outflow were included in this study. All patients received postinterventional VKA. The quality of VKA anticoagulant therapy was expressed as the time within therapeutic range (TTR) calculated using the linear interpolation method and as the proportion of International Normalized Ratio (INR) values less then 2.0. In-stent thrombosis was assessed by the use of duplex ultrasound. Survival analysis (Kaplan-Meier curves, Cox regression) was used to analyze the data. Results In-stent thrombosis developed in 16 patients (20.3%). The total population had a mean TTR of 64.0% (±19.0) and a mean proportion of INR values less then 2.0 of 11.6% (±12.0). Overall, a TTR less then 49.9% was associated with an increased risk of in-stent thrombosis. The multivariable adjusted analysis showed a hazard ratio (HR) of 0.96 (95% confidence interval [CI], 0.92-0.99; P = .02) per 1% increase in TTR. The proportion of INR values less then 2.0 had no significant association with the occurrence of in-stent thrombosis HR 0.98 (95% CI, 0.91-1.06; P = .66). Conclusions We conclude that the quality of anticoagulant treatment reflected in the TTR following a venous stenting procedure is an important independent determinant for the risk of in-stent thrombosis. The role of anticoagulant treatment for the prevention of in-stent thrombosis following stenting procedures therefore merits further research.Background Many patients who used vitamin K antagonists (VKAs) for long-term prevention of thromboembolism are now actively switched to a direct oral anticoagulant (DOAC). Strict adherence to a DOAC is crucial for its success. However, therapy adherence and clinical factors that predict nonadherence are currently not well studied among patients who switched from a VKA to a DOAC. Methods A questionnaire was developed and sent to 2920 former patients of 3 anticoagulation clinics in the Netherlands, who switched from a VKA to a DOAC between January 2016 and December 2017. Questions concerned demographics, treatment persistence, adherence, and the occurrence of bleeding or thromboembolic events on DOACs. To identify predictors for nonadherence, logistic regression models were used to estimate crude and age/sex-adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs). Results A total of 1399 questionnaires (response rate 48%) were used for analysis. DOAC treatment persistence (94%) and adherence (86%) rates were high.