A Liaison between Sudden Sensorineural Hearing Loss and SARS-CoV-2 Infection

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Performance of a Qualitative Point-of-Care Strip Test to Detect DOAC Exposure at the Emergency Department:A Cohort-Type Cross-Sectional Diagnostic Accuracy Study

An accurate point-of-care test for detecting effective anticoagulation by direct oral anticoagulants (DOACs) in emergencies is an unmet need. We investigated the accuracy of a urinary qualitative strip test (DOAC Dipstick) to detect relevant DOAC exposure in patients who presented to an emergency department. In this prospective single-center cohort-type cross-sectional study, adults on DOAC treatment were enrolled. We assessed clinical sensitivity and specificity of DOAC Dipstick factor Xa and thrombin inhibitor pads to detect DOAC plasma levels ≥30 ng/mL using urine samples as the testing matrix. Liquid chromatography coupled with tandem-mass spectrometry was used as the reference standard method for plasma and urine measurement of DOAC concentrations. Of 293 patients enrolled, 265 patients were included in the analysis, of whom 92 were treated with rivaroxaban, 65 with apixaban, 77 with edoxaban, and 31 with dabigatran. The clinical sensitivity and specificity of the dipstick on urine samples to detect ≥30 ng/mL dabigatran plasma levels were 100% (95% confidence interval [CI]: 87–100%) and 98% (95% CI: 95–99%), respectively. The sensitivity and specificity of the dipstick to detect ≥30 ng/mL factor Xa inhibitor plasma levels were 97% (95% CI: 94–99%) and 69% (95% CI: 56–79%), respectively. The DOAC Dipstick sensitively identified effective thrombin and factor Xa inhibition in a real-world cohort of patients presenting at an emergency department. Therefore, the dipstick might provide a valuable test to detect relevant DOAC exposure in emergencies, although further studies will be needed to confirm these findings

Determination of rivaroxaban by different factor Xa specific chromogenic substrate assays: reduction of interassay variability

Rivaroxaban and other oral direct factor Xa inhibitors (ODiXa) are currently developed for prophylaxis and treatment of thromboembolic diseases using fixed doses. Although routine monitoring is not required, assessing the intensity of anticoagulation may be useful under certain clinical conditions. ODiXa prolong coagulation times of several clotting assays and, thus, their concentration may be determined in factor Xa specific chromogenic substrate assays. So far, no standardized and validated assay is commercially available. Here, five methods (A through E) are studied and optimized to reduce interassay variability. Human pooled plasma was spiked by a serial dilution of rivaroxaban (25–900 ng/ml). The release of para-nitroaniline from the chromogenic substrates was measured by the optical density (OD) at 405 nm. Method B was identified to yield the lowest sum of deviations from the mean value of the OD concentration curve calculated from all assays. Spline functions were developed for OD versus concentration curves for all methods. The calculated OD versus concentration curves overlapped for all methods. The coefficient of variation for all assays and concentrations of rivaroxaban decreased from 25.3 ± 11.4% using the original data to 3.8 ± 2.2% using the calculated data (P < 0.0001). The robustness of the chromogenic assay (method B) remains to be corroborated in interlaboratory comparisons

Monitoring of Anticoagulant Effects of Direct Thrombin Inhibitors

ABSTRACT Monitoring of direct thrombin inhibitors with the activated partial thromboplastin time (aPTT) is limited by poor linearity and reproducibility. Recently, direct prothrombin activation methods have been developed for coagulation analysis: ecarin clotting time (ECT) and prothrombinase-induced clotting time (PiCT). Laboratory monitoring of the direct thrombin inhibitors lepirudin, argatroban, and melagatran was analyzed and compared with monitoring unfractionated heparin (UFH). Plasma samples of six healthy donors were spiked with lepirudin and argatroban extending to 3000 ng/mL, melagatran extending to 1000 ng/mL, and UFH up to 0.48 IU/mL. Clotting times of aPTT (two reagents), ECT, PiCT, and prothrombin time were determined in a KC 10a micro instrument. At 3000 ng/mL ECT values were 339.1 Ϯ 25.0 seconds with lepirudin and 457.5 Ϯ 29.5 seconds with argatroban. ECT was 586.0 Ϯ 38.2 seconds with 1000 ng/mL melagatran. The PiCT method provided clotting times of 137.0 Ϯ 8.4 seconds with UFH, 128.0 ± 23.4 seconds with lepirudin, and 151 ± 23.9 seconds with argatroban, and 153.5 Ϯ 9.9 seconds with melagatran, with the concentrations mentioned. ECT is more sensitive to therapeutic drug concentration ranges than aPTT (prolongations of 3-7 versus 2-3). PiCT provides results that are comparable with direct thrombin inhibitors and UFH. This method could therefore be suitable for monitoring both drug groups. KEYWORDS: Thrombin inhibitors, ecarin clotting time, prothrombinase-induced clotting time, hirudin, argatroban, melagatran Objectives: Upon completion of this article, the reader should be able to (1) appreciate the rationale for developing direct thrombin inhibitors and (2) judge which laboratory tests are most useful in monitoring these compounds. Accreditation: Tufts University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. TUSM takes full responsibility for the content, quality, and scientific integrity of this continuing education activity. Credit: Tufts University School of Medicine designates this education activity for a maximum of 1.0 hours credit toward the AMA Physicians Recognition Award in category one. Each physician should claim only those hours that he/she actually spent in the educational activity

The Dangerous Liaisons between Chronic Obstructive Pulmonary Disease and Venous Thromboembolism

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Does Chronic Treatment with Oral Anticoagulants Ameliorate the Clinical Course of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Coronavirus Disease 2019 (COVID-19)?

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A multi-center, prospective, open-label, 8-week study of certoparin for anticoagulation during maintenance hemodialysis – the membrane study

Background Adequate anticoagulation is prerequisite for effective hemodialysis to prevent clotting in the extracorporeal circuit. We aimed providing first data on the efficacy and safety of the low-molecular-weight heparin certoparin in this setting. Methods Multicenter, open-label, 8-week trial. Patients received a single dose of 3,000 IU certoparin i.v. with additional titration steps of 600 IU and/or continuous infusion if necessary. Results 120 patients were screened, 109 enrolled (median age 71; range 26–90 years) and 106 available for efficacy analyses. The percentage of unsatisfactory dialysis results at 8 weeks due to clotting or bleeding, was 1.9% (n = 2/106; 95% confidence interval [CI] 0.23–6.65%); no major bleeding. 1.9% had moderate/severe clotting in the lines/bubble catcher and 2.8% in the dialyser at week 8. 15.7 ± 14.3% of the dialysis filters’ visual surface area was showing redness. In subgroups of patients receiving median doses of 3000 ± 0, 3000 (2400–6000) and 4200 (3000–6600) IU, plasma aXa levels at baseline, 4 and 8 weeks were 0.24 [95%CI 0.21–0.27], 0.33 [0.27–0.40] and 0.38 [0.33–0.45] aXa IU/ml at 2 h. $C_{48h}$ was 0.01 [0.01–0.02] aXa IU at all visits. At baseline and 4 weeks $AUC_{0-48h}$ was 2.66 [2.19–3.24] and 3.66 [3.00–4.45] aXa IU*h/ml. In 3.0% of dialyses (n = 83/2724) prolonged fistula compression times were documented. Eight patients (7.34%) had at least one episode of minor bleeding. 4) 85.3% of patients had any adverse event, 9.2% were serious without suspected drug relation; and in 32 patients a drug-relation was suspected. Conclusions Certoparin appears effective and safe for anticoagulation in patients undergoing maintenance hemodialysis

A Chromogenic and Fluorogenic Peptide Substrate for the Highly Sensitive Detection of Proteases in Biological Matrices

The synthesis and application of a novel type of chromogenic and fluorogenic substrate for protease detection is described. The outstanding performance of the tripeptide substrates is exemplified by specific fluorescence detection of thrombin and factor Xa at only 500 fM concentration. The substrate is also applicable to the sensitive detection of the thrombin inhibitor dabigatran in human plasma and whole blood samples, highlighting its potential for a point-of-care test for instant monitoring the blood levels of this blockbuster anticoagulant drug in specific clinical situations