المؤلفون: Qiao, Jesse, Tran, Minh-Ha

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Hematology, Patient Safety, Humans, Administration, Oral, Anticoagulants, Drug Monitoring, Factor Xa Inhibitors, Blood Coagulation Tests, anticoagulants, bleeding reversal, coagulation, direct oral anticoagulants, direct thrombin inhibitor, rivaroxaban, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology

الوصف: Direct oral anticoagulants (DOACs) exert anticoagulation effect by directly inhibiting Factor Xa (rivaroxaban, apixaban, and edoxaban) or thrombin (dabigatran). Though DOACs are characterized by fixed-dose prescribing and generally do not require routine laboratory drug-level monitoring (DLM), circumstances may arise where the DLM may aid in clinical decision-making, including DOAC dose adjustment, anticoagulant class change, or decisions to withhold or administer reversal agents. We review the current literature that describes high-risk patient groups in which DLM may be beneficial for improved patient anticoagulation management and stewardship. The review also summarizes the limitations of conventional coagulation testing and discuss the emerging utility of quantitative methods for routine and rapid emergent evaluation of DOAC drug levels-in particular, the Anti-Xa activity to detect Factor Xa Inhibitors (rivaroxaban, apixaban, and edoxaban). Both technical and regulatory barriers to widespread DLM implementation are limiting factors to further clinical research that must be overcome, in order to propose universal DOAC DLM strategies and provide clinical-laboratory correlation to formally classify high-risk patient groups.

الوصول الحر: https://escholarship.org/uc/item/8fr1m05dTest

المؤلفون: Michael, Neethu, Grigoryan, Mher Mahoney, Kilday, Kelley, Sumbria, Rachita K, Vasilevko, Vitaly, van Ryn, Joanne, Cribbs, David H, Paganini-Hill, Annlia, Fisher, Mark J

المصدر: Frontiers in Neurology. 10(SEP)

مصطلحات موضوعية: Biological Psychology, Biomedical and Clinical Sciences, Psychology, Brain Disorders, Prevention, Stroke, Dementia, Aging, Hematology, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Acquired Cognitive Impairment, Neurodegenerative, Neurosciences, aging, cerebral amyloid angiopathy, cerebral microhemorrhage, dabigatran, direct thrombin inhibitor, intracerebral hemorrhage, Cerebral amyloid angiopathy, Cerebral microhemorrhage, Dabigatran, Direct thrombin inhibitor, Intracerebral hemorrhage, bibr 1048 ms, claudin 5, dabigatran etexilate, eosin, ferric ferrocyanide, fibrinogen, glial fibrillary acidic protein, hematoxylin, immunoglobulin G, intercellular adhesion molecule 1, aged, animal experiment, animal model, animal tissue, anticoagulation, Article, biochemistry, blood brain barrier, cell activation, chemical parameters, controlled study, drug blood level, female, male, mouse, nonhuman, staining, thrombin time, vascular amyloidosis, Clinical Sciences, Clinical sciences, Biological psychology

الوصف: Oral anticoagulants are a critical component of stroke prevention, but carry a risk of brain hemorrhage. These hemorrhagic complications tend to occur in elderly individuals, especially those with predisposing conditions such as cerebral amyloid angiopathy (CAA). Clinical evidence suggests that non-vitamin K antagonist oral anticoagulants are safer than traditional oral anticoagulants. We analyzed whether the anticoagulant dabigatran produces cerebral microhemorrhage (the pathological substrate of MRI-demonstrable cerebral microbleeds) or intracerebral hemorrhage in aged mice with and without hemorrhage-predisposing angiopathy. We studied aged (22 months old) Tg2576 (a model of CAA) and wild-type (WT) littermate mice. Mice received either dabigatran etexilate (DE) (Tg N = 7; WT N = 10) or vehicle (Tg N = 9; WT N = 7) by gavage for 4 weeks. Anticoagulation effects of DE were confirmed using thrombin time assay. No mice experienced intracerebral hemorrhage. Cerebral microhemorrhage analysis, performed using Prussian-blue and H&E staining, showed no significant change in either number or size of cerebral microhemorrhage in DE-treated animals. Analysis of biochemical parameters for endothelial activation (ICAM-1), blood-brain barrier disruption (IgG, claudin-5, fibrinogen), microglial activation (Iba-1), or astrocyte activation (GFAP) showed neither exacerbation nor protective effects of DE in either Tg2576 or WT mice. Our study provides histological and biochemical evidence that aged mice, with or without predisposing factors for brain hemorrhage, tolerate anticoagulation with dabigatran. The absence of dabigatran-induced intracerebral hemorrhage or increased frequency of acute microhemorrhage may provide some reassurance for its use in high-risk patient populations.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/70z5r6n7Test

المؤلفون: Hillarp, Andreas, Strandberg, Karin, Gustafsson, Kerstin, Lindahl, Tomas

المصدر: Journal of Thrombosis and Haemostasis. 18(8):1866-1873

مصطلحات موضوعية: dilute Russells viper venom time, direct thrombin inhibitor, direct Xa inhibitor, lupus anticoagulant, phosphatidylserine

الوصف: Introduction Dilute Russell viper venom time (dRVVT) assays can be affected by direct oral anticoagulants (DOACs), which may cause false-positive results. However, there are conflicting results indicating significant differences between different reagents and DOACs. Objectives To evaluate the effect of DOACs on dRVVT assays. Material and Methods Samples were prepared by adding DOAC (dabigatran, rivaroxaban, apixaban, or edoxaban) to pooled normal plasma in the concentration range 0 to 800 mu g/L. Six integrated dRVVT reagents were used, all composed of a screen assay (low phospholipid content) and a confirm assay (high phospholipid content). The screen/confirm dRVVT results were expressed as normalized ratios. To further evaluate the observed differences between tests and DOACs, addition of synthetic phospholipids was used. Results The dRVVT ratios increased dose dependently for all DOACs, with four of the six tests and the DOAC rivaroxaban having the greatest effect. With one test, the ratios were almost unaffected with increasing DOAC concentration, whereas another test revealed a negative dose dependency for all DOACs. Variable DOAC effects can be explained by different effects on dRVVT screen and confirm clotting time. Adding synthetic phospholipids to samples containing rivaroxaban resulted in greatly reduced screen clotting times and thereby lower calculated dRVVT ratios. Conclusions There is a great variability in the dRVVT test result with different DOACs. The dRVVT ratios are unaffected for some reagents and this can be explained by an equal dose-dependent effect on both screen and confirm assays. The phospholipid type and content of the different reagents may contribute to the observed differences.

وصف الملف: electronic

الوصول الحر: https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-167737Test
https://liu.diva-portal.org/smash/get/diva2:1454946/FULLTEXT01.pdfTest

المؤلفون: Philipp Groene, Jennifer Butte, Sarah Thaler, Klaus Görlinger, Simon T. Schäfer

المصدر: Thrombosis Journal, Vol 20, Iss 1, Pp 1-9 (2022)

مصطلحات موضوعية: Direct-acting oral anticoagulants, Direct factor Xa inhibitors, Thromboelastometry, Direct thrombin inhibitor, Diseases of the blood and blood-forming organs, RC633-647.5

الوصف: Abstract Background The detection of direct oral anticoagulants (DOACs) is still challenging but important in emergency patients. We recently demonstrated that modified thromboelastometry can detect rivaroxaban and dabigatran. Data on the detection rates of modified compared to standard thromboelastometric tests of apixaban and edoxaban, are missing. The aim of this in-vitro dose-effect-study was to add data on these DOACs and to evaluate thromboelastometric tests in-vitro using data of both studies. Methods The study was approved by the Ludwig-Maximilians-University ethics committee (No 17-525-2). Written informed consent was obtained from all individuals. Blood samples of healthy volunteers and samples of 10 volunteers for each DOAC were used. Blood samples were spiked with six different concentrations of edoxaban and apixaban (0ng/ml; 31.25ng/ml; 62.5ng/ml; 125ng/ml; 250 ng/ml; 500ng/ml). Modified tests (low-tissue-factor test TFTEM and ecarin-based test ECATEM) as well as standard tests (e.g. FIBTEM) analyzing extrinsic pathway of coagulation were used. Receiver operating characteristics analyzes were performed as well as regression analyzes. Results TFTEM CT correlated well with anti-Xa levels of apixaban and edoxaban (apixaban: r 2 = 0.8064 p 30 ng/mL) was successful with FIBTEM CT with a sensitivity and specificity of 81% and 90%, respectively. As expected, ECATEM CT was not prolonged by direct FXa-inhibitors due to its specificity for direct thrombin inhibitors. Again, TFTEM CT provided the highest sensitivity and specificity for the detection of direct FXa inhibitors with 96% and 95%, respectively. ECATEM test showed 100% sensitivity and 100% specificity for the detection of dabigatran. Conclusions Our study presents modified thromboelastometric tests with improved detection of even low DOAC concentrations > 30 ng/mL, including apixaban in-vitro. The study thus complements the previously published data on dabigatran and rivaroxaban. Validation studies must confirm the results due to the explanatory design of this study.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1477-9560Test

الوصول الحر: https://doaj.org/article/1c5a4927474748179bdea16de4cb851fTest

المؤلفون: Carlos A. Valdes, Omar M. Sharaf, Mark S. Bleiweis, Jeffrey P. Jacobs, Mohammed Mumtaz, Ramy M. Sharaf, Eric I. Jeng, Giles J. Peek

المصدر: Frontiers in Medicine, Vol 10 (2023)

مصطلحات موضوعية: anticoagulation, bivalirudin, extracorporeal membrane oxygenation (ECMO), pediatric, direct thrombin inhibitor, Medicine (General), R5-920

الوصف: IntroductionOptimal anticoagulation therapy is essential for the prevention of thrombotic and hemorrhagic complications in pediatric patients supported with extracorporeal membrane oxygenation (ECMO). Recent data have demonstrated bivalirudin has the potential to surpass and replace heparin as the anticoagulant of choice.MethodsWe conducted a systematic review comparing the outcomes of heparin-based versus bivalirudin-based anticoagulation in pediatric patients supported on ECMO to identify the preferred anticoagulant to minimize bleeding events, thrombotic complications, and associated mortality. We referenced the PubMed, Cochrane Library, and Embase databases. These databases were searched from inception through October 2022. Our initial search identified 422 studies. All records were screened by two independent reviewers using the Covidence software for adherence to our inclusion criteria, and seven retrospective cohort studies were identified as appropriate for inclusion.ResultsIn total, 196 pediatric patients were anticoagulated with heparin and 117 were anticoagulated with bivalirudin while on ECMO. Across the included studies, it was found that for patients treated with bivalirudin, trends were noted toward lower rates of bleeding, transfusion requirements, and thrombosis with no difference in mortality. Overall costs associated with bivalirudin therapy were lower. Time to therapeutic anticoagulation varied between studies though institutions had different anticoagulation targets.ConclusionBivalirudin may be a safe, cost-effective alternative to heparin in achieving anticoagulation in pediatric ECMO patients. Prospective multicenter studies and randomized control trials with standard anticoagulation targets are needed to accurately compare outcomes associated with heparin versus bivalirudin in pediatric ECMO patients.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fmed.2023.1137134/fullTest; https://doaj.org/toc/2296-858XTest

الوصول الحر: https://doaj.org/article/0bfdb9cff63449c4b0e53d2454be49e9Test

المؤلفون: Helin, Tuukka A., Pakkanen, Anja, Lassila, Riitta, Joutsi-Korhonen, Lotta

المساهمون: Medicum, Department of Clinical Chemistry and Hematology, Clinicum, Department of Diagnostics and Therapeutics, Hematologian yksikkö

مصطلحات موضوعية: DIRECT THROMBIN INHIBITOR, NONVALVULAR ATRIAL-FIBRILLATION, FACTOR XA INHIBITOR, DABIGATRAN ETEXILATE, PROTHROMBIN TIME, STROKE PREVENTION, IN-VITRO, RIVAROXABAN, ASSAYS, REVERSAL, 3141 Health care science, 3121 General medicine, internal medicine and other clinical medicine

الوصف: Peer reviewed

وصف الملف: application/pdf

العلاقة: Boehringer Ingelheim Finland and Bayer Schering Pharma Finland (study samples).; Helin , T A , Pakkanen , A , Lassila , R & Joutsi-Korhonen , L 2013 , ' Laboratory Assessment of Novel Oral Anticoagulants: Method Suitability and Variability between Coagulation Laboratories ' , Clinical Chemistry (Washington, DC) , vol. 59 , no. 5 , pp. 807-814 . https://doi.org/10.1373/clinchem.2012.198788Test; ORCID: /0000-0002-5273-8088/work/150714093; 84876943998; 44887c06-ea3e-4b6d-b3c6-d52e530ad24e; http://hdl.handle.net/10138/567611Test; 000321547700016

الإتاحة: http://hdl.handle.net/10138/567611Test

المؤلفون: Jiang, Fang, Ju, Chengsheng, Guo, Chuan-Guo, Cheung, Ka Shing, Li, Bofei, Law, Simon YK, Lau, Cheuk Yin, Leung, Wai K

المصدر: Helicobacter , 28 (4) , Article e12990. (2023)

مصطلحات موضوعية: direct thrombin inhibitor, factor Xa inhibitor, gastrointestinal bleeding

الوصف: Background: To investigate risks of hospitalization for upper gastrointestinal bleeding (UGIB) in H. pylori-eradicated patients newly started on warfarin or direct oral anti-coagulants (DOACs). Methods: We identified all patients who had previously received H. pylori eradication therapy or were found to have no H. pylori on endoscopy and were then newly started on warfarin or DOACs from a population-based electronic healthcare database. Primary analysis was the risk of UGIB between warfarin and DOACs users in H. pylori-eradicated patients. Secondary analysis included the UGIB risk between H. pylori-eradicated and H. pylori-negative patients who were newly started on warfarin or DOACs. The hazard ratio (HR) of UGIB was approximated by pooled logistic regression model incorporating the inverse propensity of treatment weightings with time-varying covariables. Results: Among H. pylori-eradicated patients, DOACs had a significantly lower risk of UGIB (HR: 0.26, 95% CI 0.09–0.71) compared with warfarin. In particular, lower UGIB risks with DOACs were observed among older (≥65 years) patients, female, those without a history of UGIB or peptic ulcer, or ischemic heart disease, and non-users of acid-suppressive agents or aspirin. Secondary analysis showed no significant difference in UGIB risk between H. pylori-eradicated and H. pylori-negative patients newly started on warfarin (HR: 0.63,95% CI 0.33–1.19) or DOACs (HR: 1.37, 95% CI 0.45–4.22). Conclusions: In H. pylori-eradicated patients, new users of DOACs had a significantly lower risk of UGIB than new warfarin users. Furthermore, the risk of UGIB in new warfarin or DOACs users was comparable between H. pylori-eradicated and H. pylori-negative patients.

وصف الملف: text

العلاقة: https://discovery.ucl.ac.uk/id/eprint/10169978/19/Lau_Helicobacter%20-%202023%20-%20Jiang%20-%20Risk%20of%20hospitalization%20for%20upper%20gastrointestinal%20bleeding%20in%20Helicobacter%20pylori%20eradicated.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10169978Test/

الإتاحة: https://discovery.ucl.ac.uk/id/eprint/10169978/19/Lau_Helicobacter%20-%202023%20-%20Jiang%20-%20Risk%20of%20hospitalization%20for%20upper%20gastrointestinal%20bleeding%20in%20Helicobacter%20pylori%20eradicated.pdfTest
https://discovery.ucl.ac.uk/id/eprint/10169978Test/

المؤلفون: Etienne Revelly, Emmanuelle Scala, Lorenzo Rosner, Valentina Rancati, Ziyad Gunga, Matthias Kirsch, Zied Ltaief, Marco Rusca, Xavier Bechtold, Lorenzo Alberio, Carlo Marcucci

المصدر: Journal of Clinical Medicine; Volume 12; Issue 3; Pages: 786

مصطلحات موضوعية: cardiac surgery, cardiopulmonary bypass, intraoperative management, heparin-induced thrombocytopenia syndrome, direct thrombin inhibitor, antiplatelet therapy

الوصف: Heparin-induced thrombocytopenia (HIT) is a major issue in cardiac surgery requiring cardiopulmonary bypass (CPB). HIT represents a severe adverse drug reaction after heparin administration. It consists of immune-mediated thrombocytopenia paradoxically leading to thrombotic events. Detection of antibodies against platelets factor 4/heparin (anti-PF4/H) and aggregation of platelets in the presence of heparin in functional in vitro tests confirm the diagnosis. Patients suffering from HIT and requiring cardiac surgery are at high risk of lethal complications and present specific challenges. Four distinct phases are described in the usual HIT timeline, and the anticoagulation strategy chosen for CPB depends on the phase in which the patient is categorized. In this sense, we developed an institutional protocol covering each phase. It consisted of the use of a non-heparin anticoagulant such as bivalirudin, or the association of unfractionated heparin (UFH) with a potent antiplatelet drug such as tirofiban or cangrelor. Temporary reduction of anti-PF4 with intravenous immunoglobulins (IvIg) has recently been described as a complementary strategy. In this article, we briefly described the pathophysiology of HIT and focused on the various strategies that can be applied to safely manage CPB in these patients.

وصف الملف: application/pdf

العلاقة: Intensive Care; https://dx.doi.org/10.3390/jcm12030786Test

الإتاحة: https://doi.org/10.3390/jcm12030786Test

المؤلفون: Eiji Nyuta, Jiro Ueno, Masao Takemoto, Takuya Tsuchihashi, Togo Sakai, Tokushi Koga, Yoshibumi Antoku

المصدر: Internal Medicine. 2022, 61(18):2747

المؤلفون: Zhiyan Liu, Guangyan Mu, Qiufen Xie, Hanxu Zhang, Jie Jiang, Qian Xiang, Yimin Chen

مصطلحات موضوعية: Atrial Fibrillation, Cardiology and Cardiovascular Medicine, Medicine, Health Sciences, Thrombosis and Coagulation Disorders, Hematology, Heparin-Induced Thrombocytopenia and Thrombosis, Surgery, Dabigatran, Direct thrombin inhibitor, Therapeutic drug monitoring, High-performance liquid chromatography, Population, Chromatography, Pharmacology, Internal medicine, Chemistry, Warfarin, Pharmacokinetics, Atrial fibrillation, Environmental health

الوصف: Dabigatran concentrations monitoring are gaining importance of special situations, but limited data are available for the expected peak and trough levels. The hemoclot thrombin inhibitor (HTI) is dabigatran-calibrated quantitative determination of dabigatran concentration. This study aims to validate HTI assay as the quantification choice of dabigatran, and providing the expected peak and trough levels.This is a multi-center methodology validate study, including seven hospitals from Beijing, Shanghai, Henan, Hunan, Chongqing, and Fujian. We retrospectively analyzed plasma samples taken from 118 healthy subjects and 183 patients receiving dabigatran. Dabigatran concentrations were measured with HTI assay and high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Linear regression, Spearman correlation and Bland-Altman analysis were used in this study.The mean concentration ratio of HPLC-MS/MS and HTI assays was 1.03 and 0.98 at 2 and 12 h, and the acceptance ranges for both the ratio ... : تكتسب مراقبة تركيزات الدابيجاتران أهمية في المواقف الخاصة، ولكن تتوفر بيانات محدودة عن مستويات الذروة والقاع المتوقعة. مثبط الثرومبين للهيموكلوت (HTI) هو التحديد الكمي المعاير للدابيجاتران لتركيز الدابيجاتران. تهدف هذه الدراسة إلى التحقق من صحة اختبار HTI باعتباره خيار القياس الكمي لـ dabigatran، وتوفير مستويات الذروة والقاع المتوقعة. هذه دراسة تحقق من صحة منهجية متعددة المراكز، بما في ذلك سبعة مستشفيات من بكين وشنغهاي وخنان وهونان وتشونغتشينغ وفوجيان. قمنا بتحليل عينات البلازما بأثر رجعي مأخوذة من 118 شخصًا سليمًا و 183 مريضًا يتلقون الدابيجاتران. تم قياس تركيزات الدابيجاتران باستخدام اختبار HTI والاستشراب السائل عالي الأداء - قياس الطيف الكتلي الترادفي (HPLC - MS/MS). تم استخدام الانحدار الخطي وارتباط سبيرمان وتحليل بلاند- ألتمان في هذه الدراسة. كان متوسط نسبة التركيز لمقايسات HPLC - MS/MS و HTI 1.03 و 0.98 عند 2 و 12 ساعة، وتم استيفاء نطاقات القبول لكل من حد النسبة وكذلك حد الاتفاق، مما يشير إلى اتفاق جيد بين تركيزات البلازما المشتقة من HTI و HPLC - MS/MS. كان النطاق المرجعي للكشف عن جرعة واحدة من ...

العلاقة: https://dx.doi.org/10.60692/5cfpr-56x47Test

الإتاحة: https://doi.org/10.60692/wj85t-jx14010.60692/5cfpr-56x47Test