Academic Journal

Calibrated automated thrombogram II: removing barriers for thrombin generation measurements

التفاصيل البيبلوغرافية
العنوان: Calibrated automated thrombogram II: removing barriers for thrombin generation measurements
المؤلفون: P. L. A. Giesen, A. J. W. Gulpen, R. van Oerle, H. ten Cate, M. Nagy, H. M. H. Spronk
المصدر: Thrombosis Journal, Vol 19, Iss 1, Pp 1-11 (2021)
بيانات النشر: BMC, 2021.
سنة النشر: 2021
المجموعة: LCC:Diseases of the blood and blood-forming organs
مصطلحات موضوعية: Thrombin generation, Calibrated automated thrombogram (CAT), ST®-Genesia, Direct oral anticoagulants (DOACS), Diseases of the blood and blood-forming organs, RC633-647.5
الوصف: Abstract Background Thrombin generation (TG) assessed by Calibrated Automated Thrombogram (CAT-I) reflects the overall capacity of plasma to generate thrombin, thus evaluating the balance between the anti- and procoagulant processes. However, with this method the calibrator curve is usually not measured until completion which has a severe impact on the calculation of the TG parameters, especially under conditions where almost all substrate is consumed. In addition, direct thrombin inhibitor (DTI) cannot be present in the calibration sample due to inhibition of the calibrator. We have developed a modified TG assay (CAT-II) and performed head-to-head comparison with the CAT-I method using the same fluorometer. Furthermore, we have compared our CAT-II method to a new automated TG instrument (ST®-Genesia) using the same calibration method. Methods TG was assessed with CAT-I and CAT-II using the same fulorometer and with ST®-Genesia in control plasma and plasma containing different anticoagulants (dabigatran, rivaroxaban, apixaban) and plasmas to which common interfering substances, bilirubin, hemoglobin and lipids were added. In CAT-I, calibration was against the same plasma containing calibrator in the presence of fluorogenic substrate (Z-GGR-AMC). In contrast, CAT-II method and ST®-Genesia used a standard concentration of thrombin in buffer and 7-amino-4-methylcoumarin (AMC) in a separate plasma sample for calibration. Results TG obtained from CAT-I using anticoagulant-free plasmas was lower compared with TG from CAT-II but both methods demonstrated an intra-assay variation less than 5% on all measured parameters. When comparing the two different calibration methods in the presence of different anticoagulants, a high correlation was seen in the presence of rivaroxaban and apixaban (R2 > 0.97), but not with dabigatran, a direct thrombin inhibitor. CAT-II method showed dose-dependent inhibition of TG in the presence of dabigatran, while CAT-I was not able to detect it. Both methods were able to correct for the interfering substances. Conclusions Our results showed high similarity between the results of CAT-I and CAT-II method when it is applied in control plasmas and plasmas not inhibited with a direct thrombin inhibitor. Furthermore, both the CAT-II method and ST-Genesia using the same calibration method were able to detect the effect of all oral anticoagulants. Taken together, applying a new calibration method is a significant improvement for monitoring patients on direct thrombin inhibitors while not introducing any bias to results obtained on other types of samples.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1477-9560
Relation: https://doaj.org/toc/1477-9560
DOI: 10.1186/s12959-021-00312-8
URL الوصول: https://doaj.org/article/4fe07f8926f849fc87c0d4668f37a7e6
رقم الانضمام: edsdoj.4fe07f8926f849fc87c0d4668f37a7e6
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:14779560
DOI:10.1186/s12959-021-00312-8