Pharmacokinetics of degradation products of fibrin and fibrinogen during alteplase therapy of acute myocardial infarction |
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| Affiliation: | 1. Department of Anesthesiology, Perioperative Medicine and;2. Zhejiang Province Key Lab of Anesthesiology, The Second Affiliated Hospital and Yuying Children''s Hospital of Wenzhou Medical University, Wenzhou, China;3. Eye Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou, China;1. Department of Clinical Experimental Research, Glostrup Research Institute, Copenhagen University Hospital, Rigshospitalet, Glostrup, Denmark;2. Research Center for Ageing and Osteoporosis, Department of Clinical Biochemistry, Copenhagen University Hospital, Rigshospitalet, Glostrup, Denmark;3. Institute of Interdisciplinary Research, IRIBHM, Université Libre de Bruxelles, Gosselies, Belgium;4. Pôle des Laboratoires, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium;5. Institute of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Denmark;1. Department of Neurology, Shanghai Ninth People''s Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shangaï, China;2. Pôle Information Médicale Evaluation Recherche Hospices Civils de Lyon, Lyon, France and Université Lyon 1 et Equipe d''Accueil 4129 Lyon, France;3. Cerebrovascular Unit, Department of Neurology, Université Claude Bernard, Lyon, France;4. Laboratoire d''hématologie, CBPE, Hospices Civils de Lyon, Lyon, France |
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| Abstract: | Pharmacokinetics of fibrin degradation products (FbDP), D-dimers, fibrinogen degradation products (FgDP) and total degradation products (TDP) in plasma were investigated using ELISA methods in 12 patients undergoing therapy with alteplase (100 mg/3 h) for acute myocardial infarction. Peak concentrations of all degradation products occurred significantly later (1.6–2.5 h) than peak alteplase levels (2 min). Peak D-dimer concentrations (mean 2.6 μg/ml) were significantly lower than those of FbDP (7.1 μg/ml) or FgDP (7.8 μg/ml). However, the half-life of D-dimers (mean 13.3 h) was more than 4.5-fold longer than that of FbDP (2.9 h) or FgDP (2.8 h) (p<0.001). Consequently, areas under the plasma concentration-time curve (AUC) of D-dimers were comparable with those of FbDP or FgDP The ratios AUC(FbDP)/AUC(FgDP) and AUC(D-dimers)/AUC(FgDP) are proposed as new indices of fibrin specificity. Their values in this study (geometric mean, 95% CI) were 1.15 (0.60–2.20) and 1.30 (0.52–3.24) respectively. It is concluded that cross-linking may prolong the half-life of fibrin degradation products, and that complete time profiles of fibrin- and fibrinogen degradation products in plasma, rather than single point measurements, are essential for reliable quantification of fibrin specificity. |
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