Effect of warfarin treatment on thrombin activatable fibrinolysis inhibitor (TAFI) activation and TAFI-mediated inhibition of fibrinolysis
Autor: | F. A. Scaraggi, F. Di Serio, Mario Colucci, Cosimo Carrieri, R. Galasso, Nicola Semeraro, B. Woodhams, Francesca Incampo |
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Rok vydání: | 2012 |
Předmět: |
Vitamin
Male medicine.medical_specialty Carboxypeptidase B2 Plasmin medicine.medical_treatment Administration Oral chemistry.chemical_compound Thrombin In vivo Nephelometry and Turbidimetry Predictive Value of Tests Internal medicine Fibrinolysis medicine Humans Fibrinolysin Aged Aged 80 and over Analysis of Variance alpha-2-Antiplasmin medicine.diagnostic_test Warfarin Anticoagulants Hematology Middle Aged In vitro Thromboelastography Peptide Fragments Thrombelastography Endocrinology chemistry Case-Control Studies Immunology Female Prothrombin Fibrin Clot Lysis Time Biomarkers circulatory and respiratory physiology medicine.drug |
Zdroj: | Journal of thrombosis and haemostasis : JTH. 11(2) |
ISSN: | 1538-7836 |
Popis: | Summary Background Severe clotting deficiencies are associated with enhanced in vitro fibrinolysis due to insufficient thrombin activatable fibrinolysis inhibitor (TAFI) activation. Because oral anticoagulant therapy (OAT) with warfarin causes a partial deficiency of vitamin K-dependent factors, its effect on clot lysability remains unclear. Objectives To evaluate plasma and blood fibrinolytic capacity in patients under stable OAT (n = 221) as compared with controls (n = 132). Methods Fibrinolysis resistance of plasma (turbidimetry) and blood (thromboelastography) clots was calculated as the lysis time of tissue factor-induced clots exposed to 30 and 100 ng mL−1 t-PA, respectively. Results Plasma PAI-1 was similar in the two groups, whereas TAFI was slightly lower in patients. OAT plasma clots lysed faster than controls (P = 0.001). The addition of the TAFIa inhibitor PTCI reduced lysis time by 14% in OAT and 34% in controls, and the difference between the groups disappeared. Similar data were obtained with blood clots. Thrombin and TAFIa generation in OAT plasma amounted to roughly 50% of controls, supporting a reduced thrombin-dependent TAFI activation. Clot resistance of OAT plasma was normalized by Ba-citrate plasma eluate or prothrombin but not by BaSO4 serum eluate, rFVIIa or FX. Surprisingly, circulating levels of TAFIa and its inactive derivative TAFIai were higher in warfarin patients (P |
Databáze: | OpenAIRE |
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