Dipartimento di Scienze Biomediche Sezione di Patologia Generale
Dipartimento di Scienze Biomediche, Sezione di Patologia Generale Università di Bari La Fibrinolisi Mario Colucci
t-PA PA I-2 Sistema Fibrinolitico u-PA a 2 -A P PAI-1 Plasminogeno Plasmina Fibrina FDP Mario Colucci
t-PA e u-PA t-PA Fibrinolisi Intravascolare Proteolisi Extravascolare − − Migrazione cellulare Angiogenesi Rimodellamento tessutale Invasione e matastatizzazione tumotale ? Mario Colucci
Sistema Fibrinolitico Intravascolare a 2 -A P t-PA Plasminogeno Plasmina Fibrina FDP Mario Colucci
Concentrazioni Emivita Origine plasmatiche Minuti Adipocita Giorni Plasminogeno Mario Colucci
t-PA e PAI-1 Stasi Epinefrina Vasopressina Ipoperfusione Mario Colucci
Fibrinolisi Fisiologica Mario Colucci
Alterazioni Fibrinolitiche e Metodi di studio Mario Colucci
Fibrinolytic Diseases Causing BLEEDING t-PA or u-PA increase Laboratory − Thrombolytic therapy − t-PA e u-PA assay: NO − Liver transplantation − TEG: suggested − APL − Trauma t-PA PAI-1 Cofactors a 2 -A P - FDP, FM - Annexin II Plasminogen Plasmin Degradation Fibrinogen Clotting Factors Mario Colucci
Fibrinolytic Diseases Causing BLEEDING Therapy Laboratory − Antifibrinolytics Tranexamic acid − PAI-1 assay: Difficult to interpret − α 2 -AP assay: Yes t-PA a 2 -A P PAI-1 Plasminogen Plasmin Mario Colucci
Fibrinolytic Changes Associated with THROMBOSIS Inherited Very few reports on t-PA or PAI-1 mutations associated with thrombosis Laboratory Plasminogen deficiency: no clear association with thrombosis − t-PA or PAI-1 assay useless − Plasminogen assay Acquired useful Reduced t-PA activity and/or increased PAI-1 in conditions associated with thrombosis Laboratory PAI-1 assay not recommended to calculate the risk Mario Colucci
Tromboelastografia TEG Mario Colucci
Tromboelastografia Persistenza Lisi Formazione Dimensioni e Compattezza ↓ Coagulazione ↓ Fibrinogeno ↑ Inibitori ↓ Piastrine Iperfibrinolisi Mario Colucci
The Fibrinolytic Process Do we know the whole story ? Mario Colucci
L’Emostasi Efficace 1. Rapida Formazione 2. Adeguate Dimensioni 3. Persistenza (resistenza alla Fibrinolisi) Mario Colucci
L’Emostasi Efficace 1. Rapida Formazione 2. Adeguate Dimensioni 3. Persistenza (resistenza alla Fibrinolisi) Mario Colucci
L’Emostasi Efficace a. Struttura fibrina 3. Persistenza (resistenza alla Fibrinolisi) Mario Colucci
L’Emostasi Efficace 3. Persistenza (resistenza alla Fibrinolisi) a. Struttura fibrina b. Cross-linking (FXIII) Trombina XIIIa Fibrina XIIIa Mario Colucci
L’Emostasi Efficace 3. Persistenza (resistenza alla Fibrinolisi) a. Struttura fibrina b. Cross-linking (FXIII) c. TAFI Mario Colucci
TAFI 3. Persistenza (resistenza alla Fibrinolisi) a. Struttura fibrina b. Cross-linking (FXIII) c. TAFI Inibizione Fibrinolisi Trombina Mario Colucci
Fibrinolytic resistance: The role of Thrombin Coagulation XIIIa Thrombin Clot Structure TAFIa ↓ Plasmin formation Mario Colucci
What Implications? • Do changes in thrombin generation resonate in the fibrinolytic process ? – Thrombophilia – Clotting deficiencies – Platelet diseases • Are anticoagulant drugs profibrinolytic ? • Can the fibrinolytic system be a therapeutic target in diseases other than those scored as “Fibrinolytic Diseases”? • Are TAFI inhibitors a new class of antithrombotic agents? Mario Colucci
- Slides: 22
