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GESTIONE DELLE EMORRAGIE MINORI E MAGGIORI

Progetto Formativo ANMCO - AIAC UNIVERSO TROMBOSI ROMPERE IL LEGAME TRA FIBRILLAZIONE ATRIALE & ICTUS CONSIGLI D’AUTORE. GESTIONE DELLE EMORRAGIE MINORI E MAGGIORI. 25 febbraio 2014 In collegamento con: Torino, Bergamo, Mestre, Bologna, Lucca, Roma, Napoli, Bari, Catania, Cagliari.

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GESTIONE DELLE EMORRAGIE MINORI E MAGGIORI

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  1. Progetto Formativo ANMCO - AIAC UNIVERSO TROMBOSI ROMPERE IL LEGAME TRA FIBRILLAZIONE ATRIALE & ICTUS CONSIGLI D’AUTORE GESTIONE DELLE EMORRAGIE MINORI E MAGGIORI 25 febbraio 2014 In collegamento con: Torino, Bergamo, Mestre, Bologna, Lucca, Roma, Napoli, Bari, Catania, Cagliari

  2. Major bleeding rates in the phase III trials with the new oral anticoagulants A. Majeed, 192 S. Schulman / Best Practice & Research Clinical Haematology 26 (2013) 191–202

  3. Non life-threatening bleeding - 1 • In addition to standard supportive measurements (mechanical compression, surgical haemostasis, fluid replacement, and other haemodynamic support), in view of the relatively short elimination half lives, time is the most important antidote of the NOACs • After cessation of treatment, restoration of haemostasis is to be expected within 12–24 h after the last dose, given plasma half-life of around 12 h for most NOACs. 2013 EHRA PRACTICAL GUIDE for NOACs, Europace (2013) 15, 625–651

  4. Non life-threatening bleeding - 2 • inquire about dosing regimen, exact time of last intake, factors influencing plasma concentrations (like P-gp therapy, chronic kidney disease), and other factors influencing haemostasis (like concomitant use of anti-platelet drugs or NSAIDs). • Blood volume repletion and restoration of normal platelet count (in case of thrombocytopenia ≤60.000/L) should be considered. 2013 EHRA PRACTICAL GUIDE for NOACs, Europace (2013) 15, 625–651

  5. Assessment of drug effect - 1 • For patients on dabigatran aPTT has a linear response to the drug concentration up to the therapeutic range, above which the response flattens out. • Therefore, aPTT is useful to assess if there is any significant concentration of dabigatran in the circulation but not to understand the extent of intoxication. • A normal aPTT essentially excludes dabigatran as the cause of bleeding. • For better understanding of therapeutic versus excessive levels of dabigatran a dilute thrombin time (Hemoclot) is required. A. Majeed, 192 S. Schulman / Best Practice & Research Clinical Haematology 26 (2013) 191–202

  6. Assessment of drug effect - 2 • A normal prothrombin time (PT) essentially excludes factor Xa inhibitors as the cause of bleeding. • For factor Xa inhibitors an anti-Xalevel using a test with the suspected drug as standard should be used. • Laboratory evaluation should be initiated simultaneously with the supportive measures. • Serum creatinine must be obtained even if the patient previously had normal renal function. Acute disease or hypovolemia can profoundly affect the renal function and reduce the elimination of the NOACs. A. Majeed, 192 S. Schulman / Best Practice & Research Clinical Haematology 26 (2013) 191–202

  7. Assessment of drug effect - 3 2013 EHRA PRACTICAL GUIDE for NOACs, Europace (2013) 15, 625–651

  8. General Management of Bleeding 2013 EHRA PRACTICAL GUIDE for NOACs, Europace (2013) 15, 625–651

  9. General Management of Bleeding 2013 EHRA PRACTICAL GUIDE for NOACs, Europace (2013) 15, 625–651

  10. General hemostatic agents • In the absence of specific antidotes, general hemostatic agents can be used to reverse the anticoagulant effects of NOACs. • Prothrombin complex concentrates (PCCs) contain inactive factor II, IX, X and VII. There is also an activated PCC (APCC) that in addition contains small amounts of these factors in active form.

  11. Available Evidence for NOACs Reversal by PCC and aPCC Liew A, Can J Cardiol 2013; 29: S34-S44

  12. Reversal strategies and pharmacologic characteristics of the currently available anticoagulants Liew A, Can J Cardiol 2013; 29: S34-S44

  13. Conclusioni • Non sono al momento disponibili antidoti specifici per i singoli NAO. Tali agenti sono, tuttavia, in avanzata fase di sviluppo. • L’effetto anticoagulante dei NAO tende a risolversi rapidamente in rapporto alle loro caratteristiche farmacocinetiche (emivita breve), che sono simili a quelle delle eparine a basso peso molecolare (anche esse prive di antidoti specifici). • In caso di necessità l’effetto dei NAO può essere comunque antagonizzato mediante i complessi protrombinici - aPCC preferibile per il Dabigatran, PCC preferibile per gli inibitori del fattore Xa.

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