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Thrombin generation in plasma from patients with cirrhosis supplemented with normal plasma: considerations on the efficacy of treatment with fresh-frozen plasma

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Abstract

Cirrhosis is characterized by a complex coagulation defect leading to the prolongation of the prothrombin and activated partial thromboplastin times (PT and APTT). Arbitrary PT cut-off values are still used as a yardstick to guide treatment with fresh-frozen plasma (FFP) or other pro-coagulant agents in patients undergoing invasive procedures. No randomized studies on the FFP efficacy are available, and are unlikely to be carried out because of their complex organization. An interim solution could be to evaluate the in vitro thrombin generation in plasmas from patients with cirrhosis when mixed with appropriate amounts of pooled normal plasma (PNP). The PT, APTT and thrombin generations in the presence of thrombomodulin were examined in 58 patients with cirrhosis and 24 healthy subjects both before and after mixing their plasmas with PNP at a proportion of 4 + 1 (patient + PNP), chosen to mimic in vivo conditions when patients are treated with 10 ml/kg of FFP. The PT and APTT, which were abnormal in the majority of unmixed patient plasmas were shortened considerably, but did not normalize completely when mixed with PNP. Thrombin generation, which was already within normal limits in all unmixed patient plasmas, remained essentially unchanged after mixing with PNP. In conclusion, thrombin generation in patients with cirrhosis does not appreciably change after in vitro addition of PNP despite PT and APTT shortening would suggest otherwise. These results question the validity of the PT as a stand-alone test to guide transfusion ofFFP in the setting of chronic liver disease.

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Authors and Affiliations

  1. Department of Internal Medicine and Medical Specialties, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Via Pace 9, 20122, Milan, Italy

    Armando Tripodi, Veena Chantarangkul, Marigrazia Clerici & Pier Mannuccio Mannucci

  2. Third Division of Gastroenterology, IRCCS Cà Granda Ospedale Maggiore Policlinico Foundation and Università degli Studi di Milano, Milan, Italy

    Massimo Primignani & Alessandra Dell’Era

  3. First Division of Gastroenterology, IRCCS Cà Granda Ospedale Maggiore Policlinico Foundation and Università degli Studi di Milano, Milan, Italy

    Alessio Aghemo

Authors
  1. Armando Tripodi
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  2. Veena Chantarangkul
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  3. Massimo Primignani
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  4. Marigrazia Clerici
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  5. Alessandra Dell’Era
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  6. Alessio Aghemo
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  7. Pier Mannuccio Mannucci
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Correspondence to Armando Tripodi.

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Tripodi, A., Chantarangkul, V., Primignani, M. et al. Thrombin generation in plasma from patients with cirrhosis supplemented with normal plasma: considerations on the efficacy of treatment with fresh-frozen plasma. Intern Emerg Med 7, 139–144 (2012). https://doi.org/10.1007/s11739-011-0528-4

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  • DOI: https://doi.org/10.1007/s11739-011-0528-4

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