title: Thrombin generation in plasma from patients with cirrhosis supplemented with normal plasma: considerations on the efficacy of treatment with fresh-frozen plasma.
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 of FFP in the setting of chronic liver disease.
authors.affiliation: Department of Internal Medicine and Medical Specialties, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Via Pace 9, 20122, Milan, Italy. armando.tripodi@unimi.it
authors.forename: Armando
authors.initials: A
authors.lastname: Tripodi
authors.forename: Veena
authors.initials: V
authors.lastname: Chantarangkul
authors.forename: Massimo
authors.initials: M
authors.lastname: Primignani
authors.forename: Marigrazia
authors.initials: M
authors.lastname: Clerici
authors.forename: Alessandra
authors.initials: A
authors.lastname: Dell'era
authors.forename: Alessio
authors.initials: A
authors.lastname: Aghemo
authors.forename: Pier Mannuccio
authors.initials: PM
authors.lastname: Mannucci
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016913:Blood Component Transfusion / Q000379:methods*; D016022:Case-Control Studies; D002908:Chronic Disease; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood* / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D010949:Plasma; D011517:Prothrombin Time; D012016:Reference Values; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D013048:Specimen Handling; D018709:Statistics, Nonparametric; D013917:Thrombin / Q000096:biosynthesis*
chemical_list: D013917:Thrombin