title: Thrombin generation in patients with cirrhosis: the role of platelets.
abstract: Coagulation factor defects, thrombocytopenia, and thrombocytopathy are associated with cirrhosis. However, bleeding in patients who have cirrhosis does not entirely correlate with abnormal coagulation tests. Recently, it was shown that because of the concomitant abnormalities of the procoagulant and anticoagulant drives, thrombin generation in plasma patients with cirrhosis is normal when assessed with assays that include thrombomodulin (the main protein C activator). However, thrombin is also generated in vivo as a function of platelets, suggesting that thrombocytopenia and thrombocytopathy might affect thrombin generation in patients with cirrhosis. We addressed this issue using an assay that accounts for the contribution of plasma and platelets. The study showed that platelet-rich plasma with platelets adjusted by dilution of autologous platelet-rich into autologous platelet-poor plasma to a standard count (100 x 10(9)/L) generates as much thrombin in patients with cirrhosis as in controls (1,063 nmol/L vs. 1,167 nmol/L; P value not significant). When platelets were adjusted to correspond to whole-blood counts, patients with cirrhosis generated significantly less thrombin than controls (949 nmol/L vs. 1,239 nmol/L; P < .001). Furthermore, thrombin generation correlated with platelet numbers (rho = 0.50; P < .001). In addition, the amount of thrombin generated as a function of the whole-blood patients' platelet counts increased significantly when the numbers were adjusted to 100 x 10(9)/L (953 nmol/L vs.1,063 nmol/L; P < .001). In conclusion, severe thrombocytopenia may limit thrombin generation in patients with cirrhosis. These findings might justify platelet transfusion in patients with low platelet counts when they bleed spontaneously or before undergoing surgery or liver biopsy. Controlled clinical trials supporting this indication are warranted.
authors.affiliation: Department of Internal Medicine and Medical Specialties, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, University and IRCCS Ospedale Maggiore, Milano, Italy. armando.tripodi@unimi.it
authors.forename: Armando
authors.initials: A
authors.lastname: Tripodi
authors.forename: Massimo
authors.initials: M
authors.lastname: Primignani
authors.forename: Veena
authors.initials: V
authors.lastname: Chantarangkul
authors.forename: Marigrazia
authors.initials: M
authors.lastname: Clerici
authors.forename: Alessandra
authors.initials: A
authors.lastname: Dell'Era
authors.forename: Federica
authors.initials: F
authors.lastname: Fabris
authors.forename: Francesco
authors.initials: F
authors.lastname: Salerno
authors.forename: Pier Mannuccio
authors.initials: PM
authors.lastname: Mannucci
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000502:physiology*; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood* / Q000150:complications / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D013917:Thrombin / Q000096:biosynthesis*; D013921:Thrombocytopenia / Q000097:blood / Q000209:etiology
chemical_list: D015415:Biomarkers; D013917:Thrombin