Comprehensive investigation of platelet function in patients with cirrhosis
Anna Lecchi a 1, Giulia Tosetti b 1, Claudia Ghali c, Silvia La Marca a, Marigrazia Clerici a, Lidia Padovan a, Eti A. Femia a, Massimo Primignani b, Vincenzo La Mura a d, Pietro Lampertico b e, Flora Peyvandi a d, Armando Tripodi a
a) IRCCS Ca’ Granda Ospedale Maggiore Policlinico Foundation, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milano, Italy
b) Division of Gastroenterology and Hepatology, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, Italy
c) Division of General Medicine II, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Milano, Italy
d) Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milano, Italy
e) CRC “A. M. and A. Migliavacca” Center for Liver Disease, Department of Pathophysiology and Transplantation, University of Milano, Milan, Italy
Abstract
Cirrhosis presents with thrombocytopenia and possibly thrombocytopathy. Previous studies exploring platelet function gave conflicting results and most controversies are explained by the variety of methods employed for investigation. We sought to assess in-vitro the overall platelet function in cirrhosis.
We investigated 34 patients by using the following tests. (i)Aggregometry. (ii)Measurement of the content of platelet granules. (iii)Cytometric platelet activation. (iv)Plasmatic markers of in-vivo platelet activation. (v)Platelet procoagulant activity by thrombin generation (TG) in platelet-rich plasma (PRP).
TG measured in PRP for patients and controls was similar. Platelets from patients with cirrhosis showed reduction of aggregation and secretion of ATP. Similar results were observed for platelet activation parameters such as P-selectin expression and PAC-1 platelet binding. Plasma levels of βeta-thromboglobulin and soluble P-selectin, were increased in patients-vs-controls. In contrast, there were no patients-vs-controls differences for plasmatic platelet-factor-4. Results are consistent with a state of in-vivo platelet activation and decreased in-vitro aggregation. Since bleeding events following invasive procedures are uncommon in cirrhosis, we speculate that in-vitro aggregometry testing does not reflect the situation occurring in-vivo. Results of the study and pathophysiological considerations support the conclusion that platelet function in cirrhosis as determined by aggregometry, although somewhat impaired, may support the overall hemostatic potential, which is needed for most invasive interventions. These conclusions are in line with the recommendations of international guidelines, warning against indiscriminate use of prophylactic preprocedural administration of platelets before invasive procedures. Decision on platelet support should not be made based on in-vitro laboratory testing for platelet function.