title: Defective aggregation in cirrhosis is independent of in vivo platelet activation.
abstract: OBJECTIVE
  Platelet function abnormalities contribute to the hemostatic defect in patients with cirrhosis. In this study we evaluated the occurrence of in vivo platelet activation as a possible mechanism of defective platelet aggregation in patients with cirrhosis.
  
  
  METHODS
  Nine patients with severe (Child B-C) cirrhosis and defective platelet aggregation were studied in comparison with age- and sex-matched healthy controls. The presence of activated platelets in the bloodstream was evaluated by fluorescence-activated flow cytometry using antibodies directed against activation-dependent platelet proteins and by measuring plasma levels of beta-thromboglobulin and platelet factor 4. Urinary levels of 11-dehydro-TXB2 and of 2,3-dinor-TXB2 were assayed by radioimmunoassay following chromatographic separation.
  
  
  RESULTS
  In unstimulated platelets, the expression of both GMP 140 and GP 53 was not significantly different in patients with cirrhosis and in controls. After stimulation with ADP and epinephrine, expression of activation-dependent antigens was lower in platelets from patients (GMP 140: 0.64 +/- 0.09 vs 0.73 +/- 0.04, p = 0.02; GP 53: 0.41 +/- 0.13 vs 0.54 +/- 0.14). Plasma levels of beta-thromboglobulin and platelet factor 4, as indexes of in vivo platelet activation, were also comparable in the two groups of subjects. Urinary levels of 11-dehydro-TXB2 and of 2,3-dinor-TXB2, the major systemic metabolites of TXA2, were significantly higher in patients with cirrhosis (1807 +/- 518 vs 341 +/- 121 ng/pg creatinine and 693 +/- 512 vs 205 (93 ng/pg creatinine, respectively, p < 0.001). However, increased excretion of TXB2 metabolites was also observed in three patients with chronic autoimmune thrombocytopenia.
  
  
  CONCLUSIONS
  These data indicate that circulating platelets are not activated in cirrhosis, and that defective aggregation is most likely dependent on the alteration of the transmembrane signaling pathways. The increased urinary excretion of systemic TXA2 metabolites may be related to increased intrasplenic platelet destruction.
authors: Istituto di Medicina Interna, Università Degli Studi di Firenze, Rome, Italy.
authors: G
authors: G
authors: Laffi
authors: S
authors: S
authors: Cinotti
authors: E
authors: E
authors: Filimberti
authors: G
authors: G
authors: Ciabattoni
authors: R
authors: R
authors: Caporale
authors: F
authors: F
authors: Marra
authors: L
authors: L
authors: Melani
authors: A
authors: A
authors: Grossi
authors: V
authors: V
authors: Carloni
authors: P
authors: P
authors: Gentilini
mesh_terms: D000368:Aged; D001780:Blood Coagulation Tests; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood* / Q000652:urine; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation; D010974:Platelet Aggregation; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000652:urine
chemical_list: D013929:Thromboxane B2; C028965:2,3-dinor-thromboxane B2; C049235:11-dehydro-thromboxane B2