Kinetic and functional studies of platelets, fibrinogen, and plasminogen in patients with hepatic cirrhosis

Abstract

To assess the nature of the hemostatic abnormalities associated with chronic liver disease, we have simultaneously evaluated the kinetic of radiolabeled platelets, fibrinogen, and plasminogen, together wit tests of platelet and fibrinogen function, and coagulation factors in 60 patients with documented, severe but stable cirrhosis of the liver. The mean platelet survival was substantially reduced (5.8 +/- 1.7 days compared with 9.5 +/- 0.6 days in normals, p less than 0.0001) and splenic sequestration of platelets was increased (mean recovery was 47% +/- 18 vs. 65% +/- 5 in normals, p less than 0.0001). Nevertheless the mean platelet count was nearly normal because platelet production was increased nearly twice normal values (mean turnover was 64,000 +/- 33,000 platelets/microliter/day; p less than 0.0001). The mean rate of fibrinogen removal was shortened (p less than 0.0001) and fibrinogen turnover increased about 20% (p = 0.008) while the mean fibrinogen concentration was not different from the results in normal control subjects (p = 0.212). Autologous and homologous fibrinogen disappeared from the circulation at equivalent rates (r = 0.751; p = 0.008), indicating that fibrinogen from cirrhotic patients was not kinetically different from normal fibrinogen. The mean plasminogen survival was significantly shortened (p less than 0.0001), but the mean plasminogen turnover was not increased (p = 0.388). Thus the plasminogen concentration was reduced (p less than 0.0001). For platelets, fibrinogen, and plasminogen, the production rate was the most important determinant of the concentration in the circulation. The administration of heparin to cirrhotic patients improved the survival of fibrinogen but not of platelets. LeVeen valve implantation generally resulted in parallel shortening of both the platelet and fibrinogen survivals and concentrations. Platelet function as assessed by template bleeding time, platelet retention by glass bead columns, and aggregation induced by ADP, epinephrine, and collagen was normal. Fibrinogen determinations by the Clauss and Jacobsson techniques were equivalent, indicating that the ability to polymerize fibrin monomer was not detectably altered. Sixty percent of patients had an abnormal prothrombin time and half that number had a prolonged partial thromboplastin time. Although most patients had a modest decrease in the prothrombin complex coagulation factors, fibrin degradation products were, in general, not elevated in the circulation. The wide range of values observed suggests that a number of different and complex processes may be ongoing in different patients. Overall, the kinetic data suggest that platelets are initially consumed, perhaps on incompletely endothelialized endovascular surfaces in the liver, and that fibrin subsequently forms secondary to local stasis. The absence of increased production of fibrinogen and plasminogen despite shortened survival times reflects the reduced capability of the cirrhotic liver to increase protein synthesis.