KINETIC AND FUNCTIONAL-STUDIES OF PLATELETS, FIBRINOGEN, AND PLASMINOGEN IN PATIENTS WITH HEPATIC CIRRHOSIS

  • 1 January 1982
    • journal article
    • research article
    • Vol. 99  (2) , 217-230
Abstract
To assess the nature of the hemostatic abnormalities associated with chronic liver disease, the kinetics of radiolabeled platelets, fibrinogen and plasminogen were simultaneously evaluated together with 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 < 0.0001) and splenic sequestration of platelets was increased (mean recovery was 47% .+-. 18 vs. 65% .+-. 5 in normals, P < 0.0001). The mean platelet count was nearly normal because platelet production was increased nearly twice normal values (mean turnover was 64,000 .+-. 33,000 platelets/.mu.l per day; P < 0.0001). The platelet count correlated directly with platelet turnover (r = 0.55, P < 0.0001). The mean rate of fibrinogen removal was shortened (P < 0.0001) and fibrinogen turnover increased .apprx. 20% (P = 0.008) while the mean fibrinogen concentration was not different from the results in normal control subjects (P = 0.312). 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 < 0.0001), but the mean plasminogen turnover was not increased (P = 0.388). The plasminogen concentration was reduced (P < 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 of platelets. LeVeen value implantation generally resulted in parallel shortening of 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 not elevated in the circulation. A number of different and complex processes may be ongoing in different patients. Platelets are apparently initially consumed, perhaps on incompletely endothelialized endovascular surfaces in the liver. 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.