A kinetic model of the circulatory regulation of tissue plasminogen activator during orthotopic liver transplantation

K. P. Crookston, C. L. Marsh, Wayne Chandler

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

To better understand the regulation of tissue plasminogen activator (t- PA) and plasminogen activator inhibitor 1 (PAI-1) during liver transplantation, we used a computer model of the human circulatory system to simultaneously evaluate the effect of t-PA secretion, t-PA inhibition by PAI- 1, hepatic clearance of t-PA, blood loss, transfusion and hemodynamics on t- PA and PAI-1 levels during liver transplantation in three patients that differed in severity of liver disease, blood loss and anhepatic changes in t- PA. Higher preoperative t-PA levels were primarily related to underlying liver disease and reduced hepatic clearance. During the anhepatic stage, when hepatic t-PA clearance was eliminated: (1) the expected rise in t-PA was modulated by the extent of bleeding, which acted as an alternate t-PA clearance mechanism; and (2) the ratio of t-PA:PAI-1 was increased due both to lower t-PA clearance and reduced PAI-1 secretion. Recirculation of the new liver was associated with renewed clearance of t-PA, an acute phase increase in PAI-1 and a drop in the t-PA:PAI-1 ratio. Understanding fibrinolytic regulation required simultaneous analysis of t-PA secretion, inhibition and clearance. Anhepatic t-PA levels could be predicted based on preoperative liver function and surgical blood loss, which acted as an alternate t-PA clearance mechanism. (C) 2000 Lippincott Williams and Wilkins.

Original languageEnglish (US)
Pages (from-to)79-88
Number of pages10
JournalBlood Coagulation and Fibrinolysis
Volume11
Issue number1
DOIs
StatePublished - Jan 1 2000

Keywords

  • Fibrinolysis
  • Liver transplantation
  • Plasminogen activator inhibitor 1
  • Tissue plasminogen activator

ASJC Scopus subject areas

  • Hematology

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