Fibrinolytic System Changes in Liver Surgery: A Pilot Observational Study

Abstract

Introduction: Bleeding occurs frequently in liver surgery. Unbalance between tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) concentrations might increase bleeding. Our aim was to analyze perioperative fibrinolytic changes during liver surgery. Materials and Methods: We evaluated 15 patients for inclusion into a prospective pilot study of liver surgery. We assessed fibrinolysis by plasma PAI-1 and t-PA: before surgery (T1), before Pringle maneuver (PM;T2), at the end of surgery (T3) and 24 h postoperatively (T4), and registered demographic and laboratory data, extent and duration of surgery, hemodynamic parameters, blood loss, and transfused volumes of blood products. Data presented as mean ± SD. Significance at P < 0.05. Results: After exclusion of six patients only undergoing biopsies, we included six women and three men aged 49.1 ± 19.6 years; two patients with liver metastases of colorectal cancer and hepatocellular carcinoma, respectively, two with focal nodular hyperplasia, two with hepatic hemangioma, and one with angiomyolipoma. Six patients underwent PM. PAI-1 plasma concentration (n = 9) rose from 6.25 ± 2.25 at T1 through 17.30 ± 14.59 ng/ml at T2 and 28.74 ± 20.4 (p = 0.007) and 22.5 ± 16.0 ng/ml (p = 0.04), respectively, at T3 and T4. Correspondingly, t-PA plasma concentration (n = 9) increased from 4.76 ± 3.08 ng/ml at T1 through 8.00 ± 5.10 ng/ml (p = 0.012) at T2 and decreased to 4.25 ± 2.29 ng/ml and 3.04 ± 3.09 at T3 and T4, respectively. Plasma t-PA level at T2 was significantly different from those at T1, T3, and T4 (p < 0.004). In PM patients, t-PA levels increased from T1, peaked at T2 (p = 0.001), and subsequently decreased at T3 and T4 (p = 0.011 and p = 0.037), respectively. Mean blood loss was 1,377.7 ± 1,062.8 ml; seven patients received blood products. Patients with higher PAI-1 levels at T3 received more fresh frozen plasma (r = 0.79; p = 0.01) and red blood cells (r = 0.88; p = 0.002). Conclusions: During liver surgery, fibrinolysis increased, as evidenced by rises in plasma PAI-1and t-PA, especially after start of surgery and following PM. Transfused volumes of blood products correlated with higher plasma concentrations of PAI-1. Confirming this tendency requires a larger cohort of patients.

Keywords: PAI-1; fibrinolysis; liver surgery; plasminogen activator inhibitor type 1; t-PA; tissue plasminogen activator.

Figure 1

Patients eligible for study of fibrinolysis in liver surgery. Six patients were excluded from the study. Nine patients were analyzed for changes in fibrinolytic markers. t-PA, tissue plasminogen activator; PAI-1, plasminogen activator inhibitor type 1.

Figure 2

(A) Plasma concentrations of PAI-1. T1, before surgery; T2, before Pringle maneuver; T3, at the end of surgery; T4, 24 h postoperatively. Data presented as mean ± SD (n = 9). Closed circles represent patients subjected to the Pringle maneuver (n = 6); open circles represents subjects in whom the Pringle maneuver was not performed (n = 3). *Denotes p < 0.05 vs. T1 as assessed by RM ANOVA followed by pairwise multiple comparisons (Student-Newman-Keuls method). PAI-1, plasminogen activator inhibitor, type 1. (B) Plasma concentrations of t-PA. T1, before surgery; T2, before Pringle maneuver; T3, at the end of surgery; T4, 24 h postoperatively. Data presented as mean ± SD (n = 9). Closed circles represent patients subjected to the Pringle maneuver (n = 6); open circles represents subjects in whom the Pringle maneuver was not performed (n = 3). ^#Denotes p < 0.05 vs. corresponding T2 value, as assessed by RM ANOVA followed by pairwise multiple comparisons (Student-Newman-Keuls method). t-PA, tissue plasminogen activator.

Figure 3

(A) Correlation between PAI-1 and transfused volume of red blood cells at the end of liver surgery (T3). Data presented as Pearson correlation coefficient (r) with p-value. PAI-1, plasminogen activator inhibitor, type 1. (B) Correlation between PAI-1 and transfused volume of fresh frozen plasma at the end of liver surgery (T3). Data presented as Pearson correlation coefficient (r) with p-value. PAI-1, plasminogen activator inhibitor, type 1.