Prothrombin Fragment 1+2 and Thrombin-Antithrombin Complex Measurements Indicate Continuous and Progressive Intraoperative Thrombin Generation in Liver Transplantation

Abstract

Prothrombin fragment 1 + 2 (F₁₊₂) and thrombin-antithrom-bin complex (TAT) have been measured in the different surgical phases in 40 patients undergoing 43 orthotopic liver transplantations (OLT), in order to study thrombin generation throughout the surgical procedure. F₁₊₂ and TAT progressively rose from preoperative values (1.47 ± 0.92 nmol/l and 22.41 ± 19.15 ng/ml, respectively) to the end of anhepatic phase (5.97 ± 2.20 nmol/l, 64.24 ± 11.30 ng/ml), whereas changes in circulating antithrombin III (ATIII) were negligible in this period. Thrombin generation continued to slightly but significantly increase immediately after liver graft reperfusion (F₁₊₂ 6.87 ± 1.65 nmol/l, TAT 89.32 ± 7.54 ng/ml), and ATIII levels decreased from 70.61 ± 12.28 to 57.16 ± 9.57%. Higher preoperative values of F₁₊₂ were associated with larger requirements of both packed red blood cells and fresh frozen plasma (FFP) in the host liver explantation phase, whereas the lowest basal levels of ATIII were related to a higher plasma expense in the whole OLT procedure. The activation of circulating prothrombin begins early in OLT, and adequate FFP infusion is capable of maintaining appropriate circulating thrombin-inhibitory activity.

The prevalence of a heparin-like effect shown on the thromboelastograph in patients undergoing liver transplantation

“…Those with more severe HLE may have greater inhibition of thrombin generation as they have greater antithrombin III binding. A previous study investigating thrombin‐antithrombin complexes during liver transplantation showed thrombin generation to slightly increase after reperfusion 23. However, this study did not investigate those with HLE separately.…”

“…Heparin acts by binding with anti‐thrombin III inhibiting thrombin generation 22. When given to patients, it demonstrates significant interindividual variability23 and behaves in a dose‐dependent linear model with saturable pharmacokinetics 22. Those with more severe HLE may have greater inhibition of thrombin generation as they have greater antithrombin III binding.…”

Increased local procoagulant action: a mechanism contributing to the favorable hemostatic effect of recombinant FVIIa in PLT disorders

“…Plasma was separated by centrifugation of the anticoagulated blood samples (1800 × g for 20 min) and frozen at –70°C. Levels of F1 + 2 were determined in plasma samples with commercially available EIAs (Enzygnost, Behring, Germany) 30 …”

“…Levels of F1 + 2 were determined in plasma samples with commercially available EIAs (Enzygnost, Behring, Germany). 30 blood, and with antibodies against TF for each concentration and controls were at least n = 6. Experiments with blood from Glanzmann's thrombastenia patients were performed with blood samples taken from two different patients (n = 2) and experimental studies with blood samples exposed to a specific MoAb against GPIIb-IIIa was n = 4.…”

Infusible platelet membranes improve hemostasis in thrombocytopenic blood: experimental studies under flow conditions

“…Blood aliquots were immediately mixed with sodium citrate (129 m M ) to prevent further activation of the coagulation system. Plasma was separated by centrifugation of the anticoagulated blood samples (1800 × g , 20 min) and frozen at –70 C. F1+2 levels were determined by commercially available EIAs (Enzygnost F1+2, Dade Behring, Marburg, Germany) according to the method already described 29 …”