Effect of an exogenous fibrin monomer on hemostatic potential and fibrin formation in the area of controlled liver injury on the background of heparin administration in experiment

Abstract

Background. In previous studies using the heparin model of post-traumatic blood loss, a hemostatic effect of exogenous fibrin monomer (FM) (0.25 mg/kg) was observed, which was comparable in intensity to the effect of protamine sulfate (PS) and remained unexplained due to the lack of morphological study data for the area of liver injury.
Aim. To compare hemostatic, hemostasiological, and morphological consequences of intravenous administration of FM 0.25 mg/kg following controlled liver injury in heparinized animals.
Methods. Hypocoagulation was simulated by i.v. administration of unfractionated heparin (UFH) 150 U/kg to 77 healthy Chinchilla rabbits. Intraoperative bleeding was prevented by i.v. administration of FM 0.25 mg/kg one hour prior to the injury or PS 1.5 mg/kg 10 minutes prior to the injury. After the controlled liver injury, blood loss was measured and expressed in % of the circulating blood volume. Blood platelet count, activated partial thromboplastin time (APTT), fibrinogen concentration, D-dimer concentration, and data of calibrated thrombography were also studied. Samples of liver tissue from the wound surface area were collected for histology after spontaneous arrest of bleeding.
Results. Heparinized animals were characterized by increased blood loss due to pronounced hypocoagulation and decreased thrombin production. The use of the UFH antidote, PS, minimized the blood loss (by 75% compared to placebo) and resulted in restoration of the hemostatic potential. According to results of the morphological study, this effect was due to increased thickness of thrombotic masses (15.1 times compared to placebo). At least equal hemostatic effect was obtained when PS was replaced with FM (80% decrease in blood loss compared to placebo). These effects were not associated with correction of the hypocoagulation shift or recovery of the thrombin generation. In this process, fibrin formation in the injury area was less pronounced (fibrin thickness 55.2 μm vs 201.8 μm with PS; p < 0.001). Another distinctive feature was the absence of the fibrillar structure of fibrin and the presence of numerous platelets in thrombotic masses while the platelet number in the lumen of blood vessels near the wound surface was minimal.
Conclusion. The study results allow identifying possible mechanisms and ways to stop post-traumatic bleeding when heparin is used.