The Immunomodulatory Effect of Antrifibrinolytic (Tranexamic Acid) in Total Knee Arthroplasty

The administration of the tranexamic acid (TRAXA), an antifibrinolytic, blocks primary fibrinolysis, and thus the haemorrhage, in the early postoperative period. Significant surgical operations, as well as trauma, initiate a similar dynamic homeostatic mechanism between the creation of a clot (primary and secondary haemostasis) and its dissolution (fibrinolysis). Antifibrinolytics are initially used in patients with an accelerated fibrinolysis of different pathogeneses. However, they have been proven effective in reducing haemorrhage in patients who have undergone significant surgical operations with normal fibrinolysis, with the use of an appropriate surgical technique.

A pharmacokinetic study has shown that peak fibrinolytic activity is present for 6 hours after the incision and it persists for 18 hours in total knee and hip arthroplasty. The administration of the tranexamic acid in optional orthopaedic surgery of total hip (THA) and knee (TKA) arthroplasty reduces the postoperative haemorrhage, as well as the number and volume of the postoperative autologous blood.

A randomized, placebo-controlled trial CRAS-2 has validated that the early post-traumatic administration of the tranexamic acid, within 8 hours after the injury, in adult patients with traumas or in patients with the risk of significant haemorrhage, reduces the fatality rate.

The tranexamic acid is a synthetic derivative of lysine, an amino acid which blocks lysine binding sites of the plasminogen molecule which are essential for its biding to fibrin. This mechanism inhibits the plasminogen activation via a plasminogen activator which also binds to fibrin. Thus, it prevents the conversion of plasminogen into plasmin, which is essential for fibrin dissolution, the integral element of a stable clot. The second important antifibrinolytic effect is blocking the lysine binding sites on the free plasmin molecule which has already been formed through the conversion from the plasminogen. This inhibits its binding to fibrin, and the TRAXA-plasmin complex is rapidly inactivated with the α-2-antiplasmin and α-2-macroglobulin. Biological half-life is approximately 2-3 hours.

A trauma in the organism triggers the immunologic response. The initial immunologic reaction occurs at the location of the injury, and it is called an inflammation. The inflammatory response is characterized by a complex interaction of macrophages (a type of leukocytes which develop from monocytes and are a part of the mononuclear phagocyte system, the main task of which are phagocytosis, i.e. the clearance of foreign materiel from the organism, performing the immunologic function - the defence against foreign materiel - antigens, and the regulation of the inflammation via interleukins which they secrete - IL1, IL-2,TNF) and dendritic cells (antigen-presenting cells), the consequence of which is the release of cytokines (interleukins - glycoproteins which regulate interactions among cells) and chemokine (small proteins from the cytokine group - able to induce chemotaxis, cell migration), and the activation of the neutrophils, monocytes and mesenchymal stem cells (cells not containing any information, located in the adipose tissue, cartilage and muscle tissue).