Fibrinolysis and blood loss in major arthroplasty. The effect of tranexamic acid

Abstract: Blood loss in major arthroplasty may be abundant and often necessitates blood transfusions. These may transmit disease and entail an immunological burden to the recipient. After trauma and surgery, the fibrinolytic system reacts with a short period of increased activity, followed by a fibrinolytic shut-down. In this thesis we investigated the impact of the early fibrinolytic activation on blood loss in total hip (THR) and knee arthroplasty (TKA), and the effect of a fibrinolytic inhibitor, tranexamic acid (TA), on postoperative blood loss and blood transfusions in these operations. A retrospective analysis of 179 TKA indicated that the use of TA decreased blood loss by a mean of 340 ml. The effect was confirmed in a double-blind randomised study of 86 TKA. Tranexamic acid (10 mg/kg) was given shortly before the release of the tourniquet and three hours postoperatively. The blood loss (mean + SD) in patients receiving TA was 730 + 280 ml versus 1410 + 480 ml in the placebo group (p<0.001). The number of blood transfusions were reduced by 2/3. In a randomised, double-blind study of 39 THR, TA was given after the cementing of the femoral component in order to avoid fibrinolytic inhibition during the pulmonary embolisation that often occurs during this procedure. The administration was repeated after three hours. There was no significant effect of TA on blood loss in THR, possibly because the drug was administered too late. Analyses of blood specimens from the wounds and peripheral veins during the operations showed an activation of coagulation and fibrinolysis, most pronounced in the wounds. TA significantly decreased D-dimers in the wounds in TKA, but not in peripheral blood. We found no significant effect of TA on oxygen saturation, measured by pulse oxymetry. In a separate study we investigated the pharmacokinetics of TA in THR and found that 10 mg/kg body weight i.v. resulted in therapeutic plasma concentrations during surgery. In conclusion we have thus found a profound local activation of fibrinolysis in TKA and THR. The prophylactic administration of TA significantly reduced blood loss and the need of blood transfusions in TKA. We found, however, no such effect when TA was given at the end of the operation in THR.