The purpose of this investigation is to determine the most effective regimen of administration of tranexamic acid to improve clinical outcome among patients undergoing total knee arthroplasty.

Tranexamic acid (TXA) is synthetic lysine analog, which acts as anti-fibrinolytic agent by preventing conversion of plasminogen in to plasmin. Various regimens of TXA administration (routes, doses, timing) have been used to decrease perioperative blood loss and improve clinical outcomes among patients undergoing different orthopedic surgeries. We are conducting this prospective randomized placebo controlled trial to compare the effect of the two most common regimens of TXA administration on hemostasis and clinical outcomes among patients undergoing total knee arthroplasty. All recruited patients receive the first dose of 15mg/kg of IV TXA prior to skin incision. The second dose of 15mg/kg IV TXA or identical placebo is administered prior to the release of the tourniquet.

The assessment of hemostasis is performed using whole blood sample via viscoelastic testing by rotational thromboelastography (ROTEM). A blood sample is collected in the preoperative area and after the administration of each dose of TXA. Clinical data is collected until 90 days after surgery.

Inclusion Criteria:

- Adult patients who are scheduled to undergo total knee arthroplasty will be approached to participate.

Exclusion Criteria:

• Known allergy to TXA
• History of venous or arterial thrombosis within 12 months
• History of thromboembolic event within 12 months
• Acute ischemic event (stroke, transient ischemic attack, myocardial infarction, ischemic retinopathy) within 6 months
• Known congenital thrombophilia

Relative Contraindications:

• History of seizures
• Impaired kidney function (Glomerular filtration rate < 30 ml/min)