Combined Topical Tranexamic Acid With Floseal® in Total Knee Arthroplasty

Total knee arthroplasty (TKA) is associated with considerable blood loss and increasing needs for allogenic blood transfusion. Tranexamic acid (TXA), an inhibitor of fibrinolysis, was reportedly effective reducing blood loss after standard TKA. Our previous experiences in minimally invasive (MIS) TKA showed that intraoperative infusion of TXA reduced 45% of postoperative blood loss and needs for transfusion from 20% to 4%. There were some reports demonstrating the cost-effectiveness of topical application of TXA in TKA patients.

Besides, thrombin-based hemostatic agents, Floseal®(Baxter, Deerfield, Illinois), have been widely used in surgical procedure. Some recent studies demonstrated that topical use of Floseal® in primary TKA can reduce hemoglobin decline and calculated total blood loss after TKA. But other studies showed Floseal® does not reduce blood loss in TKA procedures.

We believe the topical use of hemostatic agent in patients with high risk of thromboembolism can avoid its systematic effect and decrease its potential perioperative risk of thromboembolic complications (arterial thrombosis, myocardial infarction and pulmonary embolism). Recently, there were some reports demonstrating the cost-effectiveness of topical application of TXA in TKA patients. The blood saving effect of topical application of TXA in primary TKA was similar with systemic administration. The mean total blood loss of topical route of TXA inTKA patients was 940-1295 ml in different reports which was still high for patients with high thromboembolic risks. However, the efficacy and safety of topical use of TXA in TKA patients with history of thromboembolic disease is still unclear. A more effective regimen for bleeding prophylaxis afer primary TKA is necessary.

We believe that combined topical applications of two hemostatic agents of different mechanisms can bring a synergistic effect in blood saving and does not increase the risk of thromboembolic disease after TKA.

Our purpose of this study therefore is to conduct a prospective randomized controlled trial to investigate the blood-conservation effect of combined topical application of these two hemostatic agents in different time during surgery and the safety compared with single topical application of TKA in a primary TKA procedure.

• Topical tranexamic acid (Drug), also known as Topical transamine: Intraarticular application of tranexamic acid 3g in 60 ml normal saline into knee joint after closure of the joint capsule
• Floseal® (Drug), also known as Thrombin-gelatin matrix: Floseal® (Hemostatic matrix, 10ml, Baxter) was applied on potential bleeding sites: the femoral insertion of the posterior cruciate ligament, the lateral genicular artery after resection of the meniscus, the posterior capsule of the knee joint, the bony surfaces not covered by the implant as well as the pinholes (femur and tibia). The entire content of a 10 mL vial containing the active product (Floseal®) was used. The HM remained in place for 3 minutes and was then gently rinsed from the knee as recommended by the manufacturer (Baxter)
• rivaroxaban (10mg) (Drug), also known as Xarelto: Oral rivaroxaban (10mg) QD on PostOp Day 1 to 14.

Primary outcomes

• Total Blood Loss After Operation [From the operation to the postoperative day 3 or 4]: Total blood loss was calculated according to Nadler et al., which used maximum postoperative reduction of the Hb level adjust for weight and height of the patient. The formula is as follows, Total blood loss = (Total blood volume x \[change in Hb level / preoperative Hb level\])x1000+volume transfused

Secondary outcomes

• Blood Transfusion Rate [From the operation to the postoperative day 3 or 4]: We will record the event of blood transfusion, and calculate the incidence of transfusion
• Incidence of Thrombosis Events [within 30 days of the operation]: The composite of any venous thromoembolism events, ischemic heart attacks, cerebrovascular accidents

Sex: All, ages: 50 Years to 90 Years, accepts healthy volunteers

Inclusion Criteria:

1. Patients who have advanced knee osteoarthritis are scheduled to undergo primary, unilateral elective total knee replacement surgery
2. Age > 50 years and < 90 years
3. Failure of medical treatment or rehabilitation.
4. Hemoglobin > 11g/dl,
5. No use of non-steroid anti-inflammatory agent one week before operation

Exclusion Criteria:

1. Preoperative Hemoglobin ≦11 g/dl
2. History of infection or intraarticular fracture of the affective knee
3. Renal function deficiency (GFR <30 ml/min/1.73m2)which is relative contraindicated for chemical venous thromboembolism
4. Elevated liver enzyme (AST/ALT level are more than twice normal range) , history of liver cirrhosis, impaired liver function(elevated total bilirubin level) and coagulopathy (including long-term use anticoagulant)
5. History of deep vein thrombosis, ischemic heart disease or stroke
6. Contraindications of tranexamic acid, floseal, or rivaroxaban
7. Allergy to tranexamic acid, floseal, rivaroxaban, or the excipients
8. History of heparin-induced thrombocytopenia (HIT)
9. Coagulopathy or bleeding tendency caused by organ dysfunction, such as cirrhosis, bone marrow suppression etc.
10. Patient who have active bleeding disorder, such as intracranial hemorrhage, upper GI bleeding, hematuria.
11. Patients with known allergies to materials of bovine origin

Participant flow

Outcome results

• Total Blood Loss After Operation (Primary), Mean, ml: Combined Topical TXA and Floseal 678 +/- 203; Topical TXA Alone 733 +/- 217 (p 0.276)
• Blood Transfusion Rate (Secondary), Count of participants, Participants: Combined Topical TXA and Floseal 1; Topical TXA Alone 0 (p 1)
• Incidence of Thrombosis Events (Secondary), Count of participants, Participants: Combined Topical TXA and Floseal 0; Topical TXA Alone 0 (p 1)

Adverse events

Time frame: 3 months

Other adverse events by term

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• Study Protocol and Statistical Analysis Plan (PDF, 2016-11-29)

• Jun-Wen Wang, MD, Study chair, Chang Gung Memorial Hospital