Effect of Topical and Intravenous Tranexamic Acid (TXA) on Thrombogenic Markers in Patients Undergoing Knee Replacement

Hospital for Special Surgery, New York76 enrolled

Overview

Tranexamic acid (TXA) is a drug that is being used more frequently at the Hospital for Special Surgery to lessen the amount of blood loss after total knee replacement (TKR). It is an anti-fibrinolytic agent, which means that it promotes the formation of blood clots. TXA can be given either intravenously or topically (placed directly on the open wound) before wound closure. Patients with certain medical conditions have been found to have a high risk of thrombosis after being given intravenous TXA, which may lead to serious complications. However, to date, no high-risk patients have been identified for use of topical TXA. This study will look at thrombogenic markers (proteins found in blood that promote clot formation) after TXA is given either intravenously or topically. If the effect on these markers is similar between intravenous and topical use of TXA, then the safety of topical TXA should be questioned. Of note, these markers have never been measured after TXA has been given topically. As a result, this information would be important for the medical community.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Osteoarthritis, Knee

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patients undergoing primary unilateral total knee replacement with a participating surgeon * Patients aged 18-80 Exclusion Criteria: * All patients on steroid therapy regardless of dose, duration, or treatment or those requiring stress-dose steroids preoperatively * Patients who will require postoperative use of Coumadin, Xarelto, or Plavix * Use of non-steroidal anti-inflammatory drugs (NSAIDs) within 1 week of surgery * Hypersensitivity to tranexamic acid * Renal dysfunction (Creatinine clearance \< 40 ml/min) * Hepatic dysfunction (AST or ALT 2x upper limit of normal) * Cardiac exclusions: coronary stent, history of myocardial infarction, positive stress test, atrial fibrillation, advanced coronary artery disease * Advanced chronic obstructive pulmonary disease or advanced interstitial lung disease * History of venous thromboembolism * Hypercoagulability (e.g. antiphospholipid syndrome, genetic hypercoagulability with or without prior venous thromboembolism) * History of stroke or transient ischemic attack

Outcomes

Primary Outcomes

Levels of Plasmin Anti-plasmin (PAP) - Marker of Fibrinolysis

Levels of PAP will be measured in peripheral blood and wound drainage at 4 hours after tourniquet release.

Time frame: 4 hours after tourniquet release

Secondary Outcomes

Levels of Prothrombin Fragment 1.2 (PF1.2) - Marker of Thrombin Generation

Systemic PAP blood level measured at the following time points - Intraoperative - Before cementing, 1 hour after tourniquet release, 4 hours after tourniquet release

Time frame: before cementing, 1 hour after tourniquet release, 4 hours after tourniquet release

Levels of Tranexamic Acid

Time frame: Intraoperative (before cementing), 1 hour after tourniquet release (TQR), 4 hours after tourniquet release(TQR)

Calculated Postoperative Blood Loss

Time frame: Duration of inpatient hospital stay (average of 3 days)

Levels of Hemoglobin

Time frame: 1 hour after tourniquet release, POD 1, POD 2

Levels of Hematocrit

Time frame: 1 hour after tourniquet release, POD 1, POD 2

Constavac Blood Drainage

A wound drain is connected to a Constavac system, which postoperatively collects, filters, and allows for reinfusion of the patient's own blood. Shed blood passes through an internal prefilter and is collected in a reservoir.

Time frame: 4 hours after tourniquet release

Incidence of Thrombosis (DVT/PE)

Time frame: Postoperative day 14 (2 weeks after surgery)

Patients Who Had 1 Unit of Blood Transfusion Administered

Time frame: Duration of inpatient hospital stay (average of 3 days)

Time to Physical Therapy Discharge

Time frame: During Hospital Stay

Length of Hospital Stay

Time frame: Length of Hospital Stay

Levels of IL-6 in Blood

Time frame: Intraoperative, 1 hour post Tourniquet Release (TQR), 4 hour post Tourniquet Release (TQR)

Levels of Plasmin Anti-plasmin (PAP) - Marker of Fibrinolysis

Levels of PAP will be measured in peripheral blood and wound drainage

Time frame: Intraoperative, 1 hour post Tourniquet Release (TQR)

Levels of Prothrombin Fragment 1.2 (PF1.2) - Marker of Thrombin Generation in Wound Blood

The values for the wound blood levels are given as the count of patients who had a level above the threshold of \>3600 pmol/L.

Time frame: Intraoperative, 4 hour post Tourniquet Release (TQR)