Does Early Administration of Tranexamic Acid Reduce Blood Loss and Perioperative Transfusion Requirement

The use of TXA in orthopedic trauma patients is an area of current research interest. A 2010 prospective randomized, controlled trial of perioperative TXA demonstrated reduction in transfusion requirements for intertrochanteric hip fractures treated with short, cephalomedullary nails. This was clinically, though not statistically, significant. Investigators recently conducted a randomized, controlled trial at this institution to evaluated the use of TXA in patients with femoral neck fractures treated with hemiarthroplasty or total hip arthroplasty and found clinically, albeit not statistically, significant reduction in transfusion requirement (accepted for publication). Perhaps tempering the effect seen with perioperative administration of TXA is the blood loss that occurs prior to surgery, the so-called "hidden" blood loss that can be as substantial as 1/3 of total blood loss from a hip fracture. This raises the question whether administration of tranexamic acid at the time of initial presentation after fracture could improve the perioperative care of these patients by decreasing the proportion of patients requiring transfusion and decreasing total blood loss.

• Tranexamic Acid (TXA) (Drug), also known as Cyklokapron: Intravenously via bolus dose of 1g over ten minutes and an additional 1g over the subsequent 8 hours
• Placebo (Drug): Looks exactly like the study drug, but it contains no active ingredient

Primary outcomes

• Number of Subjects Transfused at Least 1 Unit of Packed Red Blood Cells [Length of hospitalization (approximately 3 to 5 days)]: Transfusion will be considered for all patients with hemoglobin values of less than 8 g/dL with persistent symptoms or history of significant cardiac disease that may render the patient less able to compensate for significant anemia. Blood transfusion will be considered in all patients with hemoglobin less than 7 g/dL, regardless of symptoms.

Secondary outcomes

• Number of Units of Packed Red Blood Cells Transfused [Length of hospitalization (approximately 3 to 5 days)]: Number of units of packed red blood cells transfused per patient
• Calculated Blood Loss [Length of hospitalization (approximately 3 to 5 days)]: Total blood loss per patient measured in milliliters (mL)
• Number of Subjects to Experience Symptomatic Venous Thromboembolism (VTE) [Within 6 months of surgery]: Number of subjects to experience symptomatic Venous Thromboembolism (VTE)
• Wound Complications [Within 6 months of surgery]: Number of subjects diagnosed with a wound complication
• (Myocardial Infarction) MI Diagnosed [Within 6 months of surgery]: Number of subjects diagnosed with a myocardial infarction
• Cerebrovascular Accident (CVA) Diagnosed [Within 6 months of surgery]: Number of subjects diagnosed with a cerebrovascular accident
• All-cause Mortality [At 6 months after surgery]: Number of subject deaths

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* AO/OTA fracture classification 31A
* Surgically treated with sliding hip screw or cephalomedullary nail (short or long)
* Low energy, isolated injury

Exclusion Criteria:

* Intracapsular hip fractures: AO/OTA fracture classification 31B-C
* Polytrauma patients
* Creatinine clearance less than 30 mL/min
* History of unprovoked VTE and/or recurrent VTE
* Known history of Factor V Leiden, protein C/S deficiency, prothrombin gene mutation, anti-thrombin deficiency, anti-phospholipid antibody syndrome, lupus anticoagulant
* Pregnancy or breastfeeding (pregnancy tests will be performed on all patients of child-bearing potential)
* History of CVA, MI, or VTE within the previous 30 days
* Coronary stent placement within the previous 6 months
* Disseminated intravascular coagulation
* Intracranial hemorrhage

Participant flow

Outcome results

• Number of Subjects Transfused at Least 1 Unit of Packed Red Blood Cells (Primary), Count of participants, Participants: Tranexamic Acid Arm (TXA) 17; Control Arm 19
• Number of Units of Packed Red Blood Cells Transfused (Secondary), Mean, units of packed red blood cells: Tranexamic Acid Arm (TXA) 1.9 +/- 1.9; Control Arm 2.3 +/- 1.7
• Calculated Blood Loss (Secondary), Mean, mL: Tranexamic Acid Arm (TXA) 1600 +/- 1200; Control Arm 2000 +/- 1400
• Number of Subjects to Experience Symptomatic Venous Thromboembolism (VTE) (Secondary), Count of participants, Participants: Tranexamic Acid Arm (TXA) 3; Control Arm 1
• Wound Complications (Secondary), Count of participants, Participants: Tranexamic Acid Arm (TXA) 4; Control Arm 1
• (Myocardial Infarction) MI Diagnosed (Secondary), Count of participants, Participants: Tranexamic Acid Arm (TXA) 0; Control Arm 2
• Cerebrovascular Accident (CVA) Diagnosed (Secondary), Count of participants, Participants: Tranexamic Acid Arm (TXA) 0; Control Arm 3
• All-cause Mortality (Secondary), Count of participants, Participants: Tranexamic Acid Arm (TXA) 7; Control Arm 6

Adverse events

Time frame: Adverse events were collected from baseline to end of study for a total of approximately 6 months on all participants.

Serious adverse events by term

• Study Protocol and Statistical Analysis Plan (PDF, 2019-06-13)

• Brandon Yuan, MD, Principal investigator, Mayo Clinic