Analysis of Efficacy of Tranexamic Acid in Reduction of Blood Loss and Postoperative Blood Transfusions Following Orthopedic Trauma Surgery

INTRODUCTION

Major elective orthopedic surgery is often associated with blood loss, requiring the need for blood transfusion. Up to 37% of patients undergoing primary total hip arthroplasty (THA) and 25% undergoing primary total knee arthroplasty (TKA) require blood transfusion for postoperative anemia.¹ It is estimated that the average blood loss during primary THA can be between 1,000 mL and 2,000 mL.² Likewise, primary TKA may result in a postoperative loss of up to 2,000 mL of blood.³ Even more blood loss is expected in the trauma surgeries compared with the arthroplastic surgeries.

A possible pharmacological option to prevent surgical bleeding in elective orthopedic surgery is the use of tranexamic acid (TXA). Tranexamic acid was originally discovered in 1962 by two independent research groups.^4,5 The researchers had found that the trans form of 4-(aminomethyl)-cyclohexane-carbonic acid had antifibrinolytic properties. As a synthetic derivative of lysine with a molecular weight of 157 g/mol, TXA exerts its antifibrinolytic effect by a reversible interaction with plasminogen and the active protease, plasmin.⁶ One of the earliest randomized studies examining the efficacy of TXA in reducing blood loss following total joint arthroplasty was in 1997 by Hiippala et al.⁷ In their study, 75 patients undergoing primary TKA were randomized to receive either normal saline or intravenous (IV) TXA. The TXA group showed a significant reduction in blood loss and mean number of transfused units without an increase in venous thromboembolic events.

While extensive research has been done on the role of TXA on the arthroplasty group, the role of it in the trauma patients has yet to be proved, and hence, this is an attempt to establish the effect of it in trauma group.

MATERIALS AND METHODS

After Institutional Review Board approval, a double-blinded, prospective, randomized, placebo-controlled study was performed at a tertiary trauma care center involving 50 patients undergoing internal fixation of fracture of both bones of leg by open interlocking nailing for tibia. Written informed consent was taken from all the patients before screening in study. This randomized study comprised 50 patients of any sex- and age-wide ASA grade I or II, who were scheduled for elective open intramedullary nailing of tibia who had late presentation with preoperative reduction unfavorable to facilitate closed reduction. Twenty-five patients were taken in control group and 25 patients in study group.

Exclusion criteria include history or evidence of coagulopathy and bleeding disorders, renal dysfunction, current use of antiplatelet medication and anticoagulants, acute infection, history of malignancy or coronary artery disease, thromboembolic event in past one year prior to surgery, and hemoglobin (Hb) less than 8 g/dL.

All patients were evaluated in preanesthesia examination by central assessment team and were advised premedication with tablet diazepam 5 mg and ranitidine 150 mg orally a night prior and day of surgery in the morning. Intravenous access was achieved in operation theater with 18 G intravenous catheter, and all patients were preloaded with normal saline 500 mL prior to spinal anesthesia. Combined spinal and epidural anesthesia was given with aseptic precautions with patient lying in lateral position. Surgery was conducted under combined epidural spinal anesthesia and postoperatively followed by epidural infusion for postoperative analgesia. Randomization was done using a simple computer program for randomly allocating treatment.⁸ The anesthetist, the surgeon, and the observer were blinded to the study drug. A person not further involved in the study prepared and started the test/placebo drug.

RESULTS

No significant statistical difference was found among the study groups in respect of age, sex, weight, height, duration of surgery, baseline Hb, and baseline laboratory investigations such as pulse rate, mean arterial pressure, and respiratory rate. As shown in Table 1, there is a statistically significant difference found between two groups in respect of Hb level at postoperative day 4 (10.76 ± 0.83 vs 10.08 ± 0.75, p %3C; 0.05). As shown in Table 2, BV is found statistically insignificant between two groups (p %3E; 0.05). Blood loss and Hb loss is found decreased in TXA group than control group, and the difference is statistically highly significant (p < 0.001). Table 3 shows that number of patients requiring blood transfusion is very less in TXA group compared with control group, and this difference is statistically significant (p < 0.01).

DISCUSSION

Major blood loss has always been a matter of concern in patients undergoing surgery, particularly in major surgeries such as cardiac, vascular, liver transplantation, hepatic resections, trauma, and major orthopedic procedures.^9,10 Blood loss and its replacement are a serious problem in elective trauma surgeries and are attended to through numerous blood conservation strategies.

The present study shows nearly 60% reduction in postoperative blood loss with prophylaxis, using TXA. The results of this study can be broadly comparable with other similar studies done on arthroplasty group. Hippala et al. in two studies demonstrated 45% and 48% reduction in blood loss with the use of TXA in total knee replacement (TKR).^3,4 Another study by Good et al.^10,11 in 2003 showed that TXA in knee arthroplasty reduces blood loss by nearly 50% and the number of transfused blood units by one-third, with treatment.

The present study also demonstrated that the number of patients in the placebo group requiring blood transfusion was high when compared to the TXA group. A meta-analysis of nine randomized control studies demonstrated that the use of TXA for patients undergoing TKR significantly reduces the proportion of patients requiring blood transfusion.¹ Other clinical studies have demonstrated a decrease in the percentage of patients receiving transfusion with TXA therapy.⁸ A study by Lozano et al. demonstrated that only 17.6% patients on TXA received red blood cells transfusion, while 54% of patients in the control group needed the same in TKR.¹² Alvarez et al. also reported similar findings. The authors questioned the usefulness of the postoperative reinfusion drains and autologous transfusion in addition to the reduction of blood loss and transfusion after the administration of TXA.¹³

The acceleration of fibrinolysis is due to tissue plasminogen activator released from the vascular endothelium, which is triggered by anoxia or venous distension. The restoration of circulation could be expected to wash out and dilute factors, and turn the fibrinolytic activity toward normal. Apparently, the local acceleration of fibrinolysis and the hemostatic consequences last considerably longer and are more pivotal to postoperative bleeding than anticipated. The impact of TXA on blood loss is strong evidence supporting the role of enhanced fibrinolysis in this clinical setting.

The results are comparable to Cochrane review on “antifibrinolytic use for minimizing perioperative blood transfusion.” It included 21 trials of TXA vs control (hip and knee replacement) and reviewed 993 patients in orthopedic surgery. It showed that TXA significantly reduced allogenic blood transfusion (56%) and total amount of blood lost during perioperative period (avg. 440 mL) in orthopedic surgery.¹⁴

Our study has a few limitations as we did not monitor plasminogen levels, D-dimer, fibrin degradation products, and thromboelastography. This would have given us the objective direct evidence of fibrinolysis and antifibrinolytic activity. Secondly, we did not weigh sponges and measure Hb levels of transfused blood, which might have affected the precision of calculations. However, the similar techniques and methodologies were used in both groups to assess the blood loss and conduct the study to minimize bias. We used TXA before start of the surgery because fibrinolytic activation is a cascade process that is most easily inhibited in its earlier phases.

Hence, we observe that there is sufficient clinical evidence and support of other studies in favor of using TXA to prevent blood loss and decrease requirement of blood transfusion postoperatively.

CONCLUSION

The finding of this study indicated that TXA results in significant reduction in blood loss (nearly 60%) and amount of blood transfusion required in patients undergoing trauma surgeries. Routine administration of TXA may benefit patients undergoing TKR where significant blood loss is expected.

REFERENCES

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